Crystallographic investigation, Hirshfeld surface analysis, and computational studies approach of 4,5,8a-triphenylhexahydropyrimido[4,5-d]pyrimidine-2,7(1 H ,3 H )-dithione

When benzaldehyde, acetophenone, and thiourea are condensed in the presence of HCl, a compound, which is 4,5,8a-triphenylhexahydropyrimido[4,5-d]pyridine-2,7(1H,3H)-dithione (THPD) is derived (Barbero et al., A Brønsted acid catalysed enantioselective Biginelli reaction. Green Chem. 2017;19:1529–1535. doi:10.1039/C6GC03274E). The structure of the compound synthesized was confirmed by using the single crystal X-ray diffraction technique, which showed that the asymmetric unit consisted of two crystallographically independent molecules with the core being a fused hexahydropyrimido[4,5-d]pyrimidine. The hydrogen bonding and aromatic ring interactions to support crystal packing were investigated by Hirshfeld surface analysis. The electronic structure and charge-transfer properties of the title compound were investigated using density functional theory (DFT) calculations to complement the experimental crystal structure. The results of single-crystal X-ray and optimized geometrical parameters are satisfactory and support each other. The frontier molecular orbital analysis reveals a moderate HOMO–LUMO energy gap, indicating balanced charge-transfer capability and chemical stability. Natural bond orbital investigations and molecular electrostatic potential studies underline strong intramolecular N–S–C conjugation and donor–acceptor nature, which is consistent with the solid-state packing nature, as reported. Molecular docking studies against human DNA topoisomerase IIα revealed moderate binding affinity and favorable interactions within the protein–DNA binding region.