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 CuII. Computational ΔG2 < ΔG, and bond length (CuN)1 < (CuN)2 revealed that the coordinated 2,9-dmp is easier to dissociate with CuII than phen, which is confirmed by the absorption peak at 460 nm in UV–visible (UV–vis) spectra of complex 2. In summary, the phenanthroline is activated by CuII-coordination, which is beneficial for anticancer. More importantly, the substituted-methyl radicals stimulated the phenanthroline and enhanced the anticancer properties more efficiently.

Two new complexes exhibited higher inhibitions than anticancer drug 5-Fu against cancer cells in vitro. Complex 2 is much more efficient than 1 thanks to the di-substituted-methyl in 2,9-dmp. Computational Δ and ΔG, bond length CuN, and UV–vis spectra revealed that the coordinated 2,9-dmp is more active than coordinated phen.Figure optionsDownload as PowerPoint slide