Catalytic promiscuity, cytotoxicity and protein cleavage mediated by mononuclear copper(II) complexes: oxidative and hydrolytic activities

Abstract

In this work, we describe the synthesis and structural and spectroscopic characterizations of two copper(II) complexes, [(Cu)(L1)(Cl2)].4H2O (1), where L1 is 2-(pyridin-2-yl)-1,3-bis(pyridin-2-ylmethyl)-hexahydropyrimidine, and [Cu(L2)](ClO4)2 (2), where L2 is N1,N1,N3-tris(pyridin-2-ylmethyl)propane-1,3-diamine. The crystalline structure analysis indicates that both complexes are mononuclear and pentacoordinated compounds. In the case of complex 1, it bears a neutral charge, with the ligand coordinating to the Cu(II) center in a tridentate manner, utilizing N-donor atoms. Additionally, two cis-chlorido ligands completing the coordination sphere. On the other hand, complex 2 is a cationic complex, with the ligand coordinated in a pentadentate manner, with only N-donor atoms for coordination around the Cu(II). Complex 1 showed catalytic promiscuity, displaying hydrolytic and oxidative activity. The hydrolytic activity was investigated using bis(2,4-dinitrophenyl) phosphate (2,4-BDNPP) as a phosphodiester substrate and applying the Michaelis–Menten approach, obtaining the following kinetic parameters: kcat = 1.21 × 10-4 s−1; KM = 3.35 × 10-3 molL-1. Complex 1 also accelerates the oxidation of the 3,5-di-tert-butylcatechol (3,5-DTBC) substrate with catalytic efficiency equal to 6.11 L mol-1s-1. Interestingly, we demonstrated that this Cu(II) complex 1 can also cleave the very stable peptide bonds from BSA (bovine serum albumin) through an oxidative mechanism using ascorbate as a reducing agent. Complexes 1 and 2 show good cytotoxic activity against two cancer cell lines: A431 from human squamous cell carcinoma and K562 from chronic myeloid leukemia. This study showed that complexes 1 and 2 are selective towards cancer cells.