Salmon sperm DNA, treated with the antitumor agent cis-diamminedichloroplatinum(II) (cis-DDP), was enzymatically degraded to (oligo)nucleotides. Four Pt-containing products were identified by 1H NMR after preparative chromatography on a diethylaminoethyl-Sephacel column at pH 8.8. In all identified adducts, comprising approximately 90% of the total Pt in the DNA, Pt was linked to the N7 atoms of the nucleobases guanine and adenine. The two major adducts were cis-Pt(NH3)2d(pGpG) and cis-Pt-(NH3)2d(pApG), both derived from intrastrand cross-links of cis-DDP on neighboring nucleobases. Only the d(pApG) but not the d(pGpA) adduct could be detected. Two minor adducts were Pt(NH3)3dGMP, resulting from monofunctionally bound cis-DDP to guanine, and cis-Pt(NH3)2d(GMP)2, originating from interstrand cross-links on two guanines as well as from intrastrand cross-links on two guanines separated by one or more bases. For analytical purposes we developed an improved method to determine cis-DDP adducts. Routinely, 40-micrograms samples of enzymatically degraded cis-DDP-treated DNA are now analyzed by separation of the mononucleotides and Pt-containing (oligo)nucleotides on the anion-exchange column Mono Q (FPLC) at pH 8.8 (completed within 14 min) and subsequent determination of the Pt content in the collected fractions by atomic absorption spectroscopy. The method was used to optimize the digestion conditions for cis-DDP-treated DNA. In kinetic studies on the formation of the various adducts, a clear preference of the Pt compound to react with guanines occurring in the base sequence d(pGpG) was established.

Adducts of the antitumor drug cis-diamminedichloroplatinum(II) with DNA: formation, identification, and quantitation

https://www.jbc.org/content/273/24/14721.full.pdf

Cisplatin Binding Sites on Human Albumin

The coordination chemistry of platinum anticancer drugs and related compounds with DNA

This study calls into question the conclusions of many preclinical studies using platinum drugs dissolved in DMSO, which was discovered to greatly attenuate the cytotoxic properties of these drugs

https://cancerres.aacrjournals.org/content/canres/early/2014/07/01/0008-5472.CAN-14-0247.full.pdf

Say No to DMSO: Dimethylsulfoxide Inactivates Cisplatin, Carboplatin and Other Platinum Complexes

This critical review highlights the progress in (195)Pt NMR over the last 25 years. In particular, some of the recent applications of (195)Pt NMR in catalytic and mechanistic studies, intermetallics and drug binding studies are discussed. (195)Pt NMR chemical shifts obtained from both theoretical studies and experiments are presented for Pt(0), Pt(II), Pt(III) and Pt(IV) complexes. (195)Pt coupling with various nuclei (viz. coupling constants) have also been collected in addition to data on (195)Pt relaxation. The latest developments in the theoretical knowledge and experimental advances have made (195)Pt NMR into a rich source of information in many fields. (164 references.).

195Pt NMR—theory and application

The formation of six products from the solvolysis of cis-[Pt(NH3)2Cl2] in Me2SO has been monitored by 195Pt n.m.r. shifts and 195Pt–15N coupling constants, the products including mono- and tri-ammine species; the same method allows a ready identification of the more thermodynamically stable isomer of [Pt(glycinate)(Me2SO)Cl] as that with O trans to S.

Solvolysis of cis-[Pt(NH3)2Cl2] in dimethyl sulphoxide and reactions of glycine with [PtCl3(Me2SO)]– as probed by 195Pt nuclear magnetic resonance shifts and 195Pt–15N coupling constants

Effects of chemical shift anisotropy and 14N coupling on the 1H and 195Pt nuclear magnetic resonance spectra of platinum complexes

195Pt NMR studies of platinum(II) dimethylsuphoxide complexes

35 Cl, 37Cl and 79Br, 81Br Isotope shifts of 0·167 and 0·028 p.p.m. per Cl or Br isotope substitution, respectively, are clearly resolved in 86 MHz 195Pt n.m.r. spectra of PtIV halides, and, even in mixed complexes, the number of Cl– and Br– ligands can be counted from the multiplet splitting patterns; relaxation by chemical shift anisotropy appears to contribute little to the linewidths of the isotopomers of PtIICl42–.

Chlorine and bromine isotope shifts in 195Pt n.m.r. spectra

Reactions of chloro–bromo- PtII and -PtIV complexes with sodium nitrite in aqueous solution have been studied by l95Pt n.m.r. spectroscopy. Chemical shifts and 1J(195Pt–15N) coupling constants of all 21 possible PtII complexes, and 47 of the possible 56 PtIV complexes are reported. Regular incremental shift patterns were observed for Cl–/Br– substitutions in each set of complexes, but only partially for NO2– substitutions for PtIV, and not for PtII NO2–/Cl– substitution shifts were in opposite directions for PtII(to low frequency) and PtIV(to high frequency), but in the same direction for NO2–/Br–substitutions. 1J(195Pt–15N) coupling constants were linearly dependent on the number of nitrite ligands for both PtII and PtIV. Both chemical shift and coupling constant changes upon ligand substitution are dominated by the nature of the trans ligand. trans Pairs of nitrite ligands destabilize complexes and account for the nine undetected PtIV complexes.

The trans influence in platinum chemistry. A platinum-195 nuclear magnetic resonance study of [15N]nitrito-, chloro-, and bromo-platinum-(II) and -(IV) complexes

S. John S. Kerrison

Papers

Solvolysis of cis-[Pt(NH3)2Cl2] in dimethyl sulphoxide and reactions of glycine with [PtCl3(Me2SO)]– as probed by 195Pt nuclear magnetic resonance shifts and 195Pt–15N coupling constants

Effects of chemical shift anisotropy and 14N coupling on the 1H and 195Pt nuclear magnetic resonance spectra of platinum complexes

195Pt NMR studies of platinum(II) dimethylsuphoxide complexes

Chlorine and bromine isotope shifts in 195Pt n.m.r. spectra

The trans influence in platinum chemistry. A platinum-195 nuclear magnetic resonance study of [15N]nitrito-, chloro-, and bromo-platinum-(II) and -(IV) complexes