Two decades of ceria nanoparticles research: structure, properties and emerging applications

Introduction

Cerium, a member of the lanthanide series, is the most abundant of all rare earth metals. Unlike others in the series that typically exist in the +3 state, cerium changes between +3 and +4 oxidation states, giving unique redox properties and reactivity. Its oxide form, e.g. ceria, cerium oxide or cerium dioxide (CeO2) has gained significant interest in both industry and academia. Ceria-based materials, composed of CeO2, embodies an array of distinctive features that make them highly desirable across many scientific areas and a wide range of industries. The nanosized form of ceria has gained significant attention over the past twenty years owning to its exceptional properties at the nanoscale. The unique crystal structure, characterized by the presence of oxygen vacancies and cerium cations with variable oxidation states confer a plethora of properties including high oxygen storage capacity, redox activity, high surface functionality and catalytic power. Notably, nanoscale ceria can accommodate more oxygen vacancies in its crystal structure than its bulk counterpart 1 . This attribute enables ceria nanoparticles (CeNPs) to exhibit very high oxygen mobility and exceptional oxygen storage capacity (OSC), making them adept at releasing and storing oxygen depending on the redox environment. These distinctive features have spurred intense investigation into CeNPs research and exploration of their properties in applications ranging from catalysis, energy conversion, semiconducting industries to environmental remediation, biosensing and biomedicine.

Ceria-based materials are utilized in catalytic converters, solid oxide fuel cells (SOFCs), catalysts for volatile organic compounds (VOCs) oxidation, sensors and chemical mechanical planarization (CMP). More recently, the scope of CeNPs has expanded to water and CO2 splitting for hydrogen production and biomedical applications as enzyme mimetics, theranostic probes and therapeutic materials. Over 30,000 articles have been published on synthesis, properties and applications of ceria-based materials, [2][3][4][5][6][7] many focusing on their role in catalytic, energy and environment. An emerging trend is the exploration of CeNPs in fields like pharmacology, medicine, biosensing and bioimaging 8,9 . However, challenges like biodistribution, cross-reactivity with clinically relevant species, and potential toxicity constrain their commercial potential 10 11 . This review aims to offer readers a comprehensive understanding of critical physicochemical properties of the CeNPs, focusing on surface modification, doping and structure-activity relationships followed by an exploration of their significant applications. Throughout this review, we will highlight the importance of CeNPs' structural design parameters, interactions, and reactivity in the context of next-generation devices. We will commence by examining the structural and shape-dependent properties of CeNPs, followed by a discussion of size-dependent characteristics, with a particular emphasis on the Ce 3+ /Ce 4+ ratio and oxygen vacancies, along with the mechanisms underlying oxygen vacancy formation. Ceria doping is a pivotal focus, as it can substantially enhance ceria's properties, opening doors to innovative applications. We delve into the intricacies of the doping process and the role of doped-ceria in catalytic reactions.

Subsequently, we address the antioxidant properties of CeNPs and their interactions with reactive oxygen species (ROS), touching upon their potential applications in catalysis, sensing, and biomedicine. A dedicated section will cover surface functionalization and its crucial role in modulating interactions between NPs and their surrounding environment. Additionally, we will explore the incorporation of CeNPs into composite and nanohybrid structures interfaced with other metals or rare-earth metal oxides, 12 enhancing their performance and augmenting their area of applicability. Finally, we will delineate applications and future directions, encompassing catalysis, CMP, biosensing, and environmental remediation.

Structural and defect properties

Bulk cerium oxide or ceria has a fluorite crystal structure with face-centered cubic unit cell (space group Fm3 ̅ m) and a lattice parameter of 5.411 Å at room temperature. In this arrangement, each Ce 4+ ion (yellow spheres) is surrounded by eight nearest-neighbor O 2-ions (red spheres) forming a cube structure. Each O 2-ion is tetrahedrally coordinated to four closest Ce 4+ ions as depicted in Figure 2a.

Defects within ceria can be introduced by altering factors such as temperature, oxygen partial pressure, electrical field or surface stress, or through the incorporation of other ions, and these defects can be broadly categorized into intrinsic and extrinsic types 1 . Intrinsic defects primarily arise due to thermal fluctuations or interaction with the surrounding environment such as redox processes. In contrast, extrinsic defects emerge from impurities or the introduction of dopants 1 (will be covered in section 2.4.). The two most noteworthy intrinsic defects observed in ceria are oxygen vacancies 13,14 and anion Frenkel defect. In an anion Frenkel defect, an oxygen ion is displaced from its lattice position to an interstitial position, resulting in a defect at the interstitial location and a vacancy at the original position 15 . These defects are typically present in low concentrations and do not impact the lattice change.

In oxygen vacancy type defect, an oxygen vacancy is created due to the liberation of an oxygen ion from a lattice site. The two excess electrons generated by the vacancy created are localized on two neighboring cerium ions thereby reducing Ce 4+ to Ce 3+ 16, 17 . This process can be represented as: Formation of an oxygen vacancy results in a decrease in the coordination number of Ce 4+ to O 2-ions and introduces Ce 3+ ions into the crystal lattice as shown in Figure 2b. Ce 3+ ions have a larger ionic radius (1.034 Å) as compared to Ce 4+ ions (0.92 Å) 18 . Therefore, the introduction of Ce 3+ ions and oxygen vacancies results in a distortion (dislocation of atoms from their equilibrium lattice points) of the local symmetry and generates strain in the lattice. Ceria particles release strain by undergoing lattice expansion 19,20 as shown in Figure 2b. Different distortions can be induced due to different Ce 3+ localization motifs with correspondingly different vacancy formation energies. The localization of electrons upon vacancy formation occurs either on the cerium ions neighboring the vacancy (i.e., Ce-O) or cerium ions next to the nearest neighbor (i.e., Ce-Ce) 21,22 .

Oxygen vacancies

Oxygen vacancy defects can be categorized into surface (present on the surface) and subsurface oxygen vacancies (present in the bulk) depending on their location 23,24 . Oxygen vacancies can either be isolated (single oxygen vacancy) or form clusters. Vacancy clusters of different shapes including triangular, dimers and straight lines have been reported 25,26 . Scanning tunneling microscopy (STM) provided the most visually convincing demonstrations of clusters of oxygen vacancies. Clusters of oxygen vacancies like linear surface vacancy clusters (LSVCs) are more favorable for migration of oxygen in ceria that happens through a vacancy hopping mechanism.

STM images showed that one subsurface vacancy per LSVC is necessary 24 . This structural requirement reveals the high reduction tendency of cerium ion upon liberation of an oxygen ion. oxygen vacancies, respectively, on a (111) surface, implying that the energies for formation of surface and subsurface vacancies are relatively close to each other 27 . Using state-of-the-art STM as well as DFT calculations, Esch and co-workers showed in an elegant study that the surface oxygen vacancies on (111) a ceria surface are immobile at room temperature and that direct diffusion (movement of lattice oxygen) needs higher temperatures (>400 °C) 24 . Note, that with increasing annealing time, the number of surface defects should decrease due to the small diffusion barrier offering it highly mobile at the elevated temperatures in which the clustering of surface vacancies is energetically unfavorable 28 .

Figure 3a and Figure 3b show the two types of vacancies, namely surface and subsurface oxygen vacancies, identified on a partially reduced ceria surface in filled-state and empty-state, respectively. Both types of vacancies were present with similar coverages. This observation was indeed in line with their DFT calculations, which predicted the same vacancy formation energy for both the defects, as shown in Figure 3c. Furthermore, on a fully reduced ceria surface, three Both surface and subsurface oxygen vacancies on a partially reduced (111) ceria surface were observed by several other researchers [29][30][31] . Oxygen vacancies are located at the third surface atomic layer. When the concentration of subsurface oxygen vacancies is very high, the defects form arrays with a propensity to form linear motifs 29 . The oxygen vacancies initially form triangular clusters and upon annealing form line defects. The clustering of oxygen vacancy defects on ceria surface is energetically more favorable than the formation of isolated surface oxygen vacancy defects 30 .

Figure 3. STM images of surface and subsurface oxygen vacancies in (a) filled-state and (b) empty-state. Pink and blue triangles represent surface and subsurface vacancies, respectively. (c) Density of states (DOS) calculations along with STM images in filled-state (inset). Structures of the observed vacancy dimers and trimers.

Reprinted with the permission from Ref 24 .

The so-called α phase non-stoichiometric oxides have compositions in the range of 0 < x < 0.286 for CeO2-x (CeO1.714 -CeO2). The α phase shows a disordered nonstoichiometric fluoriterelated structure that is stable at high temperatures (above 685 °C). XRD patterns obtained at high temperatures do not show superstructures and the lattice parameter of the cubic phase increases with x 34 . At lower temperatures however, the α phase transforms into a series of fluorite related phases described by the general formula CenO2n-2m. The lattice parameters at low temperatures are close to those reported for α phase although the α phase is disordered and low temperature phases show structural changes [35][36][37] . This implies that variation in oxygen partial pressure and temperature does not alter the positions of cerium ions and that the change in symmetry arising due to the reduction of ceria is primarily due to the formation of oxygen vacancies. Some examples of these phases are Ce10O18 (the ε phase), Ce6O11 (the β phase, monoclinic) and Ce11O20 (the δ phase, triclinic) 37,38 .

The CeO2-x oxides with the compositions x>0.286 at high temperature are dominated by the σ phase, a nonstoichiometric phase with body-centered cubic crystal structure. The C-type sesquioxide (Ce2O3), end member of the σ phase, shows bixbyite crystal structure (space group Ia3) 35 . The structures of CeO2 and Ce2O3 are closely related in that their cerium ion arrays are almost identical and oxygen ions occupy tetrahedral positions in both cases. The oxygen ions occupy all available locations in the fluorite structure while only three-quarters are occupied in the bixbyite structure 19,36 . As a result, the lattice parameter of Ce2O3 is almost twice that of CeO2.

The nonstoichiometric σ phase is very difficult to distinguish from the C-type sesquioxide.

Crystal plane and shape dependent properties

The reactivity of ceria-based materials is significantly affected by the morphology, oxidation states and the exposed crystal planes [39][40][41] . In this section, we will discuss the three thermodynamically stable low-index crystallographic planes of ceria namely (100), ( 110) and ( 111) [42][43][44] shown in Figures 4a-c. Some of the important characteristics of these three crystal planes are summarized in Table 1. Other ceria surfaces like ( 211), ( 210) and ( 310) are less stable and suffer severe reconstruction 40 . The (110) surface is a type 1 surface which exposes both cerium and oxygen ions and each layer has zero charge as the anions and cations are present in stoichiometric proportions in each plane (six coordinate cerium ions and three coordinate oxygen ions) 45,46 . The (111) ceria surface is a type 2 surface which is terminated with oxygen ions. There is no net dipole moment as the three O-Ce-O layers (stacked one on top of the other) maintain charge neutrality. The coordination number is three and seven for oxygen and cerium, respectively 44 . The (100) surface of ceria is a type 3 surface which is intricate because an ideal surface could have either oxygen or cerium ions in the top surface thereby leading to a polar and unstable surface 46 . Oxygen and cerium have coordination numbers of two and six, respectively.

The structures and stabilities of the three low-index lattice planes of ceria have been extensively investigated by many researchers. Although the results vary, the stability generally follows the order (111) > ( 110) > (100) 27,47 . Vacancies are the active sites for oxygen activation in oxidation reactions in many catalytic applications. ( 110) and ( 111) ceria surfaces have the lowest and highest vacancy formation energies, respectively. The (111) surface is less prone to accommodate a vacancy and hence energy needed for vacancy formation on its surface is the highest among the three 47 . The subsurface vacancy site is the most stable vacancy on the (111) surface 48 . In (110) surface, the vacancy with one Ce 3+ ion in both surface and first subsurface layers is determined to be the most stable. In (100) surface, two Ce 3+ ions neighboring the vacancy site is the most stable; the next most stable site is 0.30 eV higher in energy 22 . In case of ( 110) and

(100) ceria surfaces, for the same oxygen vacancy, more than one distribution of Ce 3+ sites are observed. The morphology and crystal plane of ceria can be affected by the synthesis method and the cerium precursor salt [49][50][51][52][53] . Ceria with well-defined lattice planes and morphologies can be obtained by modulating some of the critical synthesis parameters. Synthesis of ceria nanomaterials with different shapes like cube, octahedron, tetrahedron, sphere, rod and plate have been reported in literature. The most widely employed synthesis procedure to produce ceria in industrial applications is by chemical precipitation, which results in the formation of NPs. Factors like pH, base concentration, reaction temperature and time affect the physicochemical properties of NPs including the shape and size [54][55][56][57][58] . Facet engineering can be used as a powerful tool to enhance modification of CeNPs, for example silanization through favorable adsorption of tetraethyl orthosilicate (TEOS) on the (100) facets and spontaneous breakage of the Si-O bonds of TEOS, as the rate determining step for silanization 59 . -, urea and H2O2 can also be used for hydrothermal synthesis of ceria nanomaterials [60][61][62][63][64][65] .

Surfactant-or organic-assisted synthesis, with organic molecules used as coating agents, are often used to control the particle growth as the organic material adsorbs on specific planes of nanocrystals and directs the oriented growth. As mentioned above, the concentration of surfactant and cerium precursor salt, reaction temperature and time are some of the crucial factors that affect the morphology of ceria nanomaterials [66][67][68][69][70] molecules can also be used to selectively fabricate ceria nanomaterials with specific shapes. For example, addition of oleic acid (OA) as a co-surfactant to a solution of Ce(NO3)3 and diphenyl ether in oleylamine at 320 °C in sol-gel synthesis method led to the generation of nanowires and tadpole-shaped ceria nanocrystals due to anisotropic growth of nuclei 71 .

