Methyl-substituted enhancement of antitumor activity in square-planar metal complex and analysis of ΔE, ΔG, CV, UV-vis and luminescence

Abstract

Two novel Ala-based copper(II) compounds with formulas [(1,10-Phen)Cu(Ala)·(H₂O)]·Cl·H₂O (1) and [(2,9-DMP)Cu(Ala)·(H₂O)]·NO₃·H₂O (2) have been synthesized and determined by X-ray diffraction. The two complexes stack in a square-planar structure and exhibit excellent anticancer activities. In particular, complex 2 with methyl-substituted phenanthroline shows higher anticancer properties than complex 1 with Phen. Computational ΔE (ΔE_1,10-Phen > ΔE₁ and ΔE_2,9-DMP > ΔE₂) has shown that the two substituted methyl groups can activate the conjugated system of π₁₄¹⁴ in the aromatic phenanthroline ring to inhibit cancer cell growth. ΔG calculation illustrates that complex 2 is more easily decomposed into free Cu^II and ligands than 1. UV-vis and luminescent spectra also reveal that 2,9-DMP in complex 2 is partially dissociated, which might be responsible for the superiority of anticancer activities. In addition, E_{2pCu(II)/Cu(I)} is more positive than E_{1pCu(II)/Cu(I)}, which might be the reason that Cu^II-SOD is more effective in transferring O₂⁻˙ into O₂ for inhibiting cancer cell growth.