Porphyrin aggregation has long been reported to weaken its ability for photosensitizing the generation of 1O2 for photodynamic therapy, but cannot be avoided for yet reported single molecule porphyrins. To address this challenge, we here report the design and synthesis of a new series of amphiphilic porphyrin compounds that bear three sulfonate groups and one aliphatic chain. Dynamic light scattering and transmission electron microscopic imaging experiments show that one of the compounds, TSC18P, that bears the longest hydrophobic stearamide unit undergoes ordered H-aggregation to form highly stable uniform single molecule nanomicelles in both water and the solid state. UV-vis, fluorescence and electron spin resonance experiments support that the formation of the single molecule nanomicelles significantly increases the ability of TSC18P in photosensitizing the generation of 1O2 and also enables important intracellular self-delivery. In vivo test demonstrates that TSC18P has an excellent biocompatibility, a therapeutic index of 17.5 and can achieve remarkably higher anti-tumor photodynamic therapeutic activity compared with aggregation-free porphyrin control.

The selective incorporation of a deuterium atom into small molecules with high selectivity is highly valuable for medical and chemical research. Unfortunately, this remains challenging due to the complete deuteration caused by commonly used hydrogen isotope exchange strategies. We report the development of a photocatalytic selective monodeuteration protocol utilizing C-C bond as the unconventional functional handle. The synergistic combination of radical-mediated C-C bond scission and deuterium atom transfer processes enables the effective constructions of benzylic CDH moieties with high selectivity for monodeuteration. The combinational use of a bisphosphonium photocatalyst, thiol catalyst, and CH3OD deuteration agent provides operationally simple conditions for photocatalytic monodeuteration. Moreover, the photoinduced electron transfer process of the bisphosphonium photocatalyst is elucidated through a series of spectroscopy experiments, identifying a peculiar back electron transfer process that can be regulated by subsequent nucleophilic additions. Incorporation of deuterium into small molecules in the place of hydrogens can alter the properties of the molecule in ways that provide benefits without affecting the core function of the molecule. Here, the authors report a ring-opening deuteration of cyclic alkanes via biphosphonium photocatalysis.

alpha- synuclein (alpha- syn) assembles into structurally distinct fibril polymorphs seen in different synucleinopathies, such as Parkinson's disease and multiple system atrophy. Targeting these unique fibril structures using chemical ligands holds diagnostic significance for different disease subtypes. However, the molecular mechanisms governing small molecules interacting with different fibril polymorphs remain unclear. Here, we investigated the interactions of small molecules belonging to four distinct scaffolds, with different tures of these molecules when bound to the fibrils formed by E46K mutant alpha- syn and compared them to those bound with wild- type alpha- syn fibrils. Notably, we observed that these ligands exhibit remarkable binding adaptability, as they engage distinct binding sites across different fibril polymorphs. While the molecular scaffold primarily steered the binding locations and geometries on specific sites, the conjugated functional groups further refined this adaptable binding by fine- tuning the geometries and binding sites. Overall, our finding elucidates the adaptability of small molecules binding to different fibril structures, which sheds light on the diagnostic tracer and drug developments tailored to specific pathological fibril polymorphs.

An efficient Pd-catalyzed regioselective intramolecular aerobic oxidative dehydrocoupling of BH/CH between o-carborane and arenes has been achieved with the construction of a series of five-, six- and seven-membered rings under mild reaction conditions. Control experiments indicate that B-H activation proceeds preferentially over the aryl C-H. These new polyarene-carborane conjugates have potential applications in materials as demonstrated by pyrene fused o-carborane that exhibits unique dual-phase emission, intramolecular charge transfer (ICT), and aggregation-induced emission (AIE) properties.

2-Deoxy-beta-glycosides are essential components of natural products and pharmaceuticals; however, the corresponding 2-deoxy-beta-glycosidic bonds are challenging to chemically construct. Herein, we describe an efficient catalytic protocol for synthesizing 2-deoxy-beta-glycosides via either IPrAuNTf2-catalyzed activation of a unique 1,2-trans-positioned C2-S-propargyl xanthate (OSPX) leaving group or (PhO)3PAuNTf2-catalyzed activation of a 1,2-trans-C2-ortho-alkynylbenzoate (OABz) substituent of the corresponding thioglycosides. These activation processes trigger 1,2-alkyl/arylthio-migration glycosylation, enabling the synthesis of structurally diverse 2-deoxy-beta-glycosides under mild reaction conditions. The power of this strategy is demonstrated by the first synthesis of the pentasaccharide chain corresponding to velutinoside A, which features gold(I)-catalyzed construction of four successive beta-l-oleandrosidic bonds in both a convergent and a one-pot glycosylation manner. Mechanistic studies, including control experiments and deuterium-labeling experiments, emphasize the crucial role of the OSPX and the involvement of the gold(I)-activated C equivalent to C triple bond during the glycosylation process. The low-temperature NMR experiments unveiled a unique dual-coordination pattern of the gold(I) catalyst to the thiocarbonyl group and the alkynyl group of the OSPX, initiating a 5-exo-dig cyclization process. Furthermore, density functional theory (DFT) simulations reveal the ligand-induced match-mismatch effect between leaving groups OSPX and OABz and gold catalysts IPrAuNTf2 and (PhO)3PAuNTf2. The DFT simulations also suggest that the formation of 2-deoxy-beta-glycosidic bonds occurs via the bottom-face attack of the acceptor to the oxocarbenium intermediate, which adopts a 4 H 3 half-chair conformation, leading to an energetically favored, 4 C 1-conformed intermediate D beta that is stabilized by a hydrogen bonding interaction.