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

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 (ΔE1,10-Phen > ΔE1 and ΔE2,9-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 CuII 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, E2pCu(II)/Cu(I) is more positive than E1pCu(II)/Cu(I), which might be the reason that CuII-SOD is more effective in transferring O2−˙ into O2 for inhibiting cancer cell growth.