Experimental and computational studies of tautomerism pyridine carbonyl thiosemicarbazide derivatives

Abstract

Tautomerism is one of the most important phenomena to consider when designing biologically active molecules. In this work, we use NMR spectroscopy, IR, and X-ray analysis as well as quantum-chemical calculations in the gas phase and in a solvent to study tautomerism of 1- (2-, 3- and 4-pyridinecarbonyl)-4-substituted thiosemicarbazide derivatives. The tautomer containing both carbonyl and thione groups turned out to be the most stable. The results of the calculations are consistent with the experimental data obtained from NMR and IR spectroscopy and with the crystalline forms from the X-ray studies. The obtained results broaden the knowledge in the field of structural studies of the thiosemicarbazide scaffold, which will translate into an understanding of the interactions of compounds with a potential molecular target.

3a-(4-Chlorophenyl)-1-thioxo-2,3,3a,4-tetrahydroimidazo[1,5-a]quinazolin-5(1H)-one

“…In particular, the values 182.31 ppm and 163.44 ppm attributable to C-10 and C-4 respectively, suggest the thione tautomer, if referred to what is reported in the literature according to which the C=S nucleus resonates ca. 20-30 ppm downfield relative to the corresponding C=O [16,17].…”

Retention Behavior of Anticancer Thiosemicarbazides in Biomimetic Chromatographic Systems and In Silico Calculations

“…The low correlation of log P (log D) parameters with log k w , even after the elimination of outlier compounds, indicates that in the case of the considered thiosemicarbazides, fast in silico methods do not provide satisfactory results, and experimental measurements (HPLC) are advantageous. This may be related to the existence of equilibrium tautomeric forms for the considered compounds, which is the result of migration of labile protons from -NHgroups into carbonyl (=C=O) or thiocarbonyl (=C=S) groups (Figure 3) [41,42]. This phenomenon is not taken into account in the case of calculation methods, but it was revealed in chromatographic analysis as well as biological systems.…”

Multiple Intramolecular Hydrogen Bonding in Large Biomolecules: DFT Calculations and Deuterium Isotope Effects on 13C Chemical Shifts as a Tool in Structural Studies

“…The situation can be complex in the cases in which several donors and acceptors forming hydrogen bonds with each other. Such a situation is found in rifampicin [2,10]. The use of theoretical calculations to calculate structures and NMR parameters have reached a very high level [11].…”

“…[1]. Furthermore, the correct structure is a prerequisite for binding studies of molecules with biological activity [2] such as rifampicin. Rifampicin has important biological actions and is mentioned as a possible remedy against tuberculosis in combination with other drugs [3].…”

“…The use of a combination of DFT calculations, and measurements of chemical shifts and isotope effects on 13 C chemical shifts is a general method that can be used in other biological systems, e.g., more complex derivatives of rifampicin such as the aldehyde [2].…”