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1. Self-assembly of a robust, reduction-sensitive camptothecin nanotube

   https://doi.org/10.1039/d0cc03528a  

   Sun, Yuan; Fry, Cathleen M.; Shieh, Aileen; Parquette, Jon R. (September 2020, Chemical Communications)

   null (Ed.)

   The self-assembly and covalent crosslinking of a camptothecin (CPT) tetrapeptide nanotube is reported. Intermolecular disulfide bond formation of a self-assembled CPT-peptide reversibly stabilized the nanotubes toward dissociation at low concentrations, resulting in inhibited release of CPT. In the presence of dithiothreitol (DTT), the release of CPT was significantly accelerated. The crosslinked nanotubes also exhibited in vitro cytotoxicity against human non-small cell lung cancer cell lines A549 and H460. 

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2. Self-assembly of a 5-fluorouracil-dipeptide hydrogel

   https://doi.org/10.1039/C6CC01195K  

   Sun, Yuan; Kaplan, Jonah A.; Shieh, Aileen; Sun, Hui-Lung; Croce, Carlo M.; Grinstaff, Mark W.; Parquette, Jon R. (January 2016, Chemical Communications)

   null (Ed.)

   The self-assembly of 5-fluorouracil dilysine conjugates into self-supporting hydrogels, comprised of entangled nanofibers or rigid nanotubes with diameters of 10 and 16 nm, respectively, is reported. The rate of release of 5-Fu from the conjugates was highly dependent on concentration in solution, whereas, release from the fully formed hydrogels was significantly slower. The 5-Fu conjugate also exhibited promising in vitro cytotoxicity against human tumor cell lines A549, H460 and H23. 

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3. Fragment‐Based Approach for Hierarchical Nanotube Assembly of Small Molecules in Aqueous Phase

   https://doi.org/10.1002/chem.202404630  

   Zia, Ayisha; Yi, Meihui; Liu, Zhiyu; Wang, Fengbin; Xu, Bing (February 2025, Chemistry – A European Journal)

   Abstract A fragment‐based approach has proven successful in drug design and protein assemblies, yet its potential for constructing biomaterials from simple organic building blocks remains underexplored, particularly for self‐assembly in aqueous phases, where water disrupts intermolecular hydrogen bonding. To the best of our knowledge, this study introduces the first case of integrating fragments from self‐assembling molecules to design a small organic molecule that forms novel hierarchical nanotubes with polymorphism. The molecule's compact design incorporates three structural motifs derived from known nanotube assemblies, enabling a hierarchical assembly process: individual molecules with two conformations form dimers, which organize into hexameric units. These hexamers further assemble into nanotubes comprising 2‐, 5‐, and 6‐protofilament fibers. The nanofibers share a nearly identical asymmetric unit – a hexameric triangular plate – with similar axial and lateral interfaces. The lateral interface, involving interactions between phosphate groups and aromatic rings, exhibits plasticity, allowing slight rotational variations between adjacent units. This adaptability facilitates the formation of diverse nanofiber architectures, showcasing the flexibility of these systems in aqueous environments. By leveraging fragments of self‐assembling molecules, this work demonstrates a straightforward strategy that combines conformational flexibility and self‐assembling fragments to construct advanced supramolecular biomaterials from small organic building blocks in aqueous settings. 

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4. Enhanced photodegradation of dimethoxybenzene isomers in/on ice compared to in aqueous solution

   https://doi.org/10.5194/acp-22-5943-2022  

   Hullar, Ted; Tran, Theo; Chen, Zekun; Bononi, Fernanda; Palmer, Oliver; Donadio, Davide; Anastasio, Cort (January 2022, Atmospheric Chemistry and Physics)

