A combined DFT and molecular docking study on novel tricarbonylrhenium(I) complexes bearing mono- and bivalent benzenesulfonamide scaffolds as human carbonic anhydrase IX and XII inhibitors

Abstract

The aim of this study was to determine the reactivity and stability properties of a novel series of tricarbonylrhenium(I) complexes with 1,2,3-triazole-pyridine based on monovalent and bivalent benzenesulfonamide ligands as well as analyze their binding affinity within the active site of carbonic anhydrases IX and XII, using DFT and molecular docking. In the first setup, the DFT method was used to investigate the molecular geometries and vibrational frequencies of ligands and their Re(I) complexes. The basis set used was B3LYP/LanL2DZ-ECP/6-31G(d). The optimized geometric parameters (bond lengths and bond angles) and vibrational frequencies agree well with the experimental results. TD-DFT calculations were also performed to determine the influence of the methylene linker (-CH2-) on the bands found in the electronic spectra of these compounds. Global reactivity indices calculated from the energies of frontier molecular orbitals were used to assess their reactivity and stability properties (FMOs). Molecular electrostatic potential maps of the molecules were calculated to provide information about their chemical reactivity and to explain their intermolecular interactions. The computational data showed that bivalent ligands and their bivalent Re(I) complexes are more reactive than their monovalent counterparts. The second setup involves docking studies of the compounds within the active sites of the receptors (6QN2 for hCA IX and 1JD0 for hCA XII), which are performed using the Molegro Virtual Docker and AutoDock 4.2 programs, respectively. Our results indicate that bivalent ligands and their associated Re(I) complexes have a greater binding affinity than monovalent ligands and their associated Re(I) complexes. Compounds bis-L1 and bis-L2 exhibited the best affinity potential for hCA IX and hCA XII inhibition, making them the most promising candidates among those examined.