Transition Metal Complexes of a Diaza-Crown Ether with two Carbamoylmethyl Substituents: Synthesis and Assessment as a Functional Nuclease

We report the synthesis, catalytic function and catalytic mechanism of two transition metal complexes (CuL, ZnL) of a diaza-crown ether with two acetylamino side arms [L = 2,2′-(1,4,10,13-tetraoxa-7,16-diazacyclooctadecane-7,16-diyl)diacetamide] in the hydrolysis of DNA. Their nuclease functions on pUC19 DNA cleavage were investigated. The results indicated that the active species might be formed by the deprotonation of the water-coordinated molecules in the complex and the optimum pH is 8.0 for both CuL and ZnL. The catalytic activity of CuL is higher than that of ZnL in DNA hydrolytic cleavage due to the difference in the Lewis acidity of the central metal ions, which is contrary to the result with the Cu and Zn complexes of the parent ligand L0 (1,4,10,13-tetraoxa-7,16-diazacyclooctadecane) as artificial nuclease. Comparison studies of DNA cleavage in the presence and absence of several oxygen scavengers showed that these complexes can promote DNA cleavage by a hydrolytic pathway. Our proposed mechanism suggests that the negative charge on the phosphorus oxygen atom of the substrate molecule is dispersed and the intermediate is formed and stabilised by hydrogen bonding between the DNA molecule and the acetylamino group of the complex.