Abstract
Recent studies have shown that 4-methoxyacetophenone thiosemicarbazone (MAPTSC) and its complexes with some transition metal chlorides are potent antimicrobial agents. To deepen the understanding of their structure-activity relationships necessary for rational drug design, their structural and spectral properties, along with thione-thiol tautomerism of MAPTSC, have been studied herein using the density functional theory (DFT). From our results, the thione tautomer of MAPTSC is more stable than the thiol counterpart in ethanolic solution, and thione-to-thiol tautomerization is highly precluded at ambient temperature (25°C) by a high barrier height ≈46.41 kcal/mol. MAPTSC can therefore exist as a mixture of the thione (major) and thiol (minor) tautomers in ethanolic solution at room and higher temperatures. Conformational analysis has revealed five possible conformers of the thione tautomer, of which two are stable enough to be isolated at 25°C. Based on our computed values of MAPTSC-metal(II) binding energies, enthalpies, and Gibbs free energies, the thione tautomer of MAPTSC exhibits a higher affinity for the d8 metal ions Ni(II), Pd(II), and Pt(II) and can therefore efficiently chelate them in chemical and biological systems. Natural population analysis has revealed ligand-metal charge transfer in the MAPTSC complexes studied. A good agreement has been found between calculated and experimentally observed spectral properties (IR, UV-Vis, and NMR).
Highlights
The coordination chemistry of thiosemicarbazones (TSCs) has recently attracted considerable attention because of their variable bonding modes, structural diversity, nonlinear optical properties, and ion-sensing abilities [1, 2]
To determine the coordinating ability or affinity of the thione tautomer of methoxyacetophenone thiosemicarbazone (MAPTSC) towards the transition metal ions studied in ethanol, the A1–MCl2 binding energies (ΔEint), enthalpies (ΔHint), and Gibbs free energies (ΔGint) at room temperature were calculated for M = Ni2+, Pd2+, Pt2+, and Zn2+
The barrier heights for thione-to-thiol and thiol-to-thione tautomerization of MAPTSC, determined via hydrogen atom migration studies in ethanol as solvent, are ≈46.41 and 32.51 kcal/mol, respectively. These high barrier heights indicate that thionethiol interconversions of MAPTSC in ethanolic solution are nearly hindered at room temperature
Summary
The coordination chemistry of thiosemicarbazones (TSCs) has recently attracted considerable attention because of their variable bonding modes, structural diversity, nonlinear optical properties, and ion-sensing abilities [1, 2]. We have pursued theoretical studies on these molecules in order to provide detailed information on their structures, properties, and relative stability of the thione-thiol tautomers of MAPTSC, all of which is essential for better understanding of their structure-activity relationships as well as their reactivity in chemical and biological systems. In this regard, the current study is aimed at providing a detailed analysis of the structural and spectral properties of MAPTSC along with some of its transition metal chloride complexes, in a bid to facilitate rational drug design using these molecules as precursors. The DFT has been proven to be a very reliable method for transition metal complexes [13] and is generally considered to be a good compromise between accuracy and computational time
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