Surfactants or surface coating agents play an important role in the synthesis, and later dictate the properties of the CeNPs. For instance, nanospheres were obtained by using diethylene glycol as the reaction solvent and polyvinylpyrrolidone (PVP) as the surfactant but when the synthesis was carried out in the absence of PVP, agglomerated and irregular shaped nanoparticles were obtained 72 . The charge of the surfactant can affect the morphology and the stability of ceria nanomaterials and should be considered. Anionic surfactants can adsorb on the positively charged ceria and effectively stabilize them while cationic surfactants repel away from cerium cations and result in agglomeration of nanocrystals. The ceria nanomaterials prepared by surfactant-assisted synthesis usually have good dispersibility and uniform size distribution. This technique can be employed to fabricate different shapes ceria which cannot be obtained using the conventional methods. Nonetheless, the use of organic solvents and surfactants can results in impurities and depending of the solvent and surfactant used can increase manufacturing costs. The effect of other synthesis methods on different ceria nanoshapes and the associated formation mechanisms are presented in several comprehensive reviews and the readers can refer to them for additional information [73][74][75] . The anions of the cerium precursor salt can selectively interact with specific crystal planes and hence form nanocrystals with different morphologies. The Br -, I -, Cl -and SO4 2- counter anions of cerium precursor salt form nanorods whereas NO3 -and BrO3 -anions lead to the formation of nanocubes and NPs, respectively 50 . The anisotropic growth of Ce(OH)3 nuclei formed by Br -, I -, Cl -and SO4 2-results in nanorods formation. In the presence of NO3 -and BrO3 -, CeO2 nuclei are formed due to the oxidizing ability of these anions and the growth of isotropic CeO2 nuclei results in the formation of nanocubes/NPs. CeCl3 precursor salt exposes ( 100) and ( 110) planes due to the formation of nanorods while Ce(NO3)3 exposes (100) planes due to the formation of nanocubes 51 .

The shape of nanoceria can also affect the concentration of oxygen vacancy defects and hence their reactivity. Numerous studies have indeed investigated the effect of shape on vacancy concentration and catalytic activity. For instance, Cao and collaborators studied the effect of shape or crystal plane on catalytic activity of ceria for CO oxidation 39 . Different morphologies, e.g.

nanorods, nanooctahedra and nanocubes, with all having similar crystallite sizes were synthesized.

The high-resolution transmission electron microscopy (HRTEM) images of the synthesized ceria nanoshapes are shown in Figures 4d-j. The ceria nanocubes and nanorods exposed (100) crystal plane while the nanooctahedra exposed (111) crystal plane. The concentration of Ce 3+ ions, however, was similar in all three nanoshapes. Electron paramagnetic resonance (EPR) spectra suggested the presence of isolated vacancies on (100) facets of ceria nanorods and nanocubes and vacancy clusters on (111) facets of ceria octahedra. Furthermore, the type of oxygen vacancies and surface properties of ceria nanoshapes were correlated to their catalytic activity.

Ceria octahedra expose eight (111) planes while ceria cubes expose six (100) planes. Ceria nanorods expose ( 100) and ( 110) surfaces 76 . The reactivity of different facets, as determined by theoretical calculations, follows the order (110)>( 100)>( 111) 1,77,78 . This order, in fact, is in agreement with the experimental results on the activity of different crystal planes of ceria.

Nevertheless, different vacancy formation energies in a given surface can be obtained, which is due to some of the limitations of techniques used for theoretical calculations, discussed in detail elsewhere 1,44 .

Size impact on the reactivity and catalytic activity properties

Particle size has a significant impact on the reactivity and catalytic activity of ceria nanomaterials. The effect of particle size was first experimentally probed by Tsunekawa's group.

In a series of publications, they showed that the lattice parameter (calculated from electron diffraction patterns) increases with the decrease in the particle size from 6.7 to 2.1 nm 18,19 . Three possible models were proposed to explain the increase in lattice parameter value based on the fact that oxygen forms peroxide, O2 2-, and superoxide, O2 -, on the surface of reduced CeO2. One model suggests that the CeNPs consist of a layer of Ce2O3 with an estimated thickness of 0.561 nm on the outside while the core is CeO2. Several studies also observed size-induced lattice expansion in CeNPs particularly for sizes below 20 nm due to increase in the oxygen vacancies and Ce 3+ .

Wu et al. determined the concentration of Ce 3+ as a function of particle size using electron energy loss spectroscopy (EELS) 79 . The fraction of Ce 3+ ions rapidly increased with decreasing particle size below 15 nm. Interestingly, their EELS spectra revealed completely reduced ceria, Ce2O3, at a diameter of 3 nm. This reduced ceria was found to have a fluorite structure like that of bulk CeO2. Also, EELS spectra acquired from the edge and the center of the particles showed that, for larger particles, the reduction of Ce 4+ to Ce 3+ happens mainly at the surface, resulting in a Ce2O3 surface layer but leaving the core as CeO2. Hailstone and collaborators studied the sizedependent lattice expansion of colloidal ceria NPs using TEM 80 . The lattice constant increased with a decrease in particle size, with 1.1 and 11.8 nm particles having values of 0.578 and 0.547 nm, respectively. The corresponding lattice expansion was found to be about 6.8% and 1.1% for 1.1 and 11.8 nm CeNPs, respectively. The diffraction patterns for all the three different sized particles were found to be consistent with that of the fluorite crystal structure of CeO2 and not with the predicted cubic or the hexagonal structure of Ce2O3. Most of the surface ions were Ce 3+ and correspondingly there were substantial oxygen vacancies. The larger radius of Ce 3+ along with the associated oxygen vacancies corroborate the higher lattice constant and hence the greater lattice expansion observed for smaller particles.

As the size of ceria NP decreases, more and more oxygen vacancies are formed and hence the concentration of Ce 3+ increases as shown in Figure 5a. Since Ce 3+ ions have a larger ionic radius than Ce 4+ ions, the particle size reduction leads to lattice distortion and introduces strain in the lattice. This strain is liberated after lattice expansion and therefore the lattice parameter increases (Figure 5a) 16, 17, 19 4,6,8 . Xu et al. studied the size-dependent structural, chemical and electronic properties of ceria 81 . The lattice parameter increased with the decrease in particle size as shown in Figure 5b, but their results did not provide any proof for increase in Ce 3+ concentration and oxygen vacancies. Nonetheless, a dramatic increase in the concentration of reducible oxygen was observed at sizes below 5 nm due to peroxide formation on ceria surface. It is now established that the CeNP size influences the degree of hydroxylation and hydroxyl stability, with particles <5 nm having a higher density of more thermally stable hydroxyl groups as compared to larger particles 82 . These functional groups dictate the surface reactions and the behavior of the CeNPs in aqueous environments, which is relevant for many processes, e.g. pro-or anti-oxidant activity, surface sorption. This also suggests that, beyond the varying Ce 3+ /Ce 4+ ratios, the surface hydroxyl groups also play a critical role to the CeNP reactivity. The surface oxygen concentration varies inversely with the bulk oxygen concentration as a function of particle size as shown in Figure 5c. The concentration of surface oxygen increases at the expense of the concentration of bulk oxygen. It is likely that the significant increase in the concentration of reducible/surface oxygen is due to the increased Ce 3+ concentration as Ce 3+ ions interact with O2 and form cerium superoxide (Ce 4+ O2 -). A decrease in particle size leads to increased Ce 3+ species and hence a higher concentration of Ce 4+ O2 -species. The formation of cerium superoxide (Ce 4+ O2 -) and cerium peroxide (Ce 3+ O2 2-) species will be discussed in section properties of ceria particles using TEM, XRD, X-ray spectroscopy (XPS), extended x-ray absorption fine structure (EXAFS) and XANES 83 . These analyses revealed that the Ce 3+ concentration does not vary with size under ambient conditions although the lattice parameter increases with the decrease in particle size. As can be seen in Figure 5d, the Ce 3+ concentration remained at the same ~4% value with the decrease in particle size from 8 nm to 2 nm. This value of 4% is way lower than that reported in other studies which are in the range of 20-30% for about the same particle size. The presence of Ce 3+ ions in traces was attributed to the use of Ce 3+

precursors used for synthesis.

While most studies reported lattice expansion in the range of 0.1-0.5% for particles smaller than 5 nm, Tsunekawa et al. 19 and Wu et al. 79 observed lattice expansion in the range of 2-3.5%

for similar particle sizes. Hailstone and collaborators reported a very high lattice expansion of 7% for 1 nm CeNPs 80 . These dramatic differences in lattice expansion is potentially attributed to the effect of surface stabilizers used in the synthesis to control the particle growth. Another aspect that is worth highlighting is the relative Ce 3+ concentration. Majority of the studies reported Ce 3+ concentrations greater than 15% for particles smaller than 5 nm. Nevertheless a few studies reported very low (<5%) relative Ce 3+ concentration values for particles smaller than 5 nm. These apparent differences could be due to variations in preparation method, synthesis conditions, surface coating agents, or the characterization method employed to estimate Ce 3+ concentration.

A thorough knowledge of the particle synthesis chemistry is necessary to understand the effect of synthesis method on Ce 3+ concentration. In this regard, it is critical to create standards for the synthesis method and the determination of relative Ce 3+ concentration.

The size-dependent oxygen vacancy formation energies in (CeO2)n with n values in the range of 20-140 was investigated using DFT calculations [92][93][94] . The removal of a low-coordinate O atom from ceria needs the least energy, consistent with the results reported for other metal oxides. The removal of such O atoms from nanosized particles is more favored than from the extended surfaces.

The increase of particle size is associated with a marked decrease in the oxygen vacancy formation energy, indicating that this energy reaches a minimum at certain sizes. The size dependence of the oxygen vacancy formation energy is controlled by electrostatics. The bandwidth of the unoccupied density of states projected on to the cerium 4f orbital levels is a crucial factor that affects energy of vacancy formation. Presence of corner cerium atoms is identified as the structural pattern necessary for a significant reduction of vacancy formation energy.

By summarizing these results, the following conclusions can be drawn. ( 1) With a decrease in particle size, more and more oxygen vacancies are formed and, consequently, the Ce 3+ concentration is enhanced. (2) An increase in Ce 3+ concentration increases the lattice parameter due to the lattice expansion as Ce 3+ ions have higher ionic radius than Ce 4+ ions. (3) Most of these changes (formation of oxygen vacancies and generation of Ce 3+ ions) occur on the surface. As a result, the surface is very similar to that of Ce2O3 while the bulk remains as CeO2. When the particle size decreases to about a nanometer or two, the particle transforms from CeO2 to Ce2O3 as showed by several studies and the particle mostly consists of Ce 3+ ions. The conversion from CeO2 to Ce2O3 C-type sesquioxide does not require a change in the crystal structure. Hence, in some studies, even ~1-2 nm particles showed fluorite structure as the C-type is a combination of three types of fluorite like unit cells. (4) The oxygen vacancy formation is thermodynamically more favorable on CeNP' surfaces than in the bulk. (5) The corresponding formation energies of the Ce 3+ ions are also lower on the nanoceria surfaces than in the bulk. Clearly, these findings suggest that the concentration of surface Ce 3+ ions, the surface functional groups and the associated oxygen vacancies and, hence, the reactivity of NPs increases with a decrease in particle size while the oxygen vacancy formation energy diminishes markedly.

Modification by doping

Due to the increased surface area to volume ratio and relative ease of vacancy defect formation, CeNPs show enhanced reactivity and outstanding catalytic activities enabling their use in many commercial applications. However, pure CeNPs are associated with some drawbacks like deactivation of OSC and catalytic activity, and a loss of surface reactivity due to thermal sintering at high temperatures which limit their use in some commercial applications 95,96 . It is therefore of interest to modify the properties of CeNPs, and alter the surface energies, to facilitate their use in such applications. Any chemical modification or doping of CeNPs involving an increase in the concentration of oxygen vacancies should in principle increase their reactivity. This is true only if (a) the chemical modification process does not lead to a significant reduction in the concentration of active redox species and (b) the defects formed at high degrees of reduction do not cluster, making ion transport difficult.

One of the important strategies to overcome these limitations is to incorporate other metal ions into the crystal structure of CeNPs by doping. Addition of dopants results in higher resistance to sintering at elevated temperatures and an enhancement of reducibility and OSC of CeNPs and therefore improves the overall catalytic performance 97,98 . The concept of modifying CeNPs by doping with foreign materials indeed led to enhanced thermal stability and improved catalytic activity. In a typical doping process, cerium atoms in the crystal lattice are replaced with noble metals, transition metals or rare earth metals.

Doping is done during synthesis and the dopants substitute Ce 4+ . The result is that oxygen vacancies are introduced in the crystal structure of ceria for charge compensation 99 as shown in Figure 6a. Doped CeNPs show very high oxygen mobility through a vacancy diffusion mechanism and hence high ionic conductivity 100,101 . Given the importance of oxygen vacancy defects of CeNPs in many applications, this topic has garnered a lot of attention. Most reported works explored the use of rare earth (Y 3+ , Gd 3+ , Sc 3+ , Sm 3+ , Er 3+ , Eu 3+ , La 3+ , etc.), noble (Pt, Pd, Au, and Rh) and transition metals (Cu, Co, Ni, Mn, Zr, Zn, Fe, etc.) as dopant materials to modify the physicochemical properties of CeNPs (Figure 6b). The dopants are further categorized into two types, isovalent and aliovalent, based on their oxidation state 102,103 . Isovalent dopants are the ones that have a 4+ oxidation state (same as that of the host Ce 4+ ) and aliovalent dopants have an oxidation state that is different from that of the host. Substitution of Ce 4+ with the isovalent dopants in the crystal lattice of ceria introduces intrinsic oxygen vacancies and reduces the oxygen vacancy formation energy because of structural distortion 72 . On the other hand, substitution with aliovalent dopants incorporates both extrinsic and intrinsic defects and reduces vacancy formation energy due to structural distortion and electronic modifications.

