Deepening bis-(thio)carbohydrazones conformational dynamics and hydrogen bond interactions in a non-protic solvent: DFT, molecular dynamics, NMR, and Raman investigations.

This article focuses on the solution behavior and solvent interactions of two recently synthesized metalloligands: a bis-thiocarbohydrazone (bis-TCH) and a bis-carbohydrazone (bis-CH), both isolated as sodium salts and known for their metal-chelating and cytotoxic properties. Using a combination of density functional theory (DFT), molecular dynamics (MD) simulations, nuclear magnetic resonance (NMR), and Raman spectroscopy in dimethylsulfoxide (DMSO), the study reveals that these ligands exhibit distinct conformational dynamics and solvation patterns influenced by their central heteroatoms (sulfur in bis-TCH and oxygen in bis-CH). The findings demonstrate that explicit modeling of hydrogen bonding interactions with DMSO is essential to accurately interpret their spectroscopic data and understand their conformational behavior, with bis-TCH showing stronger solvent interactions that slow its conformational dynamics compared to bis-CH. These insights provide a molecular-level understanding crucial for the rational design of metalloligands with optimized properties for pharmaceutical applications.