Heavy metal-nucleoside interactions. 10. Binding of cis-diammineplatinum(II) to cytidine and uridine in aqueous solution: necessary conditions for formation of platinum-uridine "blues"

Abstract

Both cytidine and uridine react with (H3N)2Ptn and enPt11 in aqueous solution over a wide pH range. The reactions with cytidine are complete within a few hours, while those with uridine are considerably slower. In both cases mono and bis complexes are formed. In acidic solution, (H3N)2Ptn behaves as a bifunctional electrophile toward cytidine, while at pH 7 it acts as a unifunctional electrophile. The equilibrium constant for [(H3N)2Pt(OH2)2]2+ + Cyd <=± [(H3N)2PtCyd(OH2)]2+ + H20 was estimated from Raman spectra to have the value log K = ca. 2.9 (0.1 M C104~). The hydroxo ligand produced by hydrolysis of [(H3N)2Pt(OH2)2]2+ is an effective blocking group. Raman and and l3C NMR spectra all identify N(3) as the sole binding site. In particular, no interaction occurs at high pH with a deprotonated amine group. With uridine, the Raman and *H and l3C NMR experiments all show that binding occurs at N(3) of the conjugate base UrdH_f.No reaction takes place under comparable conditions with 3-methyluridine. The equilibrium constant for [(H3N)2Pt(OH2)2]2+ + UrdH-f [(H3N)2PtUrdH-1OH2]+ has a value log K > 9.6 (0.1 M C104~), comparable to H3CHgOH2+. The selectivity of the bases in a native polynucleotide for binding the substitutionally inert (H3N)2Ptn and related species is kinetic not thermodynamic in origin as also is the case with alkylating agents. Binding will occur preferentially at nonprotonated sites rather than N(3) of uridine or thymidine or N(l) of guanosine, the principal binding sites for labile heavy metal species.Kinetic and thermodynamic effects governing heavy metal binding are discussed. The binding behavior of labile species such as H+ or CH3Hg+ is of little use in predicting the reactions of the inert platinum(II) complexes. At pH 6-7, the monouridine complex undergoes a change which causes small shifts in the NMR spectrum. Exposure of solutions containing equimolar (H3N)2Ptn and uridine with pH <8 to the atmosphere results in the characteristic platinum-uracil "blue". The Raman spectra suggest that the principal species in these solutions is the colorless [(H3N)2PtUrdH_!OH2]+.

ESR Study on Complexes Formed on Reaction of cis-Dichlorodiammineplatinum(II) with Cytosine and Cytidine

“…It is likely that both platinum atoms are bound to the same types of ligands through N(3) of cytosine and Notizen cytidine, resp., although no nitrogen hf coupling can be resolved. The complexes are formed at a pH value, where usually bis-complexes are found after short reaction times [4], Therefore, the ESR spectrum shown in Fig. 1 might be attributed tentatively to a binuclear platinum complex, with each of the platinum centers bound to two cytosine or cytidine molecules.…”

“…Concerning its interaction with cytosine and cytidine it is known that bis complexes are formed in the pH range 3-5.5 whereas mono complexes occur in the pH range 5.5-8.5. The binding site is the N(3) nitrogen [4]. These results have been obtained with solutions containing 25 mM of c/s-diaquodiammineplatinum-(II), an hydrolysis product of c?s-PDD, and 50 mM of cytidine reacting at 25 c C. Under different experimental conditions, e.g.…”

The Coordination Chemistry of DNA Nucleosides on Gold Nanoparticles as a Probe by SERS

“…It is known that the N(3) and the C=O group in cytosine have deep potential minima for the interaction with an external point charge. 27 With cytidine, it has been reported that hard metal ions bind to the C=O group whereas soft metals such as silver bind to N(3), in general. From X-ray crystallographic studies, 28 1methylcytosine, was found to bind to Pt via N(3) and to Ag through N(3) and C=O.…”

Discovery of Cisplatin Binding to Thymine and Cytosine on a Single-Stranded Oligodeoxynucleotide by High Resolution FT-ICR Mass Spectrometry

“…The order of reactivity of the four nucleotides with cisplatin was established as GMP > AMP >> CMP > UMP/TMP by Raman difference spectrophotometry [11]. Although it seemed that pyrimidine nucleobases have low reactivity to cisplatin, numerous studies have demonstrated the existence of “platinum pyrimidine blues” obtained from reactions of cisplatin and pyrimidine nucleobases such as uracil, 1-methyluracil, thymine, 1-methylthymine, uridine, and thymidine [12,13,14,15,16]. Moreover, Tobias et al, using Raman plus 1 H-NMR and 13 C-NMR spectroscopy, observed the coordination of cis -[(NH 3 ) 2 Pt(H 2 O) 2 ] 2+ to cytidine-N(3) and the deprotonated uridine-N(3) [14].…”