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In our work with a Au thiolate nanocluster (Au20(SG)16, where SG is the tripeptide glutathione), we noticed it underwent a self-photooxidation reaction in the presence of white light and oxygen. We now report on mechanistic studies using photophysical, photochemical, theoretical, and indirect trapping methods. We find rapid total quenching of singlet oxygen (1O2) by ground-state Au20(SG)16, with evidence for dioxygen insertion into the nanocluster. Supported by analyses with IR, ESI-MS, and density functional theory, we propose the formation of Au–O–O–SG bonds in the Au nanocluster. The expansion of the staple motif from dioxygen insertion is attributed to heightened lability and blebbing (a protrusion) arising from the O–O group. We then demonstrated that the self-photooxidized Au20(SG)16 undergoes oxygen-atom transfer a phosphine trap in the dark. 

ABSTRACT The Curtin–Hammett principle, widely recognized in thermal reactions, has been extended to photosensitization processes in this study, providing new insights into the reactivity of photogenerated singlet oxygen (¹O₂) with phenol and phenolate anion species. Here, we explore mechanistic and Curtin–Hammett studies of the equilibrium between the phenol and phenolate anion forms of a prenylated natural product, prenylphloroglucinol. This study uses density functional theory (DFT) to examine phenol and phenolate anion‐quenching pathways of ¹O₂ showing distinct pathways for each form. In the phenolate anion,¹O₂ is quenched to form a peroxy anion. In contrast, in the phenol form,¹O₂ leads to a potent epoxidizing agent in a seemingly pro‐oxidant path. Aniso‐hydroperoxyhydrofuran intermediate is proposed to be key in the epoxidation. Meanwhile, the phenolate anion cyclizes and protonates forming a comparatively benign hydroperoxyhydrofuran species. The phloroglucinol is next to the C‐prenyated group directs the reaction pathway towards the formation of a dihydrobenzofuran, deviating from the conventional ¹O₂ “ene” reaction mechanism and the production of allylic hydroperoxides typically observed in trisubstituted alkenes. 

To assess tunneling, we studied the Guanine-Cytosine base pair tautomerization in gas phase (GC). We applied multidimensional semiclassical reaction path methodology with microcanonically optimized multidimensional tunneling (OMT) using POLYRATE. The minimum energy path (MEP) has a single saddle point for the double proton transfer. Addition of vibrational zero-point energy (ZPE) to the MEP gives the vibrationally adiabatic ground state curve, V_a^G, the barrier through which tunneling occurs. Unexpectedly V_a^G has not one but two well-separated barriers in the transition state region. The first is near the saddle point. The second barrier is entirely due to a large amount of ZPE associated with local reaction path curvature. We refer to it as a quantum barrier. Its height and width reduce the tunneling transmission coefficient. In other words, GC tautomerization has two competing quantum effects, tunneling and ZPE, that have opposite effects on the reaction rate. The transmission coefficient  is 1.57 and tunneling constitutes 36% of the rate constant at 298 K. Our computed kinetic isotope effects are lower than expected, e.g. KIE = 5.05 at 298 K. In the discussion we show that the quantum barrier is a consequence of reaction path curvature as the tautomer begins to form. 

Abstract This article is a highlight of the paper by Huang et al. in this issue ofPhotochemistry and Photobiology. It describes shades of phototoxicity in fluorescent imaging agents that are not intended to be phototoxic. Phototoxicity was assessed using a modified neutral red uptake (NRU) in vitro assay with mean photo‐effects (MPE) for the fluorescent agents IRdye800, indocyanine green (ICG), proflavine, and methylene blue (MB), with comparisons to known phototoxic agents benzoporphyrin derivative (BPD) and rose bengal (RB). The experimental conditions were aimed to mimic clinical settings, using not only visible light, but also near‐infrared light for insight to photosafety and deep tissue damage. Molecular mechanisms underlying the phototoxicities were not sought, but IRdye800 and ICG were mainly deemed to be safe, whereas proflavine and MB would require precautions since phototoxicity can overshadow their utility as fluorescent imaging agents. 

