title: New bimetallic palladium(ii) and platinum(ii) complexes: studies of the nucleophilic substitution reactions, interactions with CT-DNA, bovine serum albumin and cytotoxic activity.
abstract: Two new dinuclear bimetallic complexes, [{PdCl(bipy)}{μ-(pyrazine)}{PtCl(bipy)}]Cl(ClO4) (1) (bipy is 2,2'-bipyridine) and [{PdCl(en)}{μ-(pyrazine)}{PtCl(en)}]Cl(ClO4) (2) (en is ethylenediamine), have been synthesized and characterized by elemental microanalysis, IR, (1)H NMR spectroscopy and MALDI-TOF mass spectrometry. The pKa values of the coordinated water molecules of the diaqua species were determined as well. Substitution reactions of complexes (1) and (2) with thiourea (Tu), l-methionine (l-Met), l-cysteine (l-Cys), l-histidine (l-His) and guanosine-5'-monophosphate (5'-GMP) were studied under the pseudo-first order conditions as a function of nucleophile concentration and temperature. The order of reactivity of nucleophiles was: Tu > l-Met > l-Cys > l-His > 5'-GMP. Substitution reactions with Tu, l-Cys and l-His were followed by decomposition of bimetallic complexes to the corresponding substituted mononuclear complexes [Pd(N-N)(Nu)2] and [Pt(N-N)(Nu)2] (N-N = bipy, en), releasing the bridging ligand. However, the structures of starting bimetallic complexes were preserved during the reactions with l-Met and 5'-GMP. The absorption spectroscopic study of interactions of calf-thymus DNA (CT-DNA) with complexes (1), (2) and [{PdCl(bipy)}{μ-(NH2(CH2)6H2N)} {PtCl(bipy)}]Cl(ClO4) (3), has shown that all the complexes exhibit high intrinsic binding constants (Kb = 10(4)-10(5) M(-1)). DNA-ethidium bromide (DNA-EB) fluorescence was quenched after addition of complexes (1), (2) or (3), indicating displacement of intercalating EB by complexes. All complexes have shown good binding affinity to bovine serum albumin protein (BSA). Chemosensitivity of A375 (human melanoma) and HeLa (human cervical cancer) cell lines toward complexes (1), (2) and (3) was analyzed by SRB assay. Complex (1) displayed significant inhibitory effect on the growth of both cell lines.
authors.affiliation: Faculty of Science, University of Kragujevac, Domanovića 12, P. O. Box 60, 34000 Kragujevac, Serbia. biljanap@kg.ac.rs.
authors.forename: Snežana
authors.initials: S
authors.lastname: Jovanović
authors.affiliation: Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Obrenčević
authors.affiliation: Faculty of Science, University of Kragujevac, Domanovića 12, P. O. Box 60, 34000 Kragujevac, Serbia. biljanap@kg.ac.rs.
authors.forename: Živadin D
authors.initials: ŽD
authors.lastname: Bugarčić
authors.affiliation: Institute of Nuclear Sciences "Vinča", University of Belgrade, Mike Petrovića Alasa 12-14, 11001 Belgrade, Serbia.
authors.forename: Iva
authors.initials: I
authors.lastname: Popović
authors.affiliation: Institute of Nuclear Sciences "Vinča", University of Belgrade, Mike Petrovića Alasa 12-14, 11001 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Žakula
authors.affiliation: Faculty of Science, University of Kragujevac, Domanovića 12, P. O. Box 60, 34000 Kragujevac, Serbia. biljanap@kg.ac.rs.
authors.forename: Biljana
authors.initials: B
authors.lastname: Petrović
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D005029:Ethylenediamines / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology; D011719:Pyrazines / Q000737:chemistry / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D005029:Ethylenediamines; D011719:Pyrazines; D012710:Serum Albumin, Bovine; D010984:Platinum; D015082:2,2'-Dipyridyl; D010165:Palladium; C031234:ethylenediamine; D004247:DNA; C427203:calf thymus DNA