Abstract: The fleeting lifetimes of reactive intermediates in C–H functionalization chemistry often prevent their direct characterization. For example, the critical nitrenoid intermediates that mediate Rh₂-catalyzed C–H amination have eluded characterization for more than 40 years. In the absence of structural characterization of these species, methodological development is often computationally guided. Here we report the first X-ray crystal structure of a reactive Rh₂ nitrenoid, enabled by N₂ elimination from an organic azide ligand within a single-crystal matrix. The resulting high-resolution structure displays metrical parameters consistent with a triplet nitrene complex of Rh₂. The demonstration of facile access to reactive metal nitrenoids within a crystalline matrix provides a platform for structural characterization of the transient species at the heart of C–H functionalization.

Anuvab Das, Yu-Sheng Chen, Joseph H. Reibenspies, David C. Powers. Characterization of a Reactive Rh₂ Nitrenoid by Crystalline Matrix Isolation.  J. Am. Chem. Soc., 141 (41), 16232-16236 (2019). doi: 10.1021/jacs.9b09064

Abstract: When nanoparticles interact with cellular or organelle membranes, the coating ligands are known to affect the integrity of the membranes, which regulate cell death and inflammation. However, the molecular mechanisms of this modulation remain unresolved. Here, we use synchrotron X-ray liquid surface scattering and molecular dynamics simulations to study interface structures between phospholipids and gold nanorods (AuNRs) coated by surfactant and polyelectrolyte. These ligands are two types of widely used surface modification with different self-assembled structures and stabilities on the surface of nanoparticles. We reveal distinct mechanisms of the ligand stability in disrupting membrane integrity. We find that the cationic surfactant ligand cetyltrimethylammonium bromide detaches from the AuNRs and inserts into phospholipids, resulting in reduced membrane thickness by compressing the phospholipids to align with the shorter ligand. Conversely, the cationic polyelectrolyte ligand poly(diallyldimethylammonium chloride) is more stable on AuNRs; although it adsorbs onto the membrane, it does not cause much impairment. The distinct coating ligand interactions with phospholipids are further verified by cellular responses including impaired lysosomal membranes and triggered inflammatory effects in macrophages. Together, the quantitative analysis of interface structures elucidates key bio–nano interactions and highlights the importance of surface ligand stability for safety and rational design of nanoparticles.

Liming Wang, Peiyu Quan, Serena H. Chen, Wei Bu, Yu-Feng Li, Xiaochun Wu, Junguang Wu, Leili Zhang, Yuliang Zhao, Xiaoming Jiang, Binhua Lin, Ruhong Zhou, Chunying Chen. Stability of Ligands on Nanoparticles Regulating the Integrity of Biological Membranes at the Nano–Lipid Interface. ACS Nano, 13(8), 8680-8693 (2019). doi: 10.1021/acsnano.9b00114