A boron-transfer mechanism mediating the thermally induced revival of frustrated carbene–borane pairs from their shelf-stable adducts

Chemists have designed strategies that trigger the conformational isomerization of molecules in response to external stimuli, which can be further applied to regulate the complexation between Lewis acids and bases. We have recently developed a system in which frustrated carbene–borane pairs are revived from shelf-stable but external-stimuli-responsive carbene–borane adducts comprised of N-phosphine-oxide-substituted imidazolylidenes (PoxIms) and triarylboranes. Herein, we report the detailed mechanism on this revival process. A thermally induced borane-transfer process from the carbene carbon atom to the N-phosphinoyl oxygen atom initiates the transformation of the carbene–borane adduct. Subsequent conformational isomerization via the rotation of the N-phosphinoyl group in PoxIm moieties eventually leads to the revival of frustrated carbene–borane pairs that can cleave H2. We believe that this work illustrates an essential role of dynamic conformational isomerization in the regulation of the reactivity of external-stimuli-responsive Lewis acid-base adducts that contain multifunctional substituents.

Structures of HIV-1 Neutralizing Antibody 10E8 Delineate the Mechanistic Basis of Its Multi-Peak Behavior on Size-Exclusion Chromatography

Antibody 10E8 is capable of effectively neutralizing HIV through its recognition of the membrane-proximal external region (MPER), and a suitably optimized version of 10E8 might have utility in HIV therapy and prophylaxis. However, 10E8 displays a three-peak profile on size-exclusion chromatography (SEC), complicating its manufacture. Here we show cis-trans conformational isomerization of the Tyr-Pro-Pro (YPP) motif in the heavy chain 3rd complementarity-determining region (CDR H3) of antibody 10E8 to be the mechanistic basis of its multipeak behavior. We observed 10E8 to undergo slow conformational isomerization and delineate a mechanistic explanation for effective comodifiers that were able to resolve its SEC heterogeneity and to allow an evaluation of the critical quality attribute of aggregation. We determined crystal structures of single and double alanine mutants of a key di-proline motif and of a light chain variant, revealing alternative conformations of the CDR H3. We also replicated both multi-peak and delayed SEC behavior with MPER-antibodies 4E10 and VRC42, by introducing a Tyr-Pro (YP) motif into their CDR H3s. Our results show how a conformationally dynamic CDR H3 can provide the requisite structural plasticity needed for a highly hydrophobic paratope to recognize its membrane-proximal epitope.

Photoluminescent manipulation of phenoxazine-based molecules via regulating conformational isomerization, and the corresponding electroluminescent properties

Systematic and detailed research on mechanochromic luminescence reveals the conformational isomerization mechanism behind single-molecule white-light emission.

UV-promoted radical formation, and near-IR-induced and spontaneous conformational isomerization in monomeric 9-methylguanine isolated in low-temperature Ar matrices

An H-atom detaches from UV-excited 9-methylguanine. Excitation with monochromatic near-IR light selectively transforms a chosen amino-hydroxy conformer (AH1 or AH2) into the other. The AH2 form spontaneously converts, via H-atom tunneling, into AH1.