Catalogue on Research and Innovation
Potential of University of Kragujevac

One of the objectives of the Research Group of Prof. Dr. Živadin D. Bugarčić is the synthesis of new complexes of transition metals ions that show higher biological activity and lower toxicity at the same time. The complex synthesis that would have better properties in vivo than those used so far is a great challenge, especially because the complexes of transition metals ions are hardly soluble in physiological conditions, and some of them are very unstable as well. This is why the research on the relation between the structure and activity of newly synthetized complexes is very significant. 
Special attention is paid to the change of coordination sphere of a complex, i.e. on the introduction of new inert and unstable ligands, with the aim to achieve better dissolubility of synthetized complexes. Internal and unstable ligands are selected on the basis of chemical properties of metal ions that are being complexed, as well as on the basis of recent experience in the research of reaction mechanisms and potential antitumor complex properties.

Activities:

Having in mind the significance and role of transition metals ions and their complexes in different biochemical and metabolic processes, the group decided to perform detailed research of reactions of some new complexes with bio-molecules. The subject of the group’s research is: synthesis and characterisation of new complexes of transition metals ions, e.g. Pd(II), Pt(II), Pt(IV), Ru(II), Ru(III) and Au(III), as well as study of interactions of these complexes with different bio-molecules such as essential amino acids, peptides and DNA fragments. This research is very significant at fundamental, biological and medical aspects. It is well known that some complexes, such as complexes Pt(II) and Pt(IV), have been used for several decades in chemotherapy as anti-cancerogenous substances. However, besides antitumor activity, these complexes also show toxic effects, such as nephrotoxicity, ototoxicity, resistance, etc. Toxic property of platinum complex is explained exactly by the interaction of these complexes with bio-molecules that contain sulphur, e.g. glutathione. Taking all this into account, in order to study better the mechanism of antitumor effects of platinum complex, it is essential to continue with research of interactions of platinum complex with bio-molecules containing sulphur and nitrogen. It is necessary to determine the complexing mechanism, constants of reaction substitution speeds and stability of the built complexes. Also, it is important to examine the influence of various factors affecting the constant of substitution speed such as temperature, pressure, pH, ionic strength, solvent and catalyst effect. As it is known, some complexes Pt(IV) are also used in chemotherapy. It has been shown that the first process of their antitumor activities is reduction of Pt(IV) to Pt(II), and then the activity mechanism is the same as in cisplatinum or carboplatin. Thus, it is very important to perform detailed research of the reduction mechanisms of Pt(IV) complex with bio-molecules containing sulphur (cysteine, glutathione), as well as with ascorbic acid. Also, new potentially biologically active complexes Ru(II), Au(III) and Ru(III) were synthetized. For characteristics of new complexes, as well as for studying the mechanisms of substitution reactions, modern methods and techniques are used, such as UV-VIS, IR, NMR, stopped-flow, HPLC, roentgen structure analysis and others.  

