A Thermodynamic Study ofNew Designed Complex Bull. Korean Chem. Soc. 2009, Vol. 30, No. 9 1951 A Thermodynamic Study of New Designed Complex of Ethylendiamine 8-Hydroxyquinolinato Palladium(II) Chloride with C f Thymus DNA M. Saeidfar,§ H. Masouri-Torshizi,§ G. Rezaei Behbehani,* A. DivsalarJ* and A. A. Sabouryf Chemistry department, Imam Khomeini International University, Qazvin, Iran. *E-mail: grb402003@yahoo.com ‘Institute ofBiochemistry and Biophysics, University of Tehran, Tehran, Iran *Department ofBiological Sciences, Tarbiat Moallem University, Tehran, Iran § Chemistry department, University ofSistan & Baluchestan, Zahedan, Iran Received April 30, 2009, Accepted July 8, 2009 A Thermodynamic study on the interaction of bovine calf thymus DNAwith new designed Pd(II) complex (Ethylendiamine- 8-hydroxyquinolinato Palladium(II) chloride) was studied by using isothermal titration calorimetry (ITC) at 27 oC in Tris buffer solution at pH = 7.5. The enthalpies of Pd(II) complex + DNA interaction are reported and analysed in terms of the new solvation theory. It was indicated that there are three identical and non-cooperative sites for Pd(II) complex. The binding of a Pd(II) complex is endothermic with association equilibrium constants of 428.03 mM"1 at 27 oC. The binding of Pd(II) complex can cause some changes in the stability of the DNA at low and high Pd(II) complex concentrations. Our results suggested that this complex might interact with DNA as an intercalator, thus interfering with DNA replication and cell proliferation. Key Words: DNA, Pd(II) complex, Isothermal titration calorimetry Introduction DNA plays an important role in the life process, because it bears heritage information and instructs the biological synthesis of proteins and enzymes through the replication and trans- cription of genetic information in living cells.1 The main target of anti-tumor chemotherapies is DNA.1,2 Alteration of DNA structure affects its synthesis and function which usually leads to disruption of cell proliferation and can eventually elicit cell death via apoptosis. These effects are currently being exploited to develop novel biologically active drugs with potential appli- cations as anti-proliferative therapies, e.g. ligands that will form ternary complexes with DNA and the enzyme (s) topo- isomerase.3-5 Several experiments have also demonstrated that DNA is the primary intracellular target of anticancer drugs due to the interaction between small molecules and DNA, which can cause DNA damage in cancer cells, blocking the division of cancer cells and resulting in cell death.4-6 In addition, the apoptosis can also cause the cell death.7 The ability of small molecules to interfere with transcription and DNA replication makes it a major target for drug interaction studies.7 Transition metal complexes have attracted considerable attention as catalytic systems for use in the oxidation of organic compounds,8 probes in electron-transfer reactions involving metallo-proteins, and intercalators with DNA.3,9 During recent years, the interest for metal complexes containing planar ex- tended polyaromatic ligands has increased tremendously, mainly for their usage as probes capable to utilize the nucleic acid structures1,2 and as DNA-molecular light switches.10 There are several types of sites in the DNA molecule where binding of metal complexes can occur: (I) between two base pairs (inter- calation), (II) in the minor groove, (III) in the major groove, and (IV) on the outside of the helix.11 Among these complexes, the role of the Pt(II) and Pd(II) complexes is crucial since they can bind to DNA covalently as well as noncovalently. Several reports have shown that palla- dium complexes are expected to have lower kidney toxicity than cisplatin due to the inability of proteins in the kidney tu- bules to replace the tightly bound chelate ligands of Pd(II) with sulfydril groups.12-15 Concerning the noncovalent interactions between transition-metal complexes and DNA, they can occur by intercalation, groove binding, or external electrostatic bind- ing. 10-11 Many anticancer drugs are known to interact with DNA to exert their biological activities. Generally, DNA-acting anti- cancer drugs can be classified into three categories. Drugs of the first category form covalent linkages with DNA while drugs of the second category form noncovalent complexes with DNA by either intercalation or groove-binding. Drugs of the final cate- gory cause DNA backbone cleavages. 8 A search for new, low-molecular weight ligands which can specifically bind to DNA has been conducted for many years in the hope that new therapeutics could selectively modulate aberrant gene expression.1 Since design of new drugs that directly interacted with DNA is very important, in present study, we have investigated the effect of the new designed Pd(II) complex (Ethylendiamine 8-hydroxyquinolinato Palladium(II) chloride) (Scheme 1) on the stability of the calf thymus DNA, in addition to some investigations on the binding parameters of complex to the DNA has been considered. Information obtained Scheme 1. The molecular structure of ethylendiamine 8-hydroxy- quinolinato palladium(II) chloride (Pd(II) complex)