The strength and directionality of a halogen bond are co-determined by the magnitude and size of the sigma-hole

0429491 - ÚOCHB 2015 RIV GB eng J - Journal Article
Kolář, Michal - Hostaš, Jiří - Hobza, Pavel
The strength and directionality of a halogen bond are co-determined by the magnitude and size of the sigma-hole.
Physical Chemistry Chemical Physics. Roč. 16, č. 21 (2014), s. 9987-9996. ISSN 1463-9076. E-ISSN 1463-9084
R&D Projects: GA ČR GBP208/12/G016
Institutional support: RVO:61388963
Keywords : adapted perturbation theory * basis set * noncovalent interactions
Subject RIV: CF - Physical ; Theoretical Chemistry
Impact factor: 4.493, year: 2014

The sigma-holes of halogen atoms on various aromatic scaffolds were described in terms of their size and magnitude. The electrostatic potential maps at the CAM-B3LYP-D3(bj)/def2-QZVP level were calculated and the sigma-holes of more than 100 aromatic analogues were thoroughly analysed to relate the sigma-holes to the binding preferences of the halogenated compounds. Both the size and magnitude of the sigma-hole increase when passing from chlorinated to iodinated analogues. Also, the sigma-hole properties were studied upon chemical substitution of the aromatic ring as well as in the aromatic ring. Further, the angular variations of the interactions were investigated on a selected set of halogenbenzene complexes with argon and hydrogen fluoride (HF). In order to analyse interaction energy components, DFT-SAPT angular scans were performed. The interaction energies of bromobenzene complexes were evaluated at the CCSD(T)/complete basis set level providing the benchmark energetic data. The strength of the halogen bond between halogenbenzenes and Ar atoms and HF molecules increases while its directionality decreases when passing from chlorine to iodine. The decrease of the directionality of the halogen bond is larger for a HF-containing complex and is caused by electrostatic and exchange-repulsion energies. These findings are especially valuable for protein-halogenated ligand-binding studies, applied in the realm of rational drug development and lead optimisation.
Permanent Link: http://hdl.handle.net/11104/0234609