Photooxidative damage is heavily influenced by the presence of bioactive agents. Conversely, bioactive agents influence the local environment, which in turn is perturbed by photooxidative damage. These sorts of processes give rise to a version of the “chicken-and-egg” quandary. In this Perspective, we probe this issue by referring to photooxidative damage in one direction as the light-dark (L-D) sequence, and in a second direction as the dark-light (D-L) sequence with a reversed cause and effect. The L-D sequence can lead to the downstream production of reactive molecular species (RMS) in the dark, whereas the D-L sequence can be a pre-irradiation period, such as an additive to limit cellular iron levels to enhance biosynthesized amounts of a protoporphyrin sensitizer. A third direction comes from L-D or D-L sequences, or both simultaneously, which can also be useful for optimizing photodynamics. Photodynamic optimization will benefit from understanding and quantitating unidirectional L-D and D-L pathways, and bidirectional L-D/D-L pathways, for improved control over photooxidative damage. Photooxidative damage, which occurs during anti-cancer photodynamic therapy (PDT), will be shown to involve RMS. Such RMS include persulfoxides (R2S+OO−), NO2•, peroxynitrate (O2NOO−), OOSCN–, SO3•−, selenocyanogen ((SeCN)2) and triselenocyanate anion ((SeCN)3−), I• , I2•−, I3−, and HOOI, as well as additives to destabilize membranes (e.g., caspofungin and saponin A16), inhibit DNA synthesis (5-fluorouracil), or sequester iron (desferrioxamine). In view of the success that additive natural products and repurposed drugs have had in PDT, a Perspective of additive types is expected to reveal mechanistic details for enhanced photooxidation reactions in general. Indeed, strategies on how to potentiate photooxidations with additives remains highly underexplored. 

Abstract Singlet oxygen (¹O₂) is a reactive species that plays a role in environmental and biological surface chemistry; however, the mechanisms of the association of airborne¹O₂at the air/surface interface are poorly known. Here, we help resolve this problem using¹O₂'s near‐infrared (NIR) phosphorescence and geometric analysis based on the slope inflection angle (θ) of air‐to‐particle transfer. This offers insight into¹O₂‐surface binding as opposed to conventional kinetic analysis. Two 9,10‐disubstituted anthracene quenchers were adsorbed to the particle surface, producing θ ranging from ~91° (greater quenching) to ~99° (less quenching) due to the reduction of airborne¹O₂lifetime (τ_airborne) by 43% to 95%. A more efficient (lower θ)¹O₂quenching is observed in the order dimethylanthracene‐coated particle > anthracene dianion‐coated particle > native silica. The anthracene dianion charges and surface silanols did not enhance the¹O₂surface quenching. Indeed, the quenching of airborne¹O₂by native silica was minimal, in which a slight reduction in its surface lifetime (τ_surf) was observed (0–5%). This θ approach opens up opportunities in fields such as surface oxidation processes in nanoplastics, which is an emerging concern. 

Abstract Tandem reactions of singlet oxygen (¹O₂) with nonconjugated natural products, such as plastoquinones, have attracted attention. However, mechanistic clarity is needed for the¹O₂uptake sequence and regioselectivity. Our strategy was to study a tandem¹O₂reaction in a diprenylated phenol (geranyl phenol) bearing an inner and an outer prenyl group in the chain. Singlet oxygen first added to the inner prenyl group by H‐bonding to the phenol OH, forming agem‐disubstituted and atri‐substituted dienyl dihydrobenzofuran. H₂O₂was also released as a by‐product. A second equivalent of¹O₂added by an “ene” reaction, but now to the outer rather than the inner site of the nonconjugated diene to reach four hydroperoxy‐dihydrobenzofurans. There was no evidence for¹O₂“ene” reactions on the inner prenyl sites, but product decomposition included the formation of oxygen‐centered radicals and even methane by a β‐scission process. The results are an essential step in resolving mechanistic puzzles of reactive oxygen uptake in natural prenylated systems, which are important topics not only in physical‐organic and synthetic chemistry but also in plant oxidation chemistry. 

Abstract A density functional theoretical (DFT) study is presented, implicating a¹O₂oxidation process to reach a dihydrobenzofuran from the reaction of the natural homoallylic alcohol, glycocitrine. Our results predict an interconversion between glycocitrine and aniso‐hydroperoxide intermediate [R(H)O⁺–O⁻] that provides a key path in the chemistry which then follows. Formations of allylic hydroperoxides are unlikely from a¹O₂‘ene’ reaction. Instead, the dihydrobenzofuran arises by¹O₂oxidation facilitated by a 16° curvature of the glycocitrine ring imposed by a pyramidalN‐methyl group. This curvature facilitates the formation of theiso‐hydroperoxide, which is analogous to theisospecies CH₂I⁺–I⁻and CHI₂⁺–I⁻formed by UV photolysis of CH₂I₂and CHI₃. Theiso‐hydroperoxide is also structurally reminiscent of carbonyl oxides (R₂C=O⁺–O⁻) formed in the reaction of carbenes and oxygen. Our DFT results point to intermolecular process, in which theiso‐hydroperoxide's fate relates to O‐transfer and H₂O dehydration reactions for new insight into the biosynthesis of dihydrobenzofuran natural products.