Computational Study of B(C₆F₅)₃‑Catalyzed Selective Deoxygenation of 1,2-Diols: Cyclic and Noncyclic Pathways

The selective deoxygenation of polyols has emerged as an attractive approach to transform biomass-derived polyols into valuable building blocks. Herein, we present a theoretical study on the boron-catalyzed selective deoxygenation of terminal 1,2-diols. The computational results explain the different product distributions obtained with different silanes and unveil the critical role of the cyclic siloxane intermediate. Compared to noncyclic pathways, the cyclic pathway facilitates the initial deoxygenation process because the cyclic structure minimizes the steric repulsions between the reagents. It avoids overreduction because the generated bulky disiloxane moiety hinders the second deoxygenation

Discovery and optimization of a selective ligand for the switch/sucrose nonfermenting-related bromodomains of polybromo protein-1 by the use of virtual screening and hydration analysis

Bromodomains (BRDs) are epigenetic interaction domains currently recognized as emerging drug targets for development of anticancer or anti-inflammatory agents. In this study, development of a selective ligand of the fifth BRD of polybromo protein-1 (PB1(5)) related to switch/sucrose nonfermenting (SWI/SNF) chromatin remodeling complexes is presented. A compound collection was evaluated by consensus virtual screening and a hit was identified. The biophysical study of protein-ligand interactions was performed using X-ray crystallography and isothermal titration calorimetry. Collective data supported the hypothesis that affinity improvement could be achieved by enhancing interactions of the complex with the solvent. The derived SAR along with free energy calculations and a consensus hydration analysis using WaterMap and SZmap algorithms guided rational design of a set of novel analogues. The most potent analogue demonstrated high affinity of 3.3 µM and an excellent selectivity profile, thus comprising a promising lead for the development of chemical probes targeting PB1(5)