El Hage, Krystel; Piquemal, Jean-Philip; Hobaika, Zeina; Maroun, Richard G.; Gresh, Nohad published the artcile< Could the ""Janus-like"" properties of the halobenzene CX bond (X=Cl, Br) be leveraged to enhance molecular recognition?>, Application of C6H3ClF2, the main research area is chlorobenzene bromobenzene bond mol recognition; anticooperativity; cooperativity; electron-donating substituents; electron-withdrawing substituents; halobenzyl ring; protein-ligand interactions; quantum chemistry; rational drug design; sigma-hole.
The CX bond in halobenzenes (X = Cl, Br) exhibits a dual character, being electron-deficient along the CX direction, and electron-rich on its flanks. We sought to amplify both features by resorting to electron-withdrawing and electron-donating substituents, resp. This was done by quantum chem. (QC) computations in the recognition sites of three protein targets: farnesyl transferase, coagulation factor Xa, and the HIV-1 integrase. In this context, some substituents, notably fluorine, CF3, and NHCH3, afforded significant overall gains in the binding energies as compared to the parent halobenzene, in the 2-5 kcal/mol range. In fact, we found that some di- and up to tetra-substitutions enabled even larger gains than those they contribute sep. owing to many-body effects. Moreover, desolvation was also found to be a key contributor to the energy balances. As a consequence, some particular substituents, contributing to reduce the halobenzene dipole moment, accordingly reduced solvation: this factor acted in synergy with their enhancement of the intermol. interaction energies along and around the CX bond. We could thus leverage the “”Janus-like”” properties of such a bond and the fact that it can be tuned and possibly amplified by well-chosen substituents. We propose a simple yet rigorous computational strategy resorting to QC to prescreen novel substituted halobenzenes. The QC results on the recognition sites then set benchmarks to validate polarizable mol. mechanics/dynamics approaches used to handle the entirety of the inhibitor-protein complex. © 2014 Wiley Periodicals, Inc.
Journal of Computational Chemistry published new progress about Aryl bromides Role: PEP (Physical, Engineering or Chemical Process), PRP (Properties), PROC (Process). 1435-43-4 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H3ClF2, Application of C6H3ClF2.
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