Cytotoxic Studies on Hybrid Inorganic Organic Hydrazone Metal (II) Complexes: Synthesis and Characterization of Geminal Multisite Assembly on Cyclotriphosphazene

Abstract

Herein, a new hybrid inorganic–organic ligand was designed and synthesized to form a series of transition metal (II) complexes as potential substrate towards cytotoxicity studies. The inorganic heterocycle, cyclotriphosphazene (N₃P₃Cl₆, CTP) was chosen as the core unit to synthesize geminal hydrazone Schiff bases as multisite coordination ligand via substitution of six reactive chlorine. Herein, CTP was substituted by nucleophilic reaction at six chlorine atoms that exist on three phosphorus (V) centers of CTP with salicylaldehyde to form hexakis salicylaldehyde derivative. Further, salicylic hydrazide tethered with terminal amine group was condensed with above hexakis salicylaldehyde derivative of CTP at ratio of 1:6 afforded SBCTP ligand. Indeed, a series of M (II) complexes (M = Co, Ni, Mn, Cu and Zn) were obtained from SBCTP ligand with characteristic functional groups to manifest the cytotoxic activity, in order to venture as the active anticancer agent in pharmaceutics. Despite the Schiff base of aromatic rings tend to exhibit inherent cytotoxic properties, the complementary influence of CTP appended with two consecutive salicylic units in SBCTP found to show unique properties. In particular, metal (II) complexes via imine bonds of SBCTP oriented from CTP ring found to reveal essential properties to treat cancerous cells. The above ligand and prospective metal complexes were investigated individually for the cytotoxic activity with normal and cancerous cells at five different concentrations, with/without addition of the above samples into MTT assay. Structural characterization of above samples was conducted by multinuclear NMR, ¹H, ¹³C, and ³¹P as well as ESI, HRMS, FTIR, EDS, and TGA data.