Substitution reactions of [Pt(terpy)X]2+ with some biologically relevant ligands. Synthesis and crystal structure of [Pt(terpy)(cyst-S)](ClO4)2·0.5H2O and [Pt(terpy)(guo-N7)](ClO4)2·0.5guo·1.5H2O

Abstract

Substitution reactions of the complexes [Pt(terpy)(H₂O)]²⁺, [Pt(terpy)(cyst-S)]²⁺ and [Pt(terpy)(guo-N⁷)]²⁺, where terpy = 2,2′:6′,2″-terpyridine, cyst = L-cysteine and guo = guanosine, with some biologically relevant ligands such as inosine (INO), inosine-5′-monophosphate (5′-IMP), guanosine-5′-monophosphate (5′-GMP), L-cysteine, glutathione, thiourea, thiosulfate and diethyldithiocarbamate (DEDTC), were studied in aqueous 0.10 M NaClO₄ at pH 2.5 and 6.0 using variable-temperature and -pressure stopped-flow spectrophotometry. The reactions of [Pt(terpy)(H₂O)]²⁺ with INO, 5′-IMP and 5′-GMP showed that these ligands are very good nucleophiles. The second order rate constants varied between 4 × 10² and 6 × 10² M⁻¹ s⁻¹ at 25 °C. The [Pt(terpy)(cyst-S)]²⁺ complex is unreactive towards nitrogen donor nucleophiles, and cysteine cannot be replaced by N⁷ from INO, 5′-IMP and 5′-GMP. However, sulfur donor nucleophiles such as thiourea, thiosulfate and diethyldithiocarbamate could displace the Pt–cysteine bond. Diethyldithiocarbamate is the best nucleophile and the order of reactivity is: thiourea < thiosulfate < DEDTC with rate constants of 0.936 ± 0.002, 5.99 ± 0.02 and 8.88 ± 0.07 M⁻¹ s⁻¹ at 25 °C, respectively. The reactions of [Pt(terpy)(guo-N⁷)]²⁺ with sulfur donor ligands showed that these nucleophiles could substitute guanosine from the Pt(II) complex, of which diethyldithiocarbamate and thiosulfate are the strongest nucleophiles. The tripeptide glutathione is also a very efficient nucleophile. Activation parameters (ΔH^≠, ΔS^≠ and ΔV^≠) were determined for all reactions. The crystal structures of [Pt(terpy)(cyst-S)](ClO₄)₂·0.5H₂O and [Pt(terpy)(guo-N⁷)](ClO₄)₂·0.5guo·1.5H₂O were determined by X-ray diffraction. Crystals of [Pt(terpy)(cyst-S)](ClO₄)₂·0.5H₂O are orthorhombic with the space group P2₁2₁2₁, whereas [Pt(terpy)(guo-N⁷)](ClO₄)₂·0.5guo·1.5H₂O crystallizes in the orthorhombic space group P2₁2₁2. A typical feature of terpyridine complexes can be found in both molecular structures: the Pt–N (central) bond distance, 1.982(7) and 1.92(2) Å, respectively, is shorter than the other two Pt–N distances, being 2.043(7) and 2.034(7) Å in [Pt(terpy)(cyst-S)](ClO₄)₂·0.5H₂O and 2.03(2) and 2.04(2) Å in [Pt(terpy)(guo-N⁷)](ClO₄)₂·0.5guo·1.5H₂O, respectively. In both crystal structures two symmetrically independent cations representing different conformers are present in the asymmetric unit. The results are analysed in reference to the antitumour activity of Pt(II) complexes, and the importance of the rescue agents are discussed.