Theoretical investigation of the structural and electronic features of SLC-0111, a novel inhibitor of human carbonic anhydrase IX, and its anion

Abstract

The various tautomers and conformers of SLC-0111, a well-known biologically potent compound, have been investigated using density functional theory (DFT) calculations in the gas phase and aqueous solution. The amide form is found to be the only stable tautomeric form in both the phases, with the trans-cis conformer as the most stable structure in the gas phase and the trans-trans conformer in aqueous solution. The deprotonation of the sulfonamide nitrogen leading to the formation of the SLC-0111 anion occurs at pH > 10. The various intramolecular interactions and reactivity of the molecule have been characterized using natural bond orbital (NBO) analysis and calculation of global reactivity parameters. The effect of the solvent polarity on the energies and nature of the frontier molecular orbitals has been investigated for both the neutral and anionic forms. Further, the electronic spectra and vibrational spectra of both the states have also been computed and the effect of changing solvents on the electronic spectra has been investigated. The calculated nonlinear optical (NLO) properties of the molecule show that the molecule has potential to be featured as an NLO material.