Analytical Chemistry 2004, 76, 7094 - 7101
Multivariate Curve Resolution applied to the analysis and resolution of two - dimensional [1H, 15N]-NMR reaction spectra
Joaquim Jaumot, Vicente Marchán, Raimundo Gargallo, Anna Grandas
and Romà Tauler
Abstract
Multivariate Curve Resolution is proposed for the study of complex chemical reactions monitored by two -dimensional NMR spectroscopy. In particular, in this work, Multivariate Curve Resolution is applied to the study of the reaction between
15N-labelled cisplatin and the amino acid-nucleotide hybrid (Phac-Met-linker-p5’dG). At several stages of the reaction, two-dimensional (2D) [1H,15N]-HSQC NMR spectra were acquired and stored in data matrices. In a first step, Multivariate Curve Resolution was applied to analyze individually each one of these 2D spectra, allowing the resolution of the corresponding 1H and 15N onedimensional correlation spectra. In a second step, the whole set of 2D spectra recorded along the reaction were simultaneously analyzed by Multivariate Curve Resolution, allowing the resolution of the kinetic concentration profiles and of the pure 2D NMR spectra of each of the species detected along the reaction. Results finally obtained confirmed previously postulated reaction mechanisms involving the existence of two monofunctional adducts and of two bifunctional adducts, with the structure of one of them not completely resolved.
Keywords
2D NMR, Multivariate Curve Resolution, peptide-oligonucleotide hybrid, cisplatin, kinetics
Resolved reaction concentration profiles of the whole data set. Inset: Resolved concentration profiles for the first 5 hours of the reaction. Circles: resolved points, solid line: interpolated concentration profiles with the Curve Fitting Toolbox of the Matlab Software. Blue markers: 15N-labelled cisplatin, green markers: Pt-S monofunctional adduct, red markers: Pt-N7 monofunctional adduct, cyan markers: Pt-S,N7 chelate, magenta markers: final product.