Accurate Rate Constants for Chemical Exchange from Improved Weighted Linear-Least-Squares Analysis of Multiple 1D-EXSY Data

Abstract

The 1D-EXSY pulse sequence 90°—t₁—90°—t_m—90°—t₂(obs), with a minimum number of judiciously chosent₁values and a series of mixing timest_m, can provide NMR data for measurement of site-to-site rate constants in multisite systems undergoing chemical exchange. A condition can be specified for optimizing the choice oft₁values. The data are analyzed by an improved weighted linear-least-squares fitting procedure that uses matrix algebra to help evaluate the weighting factors. This method is capable of providing highly accurate rate constants and realistic error estimates, without an inordinate demand on instrument time. Three experimental applications, to E/Z methyl exchange inN,N-dimethylpropionamide, to H_E/H_Z/H_Solventproton exchange in acrylamide, and to methoxy exchange between stereoisomeric 4,6-dimethyl-2-methoxy-1,3-dioxanes and methanol, are demonstrated.