TOPOLOGICAL ANALYSIS OF THE NETWORK OF NON-COVALENT INTERACTIONS IN HALOGEN BONDED BIOMOLECULAR COMPLEXES

ANGELINA, EMILIO L.; DUARTE, DARÍO J. R.; ANDUJAR, SEBASTÍAN A.; NÉLIDA M. PERUCHENA D.; PERUCHENA, NÉLIDA M.

Santiago de Chile

Congreso; 10th Congress of the World Association of Theoretical and Computational Chemists WATOC 2014; 2014

Currently, many efforts have been dedicated to the study of the structural, energetic, spectroscopic and topological characteristics of small complexes bonded by halogen in gas phase, however in the field of medicinal chemistry and green chemistry is becoming more recognized the importance of the halogen bonds in molecular recognition events where the occurrence of these interactions could trigger new molecular arrangements as well modify, enhance or diminish the strength of other interactions already present in the binding pocket.Going from strong and moderate halogen/hydrogen bonds to weaker polar interactions and stacking and T-shape like interactions between aromatic rings, all of them are usually present simultaneously in a receptor-ligand complex modifying their (structural, electronic) characteristics as compares with the same interactions in small complex in gas phase where this interplay between different kinds of interactions does not exist.In this work, we reported the results obtained by charge density analysis of the network of non-covalent interactions established in the binding pocket of the receptor by halogenated analogues. These interactions have been investigated within the framework of the density functional theory (DFT) and the quantum theory of atoms in molecules (QTAIM) using a reducedmodel of the receptorincluding hundreds ofatoms. Although the approach used here was traditionally applied to the study of non-covalent interactions in small molecules complexes in gas phase, we show through this work that this methodology is also a very powerful tool for the study of halogen bonded biomolecular complexes, providing a very detailed description of the binding event as well as the structural and electronic characteristics of the halogen bond in intricate systems.The ultimate goal of this work is to study the characteristics of the electronic distribution on the halogen atom in intricate biological systems, taking advantage of this information to improve the design of new analogous/inhibitors compounds