Doping with rare-earth metals

Rare earth doped CeNPs are attractive candidates for many industrial oxidation reactions, biomedical and biosensing applications and electrodes in solid oxide fuel cells (SOFCs). The introduction of oxygen vacancies upon doping ceria with rare-earth ions can be represented as follows in Kröger-Vink defect notation (Eq. 2.4)

Where 𝑅𝑒 𝐶𝑒 ′ represents a Re 3+ ion on a Ce lattice site.

Increase in the concentration of Gd from 0 to 15% increased the OSC of CeNPs but with a further increase, the OSC decreased 104 . The enhanced OSC was attributed to the increased specific surface area and decreased particle size. In contrast, Hennings et al. reported that the OSC decreased after with Gd 105 . Nevertheless, the concentration of oxygen vacancies increased with the increase in Gd concentration. They argued that the drop in OSC was due to the replacement of reducible Ce 4+ by non-reducible Gd 3+ and suppressed reduction of Ce 4+ . Trivalent La, Sm, Y and Gd increase the concentration of Ce 3+ ions on the surface of particles 106 . Increase in Ce 3+ concentration enhances oxygen vacancies and facilitates transport of oxygen from the bulk to the surface. La and Pr doping boosted the concentration of surface reducible Ce 4+ ions and shifted the reduction peak of CeNPs to lower temperatures 107 . It is important to point out that the optimal concentration of dopant required to obtain maximum increase in the concentration of Ce 3+ and oxygen vacancies depends upon the type of the dopant. For instance, in one study, it was shown that the optimal concentration of La and Pr was about 5% and 50%, respectively 108 . Of all RE elements, Pr yields the maximum concentration of oxygen vacancies. In case of Pr doping, the presence of both Ce 3+ and Pr 3+ ions increased the concentration of oxygen vacancies due to the reduction of Pr 4+ to Pr 3+ and Ce 4+ to Ce 3+ 107 . Of Nd-and La-doped CeNPs prepared using microemulsion method, the oxygen vacancy defect concentration was higher for La-doped ceria than for Nd-doped ceria and this difference was attributed to the larger ionic radius of La as compared to Nd 109 . Y, Sm and Gd doping increased the Ce 3+ and oxygen vacancy defect concentration while Yb doping reduced it due to the smaller ionic radius of Yb 3+ as compared to that of the other three ions 110 . Er and Ho also decreased the density of oxygen vacancies due to a similar reason 111 . Using DFT calculations, Kim et al. established a trend between the radius of the RE metal ion and oxygen vacancy formation energy, which is related to the catalytic activity 112 .

The relationship between the oxygen vacancy formation energy and the ionic radius of RE metal, and the highest reaction energy and ionic radius of RE metal ion (Figures 7a and7b) showed an increase in the vacancy formation energy with the ionic radius whereas the maximum reaction energy (for the case of CO oxidation considered as an example) decreases with the ionic radius.

The contribution of the dopant to oxygen vacancy formation energy was also investigated. The ionic radius of the dopant (Rion) was also found to influence the RE-O interaction which in turn with La being an exception. As a result, structural stress is induced along RE-O. The stress created by the dopant ion having a smaller ionic radius weakens the strength of the RE-O as shown in Because lanthanide complexes have excellent luminescence, these structures can be widely used in biosensing and bioimaging applications 113,114 concentration enhanced the photoluminescence properties whereas an increase in vacancy defect concentration adversely affected the photoluminescence by interfering with the radiative route of emission 117 . Erbium (Er) is another rare-earth element that has been used by several investigators as a dopant to impart fluorescence in ceria particles 118,119 .

Not all trivalent rare-earth metals increase the concentration of Ce 3+ and of oxygen vacancies.

An important question that then needs to be answered is -what cations can be used for doping ceria particles? Several studies suggested that dopants having ionic radii lesser than that of Ce 4+ ion can be doped into ceria lattice. However, this is not always the case as evidenced from many contradictory results reported in literature. 2,120 When the dopant substitutes a Ce 4+ ion in the crystal lattice of ceria, the periodic electrostatic field distribution changes due to different electronegativity, oxidation state and ionic radius of the dopant with respect to the Ce ion. The thermodynamics (enthalpy) of dopant incorporation and other thermodynamically relevant factors can potentially be helpful in identifying the right dopant. Computational techniques can also provide some guidance in understanding the thermodynamics of dopant addition to ceria lattice.

Doping with transition and noble metals

Apart from rare earth metals, transition and noble metals were also used to dope CeNPs to enhance their catalytic properties. CeNPs doped with transition metals like Co, Zr, Cu, Fe, Mn, Cr, etc. have good redox ability and can therefore act as active materials for oxidation reactions.

The reactivity of these ceria-mixed materials is influenced by various factors like valency of the dopant, catalyst composition, nature and type of the support, as well as the synthesis technique, particle size and shape and crystal structure.

Among composite structures, zirconia doped ceria (ceria-zirconia) has been studied intensively due to its significance in various industrial catalytic reactions. Ceria forms a substitutional type solid solution with zirconia. When CeNPs are doped with zirconia, the smaller Zr 4+ ion causes lattice distortion, leading to an increase in oxygen mobility. After introducing Zr 4+ ions into the crystal lattice of ceria, both Ce-O-Zr and Ce-O-Ce bond lengths in CexZr1-xO2 lattice decrease and oxygen shows a centro-symmetric eight-fold coordination 121 . This change in the local environment of oxygen around Ce 4+ and Zr 4+ cations leads to the formation of active oxygen species that plays an important role in the OSC property, and therefore its catalytic activity. The reduction of ceria in ceria-zirconia solid solutions can be described by the following chemical reaction:

The oxygen nonstoichiometric (δ) value in the above equation changes with composition x. The enhanced reducibility is due to the improved oxygen mobility of solid solutions as compared to the pure oxides. The high concentration of oxygen vacancy defects increases the active sites for ionic conduction and provides a high diffusion path through the nanosized grain boundaries that promote fast kinetics 122,123 . Introduction of Zr 4+ ions in the fluorite crystal structure of ceria decreases the specific surface area at the operating conditions. Nonetheless, the increased thermal resistance to sintering, decreased oxidation enthalpies, higher reduction efficiency and increased OSC of zirconia doped ceria contribute to the enhanced performance of ceria-zirconia system in designing a new generation of three-way catalytic converters (TWCs) 124 .

Ceria-zirconia catalysts have gradually replaced pure ceria whose properties did not meet the requirements of high conversion efficiency and thermal resistance needed to sustain stringent emission regulations. Additionally, a critical need for more thermally stable materials to improve performance of TWCs during cold start led to the development of several strategies. Among them, doping of ceria-zirconia with rare earth elements like La, Pr, Y, Sm and Nd resulted in an increased thermal stability and OSC 125 . The cerium precursor salt was found to have a significant influence on the catalytic properties. The ceria-zirconia catalysts prepared using cerium salt having +4 oxidation state, (NH4)2Ce(NO3)6, was found to have higher Ce 3+ concentration than those prepared using cerium salt having +3 oxidation state Ce(NO3)3•6H2O 126 . Also, the catalysts prepared with Ce 4+ precursor salt had higher Zr concentration and showed improved oxygen mobility than those prepared by Ce 3+ precursor. The catalytic activity of ceria-zirconia catalysts is dependent on both the BET surface area and Ce/Zr surface atomic ratio. The Ce/Zr value in turn depends on the synthesis technique and therefore the catalytic activity strongly depends on the preparation method. Thus, the BET surface area of the catalyst prepared using Ce(NO3)3•6H2O was higher than that prepared using (NH4)2Ce(NO3)6; the latter showed higher catalytic activity which was attributed to the higher Zr concentration on its surface.

In other reports, the addition of Cu to the ceria lattice increased its OSC and redox properties by reducing the activation energy for Ce 4+ reduction as showed by Hu et. al., 127,128 . Their results

showed that the Cu/Ce ratio in the catalyst strongly influenced the catalytic and redox properties.

The pore structure and morphology of Cu-doped ceria NPs can be affected by the precursor used for synthesis. CuCeOx nanofiber catalysts prepared by electrospinning technique showed higher catalytic activities as compared to those prepared by other conventional methods 129 . The enhanced catalytic activity of nanofibers was ascribed to the large specific surface area and increased concentration of Ce 3+ ions and oxygen vacancy defects. Doping of CeNPs with Cu also increased the overall surface area and improved the redox properties.

Mn doping into ceria lattice has also showed to increase the concentration of oxygen vacancy defects. XPS analysis of the surface indicated that the Ce is present in +4 or +3 oxidation states while Mn exists in +3 or +2 oxidation state 130 . EPR analysis indicated the presence of Mn 2+ and Mn 3+ species in defect sites of ceria lattice, interstitial spots and on the surface of ceria. Doping with Mn decreased the particle size of calcined CeNP powders and dramatically increased the BET surface area 131 . Impedance spectroscopy measurements have revealed that the Mn ions enter into solid solution and increased the conductivity by decreasing the apparent activation energy.

DRIFTS results showed that a fraction of Mn ions remain segregated on particle surface. The remarkable enhancement in catalytic activity of Mn doped ceria at low temperature is ascribed to good dispersion of Mn 2+ /Mn 3+ ions in the ceria matrix, high OSC, increased redox properties and synergistic interaction between the Mn and Ce. Among co-precipitation (CP), sol-gel (SG) and hydrothermal methods used to prepare Mn-doped ceria, the catalyst synthesized by HT method showed very high catalytic activity at low temperature 131 . The larger surface area, increased reducibility, higher concentration of surface adsorbed active oxygen species and an increased number of oxygen vacancy sites are the possible reasons for the enhanced catalytic activity of the mixed catalyst prepared by hydrothermal method.

In other structures, the presence of Ni 3+ ions and a very high concentration of oxygen vacancy defect sites in Ni-doped ceria NPs (Ni0.1Ce0.9O2-x) has showed an increase in the surface reducibility of these doped structures as compared to pure ceria 132 . Ni-doped ceria showed superior electrochemical properties due to increased concentration of Ce 3+ , Ni 3+ and oxygen vacancy defects used to boost Faradaic surface redox reactions 133 . Doping with Ni leads to additional structural stress and lattice expansion and extrinsic defects on the particle surface and near grain boundaries. It also results in enhanced surface oxygen reactivity and thus more active reduction sites at their surface. Other reports explored the use of Co to increase catalytic properties of CeO2 and found enhanced performance of Co-CeO2 catalyst as compared to that of bulk Co3O4

or ceria due to a synergetic effect between Co and CeO2, leading to increased concentration of oxygen vacancy defects and enhanced reducibility 134 . The preferential exposure of (112) crystal plane of Co-CeO2 which contained a large concentration of Co 3+ active sites was also suggested to be responsible for the higher catalytic activity. The increase in cobalt dopant concentration also increased the band gap energy and reducibility of the catalyst 135 .

Fe doping of ceria enhanced the catalytic activity due to the increased concentration of surface Ce 3+ and chemisorbed reactive oxygen species 136 . Addition of iron into the crystal lattice of ceria decreased the crystallite size and increased the specific surface area 137 . Fe-doped ceria favors sintering at lower temperatures, enhances the reducibility and increases the number and strength of basic sites 138 . Doping of ceria with iron can also improve the conductivity, decrease the activation energy and enhance the dynamic oxygen storage capacity (DOSC). Therefore, the Fedoped ceria catalyst showed low temperature activity and increased total oxygen storage capacity (TOSC). It was suggested that the incorporation of Fe into the crystal lattice of ceria strongly modifies the kinetics of oxygen diffusion and enhances the OSC.

Ag, Au, Pt and Pd doping are other suitable approaches to enhance the catalytic activity of CeNPs. The addition of Ag favors the formation of reducible oxygen species that is suggested to be responsible for the improved catalytic activity 139 . The synergistic interaction between Ag and ceria is the key for low temperature reduction of ceria 140 . Three different methods used to prepare Pt-doped ceria catalyst resulted in different values of ionic Pt/Pt 0 ratios 141 . Furthermore, these three different catalysts were found to achieve varying catalytic activities, increasing with the increasing concentration of ionic Pt species. DFT calculations suggested that the presence of ionic Pt species activated the oxygen atoms on the cerium next to it resulting in decreased activation energy for dissociative methane adsorption. As a result, the novel square-planar configuration of PdO4 in Pddoped ceria is shown to be more reactive 142 . Creation of an oxygen vacancy in this structure is energetically more favorable. The structural and chemical attributes of Pd-O-Ce moieties were found to contribute to the higher catalytic activity of Pd-doped ceria 143 . All Ce ions in the crystal are in 4+ oxidation and they are not reduced to 3+ state upon formation of oxygen vacancies as evident from the density of electron states where the filled Ce4f gap states associated with the reduced ceria are not present. The physicochemical properties of rare earth, transition and noble metal doped ceria particles are summarized in Figure 8.

Figure 8. Schematic of the physicochemical properties of rare earth, noble and transitional metal doped ceria particles used to obtain mixed and doped structures with CeO2.

The improved catalytic activity of doped CeNPs has been generally attributed to an increased concentration of oxygen vacancies and Ce 3+ , and OSC. Other factors like large surface area, improved redox activity, enhanced thermal resistance and the synergistic interaction between the metal and ceria also contribute to the enhanced activity. Almost all transition and noble metals investigated were reported to enhance catalytic activity. Nevertheless, other factors like the preparation method, concentration of the dopant, type of dopant, oxidation state, crystal structure, also influence the catalytic properties of doped ceria [144][145][146] .

Experimental studies provide critical information on the characteristics of the catalyst, oxidation reactions, surface processes and its mechanism. Selection of appropriate characterization methods is essential in gaining mechanistic details on important aspects of the ceria's activity such as metal-ceria interactions, role of the dopant, oxygen vacancy defect and surface oxygen species 125 . In addition to experimental tools, theoretical studies based on computer simulations can provide atomistic understanding of the structure of ceria-based catalysts, the role of dopant, oxygen vacancy defect and Ce 3+ ions on catalytic properties of catalysts.

