Study of the interaction of a cis-dichloroaminopyrrolidine Pt(II) complex and the polynucleotide poly(I)–poly(C) acid by means of [formula omitted]-NMR and multivariate curve resolution

Abstract

Multivariate curve resolution is proposed for the analysis of spectroscopic data obtained from kinetic studies on the interaction of compounds analogous to cis-platinum (cisplatin) and nucleic acids. In particular, the interaction between the cis-dichloro-(1,2-diethyl-3-aminopyrrolidine) Pt(II) compound (Ptpyrr) and the polynucleotides poly(inosinic) (poly(I)), poly(cytidylic) (poly(C)) and poly(I)–poly(C) acids were monitored by 1 H -NMR spectroscopy. Multivariate curve resolution was applied for the first time to analyze 1 H -NMR spectroscopic data, which allowed to determine the number of interaction complexes and the recovery of both kinetic concentration profiles and pure NMR spectra for all the detected species. For poly(I) and poly(C), two complexes were detected upon interaction with Ptpyrr, which corresponded to the mono-adduct and to the bis-adduct complex formation. For poly(I)–poly(C), three components were detected, which corresponded to: (a) the initial non-platinated double-stranded polynucleotide, (b) to a mixture of non-platinated single-stranded poly(C) and platinated poly(I), and (c) to a mixture of poly(C) and poly(I), both platinated. Multivariate curve resolution chemometric procedure based on an alternating least-squares optimization (MCR–ALS) is, thus, proposed as a useful tool for the recovery of analytical information from 1 H -NMR data.