Dynamical Models of Chemical Exchange in Nuclear Magnetic Resonance Spectroscopy.

Abstract

Chemical exchange line-broadening is an important phenomenon in nuclear magnetic resonance (NMR) spectroscopy, in which a nuclear spin experiences more than one magnetic environment as a result of chemical or conformational changes of a molecule. The dynamic process of chemical exchange strongly affects the sensitivity and resolution of NMR experiments, and increasingly provides a powerful probe of the inter-conversion between chemical and conformational states of proteins, nucleic acids, and other biological macromolecules. A simple and often used theoretical description of chemical exchange in NMR spectroscopy is based on an idealized two-state jump model (the random-phase or telegraph signal). However, chemical exchange can also be represented as a barrier-crossing event that can be modeled using chemical reaction rate theory. The time scale of crossing is determined by the barrier height, the temperature, and the dissipation modeled as collisional or frictional damping. This tutorial explores the connection between the NMR theory of chemical exchange line-broadening and strong-collision models for chemical kinetics in statistical mechanics. Theoretical modeling and numerical simulation are used to map the rate of barrier-crossing dynamics of a particle on a potential energy surface to the chemical exchange relaxation rate constant. By developing explicit models for the exchange dynamics, the tutorial aims to elucidate the underlying dynamical processes that give rise to the rich phenomenology of chemical exchange observed in NMR spectroscopy. Software for generating and analyzing the numerical simulations is provided in the form of Python and Fortran source codes.