Assessing the Noncovalent Interaction of Deucravacitinib and Ethanol with Special Reference to an Independent Gradient Model Based on Hirshfeld Partition

J Phys Chem B. 2024 Oct 24;128(42):10469-10480. doi: 10.1021/acs.jpcb.4c04852. Epub 2024 Oct 14.

Abstract

The current study begins by optimizing the deucravacitinib molecule in the gas phase at the ωB97XD/cc-pVDZ level of theory using density functional theory and proceeds to study its intramolecular interactions. Further, a molecule of EtOH was introduced at different locations on the deucravacitinib molecule, and the noncovalent interactions arising from them were also investigated using several computational tools. In this way, eight deucravacitinib-EtOH systems (1-8) were identified and their electronic environment was studied after evaluating their binding energy. Using natural bond orbital analysis, the localization of charges between the donor and acceptor fragments in these interacting systems was examined. The nature of interactions was analyzed using the reduced gradient approach (NCI analysis), and few hydrogen bonding interactions (intermolecular and intramolecular) were found in each system. The strength of these hydrogen bonding interactions was further investigated by using theoretical tools such as atoms in molecules analysis and independent gradient model based on Hirshfeld partition analysis. The binding energy of deucravacitinib with EtOH was decomposed into energy components based on the domain-based local pair natural orbital coupled cluster technique using LED analysis. The results from the hydrogen bonding interaction analysis using different computational tools were found to be consistent with the calculated order of binding energy of systems 1-8 and they also pointed toward the higher stability of system 3.