   Abstract. Photochemical reactions of contaminants in snow and ice can be importantsinks for organic and inorganic compounds deposited onto snow from theatmosphere and sources for photoproducts released from snowpacks into theatmosphere. Snow contaminants can be found in the bulk ice matrix, ininternal liquid-like regions (LLRs), or in quasi-liquid layers (QLLs) at theair–ice interface, where they can readily exchange with the firn air. Somestudies have reported that direct photochemical reactions occur faster inLLRs and QLLs than in aqueous solution, while others have found similarrates. Here, we measure the photodegradation rate constants for loss of thethree dimethoxybenzene isomers under varying experimental conditions,including in aqueous solution, in LLRs, and at the air–ice interface ofnature-identical snow. Relative to aqueous solution, we find modestphotodegradation enhancements (3- and 6-fold) in LLRs for two of theisomers and larger enhancements (15- to 30-fold) at the air–ice interfacefor all three isomers. We use computational modeling to assess the impact oflight absorbance changes on photodegradation rate enhancements at theinterface. We find small (2–5 nm) bathochromic (red) absorbance shifts atthe interface relative to in solution, which increases light absorption, butthis factor only accounts for less than 50 % of the measured rate constantenhancements. The major factor responsible for photodegradation rateenhancements at the air–ice interface appears to be more efficientphotodecay: estimated dimethoxybenzene quantum yields are 6- to 24-foldlarger at the interface compared to in aqueous solution and account for themajority (51 %–96 %) of the observed enhancements. Using a hypotheticalmodel compound with an assumed Gaussian-shaped absorbance peak, we find thata shift in the peak to higher or lower wavelengths can have a minor tosubstantial impact on photodecay rate constants, depending on the originallocation of the peak and the magnitude of the shift. Changes in other peakproperties at the air–ice interface, such as peak width and height (i.e.,molar absorption coefficient), can also impact rates of light absorption anddirect photodecay. Our results suggest our current understanding ofphotodegradation processes underestimates the rate at which some compoundsare broken down, as well as the release of photoproducts into theatmosphere. 

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5. Non-covalent complexes of the peptide fragment Gly-Asn-Asn-Gln-Gln-Asn-Tyr in the gas-phase. Photodissociative cross-linking, Born–Oppenheimer molecular dynamics, and ab initio computational binding study

   https://doi.org/10.1039/c8cp06893c  

   Huang, Shu R.; Liu, Yang; Tureček, František (January 2019, Physical Chemistry Chemical Physics)

   Non-covalent complexes of the short amyloid peptide motif Gly-Asn-Asn-Gln-Gln-Asn-Tyr (GNNQQNY) with peptide counterparts that were tagged with a diazirine ring at the N-termini (*GNNQQNY) were generated as singly charged ions in the gas phase. Specific laser photodissociation (UVPD) of the diazirine tag in the gas-phase complexes at 355 nm generated transient carbene intermediates that underwent covalent cross-linking with the target GNNQQNY peptide. The crosslinking yields ranged between 0.8 and 4.5%, depending on the combinations of peptide C-terminal amides and carboxylates. The covalent complexes were analyzed by collision-induced dissociation tandem mass spectrometry (CID-MS 3 ), providing distributions of cross-links at the target peptide amino acid residues. A general preference for cross-linking at the target peptide Gln-4-Gln-5-Asn-6-Tyr-7 segment was observed. Born–Oppenheimer molecular dynamics calculations were used to obtain 100 ps trajectories for nine lowest free-energy conformers identified by ωB97X-D/6-31+G(d,p) gradient geometry optimizations. The trajectories were analyzed for close contacts between the incipient carbene atom and the X–H bonds in the target peptide. The close-contact analysis pointed to the Gln-5 and Tyr-7 residues as the most likely sites of cross-linking, consistent with the experimental CID-MS 3 results. Non-covalent binding in the amide complexes was evaluated by DFT calculations of structures and energies. Although antiparallel arrangements of the GNNQQNY and *GNNQQNY peptides were favored in low-energy gas-phase and solvated complexes, the conformations and peptide–peptide interface surfaces were found to differ from the secondary structure of the dry interface in GNNQQNY motifs of amyloid aggregates. 

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