Using methyl as substituted-radical in n-phen enhances the anticancer activities of [(DMF)Cu(n-phen)(NO3(-))2]

In order to seek better ligand for anticancer drug, we choose 1,10-phenanthroline (phen) and 2,9-dimethyl-1,10-phenanthroline (2,9-dmp) as predominant ligands, and synthetize two complexes:[(DMF)Cu(phen)(NO3)2] (1) and [(DMF)Cu(2,9-dmp)(NO3)2] (2) (DMF is dimethyl formamide). As for the five kinds of cancer cells, including A-549, Bel-7402, HCT-8, MDCK and L-1210 cells, our complexes showed higher inhibition ratio compared with anticancer drug 5-Fu (fluorouracil), ligand phenanthroline and Cu(NO3)2. It's worth noting that complex 2's anticancer activity is much more efficient than that of complex 1. This is because there are di-substituted-methyl in 2,9-dmp. By calculating, we found Δcomplexes<Δphenanthroline which showed that the energy gap between π(⁎) and π of the phenanthroline is decreased through coordination with Cu(II). Computational ΔG2<ΔG, and bond length (CuN)1<(CuN)2 revealed that the coordinated 2,9-dmp is easier to dissociate with Cu(II) than phen, which is confirmed by the absorption peak at 460nm in UV-visible (UV-vis) spectra of complex 2. In summary, the phenanthroline is activated by Cu(II)-coordination, which is beneficial for anticancer. More importantly, the substituted-methyl radicals stimulated the phenanthroline and enhanced the anticancer properties more efficiently.