Synthesis, Speciation, DNA Binding, Electrochemical and Antiproliferative Properties of Pd(II) Complexes Designed to Improve the Interaction with DNA

Document Type : Original Article

Authors

1 Chemistry Department, Faculty of Science, University of Jeddah, Jeddah , Saudi Arabia

2 Department of chemistry, Faculty of Science, Cairo University

3 Chemistry Department, Faculty of Science, University of Jeddah, Jeddah , Kingdom of Saudi Arabia

Abstract

With the success of cisplatin, extensive research resulted in the discovery of carboplatin (a second-generation drug), where the chloride is replaced by 1,1-cyclobutanedicarboxylate. In the current study, we continue our previous work on the binding behavior of [Pd(byp)(H2O)2]2+ with structural features enhancing the interaction with DNA. [Pd(byp)(gly)]+ (1) and [Pd(byp)(CBDCA)] (2), where byp is 2,2´-bipyridine, gly is glycine, and CBDCA is cyclobutane-1,1´-dicarboxylic acid, were synthesized and characterized. The stability constants and stoichiometries of the complexes formed between various DNA units and [Pd(byp)(H2O)2]2+ were investigated. The binding properties of (1) and (2) with CT-DNA were analyzed by UV-vis spectroscopy, viscosity measurements, and cyclic voltammmetry. The (Kb) value for complex (1) (Kb= 4.36x103 M−1 ) , suggests an electrostatic binding together with hydrogen bonding with the negative sites of CT- DNA. The higher (Kb) value of complex (2) (Kb= 2.11x104 M−1) indicates an intercalation binding mode, whereby a ring-opening reaction of CBDCA occurs, followed by the reaction with guanosine 5'-monophosphate to form [(Pdbyp)(CBDCA-O)(5'-GMP)]. The results from UV-Vis spectroscopy, thermal denaturation, viscosity, and cyclic voltammetry data, all reveal electrostatic binding of complex (1) and intercalation mode of complex (2). The antitumor effects of the two complexes were tested. The two complexes display dose-dependent anti-proliferation activity with a prediction of improved efficacy against cancer

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