Ethyl-2-((8-cyano-3,5,9a-trimethyl-1-(4-oxo-4,5-dihydrothiazol-2-yl)-4-phenyl-3a,4,9,9a-tetrahydro-1H-pyrazolo[3,4-g]isoquinolin-7-yl)thio)acetate (5) was synthesized, and its structure was characterized by IR, MS, and NMR (¹H and ¹³C) and verified by a single-crystal X-ray structure determination. Compound 5 adopts a “pincer” conformation. In the crystal, the hydrogen bonds of −H···O, C–H···O, and O–H···S form thick layers of molecules that are parallel to (101). The layers are linked by C–H···π(ring) interactions. The Hirshfeld surface analysis shows that intermolecular hydrogen bonding plays a more important role than both intramolecular hydrogen bonding and π···π stacking in the crystal. The intramolecular noncovalent interactions in 5 were studied by QTAIM, NCI, and DFT-NBO calculations. Based on structural activity relationship studies, leucine-rich repeat kinase 2 (LRRK2) was found to bind 5 and was further subjected to molecular docking studies, molecular dynamics, and ADMET analysis to probe potential drug candidacy.

The present work undertakes the study of newly synthesized 1,1′-(3,5-dhydroxy-3-methyl-2′-nitro-1,2,3,4-tetrahydro-[1,1′-biphenyl]-2,6-diyl)bis(ethan-1-one) whose structure has been confirmed by X-ray diffraction analysis. The title molecule, C₁₇H₁₉NO₆, is considered to be a superimposition of the two enol forms of an acetylacetone derivative. Its conformation is partly determined by intramolecular C—H···O hydrogen bonds and a C—H···π(ring) interaction. In the crystal, O—H···O and C—H···O hydrogen bonds form corrugated layers parallel to the ab plane. To confirm the results from the crystallographic study, both the Hirshfeld surface and energy framework were further calculated to investigate the interactions between the title compound and its neighboring molecules in the crystal. Due to the tautomerism of a molecule playing an important role in its biological activity, the intrinsic electronic properties of the title molecule and its tautomer were investigated by a DFT-B3LYP study. Both the Natural Bond Orbital (NBO) analysis and Quantum Theory of Atoms in Molecules (QTAIM) study were used to compare the intramolecular hydrogen bonding in the title compound with those in its tautomer. In addition, molecular docking simulations were carried out with CYP3A4, and an ADMET analysis was also performed to explore the compound's possible biological properties.