Detailed structural analysis of Ce1-xZrxO2 catalyst suggests that the formation of long and short Zr-O bonds in fluorite structure is mainly responsible for enhanced OSC observed for ceriazirconia [147][148][149] . Substitution of Ce 4+ ion with Zr 4+ increases the reducibility of Ce 4+ in ceria although ZrO2 is not a reducible oxide. Addition of reducible ions like Sn 4+ and Ti 4+ into the ceria lattice can enhance the OSC of Ce1-xSnxO2 and Ce1-xTixO2, respectively. Along with Ce 4+ /Ce 3+ couple, the Sn 4+ /Sn 2+ and Ti 4+ /Ti 3+ redox couples can also contribute to and therefore increase the reducibility of CeNPs. The coordination around Ti 4+ or Sn 4+ ion is different from the fluorite structure of ceria due to the lower ionic radius (0.74 Å for Ti 4+ and 0.69 Å for Sn 4+ ) of these ions as compared to that of Ce 4+ ion (0.97 Å) and this results in distortion of the ceria lattice [150][151][152] .

Computational methods were used to study the properties of doped ceria materials 72,153,154 .

The 111) surface of ceria 160 . The dopant can have an oxidation state anywhere between 3+ and 8+ and in such a case the Ce 4+ ions are reduced to Ce 3+ only when the dopant has an oxidation state higher than 4+. This is considered as a global effect as this mechanism is found to be independent of the distance between the vacancy formation site and the dopant. In case of non-reducible dopant like Zr, since Zr 4+ is smaller than Ce 4+ , structure relaxation effects drive the lowering of the vacancy formation energy and hence the energies of the doped and defective surfaces are about the same. On the contrary, reducible dopants like Pt, Ru, Nb and Ta exhibit both local and global effects and hence the energy required to form a vacancy near the dopant is lower than that required to create a vacancy defect away from it. The local effect with these dopants is related to the chemical interaction i.e. dopant-oxygen binding.

The catalytic properties at the interface of ceria-metal have been extensively studied, as this interface is the favored spot for exchange of oxygen and is recognized as the active site responsible for the enhanced catalytic activity 161,162 . An interfacial reaction mechanism was proposed in which CO is suggested to be adsorbed on the metal and then oxidized by oxygen transfer from ceria, which in turn is oxidized by H2O 163,164 . More detailed information has been obtained on the ceriametal interaction in which ceria is supported on the metal 165 . Additional proof of the interfacial activity involving dissociation of CO-like molecules on oxygen vacancies on the ceria surface and a systematic investigation of ceria-metal properties has been demonstrated using advanced characterization techniques [166][167][168] . Some of the important fundamental observations of these studies

Antioxidant enzyme-like mimetic and ROS scavenging activity

ROS (O2 •-, H2O2, •OH) and RNS (ONOO ─ and •NO) are powerful oxidizing and nitrating agents that play a critical role in several important biological processes including signal transduction, biochemical reactions and physiological and pathological changes 181 . While ROS/RNS are important in cell signaling, an excessive level of these species can damage the DNA, proteins and lipids and thereby cause oxidative stress that subsequently results in the damage of tissues and cells. These conditions can lead to diseases like cancer, diabetes, cardiovascular and neurodegenerative diseases and arthritis 182,183 . While conventional antioxidants can only scavenge a particular type of ROS or RNS, CeNPs can scavenge many ROS and RNS, and their effectiveness is dependent of the size and surface properties of the NPs. The deleterious effects arising from surplus O2 •-are usually controlled and alleviated by endogenous SOD enzymes located in the cytoplasm and mitochondria 184 . SOD enzymes eliminate O2 •-species by converting them to O2 and H2O2 through a catalytic dismutation reaction that occurs in two steps as follows 185,186 . This process is schematically shown in Figure 10a.

The SOD enzyme works by accepting electrons from or losing electrons to O2 •-. In reaction 2.6, the reduced (Cu + )-SOD catalyzes the oxidation of O2 •-to H2O2 while in reaction 2.7, the oxidized (Cu 2+ )-SOD catalyzes the reduction of O2 The above two reactions indicate that the Ce 3+ /Ce 4+ redox couple of ceria NPs can be regenerated. In the first step, superoxide anions bind to oxygen vacancies around two Ce 3+ species and an electron is transferred from Ce 3+ ion to an oxygen atom. In the second step, two protons in the solution bind to two oxygen atoms and form a molecule of H2O2. The second superoxide anion then binds to the remaining oxygen vacancy and a second H2O2 molecule is formed and Ce 3+ is oxidized to Ce 4+ . Furthermore, the two electrons produced will reduce the Ce 4+ ions to Ce 3+ ions and in this case H2O2 acts as a reducing agent. However, while these reactions have been postulated, the mechanisms driving the SOD-mimetic activity of ceria NPs are still subject to debate and their behavior in biological environments are subject of numerous scientific investigations. In some studies, CeNPs having higher Ce 3+ concentration were more efficient scavengers of O2 •-than those with lower Ce 3+ concentration 172 . In another study, CeNPs treated with H2O2 and hence having lower Ce 3+ concentration showed a decrease in the SOD mimetic activity as compared to bare ceria, implying that the surface Ce 3+ species play a key role in SOD mimetic activity 187 as indicated in Figure 10c. These processes take place at the surface of the metal oxide and are affected by conditions such as pH and temperature. 169 High H2O2 levels are considered detrimental to cellular homeostasis as compared to high levels of O2 •-as H2O2 forms highly toxic •OH radicals via the Fenton reaction with metals as shown in Besides, Ce 3+ concentration, factors like particle size, buffer species like PO4 3-, and solution pH can all affect the catalase and SOD-mimetic activities of ceria 189,190 . The presence of PO4 3- was shown to diminish the SOD-mimetic activity and enhance the catalase activity due to the ability of Ce 3+ ions to form strong coordination complexes on reaction with PO4 3-, which bind preferentially to ceria NPs with high Ce 3+ concentration. The mechanism by which phosphate changed the properties of ceria NPs was attributed to formation of CePO4-like complexes that blocks the redox activity of ceria NPs 189 . Since the ability of ceria particles to cycle between 3+ and 4+ oxidation states is the key to their catalytic activity, the catalase mimetic activity diminishes in the presence of any compound that can block Ce 3+ and stabilize the ceria NPs in the 3+ state.

Therefore, the ability of CeNPs to swiftly change between 3+ and 4+ oxidation states is crucial in maintaining their SOD-mimetic activity. These studies indicate the need to comprehensively study and understand the influence of phosphate ions, and other ions on SOD mimetic activity of ceria, particularly because cells contain high concentrations of phosphate ions, and other ions and their presence can potentially affect the biological activities of ceria NPs.

Contradictory results were reported in literature on the influence of pH on the antioxidant activity of CeNPs with some studies showing no effect of pH and other studies revealing marked effects on both the SOD mimetic activity and Ce 3+ concentration on the particle surface. Singh et al. 189 and Xue et al. 176 showed that the dispersion stability and SOD mimetic activity of ceria NPs are not affected by pH. In contrast, using XPS spectroscopy, Karakoti et nanowires > nanobars > NPs 194 . Better understanding of the catalytic mechanisms and the fundamental parameters affecting the 'enzyme-like' activity will enable future development of high performance nanoenzymes 195,196 as alternatives to natural oxidase and peroxidase enzymes, providing advantages such as a stability, robustness and low cost, making them suitable for many applications.

Interactions with molecular oxygen and H2O2

The characterization of different types of oxygen species formed by adsorption of O2 on CeNPs is important as these species play a key role in many oxidation reactions. One of the major applications of CeNPs is as an oxygen storage material in TWC converter in automotive exhausts.

Ceria acts as a buffer to supply O2 during O2 deficient conditions of engine operation, and extract O2 when there is surplus O2 in the exhaust stream and thus helps to maintain the concentration of oxygen. The mechanism of oxidation reactions on ceria surfaces involves the reaction of the adsorbate with the O2 present in the substrate, which is then replenished from the gas phase O2 125 .

Studies to understand the adsorption and desorption of O2 on ceria surfaces are thus critical for TWC applications. Using both experimental methods and theoretical models, it has been established that the reactivity of stoichiometric ceria (unreduced ceria) towards molecular oxygen is very low as compared to that of reduced ceria. O2 physisorbs on the surface of unreduced ceria

NPs by a weak interaction dominated by dispersion forces [210][211][212] . DFT calculations of oxygen adsorption revealed very low adsorption energies and showed that O2 adsorbs only at very low temperatures on unreduced ceria. On the other hand, molecular oxygen binds very strongly on reduced ceria surfaces [213][214][215] .

The formation mechanism involves creation of an oxygen vacancy which results in the formation of two Ce 3+ ions and hence the vacancy site is a two-electron donor center. O2 interacts with the oxygen vacancy and adsorbs such that one oxygen atom fills the vacancy and the other points out from the surface 210 . O2 adsorption at an oxygen vacancy site therefore removes the defect and results in the formation of a surface peroxo species (O2 2-) 216 . The diamagnetic O2 2-can be detected by Raman and FTIR spectroscopies. The peaks related to O2 2-typically occur in the 820-880 cm -1 region 217 . O2 -species on the other hand are formed when O2 interacts with lowcoordinated Ce 3+ ions (steps, edges, dislocations, etc.) which are one-electron donors 218 . In this case, oxygen vacancies are not involved and O2 -species are formed in the vicinity of exposed Ce 3+ ions 213 . The fingerprint of the O2 -species is, besides the characteristic EPR signal, a Raman or IR peak in the region 1110-1150 cm -1 216 .

Early experimental studies used FTIR spectroscopy to investigate the adsorption of O2 on ceria.

The adsorption of O2 on partially reduced ceria resulted in an IR peak at 1128 cm -1 attributed to O2 -species and at 883 cm -1 related to peroxide species. O2 -and O2 2-are the intermediates formed during oxygen dissociation/re-oxidation that occurs according to the following scheme 219 .

where aq stands for aqueous and ads stands for adsorbed.

As can be seen from Eq. 2.15, first, the O2 -is formed after exposure to O2. The O2 -is then converted into peroxide and finally to lattice oxygen by gaining more electrons from the surface.

As a result of this re-oxidation, the surface will become electron deficient and further electron transfer from the surface to O2 does not occur. Similar bands were also observed in studies that used Raman spectroscopy to probe the adsorption of O2 on ceria. Pushkarev et al. studied adsorption of O2 on CeNPs using in-situ Raman spectroscopy and demonstrated that O2 adsorbs on one-and two-electron defects and forms O2 -and O2 2-species, respectively 215 . Two bands each in ranges of 1120-1140 cm -1 and 830-880 cm -1 related to superoxide and peroxide species, respectively were observed. The two different bands can be ascribed to disparate configurations of the binding of superoxide species to ceria and to the peroxide species bound to defects with different geometries. Temperature-programmed experiments revealed re-oxidation of the surface by adsorbed oxygen species. The O2 -that form first due to adsorption of O2 are unstable and transform into peroxides which then translate into lattice oxygen similar to what was reported previously.

Wu et al. investigated the adsorption of O2 on ceria nanocubes, nanorods and nanooctahedra exposing ( 100), ( 110)/( 100) and ( 111)/(100) crystal planes, respectively 220 . They illustrated the mechanism of oxygen activation and transformation on these surfaces, which is pivotal in understanding the mechanism of oxidation reactions catalyzed by nanoscale ceria. Adsorption of O2 on ceria gave rise to a band at 1139 cm -1 which they attributed to O-O stretching of O2 -. The other observed peaks at 830 and 860 cm -1 were ascribed to peroxide species on isolated and clustered two-electron defects. The amount of adsorbed oxygen species on reduced ceria nanoshapes changes with the degree of reduction. The weak bands of adsorbed oxygen species in ceria nanorods suggest the presence of small amounts of defect sites. Temperature dependent oxygen adsorption experiments revealed that the adsorbed O2 -species were stable up to 350 K while the peroxide species were stable until 473 K. Based on their results, they suggested that the re-oxidation of ceria occurs as shown in Eq. 2.15. 20% of adsorbed oxygen desorbs into gas phase through disproportionation reactions of O2 2-and O2 -species as shown below.

O2 -ads + O2 -ads → O2 2-ads + O2 (2.16)

The adsorption of oxygen on (111) surface of ceria was studied using DFT calculations. O2

does not adsorb on oxidized surfaces and binds weakly to one-electron defect sites 210 . O2 -forms on hollow sites of (111) surface in a side-on configuration above Ce 4+ ions. The O2 -preferentially adsorbs on Ce 4+ surface sites due to electrostatic interaction and hence Ce 4+ O2 -is predicted to be the reactive intermediate as Ce 3+ O2 is more stable. Partially reduced ceria exposed to O2 resulted in the formation of O2 -and O2 2-and the associated Raman peaks were observed at 1131 and 825 cm -1 , respectively 217 . The energies of O2 adsorption on unreduced ceria surfaces were found to be endothermic while those on reduced surfaces were exothermic. The position of oxygen vacancies can affect the formation and dissociation of oxygen species.

Most of the experimental and theoretical results indicate that oxygen vacancy sites and Ce 3+ play crucial roles in the formation of peroxide and superoxide species, respectively, and that these adsorbed oxygen species are active intermediates in the subsequent oxidation reactions 221,222 . The possible geometries of adsorbed oxygen species at different active sites on the reduced and unreduced surfaces of ceria are depicted in Figure 12.

Figure 12. Possible complexes of adsorbed oxygen species formed due to interaction of molecular O2 with ceria NPs.

The adsorption energies, vibrational frequencies, partial charges and relevant geometrical parameters for different configurations have been calculated by several theoretical studies 210,213 .

The end-on-V configuration of peroxide adsorption on ceria is energetically the most favorable one of all the possible structures. The side-on-V structure of superoxide adsorption is the second stable structure. O2 physisorbs (adsorbs very weakly) on Ce 4+ of an unreduced surface in an endon configuration. The values of energies suggest that O2 binds very strongly above one-(Ce 3+ ) and two-electron defects (oxygen vacancies), implying that the dissociation process is energetically more favorable on the reduced ceria surface than on an oxidized surface 223 .

