Hydrogen bonding and solution state structure of salicylaldehyde-4-phenylthiosemicarbazone: A combined experimental and theoretical study

Hydrogen bonding in salicylaldehyde-4-phenylthiosemicarbazone (1) has been studied by using experimental (NMR, Raman and UV spectroscopies) and quantum chemical (DFT) methods. It has been demonstrated that 1 adopted the hydroxy-thione tautomeric form in solution as found also in the solid state and previously indicated by secondary deuterium isotope effects. Apart from the intra-molecular hydrogen bonds new interactions between 1 and solvent molecules were formed as well. Changes in NMR chemical shifts and calculations have pointed towards a formation of inter-molecular three-centered hydrogen bonds in each of the studied complexes involving OH and NH groups of 1 and associated solvent molecules. Stabilization energies of intra-molecular hydrogen bonds were found to decrease with the increase of the solvent polarity. Two-dimensional NOESY spectra indicated conformational changes in solution with respect to the structure observed in the solid state. These were accounted for by a relatively low barrier of the rotation of the NN single bond thus enabling a molecule to posses a higher conformational flexibility in solution with portions of skewed conformations. The results presented here can help in a better understanding of the role hydrogen bonds can play in bioactivity of related thiosemicarbazone derivatives and their metal complexes.