Sensitive, Efficient and Portable Analysis of Molecular Exchange Processes by Hyperpolarized Ultrafast NMR

Abstract

Molecular exchange processes are ubiquitous in nature. Here, we introduce a method to analyze exchange processes by using low-cost, portable, singlesided NMR instruments. The inherent magnetic field inhomogeneity of the single-sided instruments is exploited to achieve diffusion contrast of exchange sites and spatial encoding of 2D data. This so-called ultrafast diffusion exchange spectroscopy method shortens the experiment time by two to four orders of magnitude. Furthermore, because full 2D data are measured in a single scan (in a fraction of a second), the sensitivity of the experiment can be improved by several orders of magnitude using so-called nuclear spin hyperpolarization methods (in this case, dissolution dynamic nuclear polarization). As the first demonstration of the feasibility of the method in various applications, we show that the method enables quantification of intra-and extracellular exchange of water in a yeast cell suspension.

Frémy’s Salt as a Low-Persistence Hyperpolarization Agent: Efficient Dynamic Nuclear Polarization Plus Rapid Radical Scavenging

“…At the same time, comparable advantages can be expected for monitoring chemical reactions, materials formation, or detecting hyperpolarized 2D and 3D spectra , or chemical exchange events . The sets of reactions, reaction conditions, interactions, and conversions are significantly widened with a 3- to 4-fold longer detection time window.…”

Missing Pieces in Structure Puzzles: How Hyperpolarized NMR Spectroscopy Can Complement Structural Biology and Biochemistry

“…For this method, 2D spectra are recorded, typically, within a millisecond by pulsed gradient‐based spatial encoding of the second dimension such that high temporal sampling can be achieved while retaining higher dimensional detection. This can be particularly useful when aiming at processes taking place on the low seconds timescale [16,99–104] . The challenge to be overcome when using DDNP is sample convection upon injection of the hyperpolarized solution into the NMR tube, which impedes gradient‐encoding.…”

“…Nuclear magnetic resonance spectroscopy provides a unique intrinsic potential: atomistic resolution coupled with broad applicability for a plethora of different systems, from dynamic studies in solution [1][2][3][4] to structure elucidation in the solid state. [5][6][7][8] In particular, the range of available multidimensional pulse sequences [9,10] to measure structures, [5,11,12] distance constraints, [13,14] binding sites, pico-to millisecond dynamics, [3,15] chemical exchange, [16] interaction kinetics, [17,18] etc., continues to advance NMR applications to a constantly growing number of target molecules and complexes.…”

Ultrafast transverse relaxation exchange NMR spectroscopy

“…UF LNMR has diverse application fields ranging from the identification of intracellular and extracellular metabolites 38 to porous materials research, 36 and the methods are applicable even with low field single-sided NMR instruments. [39][40][41] The UF approach shortens the experiment time by one to three orders of magnitude. 42 Due to the singlescan nature of UF LNMR methods, the use of hyperpolarization is feasible.…”