1.        A. Mijatović, B. Šmit, A. Rilak, B. Petrović, D. Čanović and Ž. D. Bugarčić, NMR kinetic studies of the interactions between [Ru(terpy)(bipy)(H2O)]2+and some sulfur-donor ligands, Inorg. Chim. Acta, 2013, 394, 552-557. 
2.        Ž. D. Bugarčić, J. Bogojeski, B. Petrović, S. Hochreuther and R. Van Eldik, Mechanistic studies on the reactions of platinum(II) complexes with nitrogen- and sulfur-donor biomolecules Dalton. Trans., 2012, 41, 12329-12345. 
3.        S. M. Janković, A. Djeković, Ž. D. Bugarčić, S. V. Janković, G. Lukić, M. Folic and D. Čanović, Effects of aurothiomalate and gold(III) complexes on spontaneous motility of isolated human oviduct BIOMETALS, 2012, 25(5), 919-925. 
4.        R. Jelić, E. Selimović, R. Nikolić, Ž. D. Bugarčić and J. Bogojeski, Equilibrium studies between some transitions metal ions and Me6[14]dieneN4 ligand Monatsh. Chem., 2012, 143, 1357-1363. 
5.        A. Rilak, I. Bratsos, E. Zangrando, J. Kljun, I. Turel, Ž. D. Bugarčić and E. Alessio, Factors that influence the antiproliferative activity of half sandwich RuII-[9]aneS3 coordination compounds: activation kinetics and interaction with guanine derivatives Dalton. Trans., 2012, 41, 11608-11618. 
6.        M. Arsenijević, M. Milovanović, V. Volarević, D. Čanović, N. Arsenijević, T. Soldatović, S. Jovanović and Ž. D. Bugarčić, Cytotoxic properties of platinum(IV) and dinuclear platinum(II) complexes and their ligand substitution reactions with guanosine-5'-monophosphate Trans. Met. Chem., 2012, 37, 481-488. 
7.        M. Djurović, J. Bogojeski, B. Petrović, D. Petrović and Ž. D. Bugarčić, Ligand substitution reactions of some sterically hindered Pt(II) complexes. The crystal structure of [TLtBuH2](ClO4)2 .o.5 H2O Polyhedron, 2012, 41, 70-76. 
8.        A. Djeković, B. Petrović, Ž. D. Bugarčić, R. Puchta and R. van Eldik Kinetics and mechanism of the reactions of Au(III) complexes with some biologically relevant molecules Dalton. Trans., 2012, 41, 3633-3641. 
9.        A. Mijatović, J. Bogojeski, B. Petrović and Ž. D. Bugarčić Substitution reactions of some novel sterically hindered monofunctional Pd(II) complexes Inorg. Chim. Acta, 2012, 383, 300-304. 
10.    B. Petrović, Ž. D. Bugarčić A. Dees, I. Ivanović-Burmazović, F. Hainemann, R. Puchta, S. N. Steinmann, C. Corminboeuf and R. van Eldik Role of π-acceptor effects in controlling the lability of novel mono-functional Pt(II) and Pd(II) complexes. Crystal structure of [Pt(tripyridinedimethane)Cl]Cl Inorg. Chem., 2012, 51, 1516-1529. 
11.    T. Soldatović, S. Jovanović, Ž. D. Bugarčić and R. van Eldik Substitution behaviour of novel dinuclear Pt(II) complexes with bio-relevant nucleophiles Dalton Trans., 2012, 41(3), 876-884. 
12.    M. Arsenijević, M. Milovanovic, V. Volarevic, A. Djeković, T. Kanjevac, N. Arsenijević, S. Đukić and Ž. D. Bugarčić Cytotoxicity of gold(III) complexes on A549 human lung carcinoma epithelial cell line Medic. Chem., 2012, 8(1), 2-8. 
13.    A. Rilak, B. Petrović, S. Grgurić-Šipka, Ž. Tešić and Ž. D. Bugarčić Kinetics and mechanism of the reactions of Ru(II)-arene complex with some biologically relevant ligands Polyhedron, 2011, 30, 2339-2344.
14.    J. Bogojeski, R. Jelić, D. Petrović, E. Herdtweck, P. G. Jones, M. Tamm and Ž. D. Bugarčić Equilibrium studies of the reactions of palladium(II) bis(imidayolin-2-imine)complexes with biologically relevant nucleophiles. The crystal structure of [(TLtBu)PdCl]ClO4 and [BLiPr)PdCl2] Dalton Trans., 2011, 40, 6515-6523. 
15.    B. Damnjanović, T. Kamčeva, B. Petrović, Ž. D. Bugarčić and M. Petković Laser desorption and ionization time-of-flight versus matrix-assisted laser desorption and ionization time-of-flight mass spectrometry of Pt(II) and Ru(II) metal complexes Anal. Methods, 2011, 3, 400-407. 
16.    J. Bogojeski and Ž. D. Bugarčić Kinetic and thermodznamic studies on reactions of [PtCl(bpma)]+ and [Pt(bpma)H2O]2+ (bpma = bis-(2-pyridylmethyl)amine) with some azoles and diazines Trans. Met. Chem., 2011, 36, 73-78.