Structural and Conformational Analysis and Biological Activity of Adamantyl-Based Acyl-Thioureas Bearing Trihalophenyl Substituents.

A series of six closely related acyl thiourea derivatives featuring adamantyl/noradamantyl groups at the 1-acyl position and 3-trihalophenyl substituents at the thiourea moiety were comprehensively characterized through spectroscopic, computational, and X-ray crystallographic methods. Vibrational spectroscopy (IR and Raman) revealed significant redshifts in the N-H and C=O stretching bands, confirming the presence of strong intramolecular N-H···O=C hydrogen bonds. Conformational analysis using molecular mechanics and DFT calculations identified several stable conformers, with the most stable adopting an S-shaped geometry where the C=O and C=S bonds are oppositely oriented - a configuration experimentally validated by single-crystal X-ray diffraction. In the solid state, crystal packing is governed by hydrogen-bonding interactions (H···O=C and H···S=C) facilitated by the acyl-thiourea core. The bulky adamantyl/noradamantyl groups impose steric constraints, whereas the halogenated phenyl rings promote stabilizing π-stacking and halogen interactions. Biological evaluation demonstrated limited antimicrobial activity against E. coli, P. aeruginosa, B. cenocepacia, and S. aureus, but moderate cytotoxicity against A549, 16HBE14o-, and HaCaT cell lines (IC50 = 25-100 μM).