A DFT Study and Hirshfeld Surface Analysis of the Molecular Structures, Radical Scavenging Abilities and ADMET Properties of 2-Methylthio(methylsulfonyl)-[1,2,4]triazolo [1,5-a]quinazolines: Guidance for Antioxidant Drug Design

Abstract

Optimisation at B3LYP/6-311G(d,p) was used in a DFT study of the characteristics of 2-methylthio(methylsulfonyl)-triazoloquinazolines (1, 2). The design-critical role of intramolecular hydrogen bonding in stabilising both structures is emphasised. The stability of a crystal is a consequence of interactions between its molecules. According to the global index, 2-methylthio-triazoloquinazoline (1) is more electrophilic and reactive, while 2-methylsulfonyl-triazoloquinazoline (2) is more electrophilic and less reactive. Electrophilic, nucleophilic, and radicalophilic sites, polarizable atoms, and charge distributions are all identified by local descriptors. Consistent with crystal structures, negative potentials imply 1 and 2 hydrogen bond acceptors, whereas positive potentials indicate donor capabilities. Antioxidant activity may be enabled via radical stabilisation, as suggested by radicalophilic features such as hydrogen atom donors, resonance, and antioxidants. H7, H8, and H9 atoms in triazoloquinazolines 1 and 2 have been hypothesised to contribute to the compounds’ antioxidant activity through HAT, SPLET, and SET-PT mechanisms. Calculations provide insights into stability, reactivity, electrostatic profiles, radical stabilization ability, toxicity risks. Radical stabilizing ability, reactive site hierarchies suggest possible antioxidant mechanisms. ADMET profiles identify challenges impacting candidate suitability.