In summary, O2 adsorbs very strongly on the surface oxygen vacancy and forms diamagnetic peroxide species since two electrons from 4f orbitals of Ce 3+ ions are transferred to the half-filled π2p* orbitals of O2 223 . O2 2-species are formed from the adsorption of O2 at low-coordinated Ce 3+

ion that is quite far away from the oxygen vacancy site 213 . O2 preferentially binds in a side-on configuration, with the end-on mode being less favorable. This interaction results in the charge transfer of one of the two electrons in 4f orbital of Ce 3+ to the πg* orbital of O2. Simultaneously, one Ce 3+ ion is oxidized to Ce 4+ ion and a complex (Ce 4+ O2 -) is formed through ionic interaction 217 .

The interaction of H2O2 with CeNPs was also studied in great detail in many reports on antioxidant activity relevant to biomedical applications. Nonetheless, the mechanism of reaction of H2O2 with CeNPs is still not completely understood. Postulating that H2O2 oxidizes Ce 3+ to Ce 4+ , it was shown that CeNPs exposed to H2O2 and, having lower concentration of Ce 3+

suppressed the SOD mimetic activity 187 . Later, several studies demonstrated that the oxidation of Ce 3+ to Ce 4+ is reversible, and that the reduction happens after a long period (15 days) in aqueous solution following degradation of H2O2 180,190 . The mechanism of reduction reaction was investigated, and it was proposed that H2O2 reacts with Ce 4+ ions and reduces them to Ce 3+ ions while it simultaneously gets oxidized to molecular O2. Some controversies exist regarding the mechanism of oxidation/surface complexation of CeNPs, and the impact of surface coating on the oxidation/complexation in the presence of H2O2. Most of the studies ascribed the change in color of CeNPs in the presence of H2O2 to the conversion of Ce 3+ to Ce 4+ while some suggested that the color change was due to the formation of Ce 3+ O2 2-and/or Ce 4+ O2 -or Ce 4+ . 224 With respect to surface coating, some studies showed that coating does not have any influence on the reaction of H2O2 with the particles while others showed apparent differences in the reactivity depending on surface coating 225,226 . In a comparative study, the 8.2 nm ceria NPs coated with a thick layer of polyethylene imine or polymaleicanhydride-alt-1-octadecene were found to be less reactive than the smaller 3.8 nm with a thin layer of poly(lactic acid) 225 .

Yu et al., developed an E-pH diagram for the CeO2-H2O-H2O2 system to understand the role of H2O2 in preparation of cerium conversion coating processes 227 where the value of x could be 0, 2 or 6.

Ce 3+ is the more stable form in the lower pH range and Ce 4+ can be reduced to Ce 3+ by H2O2.

Conversely, Ce 4+ is the more stable form at higher pH values. Ce 3+ is soluble over a wide pH range (pH <11) as compared to Ce 4+ which is soluble at pH <4. During the oxidation of Ce 3+ to Ce 4+ with H2O2, the concentration of the intermediate Ce 3+ /Ce 4+ complexes is very high.

Scholes and co-workers performed titration of cerium-based conversion coating solutions to investigate the role of H2O2 228 . The titration results indicated the formation of a Ce(III) peroxo complex like Ce(H2O2) 3+ , and successive deprotonation led to the formation of Ce 3+ O2 2-which on oxidation gave Ce(IV) peroxo species like Ce(IV)(O2)(OH)2. Finally, the Ce(IV)peroxo complex converted to CeO2 after several months and the authors attributed the conversion to decomposition of the complex. The use of ceria NPs as colorimetric probes for the detection of glucose has been explored by several studies. Addition of H2O2 to a dilute dispersion of 20 nm ceria NPs (colorless) changed the color of the particles to reddish-orange 229 analysis shows a red-shift in the spectra of CeNPs in the presence of H2O2 with the extent of red shift increasing with the concentration of H2O2 230 231 . The coordination number of Ce ions after H2O2 addition was found to increase based on analysis of x-ray absorption fine structure (XAFS) measurements. However, the coordination number decreased back nearly to the original value at the end of the reaction (after 9 hours); the increase in the coordination number was attributed to the formation of surface adsorbed peroxide complexes. The interaction of H2O2 with oleate capped CeNPs in dichloromethane (DCM) was investigated 232 . Figure 14 shows the UV-Vis spectra of CeNPs treated with H2O2 as a function of time in the wavelength range of 200 to 700 nm. H2O2 addition was found to increase the absorbance at 2 wavelengths (λ1 = 285 nm) and (λ2 = 380 nm). Deconvolution of the UV-Vis spectra of the H2O2 adsorption by CeNPs revealed the appearance of two peaks corresponding to two processes: the peak at 285 nm was related to the oxidation of Ce 3+ to Ce 4+ while the peak at 380 nm was due to the formation of surface adsorbed peroxide species. Further, the FTIR peak at 840 cm -1 indicated the presence of peroxide/hydroperoxide species. Certainly, the ratio of these different species is dependent on the size, surface coating, preparation method, pH and ionic strength. These complexes are reversible and the particles can recover their activity after several days/weeks at room temperature, or within few minutes at high temperatures of 70-100 °C due to decomposition of the surface adsorbed peroxide and hydroperoxides 5 .

Dissolution of ceria-based systems as a promising strategy for regeneration

Every year, large quantities of ceria-based materials are used in TWC converters in automotive exhausts and CMP of dielectric films during integrated circuit (IC) fabrication. Recent reports suggest record high increases in the price of cerium-based materials due to more stringent export rules of the world's largest producer of rare earth materials and scarcity of cerium materials 233,234 .

A threefold approach which includes recycling and reuse of these materials and development of alternative materials having less hazardous ecological impacts has been proposed. Selective dissolution of ceria-based systems appears as a promising strategy to recover cerium and hence thorough knowledge about the fundamental aspects of ceria dissolution is essential 235 . Here we review the methods proposed for ceria dissolution and the impact of several parameters on dissolution.

Dissolution of ceria is not thermodynamically favorable (ΔrG° = 40 kJ/mol) even in concentrated mineral acid solutions 236,237 . However reductive dissolution of ceria is feasible due to the highly positive redox potential of Ce 4+ /Ce 3+ couple (1.4 V per SHE) 238 . A solution containing a very strong mineral acid and a reducing agent can effectively dissolve ceria 239 . While any strong mineral acid can be used, sulfuric acid and nitric acid are especially known to be effective towards ceria dissolution. As far as reducing agent is concerned, a green reducing agent like ascorbic acid, citric acid, oxalic acid, etc. would be very advantageous. Choosing the appropriate mineral acid and the reducing agent is paramount since mixing a mineral acid with reducing agents like H2O2

(which acts as a reducing agent under highly acidic pH conditions) is an exothermic reaction and hence deleterious.

Early work on ceria dissolution was reported in patents on cleaning ceria particles after polishing glass or silicon dioxide films with slurries containing ceria particles and other chemical additives. Mitani and Saito proposed compositions containing an acid and a reducing agent to clean ceria particles adhered to glass substrates after CMP 240 . Several reducing agents were tested in solutions containing sulfuric acid/nitric acid to enhance the dissolution of ceria particles. A solution containing 0.1 M HNO3 and 1 M H2O2 yielded the highest dissolution rate. However, the pH of the solutions containing H2SO4/HNO3 and H2O2 was very low (<0) and hence such compositions caused problems with subsequently deposited materials during IC fabrication and corroded the polymeric brushes used for post-CMP cleaning. Later, significant efforts were made to developing cleaning compositions that were compatible with the consumables (polymeric pads and brushes) used for post-CMP cleaning process. Avanzino and Shonauer proposed cleaning compositions containing a reducing agent (like phosphorus acid, hypophosphoric acid, oxalic acid and L-ascorbic acid) and a complexing agent (like ascorbic acid, citric acid, tartaric acid, malic acid and glutamic acid) for removing ceria particles on silicon dioxide and silicon nitride films 241 .

In an embodiment of their invention, they showed that the dissolution of ceria particles increased with the increase in phosphorus acid and ascorbic acid concentrations chosen as prototype additives.

Of all the mineral acids, nitric acid and sulfuric acid are known to yield high dissolution rates 242 . The dissolution rate in the presence of acids increases with acid concentration. Temperature has a strong influence on dissolution and the dissolution rate increases gradually with the rise in temperature 243,244 . In fact, several studies have reported an enhancement in dissolution rate by ~3-4 orders of magnitude between 20 °C and 90 °C. The surface of ceria reacts with H + ions in solution and the particle surface area decreases due to the reduction in particle radius with time 242 . The dissolution of ceria in dilute HNO3 or H2SO4 can be catalyzed by Pt NPs. Ultrasound energy can also boost the dissolution of ceria in various solutions 238 . pH has a significant impact on ceria dissolution and the dissolution is significant only below pH 5 245 . Dissolution rate of ceria, however is independent of mixing rate. The dissolution of ceria in nitric acid is controlled by chemical reaction and not by diffusion as the dissolution rate did not change with the mixing rate 244 .

The dissolution of CeNPs depends strongly on the chemical composition. For instance, incorporation of 10% trivalent lanthanide ions increased the dissolution rate by an order of magnitude 243 Recently, the dynamics of dissolution of CeNPs using in-situ liquid cell TEM coupled with high intensity electron-beam irradiation of nanoparticle dispersions 246 were studied. Very high dissolution rates, exceeding previously reported values at room temperature by several orders of magnitude were reported by the authors. It was suggested that the radicals, ions and electrons were generated by electron-water interaction and that these species assist in reductive dissolution of CeNPs. Several procedures have been demonstrated for recovering cerium from post-polish CMP slurry. The recovery process involves selectively dissolving ceria in a mixture containing nitric acid and H2O2 [247][248][249][250] . Cerium from the solution is precipitated post-dissolution as cerium(III) carbonate which is subsequently converted into ceria by annealing in a rotary kiln. However, the dissolution rates reported in most of the studies are too low to consider any practical application.

Evidently, severe conditions are required to dissolve CeNPs. Published research suggests that sulfuric acid and nitric acid yield high dissolution rates than other mineral acids. There are many unanswered questions regarding this topic and hence there is still a need to understand the dissolution of CeNPs from a fundamental perspective. In particular, it is pivotal to study the effect of preparation method, particle size and surface coating, among other factors, on dissolution of ceria particles as the results of these experiments would provide some valuable insights relevant to dissolution of ceria particles used in commercial applications.

Controlled synthesis of ceria-based hybrid nanomaterials

The synthesis conditions and the ability to control the surface properties are essential aspects influencing the morphology, crystallinity and surface chemistry of CeNPs, ultimately dictating their catalytic, redox and other functional properties. Variations in ceria surface have been obtained by incorporating of a variety of ligands or by binding or mixing them to form composite hybrid structures with other molecules. The ceria nanocrystals size and variations in morphologies play a critical role in determining the surface oxidation states, the CeO2-x stoichiometry, stability and catalytic performance. 73,251 Various synthesis methods have been employed to tailor these properties, ranging from classical precipitation routes 252 to more advanced methods such as hydrothermal, 253 sol-gel 254 and microwave-assisted synthesis. 255 The selection of solvents and capping agents is also essential, particularly for achieving ultrasmall CeNPs. For example, ultrasmall (2.5±0.2 nm) mixed valence state (Ce 3+ /Ce 4+ ) CeNPs have been obtained via a direct room temperature synthesis using ethylenediamine as a capping agent. 256 The ultimate choice of the method governs the size, shape and surface functions. Surface functionalization techniques including doping with other metals or metal oxides or organic ligands, surface oxidation/reduction treatments and deposition of metal NPs 257 allow for tailoring the surface chemistry and electronic structure to enhance catalysis activity, stability and dispersibility in various media. More recent advances include the use of green solvents and biosynthesis methods to produce less toxic NPs compatible with living tissues. 258 Furthermore, post synthesis treatments such as annealing, calcination or reduction can modify surface defects, oxygen vacancy concentration, and surface area, affecting redox behavior and reactivity. 259 Such modifications generates novel interesting properties, allowing them to be used in a variety of applications. Many emerging applications of CeNPs in biomedicine, sensing and environment require surface functionalization to make them biocompatible for target binding and molecular recognition. However, the interfacial behavior of functional particles is sensitive to changes in the environment such as pH, ionic strength, temperature, natural organic materials, and concentration, often leading to aggregation 260 and many functionalized NPs exhibit differential behavior and reactivity profiles for practical applications. In this section, we highlight the most common strategies to create functional CeNPs and CeNPs-based hybrid materials (Figure 16). In particular, CeNPs used in conjunction with carbon-based materials, polymers, metal organic frameworks (MOFs), metals and metal oxides, and supramolecular assemblies are particularly attractive, due to their chemical structures, tailorability and synergistic properties, enabling effective utilization of these materials in applications.

Figure 17. Schematic representation for the synthesis steps of the CeO2-graphene nanostructures.

Reprinted from Ref. 263 .

The intercalation of CeNPs within the layers of graphene nanosheets allowed the nanosheets to maintain their high surface area and prevent reduced graphene oxide (RGO) from restacking 264 .

Anchoring crystalline ceria onto RGO sheets revealed strong electrostatic interaction between the ceria NPs and the RGO. Therefore, the interaction of mobile holes and the increased density of the oxygen vacancies from Ce 4+ to Ce 3+ in the RGO resulted in an transforms in an n-type CeO2 -RGO composites, suitable for applications in energy devices, batteries and sensors 265 Li et. al. 266 utilized an in situ growth method to synthesize a CeO2-graphene nanocomposite, which showed a specific capacitance of 208 Fg -1 and a maximum power density of 18 kW kg -1 in supercapacitors.

