Generalized treatment of NMR spectra for rapid chemical reactions

Abstract

Application of NMR spectroscopy to fast irreversible reactions (t 1/2 < 0.7 s) has been hampered by limitations in instrumentation and general methods for modeling the complicated spectra that result. Analytical descriptions of nuclear spin dynamics during fast reactions, first solved by Ernst and coworkers, are limited to first-order reaction kinetics. We demonstrate that numeric methods enable simulation of NMR spectra for fast reactions having any form of rate law. Simulated stopped-flow NMR spectra are presented for a variety of common kinetic scenarios including reversible and irreversible reactions of first and second-order, multistep reactions, and catalytic transformations. The simulations demonstrate that a wealth of mechanistic information, including reaction rates, rate laws, and the existence of intermediates, is imbedded in a single NMR spectrum. The sensitivity of modern NMR instrumentation along with robust methods for simulating and fitting kinetic parameters of fast reactions make stopped-flow NMR an attractive method for kinetic studies of fast chemical reactions.

Cross‐Peaks in Simple Two‐Dimensional NMR Experiments from Chemical Exchange of Transverse Magnetisation

“…The origin of these cross‐peaks can be understood through analogy with non‐equilibrium stopped‐flow NMR . Following Christianson and Landis, we consider first only “A” spins present at the beginning of the t 1 evolution period, and work in the rotating frame of spin B.…”

Reaction monitoring using online vs tube NMR spectroscopy: seriously different results

“…The flow system allows for multiple time points to be easily taken by flowing more unreacted starting material into the mixing, then detection regions with different delay values in the pulse sequence. The stopped‐flow NMR technique has allowed detection of short‐lived intermediates, study of complex protein‐folding mechanisms, and insights into the effects of fast kinetics on NMR lineshape …”

Stopped‐Flow 19F NMR Spectroscopic Analysis of a Protodeboronation Proceeding at the Sub‐Second Time‐Scale

“…[39] Landis and Christianson have also reported simulations of the changes in intensity, line-width, and phase, in NMR spectra arising from very rapid reactions. [45] In 2018 we reported on a detailed study of the mechanism of anion-initiated CF 3 transfer from TMSCF 3 [23] in which we employed a stopped-flow insert (Figure 1c) that we custombuilt for the investigation. In our subsequent analyses of CF 2 generation, [24] and arene CÀ H silylation by TMSCF 3 , [46] we have optimized our design and use of the stopped-flow system.…”

“…More recent developments have included rapid mixing cells using pneumatic drives and solenoid valves, [40] customized probes for greater reagent polarization and temperature control, [42–44] and high pressure stopped‐flow devices [39] . Landis and Christianson have also reported simulations of the changes in intensity, line‐width, and phase, in NMR spectra arising from very rapid reactions [45] …”