Theoretical and computational studies on the conformation of dodecahydrospiro[isothiochromene-3,2'-thiopyran] compounds using Density Functional Theory (DFT) methods and Natural Bond Orbital (NBO) analysis.

CONTEXT: The structural, thermodynamic, and electronic properties of dodecahydrospiro[isothiochromene-3,2'-thiopyran] compounds with hydrogen and methyl substituents were systematically investigated using Density Functional Theory (DFT) to understand how substituent type and solvent polarity influence conformational stability and electronic structure in sulfur-containing heterocycles. Conformational preferences between axial and equatorial isomers were analyzed based on Gibbs free energy differences, anomeric effects, dipole moments, and key orbital interactions such as , which influence bond lengths like . This comprehensive approach provides insight into how substituent type and environment influence the conformational stability and electronic characteristics of sulfur-containing heterocycles. METHODS: All quantum chemical calculations were carried out using the B3LYP functional within the DFT framework and the B3LYP/6-311+G** basis set. Natural Bond Orbital (NBO) analysis was employed to evaluate donor-acceptor interactions, stabilization energies, and orbital delocalizations. Solvent effects were incorporated using the Polarizable Continuum Model (PCM) for both polar (water) and non-polar (n-hexane) solvents, alongside gas-phase calculations. Computational analyses were performed with Gaussian 09W, and the conformational behavior of axial and equatorial isomers was assessed by determining Gibbs free energy differences (∆G), anomeric effects (AE), dipole moments ( ), stabilization energies ( ), donor-acceptor transitions, and structural parameters.