Zn(ii) and Cd(ii) pincer complexes bearing meta alkylated pyridinium amidates; synthesis & preliminary anticancer studies

Abstract

Aiming to design economical metal-based medications to replace platinum-based drugs in the treatment of a variety of cancers, this article presents four new Zn(II) and Cd(II) complexes namely [Zn(L^m_Me)(OTf)₂] (C1), [Cd(L^m_Me)(Cl)(OAc)] (C2), [Zn(L^m_Bn)(Cl)₂] (C3) and [Cd(L^m_Bn)(Cl)(OAc)] (C4), where L^m_Me = pyridine-2,6-dicarbonyl)bis((1-methylpyridin-1-ium-3-yl)amide and L^m_Bn = pyridine-2,6-dicarbonyl)bis((1-benzylpyridin-1-ium-3-yl)amide, and their anticancer potential. These mesoionic ligands were derived in situ from their respective pro-ligands, H₂L^m_Me(OTf)₂ and H₂L^m_Bn(Cl)₂ in the presence of 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) as a base during complex formation reactions. Elemental analysis, FT-IR and NMR (¹H & ¹³C) spectroscopy were employed to systematically characterize the complexes and single crystal X-ray crystallography was used to confirm the structures. X-ray structural analysis of C3 and C4 revealed that the ligands coordinated to the metal centre in a NNN tridentate fashion, forming two five membered chelate rings. Intermolecular interactions within the crystal structure of C3 and C4 were examined by Hirshfeld surface analysis. Electronic spectroscopy, viscosity measurements and cyclic voltammetry were used to examine the mechanism of interaction of the compounds with CT-DNA. All inspected compounds showed strong affinity toward CT-DNA via non-covalent nature with intrinsic binding constant values in the range of 5.8 × 10³–9.0 × 10⁴ M⁻¹. The MTT assay was executed to test the compound's ability to inhibit the proliferation of two human cancer cell lines (MCF-7 and T47D) along with a normal cell line (Vero). The in vitro anticancer studies showed that the complexes are more efficacious towards MCF-7 and T47D in the following order C4 > C3 > C2 > C1 and the results are consistent with the DNA binding potential. Moreover, the IC₅₀ value of complex C4 in the T47D cell line (21.00 ± 1.41 μM) was comparable to that of cisplatin (25.10 ± 1.09 μM).