Dezfuli et. al., 264 developed CeO2-RGO nanocomposite electrodes which exhibited excellent supercapacitive behavior with high specific capacitance of (211 Fg -1 at 2 mVs -1 and 185 Fg -1 at 2.0 Ag -1 ) and reversibility. Combining the redox characteristics of CeNPs with graphene is an effective approach to design materials for redox supercapacitors 266 . However, their wide band gap semiconductor (~3.4 eV), limits the use as an electronic material and photocatalyst 267 . Tuning the band structure by chemical functionalization or attachment to conducting supports is an excellent method to enable their implementation in electronic and optical applications. In particular, defects, such as oxygen vacancies, generate localized electrons on the CeO2 surface, which may interact with the functional group in the RGO sheets, improving the properties of RGO 268 . Such composites also show high adsorption capacities as adsorbent materials for preventing pollution of the environment with contaminants such as heavy metal ions and phosphates, enabling applications in environmental remediation 269 . To improve selectivity (towards cationic or anionic species), sorption capacity, and overcome limitations such as the leaching of the NPs or stacking of the Csheets, the surface of these materials can be modified to enable specific applications. For example hydrous ceria modified graphene has been used as novel adsorbent for arsenic removal from aqueous solutions 270 . In other works, GO decorated with ceria showed selectivity in determination of trace metal ions and speciation for selenium. 271 Ceria-GO composites fabricated vis one-pot synthesis exhibited an almost complete (> 99.9%) and quick removal of arsenic species within 0.1 mg L -1 of the initial concentration 272 . Additional uses have been demonstrated for preparing ceriacarbon based catalysts for solid oxide fuel cells (SOFCs) and field effect transistors. The chemical vapor deposition (CVD) growth of single-walled carbon nanotubes (SWNTs) is normally performed at 800-1000 °C273 . When CeO2 , which stores oxygen, was used, the ceria-supported catalyst enabled the selective growth of SWCNTs on substrates due to the oxidative environment provided by the ceria 274 .

Ceria-based-metals and metal oxides heterostructures

Noble metals (M) and metal oxides (MO) can be used in conjunction with CeNPs to create hybrid materials with lower cost and superior characteristics for applications. For example, platinum-group metals, Pd, Rh and Pt, serve as active species in TWA exhaust catalysts and the price of these metals represents around 40% of the manufacturing cost of the catalysts 301 . To reduce the use of expensive Pt Pt-MO heterostructures have been explored. Enhanced activity can be obtained by encapsulating noble metals inside ceria, e.g. Pt@CeO2 core-shell hybrid structures, or by loading the MNPs on the surface of hollow CeO2 nanostructures. This strategy has been used

to create a variety of Au, Pt, Ag@ CeO2 hybrid nanostructures 302,303 , providing enhanced catalytic activity by stabilizing small size noble metal NPs and creating hybrid junctions at the two-phase interface 304 . Doping CeNPs with metals has emerged as a promising approach to produce supported catalysts with atomically dispersed metals 305 . The size, morphology, stability and catalytic activity of these materials can be controlled by varying the dopant, ligand used and the reducing and oxidizing conditions. Studies to assess the effects of metal dopants on the reducibility of bulk and extended surfaces of CeNPs with have been extensively reported using both experimental and theoretical approaches 142,158,306,307 .

The enhanced properties provided by these hybrid materials have found unique applications in catalysis, environmental remediation, sensing and biomedicine. For example Ag@CeO2 have demonstrate inactivation of Escherichia coli through the formation of reactive oxygen species (ROS) 308 . Similarly CeO2-CdO binary metal oxide nanocomposites showed antibacterial activity and growth inhibition towards P.aeruginosa 309 . The properties of CeNPs were also integrated with the photoinduced electron transfer of quantum dots (QDs), providing materials with significantly improved optoelectronic properties. A synthesized ceria-carbon quantum dots/RGO nanohybrid showed improved photocatalytic properties enabling rapid decomposition of organic pollutants 310 .

Catalysis

The thermal stability electron, high OSC and proton transfer abilities make CeNPs particualrly useful in catalysis 165,317 . The 3 + /4 + reversibility and oxygen mobility, which is higher compared with other oxides such as SiO2, Al2O3, and ZrO2, enable the use of CeNPs as a catalyst in redox, CO oxidation, and acid-base reactions 3,318,319 among others. Main concerns related to CeNPs are related to the deterioration of the active surface area due to sintering and segregation processes resulting in loss of catalytic activity 320 . Therefore, much attention has been paid to developCeNPbased catalysts with enhanced structural characteristicsto resist degradation, such as combining binary metal oxide catalysts. For example, CeO2-MnO2, showed enhancxed performance for processes such as CO oxidation 321 , selective catalytic reduction of NOx with NH3 322 , and oxidation of volatile organic compounds 323 . Further optimization has been accomplished by using a Ce-based MOF to maximize the exposed active sites and enhance the porosity of the system 324 . Ceria is an excellent support for high-performance metallic catalysts, enhancing stability and catalytic performance as shown for example with PtFe nanocrystals hybridized by CeOx, e.g. PtFe-PtxFeyCezOj. 12 A particular case is the use or mesoporous ceria, characterized by well-defined pores, typically ranging from 2 to 50 nm, and a high surface area which provides unique capabilities for catalysis, 325 gas sensing and energy storage. The high surface area provides enhanced accessibility to active sites and facilitates transport of reactants and products.

Additionally, the oxygen vacancies facilitate switching between CeO2 and CeO2-x. Therefore they showed improved performance in catalytic reactions including oxidation, hydrogenation and pollutant removal. A review summarizing synthesis and catalytic applications of mesoporous ceria can be found in Refs. 325 Doping CeNPs with transition metals or rare earth metal such as Cu, Cr, Ti, Y, and La, have been adopted as a promising approach to tune the catalytic activity of these materials [326][327][328][329][330] . The substitution process causes structural defects and creates more oxygen vacancies on the catalyst surface, which affects the generation and mobility of charged species such as electrons and oxygen anions. Furthermore, doped ceria can also tolerate high temperature annealing treatments due to the cooperative nature of the cations of the binary oxides 331 . The electronegativity and ionic radius of Ce 4+ , are 1.12 and 0.97 Å, respectively. A synergetic dopant would ideally have electronegativity and ionic radius close to these numbers. For instance, samarium (Sm) has an electronegativity and ionic radius of 1.17 and 1.07 Å, respectively. It is also soluble in the ceria sublattice and can stabilize the fluorite structure of ceria at low dopant concentration. A nanocrystalline CeO2-Sm2O3 (CS) solid solution, has been easily synthesized yielding a promising catalyst for the oxidation of CO at lower temperatures owing to the large number of lattice defects, high OSC and improved redox properties 331 . Sm-doped CeO2 nanopostructures have been widely used as a catalyst in methane selective oxidation 332 , allylic oxidation 333 and fuel cells applications 334 , while Gd-doped CeO2 was used for gas sensing applications 335 . The Gd-doped CeO2 gas sensor had better sensitivity, good stability and lower operating temperature over nondoped one with a detection concentration of 800 ppm CO2 gas. In addition, Ni-doped CeNPs have been hydrothermally prepared and showed an increased magnetization and electrical conductivity with increasing the dopant concentration 336 .

As diesel emission produces soot which have grown concerns on human health and the environment, several emission control strategies have been implemented to reduce environmental impact 337 . For example, over 90% of the soot can be trapped and then be continuously or periodically combusted to CO2 using the diesel particulate filter (DPF) technology. However, the periodic regeneration of DPF is not passive, which makes it complex and expensive. Ceria-based materials have been developed to decrease the soot combustion temperature (~600 °C compared to diesel exhaust temperature (~175-400 °C)) and have been extensively studied as catalysts and catalysts promoter in this research area 338 . Nascimento et al. 339 studied the performance of binary oxides CeOx/FeOy catalysts modified with AgNPs for the control of diesel soot combustion.

Catalytic tests showed a significant reduction of about 300 °C in the soot oxidation temperature with CeOx/FeOy compared to the CeO2. Shen et al. 340 also investigated the catalytic performances of Fe-doped ceria catalysts with diffeent Fe contents for the soot oxidation reaction with O2 or O2/NO gases. They demonstrated that the addition of iron increased the number of oxygen vacancies on the surface, and therefore the catalytic activities for NO oxidation and NO2-assisted soot combustion.

Uniform anchoring/decoration of CeNPs on the surface of graphene sheets improves the photocatalytic and photocapacitive performance of the nanostructures for effective charge transfer and catalytic degradation processes 263 . For example, the photocatalytic activity was examined by monitoring their ability to degrade Congo red ~94.5% and methylene blue dye ~98% under visible light irradiation. These developments indicate the borad applicability of CeNPs-based nanostructures for future energy and environment-related applications.

Chemical mechanical planarization (CMP)

CMP is a surface smoothing process that is used in semiconductors fabrication process and in a number of other manufacturing processes. It has become a critical and enabling process for the multilevel metallization necessary for interconnecting the immense number of active devices created on silicon substrates and in the device fabrication process sequence at the gate level 312,341 .

Silicon dioxide CMP, or simply oxide CMP, in which a colloidal slurry consisting of ceria abrasives is commonly used, is one of the many critical processes in the fabrication of integrated circuits (ICs) [341][342][343][344] . CeNPs are widely used as abrasives for oxide CMP since they interact strongly with the oxide leading to high removal rates (RRs). With appropriate additives to ceria slurry, it is possible to achieve a highly selective polishing of the oxide with respect to the underlying silicon nitride films as required in the planarization of shallow trench isolation structures [344][345][346] . Ce 3+ species present on the surface of CeNPs particles react with the hydrated oxide surface (Si-O -)

forming strong Ce-O-Si bonds and ultimately rupturing the underlying and weaker bonds in the oxide film leading to its continual removal 344,347,348 . There are extensive discussions of the reaction mechanisms involved in the polishing of oxide and nitride films 344,349,350 .

Two methods, namely solid-state displacement and solution-growth, are commonly used for the preparation of CeNPs particles for CMP applications 341,351 . In the solid-state displacement method, particles are prepared by calcining cerium carbonate at more than 600 o C under controlled air flow conditions, which is subsequently wet milled to obtain the desired particle size 352 . CeNPs with less than 100 nm size can be obtained by controlling the pre-treatment of cerium salt, calcination temperature, air flow conditions, and bead size of the milling process [352][353][354] . However, the particles produced by this method are faceted and have sharp edges, corners, and apexes as well as a very wide size distribution (Figure 21a). These features tend to scratch the films during polishing and generate many unacceptable defects. Consequently, the usage of these types of particles is being avoided, while the solution-grown CeO2 particles, despite of their higher cost and potential for contamination, have gained wider acceptance 87,355,356 .

In the solution growth method, cerium hydroxide (Ce(OH)3) is precipitated from a solution of cerium nitrate mixed with ammonium hydroxide, and transformed to CeO2 in the presence of oxygen (Ce(OH)3 + 1/2O2→ CeO2(s) + 3H2O). These particles are separated and washed repeatedly for removing residual precursors until the desired conductivity of the suspension is obtained 357,358 . Particles with a very narrow size distribution can be produced by this method as shown in Figure 21b. These relatively uniform-sized CeNP abrasives have polyhedral and nearly spherical shape that is expected to minimize the generation of scratches because of fewer sharp edges and corners.

Coating ceria abrasives with a layer of different materials and chemical compositions makes it is possible to change the physicochemical properties of the core abrasive, including shape, surface chemistry, surface charge, porosity, and hardness and can be tailored to increase their reactivity with films. To benefit from this strategy, core/shell type CeO2 abrasives have been investigated and showed increased removal rates as well as improved surface roughness of polished oxide films. Core/shell structured composite particles, comprising of mesoporous silica 359,360 , dendritic silica 361 , polymethylmethacrylate (PMMA) 362 , and polystyrene (PS) 363 as core materials with metal-doped CeO2 particles making up the shell, generated relatively high oxide removal rates with low surface scratch and roughness values. This was ascribed to the resilient spring-like effect of the softer core silica during polishing. Also, since smaller particles tend to produce a higher quality surface finish, coating of core CeO2 particles (~100 nm) with a layer of smaller (5 nm or so) CeO2 shell has been proposed and was shown to achieve high oxide polish rates (Figure 21c) 364 . In principle, these types of composite abrasives can result in significant cost savings for high volume manufacturing due to higher throughput, lower abrasive concentrations, and lower waste treatment cost. However, all these composite ceria abrasives are prone to form broken particles as well as peeling-off and/or brittle collapse of the shells. Therefore, further advancements in the field are necessary to avoid these issues. Various types and shapes of pure and composite CeO2 particles used in most CMP slurry formulations are summarized in

Chemical and biological sensing

The field of chemical sensors and biosensors has witnessed a radical transformation due to the rapid advancement and innovations in functional materials and biomaterials. Metal oxide nanomaterials can serve for both recognition and transduction purposes, 372 alone or in conjunction with biomolecules such as DNA or enzymes. Enzyme-based sensors are considered to be one of the most reliable sensing techniques due to their high sensitivity, selectivity and fast response 373- 375 . However, enzyme's stability can be severely compromised with temperature and pH changes.

For these reasons, researchers have focused on using nanotechnology tools to develop more robust sensors by engineering materials that mimic the function and complexities of natural enzymes 376- 379 . Metals and metal oxides NPs and nanocomposites 374,380,381 , metal organic frameworks 382,383 , and carbon-based nanomaterials [384][385][386] have demonstrated promising potential as artificial nanoenzymes 195 with peroxidase or oxidase-like mimetic activity, that could be used as receptors or transduction materials for sensing.

