Synthesis, characterization and in vitro cytotoxic properties of new silver(I) complexes of two novel Schiff bases derived from thiazole and pyrazine

Abstract

Two new ethylenediamine Schiff bases of 2-acetylthiazole and 2-acetylpyrazine (abbreviated as Th-Th and Py-Py respectively), as well as their silver(I) complexes [Ag(Th-Th)]2·2(NO3) and [Ag(Py-Py)]2·2(NO3), have been prepared and characterized by a variety of physico-chemical techniques including elemental analyses, m.p., 1H NMR, 13C NMR, ESI-QTOF-MS, FT/IR, UV–Vis and theoretical calculations including density functional theory (DFT) and time dependent density functional theory (TD-DFT) methods. All structures were solved from single crystal X-ray diffraction (SXRD) data, except [Ag(Py-Py)]2·2(NO3), whose crystal is not good enough for SXRD. Hence, conventional powder X-ray diffraction (PXRD) has to be used. As a first step, the stoichiometric formula of [Ag(Py-Py)]2·2(NO3) was ascertained by elemental analyses and ESI-QTOF-MS. IR and UV–Vis indicated the existence of coordinated Py-Py and charge-balancing NO3-. On the basis of symmetry character proved by NMR, three possible symmetrical Ag(I) coordination structures were designed and optimized by DFT method. Then, relative binding free energies were calculated to find the most appropriate molecule structure. DFT results suggest that four imine-N and four ortho-ring-N atoms from two Py-Py ligands are coordinated to two Ag(I) ions, resulting in a similar dimer structure as that of [Ag(Th-Th)]2·2(NO3). The molecule structure was further confirmed by PXRD based crystal structure, which was solved following direct space method and refined by the Rietveld method. The antitumor activities of the Schiff bases and their silver(I) complexes have been evaluated against human lung cancer cell line A549. Both silver(I) complexes were found to display cytotoxicity (IC50=3.15±0.5 and 9.73±1.1μM) that is similar to or better than that of cisplatin, while metal-free Schiff bases show very low activity.