Zero-Field NMR of Urea: Spin-Topology Engineering by Chemical Exchange.

Seyma Alcicek,Danila Barskiy,Piotr Put,Szymon Pustelny,Vladimir Kontul

doi:10.1021/acs.jpclett.1c02768

Seyma Alcicek, Danila Barskiy + Show 3 more

Open Access

https://doi.org/10.1021/acs.jpclett.1c02768

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Abstract

Well-resolved and information-rich J-spectra are the foundation for chemical detection in zero-field NMR. However, even for relatively small molecules, spectra exhibit complexity, hindering the analysis. To address this problem, we investigate an example biomolecule with a complex J-coupling network—urea, a key metabolite in protein catabolism—and demonstrate ways of simplifying its zero-field spectra by modifying spin topology. This goal is achieved by controlling pH-dependent chemical exchange rates of 1H nuclei and varying the composition of the D2O/H2O mixture used as a solvent. Specifically, we demonstrate that by increasing the proton exchange rate in the [13C,15N2]-urea solution, the spin system simplifies, manifesting through a single narrow spectral peak. Additionally, we show that the spectra of 1H/D isotopologues of [15N2]-urea can be understood easily by analyzing isolated spin subsystems. This study paves the way for zero-field NMR detection of complex biomolecules, particularly in biofluids with a high concentration of water.

Highlights

Well-resolved and information-rich J-spectra are the foundation for chemical detection in zero-field nuclear magnetic resonance (NMR)
Because chemical exchange alters spin−spin couplings and NMR relaxation rates, Zero- and ultralow-field (ZULF) NMR is capable of monitoring this process, involving chemical reactions or conformational modifications, as was shown in a recent study.[10]
The results are explained by zero-field NMR simulations, considering the combined effect of chemical exchange and nuclear spin dynamics using a simple theoretical model. [15N2]-urea was measured in the mixtures of H2O and D2O to study the effect of deuterium nuclei on the zero

Summary

■ METHODS

All chemicals were purchased from Sigma-Aldrich and used without further purification. [13C,15N2]-urea (CAS# 58069-833) and [15N2]-urea (CAS# 2067-80-3) solutions at various pH values were prepared in an 8 M concentration by dissolving in sodium hydroxide (CAS# 1310-73-2) or hydrochloric acid (CAS# 7647-01-0). Simulations of chemical exchange effects on the zero-field spectra of urea were obtained using an approach presented in ref 10. Dependence of urea zero-field NMR signal amplitude on the guiding field strength; measured ZULF NMR spectra in deuterated urea; simulated spectra of deuterated urea isotopologues; and details of chemical exchange simulations in zero-field (PDF).

■ ACKNOWLEDGMENTS

Findings

■ REFERENCES