Perylene-based profluorescent nitroxides for the rapid monitoring of polyester degradation upon weathering: An assessment

A profluorescent nitroxide possessing an isoindoline nitroxide moiety linked to a perylene fluorophore was developed to monitor radical mediated degradation of melamine-formaldehyde crosslinked polyester coil coatings in an industry standard accelerated weathering tester. Trapping of polyester-derived radicals (most likely C-radicals) that are generated during polymer degradation leads to fluorescent closed-shell alkoxy amines, which was used to obtain time-dependent degradation profiles to assess the relative stability of different polyesters towards weathering. The nitroxide probe couples excellent thermal stability and satisfactory photostability with high sensitivity and enables detection of free radical damage in polyesters under conditions that mimic exposure to the environment on a time scale of hours rather than months or years required by other testing methods. There are indications that the profluorescent nitroxide undergoes partial photo-degradation in the absence of polymer-derived radicals. Unexpectedly, it was also found that UV-induced fragmentation of the NO–C bond in closed-shell alkoxy amines leads to regeneration of the profluorescent nitroxide and the respective C-radical. The maximum fluorescence intensity that could be achieved with a given probe concentration is therefore not only determined by the amount of polyester radicals formed during accelerated weathering, but also by the light-driven side reactions of the profluorescent nitroxide and the corresponding alkoxy amine radical trapping products. Studies to determine the optimum probe concentration in the polymer matrix revealed that aggregation and re-absorption effects lowered the fluorescence intensity at higher concentrations of the profluorescent nitroxide, but too low probe concentrations, where these effects would be avoided, were not sufficient to trap the amount of polyester radicals formed upon weathering. The optimized experimental conditions were used to assess the impact of temperature and UV irradiance on polymer degradation during accelerated weathering.     

Engineered protein cages for nanomaterial synthesis

Self-assembled particles of genetically engineered human L subunit ferritin expressing a silver-binding peptide were used as nanocontainers for the synthesis of silver nanoparticles. The inner cavity of the self-assembled protein cage displays a dodecapeptide that is capable of reducing silver ions to metallic silver. This chimeric protein cage when incubated in the presence of silver nitrate exhibits the growth of a silver nanocrystal within its cavity. Our studies indicate that it is possible to design chimeric cages, using specific peptide templates, for the growth of other inorganic nanoparticles.     

Structure of a surfactant-templated silicate framework in the absence of 3d crystallinity

The structure of a novel molecularly ordered two-dimensional (2D) silicate framework in a surfactant-templated mesophase has been established by using a combination of solid-state nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, and quantum chemical and empirical force-field modeling. These materials are unusual in their combination of headgroup-directed 2D crystalline framework ordering, zeolite-like ring structures within the layers, and long-range mesoscopic organization without three-dimensional (3D) atomic periodicity. The absence of registry between the silicate sheets, resulting from the liquidlike disorder of the alkyl surfactant chains, has presented significant challenges to the determination of framework structures in these and similar materials lacking 3D crystalline order. Double-quantum (29)Si NMR correlation experiments establish the interactions and connectivities between distinct intra-sheet silicon sites from which the structure of the molecularly ordered inorganic framework is determined.     

Dual Functioning Thieno‐Pyrrole Fused BODIPY Dyes for NIR Optical Imaging and Photodynamic Therapy: Singlet Oxygen Generation without Heavy Halogen Atom Assistance

We discovered a rare phenomenon wherein a thieno‐pyrrole fused BODIPY dye (SBDPiR690) generates singlet oxygen without heavy halogen atom substituents. SBDPiR690 generates both singlet oxygen and fluorescence. To our knowledge, this is the first example of such a finding. To establish a structure–photophysical property relationship, we prepared SBDPiR analogs with electron‐withdrawing groups at the para‐position of the phenyl groups. The electron‐withdrawing groups increased the HOMO–LUMO energy gap and singlet oxygen generation. Among the analogs, SBDPiR688, a CF₃ analog, had an excellent dual functionality of brightness (82290 m ^?1 cm^?1) and phototoxic power (99170 m ^?1 cm^?1) comparable to those of Pc 4, due to a high extinction coefficient (211 000 m ^?1 cm^?1) and balanced decay (Φ_flu=0.39 and Φ_Δ=0.47). The dual functionality of the lead compound SBDPiR690 was successfully applied to preclinical optical imaging and for PDT to effectively control a subcutaneous tumor.     