CeNPs have emerged as a promising enzyme-mimetic material that possesses intrinsic oxidase or peroxidase-like properties, due to the mixed oxidation states (Ce 3+ /Ce 4+ ), which provides the ability to catalyze many chemical and biologically relevant reactions 375 . Upon reduction of Ce 4+ to Ce 3+ , the CeNPs mimics catalase activity by inducing H2O2 oxidation, generating molecular O2. On the reverse, oxidation of Ce 3+ to Ce 4+ mimics superoxide dismutase (SOD) activity by reducing O2 -to H2O2. The efficiency of CeNPs as a peroxidase mimic is strongly dependent on the low ratio of (Ce 3+ /Ce 4+ ) 387 . The high catalytic activity, oxygen rich surface and low toxicity 175 make them excellent candidates for enzyme-mimetic and enzyme immobilization purposes. 229,388 Furthermore, CeNPs have been used as a material with therapeutic potential to reduce harmful ROS/RNS due to the unique regenerative ability to scavenge ROS/RNS species 200,389 . The combination of sensing and therapeutic functions makes CeNPs a powerful theranostic platform for biomedical applications. 26,390 A ROS-scavenging tissue adhesive nanocomposite was synthesized by immobilizing ultrasmall ceria nanocrystals on the surface of uniform mesoporous silica (MSN) 391 . The ceria nanocrystals decorated MSN does not only have a strong tissue adhesion strength, but they also help minimizing the ROS-mediated deleterious effects efficiently accelerating the wound healing process as evidenced by marked skin appendage morphogenesis and limited scar formation.

Various studies have shown the ability of CeNPs to reduce symptoms of oxidative stressrelated diseases, such as chronic inflammation 392 , endometriosis 393 , cancer 394,395 , and diabetes 396,397 . However, with the diversity of methods and synthetic procedures used to synthesize these particles, each producing different types, shapes, sizes, coatings and Ce 4+ /Ce 3+ ratios, the antioxidant effects can vary significantly. Controlling the surface chemistry to efficiently regulate reducing and oxidizing efficiency (e.g. antioxidant vs pro-oxidant) in biological systems remains a challenge, as is the tendency of CeNPs to agglomerate in biological fluids 170 . In some cases, CeNPs have been found toxic, but the mechanism responsible for CeNPs toxicity -if present -is still inclear and subject to debate 11 . Therefore, it is important to develop new kinds of CeNPs with highdispersibility and enhanced catalytic activity that are able to maintain their redox properties in biological fluids. Several strategies have been reported in literature to improve these properties.

For example, CeNPs have been coupled with materials such as Cu2O 398 , TiO2 399 , and Eu 400,401 to enhance catalytic and enzyme mimetic properties. The use of CeNPs in conjunction with TiO2 nanotubes increased the peroxidase mimetic activity. 402 In another study, adding Eu to the nanocrystal structure imparted fluorescence and increased the oxidase-like activity of ultra-small CeO2 with different shapes and exposed facets (a-i), and H2O2 detection scheme using HRP/CeO2-rGO modified glassy carbon electrode (j). Reprinted with permission from Ref 405 .

Hybrid nanomaterials offer several advantages for chemical sensing and biosensing due to their ability to provide synergistic catalytic functions due to formation of hybrid junctions associated with rich redox reactions, enhancing their catalytic performance 373 . Artificial intelligence and machine learning, through the use of computer-aided designs of the CeNPs, could in the future be used to screen and rationally design particles with the desired properties for applications 406,407 . Using these tools, it is now possible to predict the optimal CeNP shape that delivers the best catalytic performance in some specific reactions 406 . For instance, facet engineering of CeNPs with the help of computational calculations made it possible to understand the crystal facet effect that plays a crucial role in determining the surface energy and reactivity 408 .

CeO2 nanorods with a dominant (110) facet showed the highest peroxidase-mimetic activity due to the rich defect chemistry on their surface (Figure 22). These studies provided an increased understanding of the fundamental CeNPs properties that drive their unique reactivity. This knowledge is essential to rationally design and tailor their activity.

Several types of chemical and biological sensing systems where CeNPs have been used as receptors for gases, enzyme mimetic materials, co-catalyst or as a label for quantifying affinity recognition reactions have been developed (Figure 23). Applications include gas, biomimetic or enzyme-based sensors, immuno, aptamer and DNA based sensors. Examples for each of these classes are discussed in the section below.

Enzyme mimetics and enzymatic biosensors

CeNPs have been widely investigated to fabricate enzyme mimetic and enzyme-CeNPs-based biosensors with colorimetric or electrochemical detection 224,417 . These sensors are using CeNPs either as an enzyme mimetic (e.g. as a synthetic replacement of a natural enzyme) 418 , or coimmobilized with a natural enzyme to catalytically amplify enzymatic reactions 419 and therefore enhance their detection sensitivity. As compared to systems based solely on biocatalytic enzymes (e.g. oxidases or peroxidases), sensors based on CeNPs are more robust, inexpensive and not susceptible to denaturation.

Sensors with optical detection measure changes in optical properties associated with redox processes at the CeNPs surface. It is known that CeNPs form charge transfer complexes with H2O2, 224 and catecholate compounds, 420 generating a distinctive concentration-dependent optical response. Based on these principles, a variety of colorimetric sensors have been reported using CeNPs as color-generating probes (e.g. as a replacement to commonly used soluble dyes) or to enhance the colorimetric signals of redox dyes such as 3,3',5,5,-tetramethylbenzidine (TMB) or azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). The high stability and rich surface functionalities of the CeNPs makes them amenable to patterning on solid surfaces, providing opportunities for the development of portable and inexpensive sensors.

One of the first demonstration of CeNPs as colorimetric probes was reported in 2011 for detection of H2O2 and oxidase enzyme substrates such as glucose. 224 The advantage of this system over conventional colorimetric assays is evident when comparing the two types of assays in Figure 25AB. When CeNPs is used as a color probe and peroxidase mimetic, in the presence of H2O2, the while/yellowish color of the CeNPs changes into bright yellow/orange, due to the oxidation of Ce 3+ to Ce 4+ and formation of peroxide-Ce complexes at the NP surface, producing a unique concentration-dependent response 224 . When CeNPs are co-immobilized with glucose oxidase on filter paper, H2O2 is generated on exposure to glucose, and the enzymatically generated H2O2 is then measured as a color change. Conventional enzyme based colorimetric assays for oxidase enzymes involve the use of two enzymes, one for the conversion of substrate to H2O2 (e.g.

glucoseoxidase), and one for the conversion of the enzymatically generated H2O2, typically a peroxidase, and a soluble redox dye. Because these reagents are soluble, they are generally used in solution or stored on specially designed reservoirs with reactions being accomplished though microfluidic channels. Conventional dyes are expensive and maintaining their stability is a challenge. Since CeNPs is a stable inorganic material that can replace both the peroxidase enzyme and the organic dye, they can be easily affixed to a solid platform such as paper, plastic or textiles for creating stand-alone portable sensors. Such reagentless sensors have significantly enhanced stability, portability low cost as compared to solution-based assays (Figure 25C). A CeNP-based biosensor for glucose developed on filter paper for example displayed a limit of detection of 0.5 mM with a linear range up to 100 mM glucose. This concept can be extended as a general platform for any oxidase enzyme system that involves generation of H2O2 as a reaction product, such as lactate, glutamate, cholesterol, uric acid, ethanol and hypoxhantine (Figure 25D). Copyright 2011 American Chemical Society.).

Similar types of colorimetric sensors based on CeNPs have been designed to detect enzyme activities, such as alkaline phosphatase (ALP). For example, a CeNPs-based sensor was developed based on color changes of CeNPs reacting with hydrolytic products of ALP-catalyzed reactions, from substrates such as catechol monophosphate, ascorbic 2-phosphate and hydroquinone diphosphate. The method, adapted to a paper-based platform, had a detection limit of 0.04 U/L ALP with a linear range up to 2 U/L when ascorbic 2-phosphate was used as substrate. 421 More recently, the activity of beta-galactosidase (beta-Gal) was determined using a procedure involving CeNP-induced oxidation of 4-aminophenol (4-AP) produced in the hydrolysis of the 4-aminophenyl-beta-d-galactopyranoside substrate (4-APG) by beta-Gal. The approach enhanced the detection sensitivity and enabled beta-Gal measurements in the visible range, reaching up a detection limit of 0.06 U/L and a linear range up to 2.0 U/L. A 30-fold amplification as compared to a commercially available beta-Gal assay was reported using the CeNP assay. 422 In addition to (Reprinted with permission from Ref 400 . Copyright 2018 American Chemical Society).

The distinctive changes in optical properties of the CeNPs reacting with compounds with phenolic or catecholoamine moieties were used to develop paper based sensors for the detection of phenolic antioxidants, with reported detection limits between 20-400 μM depending on the structure of the compound. These sensors have the capability to provide a unique optical signature generated when CeNPs interact with a single or a mixture of antioxidants. The method enabled field assessment and classification of the antioxidant capacity in tea, 423 wine, 424 medical mushrooms 425 and cosmetic products 426 . For these measurements, the CeNPs stabilized onto a paper platform form the actual sensing platform (e.g. sensing spot or label), enabling portability and reagentless operation. Similar to a pH paper, analysis is performed by adding the sample to the sensor; the antioxidants in the sample produce an immediate color change that is visible to the naked eye. Quantification is achieved by comparison with a pre-calibrated detection scheme. For more precise quantification, analysis can be performed with a color reader such as a cell phone with a color reading app; no additional reagents are needed (other than the sample). In comparison with other assays for antioxidant analysis, the CeNPs sensors have very low cost and are stable at room temperature and field deployable. Finally, biosensing systems based on CeNPs have practical utility as demonstrated by the development of several standalone devices for detection of ethanol in breath, 427 phenolic antioxidants for evaluating antioxidant activity in teas and wines, 425 and measuring the hypoxanthine content to assess freshness of fish and meat 428 , summarized in Figure 27. 425 , (B) 427 and (C) 428 .

Figure 27. Examples of practical CeNP-based paper sensors for the detection of antioxidant activity in tea (A), ethanol in breath using a 3D printed device (B) and hypoxhantine to assess the freshness of fish (C). Reprinted with permission from Refs for (A)

Several hybrid configurations of CeNPs-based enzyme biosensors have been developed in which the CeNPs are used in conjunction with oxidase enzymes to catalytically amplify the enzymatic reaction, or the product of an enzymatic reaction, significantly enhancing the sensitivity of the biosensor. Moreover, the ability of the CeNPs to store and release oxygen has been used as an oxygen reservoir to fuel oxygen to oxidase enzymes, enabling them to operate in oxygenrestrictive environments such as tissue hypoxia. This principles has been demonstrated effectively for improving sensitivity of implantable electrochemical microbiosensors fabricated by coimmobilizing the enzyme with the CeNPs at the surface of a microelectrode, typically a Pt wire or a carbon fiber brush, with diameters ranging from 100 to 150 m. Successful developments have been demonstrated with CeNPs-based biosensors for the detection of dopamine, 429 glutamate, 430 lactate 431 and glucose 432 . Enhanced selectivity has been obtained with Pt-doped CeNPs, which imparts conductivity and amplifies the electrocatalytic signal H2O2 oxidation, as shown in Figure 28A for glucose detection. The lactate biosensor for example had a detection limit of 37

M in implantable conditions and was able to quantify the real time release of lactate in vivo during cerebral ischemia and reperfusion (Figure 28B). 431 This lactate biosensor operated in a continuous mode due to the ability of the enzymatically generated H2O2 to react with the CeNPs producing oxygen in the process. This released oxygen is then utilized by the enzyme, facilitating its functionality in the hypoxic medium. Notable, the biosensors without CeNPs do not provide any quantifiable response due to the lack of oxygen, a necessary cofactor for ensuring enzyme function.

Other possibilities to enhance conductivity for electrochemical biosensors are to use the CeNP in conjunction with graphene oxide and PtNPs 433 , conductive polymers such as polyaniline 434 , or mesoporous carbon 435 , leading to enhanced sensitivities. CeNPs can also be designed in the form of a dual-tethered nanosystem in conjunction with fullerene, which combines the properties of the two materials, leading to hybrid structures with high antioxidant and UV-shielding properties 436 .

Lastly, significant improvements can be achieved by interfacing CeNPs with high surface area materials such as 2D layered MXenes producing catalytically active materials that can be used in a variety of applications. In a recent work (Figure 28C), MXene decorated with CeNPs enabled the development of an electrochemical biosensor platform broadly applied to a variety of enzymes and enzyme substrates, achieving detection limits of 0.8 µM H2O2, 0.49 µM glucose, 3.6 µM lactate and 1.7 µM hypoxanthine. 437 These materials can be integrated within flexible platforms such as carbon cloth and be used to construct wearable devices, as demonstrated for lactate monitoring in sweat. 437

Figure 30. Summary of CeNPs-based materials for environmental remediation.

Ceria coated activated carbon was synthesized in a single step and used in water purification where it demonstrated high efficiency for the removal of As(III) and As(V) 461 . Additionally, a nanocomposite prepared from graphene nanosheets and CeNPs (G/CeO2) was used for the extraction of Se(IV), As(V), As(III), Cu(II) and Pb(II) from water 462 . The maximum adsorption capacity of G/CeO2 was extrapolated from the Langmuir model and found to be 8.4 for As(V), 14.1 for Se(IV), 50.0 for Cu(II) and 75.6 for Pb(II) (expressed in mg•g -1 ). These also showed good selectivity towards Se(IV) in the presence of Se(VI). CeNP-based materials were also used for ultratrace metal ions detection and speciation via electrochemistry 271 . Enhaced arsenic removal was achieved using porous CeO2-ZrO2 hollow nanospheres due to the high sorption capacity and selectivity for As; adsorption capacities of 110.7 and 145.3 mg.g -1 were reported for As 3+ and As 5+ respectivelly 460 . As a dual Ce 3+ /Ce 4+ oxidation state material, CeNPs can participate in electron exchange reactions with As 3+ ions present in solution. The mechanism of As adsorption and redox processes occurring between the surface Ce 3+ /Ce 4+ and As 3+ at different pH conditions was demonstarted at single particle levels using nanoscale electrochemistry by monitoring the oxidation of As 3+ to As 5+ at 0.8V vs. Ag/AgCl or the reduction of As 3+ to As 0 at -0.3V (vs.

