Unraveling chemical exchanges through steady state free precession NMR

Nuclear magnetic resonance is uniquely endowed to analyze dynamics, with line shape and relaxation measurements covering timescales over several orders of magnitude. Further insights arise from pulse sequences such as chemical exchange saturation-transfer or relaxation dispersion, which facilitate, respectively, the detectability and shift characterization of even lowly populated states and the pinpointing of the exact exchange rates. The present study demonstrates that Steady State Free Precession (SSFP) experiments involving a train of pulses with flip angle α spaced by repetition times (TRs) combine valuable features from both of these experiments. Indeed, in the presence of chemical exchanges, SSFP yields, via its offset-dependent excitation and saturation profiles, detailed information about the number, the chemical shifts, and the populations of the exchanging sites-even when these involve multiple intermediates with dissimilar abundances. Simultaneously, SSFP can provide, via its TR dependence, a controllable timescale yielding kinetic information on a variety of slow/intermediate/fast exchange rates. All this is theoretically demonstrated with the aid of a Liouville-space formalism examining the steady state in the presence of chemical exchange. This formalism leads in both the slow and fast exchange regimes to analytical predictions that match well "brute-force" numerical calculations, lending themselves to rapid and accurate fittings of exchange rates, chemical shifts, and site populations. The basic features associated with this novel approach to examine chemical kinetics are experimentally verified on simple model compounds; potential extensions are briefly discussed.