Aromatic Interactions in Organocatalyst Design: Augmenting Selectivity Reversal in Iminium Ion Activation

Substituting N‐methylpyrrole for N‐methyindole in secondary‐amine‐catalysed Friedel–Crafts reactions leads to a curious erosion of enantioselectivity. In extreme cases, this substrate dependence can lead to an inversion in the sense of enantioinduction. Indeed, these closely similar transformations require two structurally distinct catalysts to obtain comparable selectivities. Herein a focussed molecular editing study is disclosed to illuminate the structural features responsible for this disparity, and thus identify lead catalyst structures to further exploit this selectivity reversal. Key to effective catalyst re‐engineering was delineating the non‐covalent interactions that manifest themselves in conformation. Herein we disclose preliminary validation that intermolecular aromatic (CH–π and cation–π) interactions between the incipient iminium cation and the indole ring system is key to rationalising selectivity reversal. This is absent in the N‐methylpyrrole alkylation, thus forming the basis of two competing enantio‐induction pathways. A simple L ‐valine catalyst has been developed that significantly augments this interaction.     

Aryl to aryl palladium migration in the Heck and Suzuki coupling of o-halobiaryls

A novel 1,4-palladium migration between the o- and o'-positions of biaryls has been observed in organopalladium intermediates derived from o-halobiaryls. The organopalladium intermediates generated by this migration have been trapped either by a Heck reaction employing ethyl acrylate or by Suzuki cross-coupling using arylboronic acids. This palladium migration can be activated or deactivated by choosing the appropriate reaction conditions. Chemical and computational evidence supports the presence of an equilibrium that correlates with the C-H acidity of the available arene positions.     

Site-specific incorporation of a (19)F-amino acid into proteins as an NMR probe for characterizing protein structure and reactivity

19F NMR is a powerful tool for monitoring protein conformational changes and interactions; however, the inability to site-specifically introduce fluorine labels into proteins of biological interest severely limits its applicability. Using methods for genetically directing incorporation of unnatural amino acids, we have inserted trifluoromethyl-l-phenylalanine (tfm-Phe) into proteins in vivo at TAG nonsense codons with high translational efficiency and fidelity. The binding of substrates, inhibitors, and cofactors, as well as reactions in enzymes, were studied by selective introduction of tfm-Phe and subsequent monitoring of the 19F NMR chemical shifts. Subtle protein conformational changes were detected near the active site and at long distances (25 Angstrom). 19F signal sensitivity and resolution was also sufficient to differentiate protein environments in vivo. Since there has been interest in using 19F-labeled proteins in solid-state membrane protein studies, folding studies, and in vivo studies, this general method for genetically incorporating a 19F-label into proteins of any size in Escherichia coli should have broad application beyond that of monitoring protein conformational changes.     

Enhanced Four-Electron Oxygen Reduction Selectivity of Clamp-Shaped Cobalt(II) Porphyrin(2.1.2.1) Complexes

The molecular structure, electrochemistry, spectroelectrochemistry and electrocatalytic oxygen reduction reaction (ORR) features of two Co^II porphyrin(2.1.2.1) complexes bearing Ph or F₅Ph groups at the two meso-positions of the macrocycle are examined. Single crystal X-ray analysis reveal a highly bent, nonplanar macrocyclic conformation of the complex resulting in clamp-shaped molecular structures. Cyclic voltammetry paired with UV/Vis spectroelectrochemistry in PhCN/0.1 M TBAP suggest that the first electron addition corresponds to a macrocyclic-centered reduction while spectral changes observed during the first oxidation are consistent with a metal-centered Co^II/Co^III process. The activity of the clamp-shaped complexes towards heterogeneous ORR in 0.1 M KOH show selectivity towards the 4e⁻ ORR pathway giving H₂O. DFT first-principle calculations on the porphyrin catalyst indicates a lower overpotential for 4e⁻ ORR as compared to the 2e⁻ pathway, consistent with experimental data.     

A Universal DNA Aptamer that Recognizes Spike Proteins of Diverse SARS-CoV-2 Variants of Concern

We report on a unique DNA aptamer, denoted MSA52, that displays universally high affinity for the spike proteins of wildtype SARS-CoV-2 as well as the Alpha, Beta, Gamma, Epsilon, Kappa, Delta and Omicron variants. Using an aptamer pool produced from round 13 of selection against the S1 domain of the wildtype spike protein, we carried out one-round SELEX experiments using five different trimeric spike proteins from variants, followed by high-throughput sequencing and sequence alignment analysis of aptamers that formed complexes with all proteins. A previously unidentified aptamer, MSA52, showed K_d values ranging from 2 to 10 nM for all variant spike proteins, and also bound similarly to variants not present in the reselection experiments. This aptamer also recognized pseudotyped lentiviruses (PL) expressing eight different spike proteins of SARS-CoV-2 with K_d values between 20 and 50 pM, and was integrated into a simple colorimetric assay for detection of multiple PL variants. This discovery provides evidence that aptamers can be generated with high affinity to multiple variants of a single protein, including emerging variants, making it well-suited for molecular recognition of rapidly evolving targets such as those found in SARS-CoV-2.