A Preliminary Investigation of Thermally Stable Schiff Base Metal Complexes for Hyperthermia: Synthesis and Biological Evaluation

A novel Schiff base ligand (L), bearing N₂O₂ donor sites, was derived from the condensation of 5-chloromethylisophthaldehyde and phenylpropanolamine (PPA). Mononuclear Co(II), Cu(II), and Zn(II) complexes were synthesized and were characterized by FTIR, UV-Vis, ¹H NMR, ESI-mass spectroscopy, molar conductance, and thermal and electrochemical studies. The thermal investigation revealed that the complexes were stable up to 150-250 °C and began to degrade in stages, resulting in the development of respective metal oxides. The Coats-Redfern integration method was used to calculate the kinetic and thermodynamic parameters, the energy of activation (Ea), and changes in enthalpy (∆H), entropy (∆S), and free energy (∆G) for each step of the degradation processes. For stage I decomposition, the calculated activation energy values of the complexes follow the order of Ea [Cu(L)] > Ea [Co(L)(H₂O)₂] > Ea [Zn(L)]. The influence of the temperature on the efficacy of antioxidant activities of the complexes with DPPH assay, ABTS assay, and hydroxy radical assay was investigated at various concentrations using ascorbic acid (AA) as the reference. Antioxidant activity was assessed at multiple temperatures to ascertain whether these complexes may be applied in radiation therapy enhanced with hyperthermia and found to be stable. Subsequently, the Cu(II) complex (C2) demonstrated a greater cytotoxicity (IC₅₀ = 5.16 µM) than Co(II), Zn(II), and conventional cisplatin when in vitro cytotoxicity was evaluated against the MCF-7 cell line using the MTT method. Analyses of the thermal stability and ROS scavenging ability of complexes have demonstrated that these complexes have potential in hyperthermic radiation therapy.