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, ¹H NMR spectroscopy and MALDI-TOF mass spectrometry. The pK_a 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 (K_b = 10⁴–10⁵ 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.

The reduction of the Pt(IV) complexes [PtCl₄(bipy)], [PtCl₄(dach)] and [PtCl₄(en)] by glutathione (GSH), L-cysteine ( L-Cys) and L-methionine ( L-Met) was investigated by stopped-flow spectrophotometry at pH 2.0 (in 0.01 M perchloric acid) and at pH 7.2 (in 25 mM Hepes buffer). Kinetic measurements were performed under pseudo-first order conditions with an excess of the reducing agent. The order of the reactivity of the studied complexes was [PtCl₄(bipy)] > [PtCl₄(dach)] > [PtCl₄(en)], and reactivity of investigated reducing agents followed the order GSH > L-Cys > L-Met. All the reactions between the selected Pt(IV) complexes and the sulfur donor biomolecules proceeded by a reductive elimination process that included nucleophilic attack by the reducing agent on one of the mutually trans-coordinated chloride ligands, which led to a two-electron transfer process. The final products of the redox reactions were the corresponding reduced Pt(II) complexes and the oxidized form of the reducing agents.

The novel dinuclear Pt(II) complexes [{trans-Pt(NH₃)₂Cl}₂(μ-pyrazine)](ClO₄)₂ (Pt1), [{trans-Pt(NH₃)₂Cl}₂(μ-4,4′-bipyridyl)](ClO₄)₂·DMF (Pt2), and [{trans-Pt(NH₃)₂Cl}₂(μ-1,2-bis(4-pyridyl)ethane)](ClO₄)₂ (Pt3), were synthesized. Acid–base titrations, and temperature and concentration dependent kinetic measurements of the reactions with biologically relevant ligands such as thiourea (Tu), glutathione (GSH) and guanosine-5′-monophosphate (5′-GMP) were studied at pH 2.5 and 7.2. The reactions were followed under pseudo-first-order conditions by stopped-flow and UV-vis spectrophotometry. ¹H NMR spectroscopy was used to follow the substitution of chloride in the complex [{trans-Pt(NH₃)₂Cl}₂(μ-4,4′-bipyridyl)](ClO₄)₂·DMF by guanosine-5′-monophosphate (5′-GMP) under second-order conditions. The results indicate that the bridging ligand has an influence on the reactivity of the complexes towards nucleophiles. The order of reactivity of the investigated complexes is Pt1 > Pt2 > Pt3.