Ag/AgCl) 463 . The highest sorption capacity was observed at pH 8. In acidic environments (pH<4), a small fraction of As 3+ was oxidized to As 5+ by surface Ce 4+ and further adsorbed onto the CeO2 surface as a As 5+ bidentate complex (Figure 31). Adsorption was common in basic conditions, confirming strong adsorption of As 3+ onto CeNPs. These findings pave the way for rationally selecting the optimal material structure and conditions to increase sorption capacity for environmental sensing and remediation applications. CeNPs exhibit high selectivity for fluoride (F -) adsorption and can be used as adsorbent for F -removal from water. F is one of the essential elements in the human body for the formation of dental enamel and normal mineralization of bones 464 . However, the excessive intake of F -is harmful to the body and can lead to various health issues ranging from mild dental fluorosis to crippling skeletal fluorosis. While CeNPs are effective adsorbents and could be used in large scale column purification technologies for water defluoridation, their small size is impractical as it could cause column blockage, high pressure drop, and low flow rate. To overcome these limitations, binary oxides and hydroxides such as CeO2-ZrO2 nanocages 465 and Ce-La binary hydroxide 466 were explored as alternative sorbents with good F -uptake, but slow adsorption rate. Further improvements were achieved using CeNPs incorporated on active supports like silica and organic polymers which provide a large specific surface, fast diffusion kinetics, low cost, high mechanical strength and low pressure drop in a packed adsorption column [467][468][469][470] . F -adsorption onto a cubical ceria nanoadsorbent has shown pH-responsive behavior during the adsorption process 471 . At lower solution pH, a release of OH -was observed during the adsorption of fluoride by inner-sphere complex formation. At higher solution pH, the pH was found to decrease due to the exchange of Na + added in the form of NaOH by outer-sphere complex formation with H + ions adsorbed electrostatically on the adsorbent surface 471 .

Other environmental applications of CeNPs are as catalysts to remove exhaust emission, 472 volatile organic chemicals (VOCs) and degrade organic pollutants from the environment. For example, CeNPs have shown high performance towards the reduction of NOx and the catalytic oxidation of NH3 from engine exhaust. 473 Owning to their oxygen storage/release and the Ce 4+ /Ce 3+ redox cycle, CeO2-based catalysts are excellent candidates for the selective catalytic reduction of nitrogen oxides (NOx) and carbon monoxide (CO) which contribute to acid rain and photochemical smog. In a typical catalytic convertor, ceria acts as a buffer adsorbing and releasing oxygen species depending on the operating conditions and temperature. It was reported that the use of CeNPs (30 nm) as an additive to fuel resulted in reduced fuel consumption by 2.5%, as well as reduction in NOx emission by 15.7% and smoke opacity by 34.7% compared to the additivefree fuel 474 . Enhanced catalytic performance for selective NOx reduction by NH3 was obtained with the CeNP-based catalysis on oxide supports such as Al2O2, TiO2 and WO3 with the highest activation ability for Ce-O-W through rich Bronsted acid sites, redox ability and strong electronic CeO2-support interactions. 475 NPs of CeO2, CuO/CeO2 and Pt-MnO2/CeO2 have shown high activity for the oxidation of phenol intermediates. [476][477][478] Nanocomposites of TiO2/CeO2 on carbon nanotubes have demonstrated photo-oxidation capabilities for the degradation of organic content in agricultural wastewaters. 479 Pd/CeO2 with carefully designed morphology and optimized shapes were effective catalysts for methanol decomposition to syngas with excellent activity at low temperatures 480 . Mn-doped CeNPs prepared by hydrothermal synthesis have shown a drastic increase in their capacity to adsorb oxygen due to intercalation of Mn 3+ and the decrease in the Ce 3+ / (Ce 3+ + Ce 4+ ) content in the doped samples, by replacement with Mn 3+ . The doped samples had a significantly higher activity for toluene oxidation 481 .

CeNPs have been also studied for the photocatalytic degradation of reactive dyes at which more than 95% of the dyes were destroyed under solar irradiation 482 . Recent work showed the ability of CeNPs to effectively degrade organic dyes such as fluorescein, rhodamine B, brilliant blue and coomassie blue, with enhanced degradability in the presence of fluoride at ambient temperature 483 . The enhanced degradability in the presence of fluoride was attributed to the increased oxygen vacancy and the strong acidic environment. Hybrid CeNPs -lanthanide oxides demonstrated H2S adsorption and dissociation with subsequent oxygen vacancy regeneration, enabling their use for the desulfurization of biomass effluents. 484 It was demonstrated that adding Ce to metal oxide catalysts enhanced the catalytic activity and SO2 resistance of Mn/Ti catalysts for the NO reduction with NH3 by inhibiting the accumulation of ammoniom sulfates and preventing sulfidation. 485 Addition of a small amount of Ce (Ce/Ti = 0. In other environemental applications, CeNPs have shown tremendous potential as sorbents for the removal of phosphorus to prevent water eutrophication. Eutrophication has become a global environmental problem due to unnatural enrichment of water bodies with phosphorus (P) and nitrogen (N) which leads to the excessive growth of harmful algae blooms, and depletion of dissolved oxygen levels creating dead zones 269,457 . Thus, removing the excess P and N is essential for prevening the negative consequences of eutrophication 269,487 . CeO2-coated nanofibers have shown high adsorption capacity for the removal of P from aqueous solutions 488 with an adsorption capacity of 17 and 12 mmol/g at low pH (2-6) and neutral pH. The removal process involved the formation of CePO4 on the nanofiber surface. In other works, a recyclable adsorbent based on CeNPs grafted on mesoporous silica beads (CeO2-SiO2) has shown reversible adsorption behavior for P, demonstrating potential for both the removal and recovery of this important nutrient from eutrophic waters (Figure 33) 459 . The adsorption mechanism involved binding of PO4 3-through ion exchange and Lewis-acid based interactions, which provided a sorption/desorption capacity of 110 mg.g -1 with 99% removal within 60 min, significantly higher as compared to other sorbents. In follow up work with this system, ultrafast removal was achieved by using a Ce(IV)-based MOF, the Ce(IV) UiO-ss, Xe 1,4-benzenedicarboxylate (Ce-BDC) which provide high surface area due to the open pores and high binding affinity of its open metal sites for phosphate. A removal capacity of 179 mg.g -1 within 4 min, and ermoval capacity ina broad range of pH (2-12) was reported. 457 Other enhancements have been obtained using binary oxides with properly designed ratios 489,490 , optimized to enhance surface defects and facilitate complexation, thus increasing adsorption capacity as compared to the single bare oxide. Su et al., developed a solvothermal process to synthesize a series of Ce/Zr binary oxide nanoadsorbents. A sorption capacity of 112.2 mg.g -1 was reported with an optimized oxides ratio of Ce0.8Zr0.2O2 491 . In order to facilitate the recovery of the adorbents after the treatment, core-shell CeNPs (Fe3O4@SiO2-CeO2) 492 and (Fe3O4@SiO2@mCeO2) 493 were designed to magnetically separate and remove of these sorbents from the water environment. These structures can be utilized in a variety of applications such as membranes for phosphate separation and purification, sorbents for solid phase extraction or as Pselective materials for environmental sensing. Recently, it was shown that the use of Ce-metal nodes in the UiO-66-NH2 MOF structure enable the fluorimetric sensing of phosphate, with a detection limit of 4.5 M in a single step measurement procedure. 494 While the properties of CeNPs are vastly explored, their potential environmental and toxicological effects are still under investigation. The release of CeNPs into the environment is expected to increase as they start to be implemented in real-world applications 493,495 . Their use as polishers in the semiconducting industry 496 and as diesel fuel additives for catalytic convertors to control auto exhaust emission 497 are just two examples that can the result in release and accumulation of CeNPs in the environment. Toxicology studied suggest that CeNPs by themselves are not particularly toxic; however, they can become toxic by adsorbtion of toxic ions (e.g. As 3+ ) or organics to their surface. 463 Therefore understanding the fate, transport, and toxicity of these NPs exposed to contaminants is becoming increasingly important and will be critical in further studies to examine their environmental and health impacts 5,498 . Green synthesis of CeNPs can provide alternative routes to prepare CeNP-based materials without the need of using environmentally harmful reagents. For example, CeNPs were synthesized using plant-mediated synthesis at which different plants such as Gloriosa superba, Acalypha indica and Aloe vera were used [499][500][501] . Additionally, honey, egg white and fungus-mediated synthesis were also used [502][503][504] .

These plant extracts and natural components act as capping and reducing agents to produce nanocrystalline CeNPs in different sizes and morphology. These methods also offer advantages such as the low cost, large-scale production, and more importantly their environmentally friendly nature, making them interesting candidates for use in biomedicine and pharmaceutical applications.

A detailed review on the green synthesis of CeNPs and their biological applications has been published 505 .

Biomedical applications

The ability of CeNPs to catalyze the detoxification of free radicals and act as artificial antioxidants provides a broad range of opportunities for using this system in biomedicine, particularly for treating disease conditions in which excess free radical formation is thought to play a role. 506 These range from relatively rare diseases, such as Amyotrophic lateral Sclerosis (ALS), to more common conditions, such as stroke, cancer, 507 traumatic brain injury, Parkinson's and Alzheimer's Disease to the ubiquitous normal processes of aging. CeNPs possess a number of advantages over other antioxidants. CeNPs have been shown to provide antioxidant, immunomodulatory, antimicrobial and antiviral, and anticancer properties, and their ability to be used as theranostic probes. 8 When administered systemically, CeNPs appear to cross the blood brain barrier. 508 Their properties can be enhanced by modification with other drugs as demonstrated with edaravone attached using poly(ethylene glycol); the combined effect provided enhanced neuroprotective action for stroke treatment through the inactivation of ROS and enhanced accessibility to cross the blood brain barrier. 509 The regenerative behavior of the CeNPs, enabling them to regain the antioxidant activity upon interaction with ROS, provide additional opportunities for these particles to remain active for long periods of time, and be used in tissue engineering to support neural survival and growth. 510 Thus, they could be administered preventatively or early in a chronic disease process. Other applications include utilization in spinal cord repair as neuroprotective agents, 511,512 support cell survival 513,514 and scavenging ROS in the eye to prevent degenerative retinal disorders. 513 When cells were exposed to H2O2, CeNPs reduced oxidative damage by over 60%. 9,511,512 CeNPs holds potential as a drug delivery platform for targeted therapy. For example, they can be conjugated with other therapeutically-effective molecules to improve drug delivery 515 or modified with specific receptors and biomolecules for targeted delivery 516 and wound healing. 517 The tunable surface and large surface to volume ration facilitate enhanced loading and potential for release, making them a versatile platform for personalized medicine. 518 They can also be incorporated in hydrogels or other biomaterial matrices and used to support cell adhesion and proliferation, and promote wound healing. 519 The tunable catalytic activity of the CeNPs has been shown to be effective in preventing chemotherapy-induced acute kidney injury and restore redox homeosthasis. 520 Biomedical imaging is another area in which CeNPs can find exciting emerging applications such as contrast agents and imaging modalities for magnetic resonance imaging (MRI) and computed tomography. This can be achieved by surface modification of the CeNPs with dyes or other imaging agents or by doping with Eu or Gd, enabling visualization of biological processes and monitoring of therapeutic response, thus facilitating early detection and monitoring of diseases. 521,522 While biomedical applications of the CeNPs are rapidly emerging, rational design and better control of the structure, properties and dose response is still needed to establish conditions that can effectively reduce the level of free radicals without impairing the normal physiological functions. Several reviews expanding on the biomedical and theranostic applications of the CeNPs can be found in literature. 8 169, 171, 523

Summary and Outlook

The unique structure, tunable reactivity and rich surface chemistry make CeNP an extremely versatile material for a wide variety of applications. Here, we have comprehensively reviewed progress made in the development of CeNPs's based materials, their structure, properties and emerging applications over the past two decades. The synthesis and control of surface properties represent key strategies for customizing the physicochemical characteristics of these materials to meet the requirements of diverse applications. Continued research in this area is essential for unlocking the full potential of the CeNPs in addressing current technological challenges and advancing new products and innovations. Understanding the structural properties at the atomic levels provides the fundamental knowledge necessary to engineer structures with controlled reactivity and surface functions. Such studies are still needed to identify key parameters in the synthetic design that can be used to predict reactivity and generate CeNP-based materials and devices with the desired properties for a given target. Further improvements in the synthesis, surface functionalization and the use of in situ characterization techniques will help achieve better with a full understanding of their unique properties in order to reduce potential risks and ensure their safe utilization and implementation into the practice.

 Finally, we expect exciting developments in several areas, highlighting versatility of these materials in addressing many societal challenges ranging from semiconducting industries to healthcare, environmental remediation and consumer products. Among those, new generations of CeNPs with controlled morphology and surface chemistry will be needed to be used as polishers in CMP to address the needs for smaller and greener semiconducting manufacturing processes.

CeNP-based photocatalysts and sorbents will continue to attract interest for environmental remediation and energy conversion. Particularly, the tunable redox chemistry and electrochemical stability make them interesting candidates for electrode materials, electrolytes and catalysis, while the catalytic activity towards pollutants such as VOCs, NOx, metals and organics make them well suited for promoting detoxification and removing contaminants through redox and surface adsorption reactions. An array of products and applications are expected to emerge from the exploration of the antioxidant activity and ability to protect cells from oxidative damage, with impact in drug delivery, biomedical imaging, neuroprotection and the cosmetic industry as antiaging and UV-protection agents in skin-care. Continued research and development will be needed to explore and optimize the performance of CeNPs in these diverse applications.

In summary, it is increasingly clear that CeNPs have huge potential as demonstrated by an already increasing number of applications in many areas of science and technology and industries such as catalysis, sensing, semiconductor and environment. The review has tried to provide in a systematic and comprehensive manner the most significant advancements to date. Scientists and engineers can use this overview as a starting point to explore this material's unique and unusual properties and pursue new avenues into the future.