Hydrogen-exchange kinetics studied through analysis of self-decoupling of nuclear magnetic resonance

Abstract

Hydrogen exchange between solute and water molecules occurs across a wide range of timescales. Rapid hydrogen-exchange processes can effectively diminish ¹H-¹⁵N scalar couplings. We demonstrate that the self-decoupling of ¹⁵N nuclear magnetic resonance can allow quantitative investigations of hydrogen exchange on a micro- to millisecond timescale, which is relatively difficult to analyze with other methods. Using a Liouvillian matrix incorporating hydrogen exchange as a mechanism for scalar relaxation, the hydrogen exchange rate can be determined from ¹⁵N NMR line shapes recorded with and without ¹H decoupling. Self-decoupling offers a simple approach to analyze the kinetics of hydrogen exchange in a wide range of timescale.

Keywords: Hydrogen exchange; Ions; Kinetics; Nuclear magnetic resonance; Self-decoupling.

Figure 1.

Self-decoupling observed in ¹⁵N spectra of 80 mM ¹⁵NH₄⁺ ions recorded at various pH values. ¹⁵N signals recorded with and without ¹H WALTZ16 decoupling (the RF strength, 4.2 kHz) are shown.

Figure 2.

Self-decoupling reflects a micro-to-millisecond timescale hydrogen exchange. (A) Simulations of self-decoupling in ¹H-coupled ¹⁵N spectra as a function of the hydrogen exchange rate k_HX for NH₄⁺ ions. ¹J_NH = 73.5 Hz was used for each simulation. Corresponding simulations for NH₃⁺, NH₂, and NH moieties are shown in Figure S1 in the Supplementary Material. (B) The spin-echo intensity ratio as a function of the hydrogen exchange rate k_HX for NH₄⁺ ions in the approach of Kateb et al.[17] Dotted, solid, and dashed lines are for three spin-echo lengths,10, 20, and 100 ms, respectively.

Figure 3.

Self-decoupling-based determination of the hydrogen exchange rate k_HX for ¹⁵NH₄⁺ ions at 25°C. (A) Fitting to the ¹⁵N spectra recorded for NH₄⁺ ions. Experimental data are shown with dots (blue: ¹H-decoupled spectra; red, ¹H-coupled spectra). The best-fit curves are shown in solid lines. (B) The hydrogen exchange rate k_HX determined from the self-decoupling data at various pH values. The solid line is the best-fit curve obtained with k_HX = k_od×10^pH + k_pi, where k_od is a rate constant for the OH^--dependent mechanism and k_pi is an overall rate constant for mechanisms involving catalysts other than OH^- and H⁺ [2, 26].