Room-temperature dynamic nuclear polarization enhanced NMR spectroscopy of small biological molecules in water

Danhua Dai; Xianwei Wang; Yiwei Liu; Xiao-Liang Yang; Clemens Glaubitz; Vasyl Denysenkov; Xiao He; Thomas Prisner; Jiafei Mao

doi:10.1038/s41467-021-27067-0

Room-temperature dynamic nuclear polarization enhanced NMR spectroscopy of small biological molecules in water

Nat Commun. 2021 Nov 25;12(1):6880. doi: 10.1038/s41467-021-27067-0.

Authors

Danhua Dai^#^{1

2}, Xianwei Wang^#^{3

4}, Yiwei Liu³, Xiao-Liang Yang^{5

6}, Clemens Glaubitz^{2

7}, Vasyl Denysenkov^{1

2}, Xiao He^{8

9}, Thomas Prisner^{1

2}, Jiafei Mao^{10

11}

Affiliations

¹ Institute of Physical and Theoretical Chemistry, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
² Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
³ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China.
⁴ College of Science, Zhejiang University of Technology, Hangzhou, Zhejiang, 310023, China.
⁵ Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
⁶ State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
⁷ Institute of Biophysical Chemistry, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
⁸ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China. xiaohe@phy.ecnu.edu.cn.
⁹ NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, 200062, China. xiaohe@phy.ecnu.edu.cn.
¹⁰ Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany. j.mao@em.uni-frankfurt.de.
¹¹ Institute of Biophysical Chemistry, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany. j.mao@em.uni-frankfurt.de.

^# Contributed equally.

Abstract

Nuclear magnetic resonance (NMR) spectroscopy is a powerful and popular technique for probing the molecular structures, dynamics and chemical properties. However the conventional NMR spectroscopy is bottlenecked by its low sensitivity. Dynamic nuclear polarization (DNP) boosts NMR sensitivity by orders of magnitude and resolves this limitation. In liquid-state this revolutionizing technique has been restricted to a few specific non-biological model molecules in organic solvents. Here we show that the carbon polarization in small biological molecules, including carbohydrates and amino acids, can be enhanced sizably by in situ Overhauser DNP (ODNP) in water at room temperature and at high magnetic field. An observed connection between ODNP ¹³C enhancement factor and paramagnetic ¹³C NMR shift has led to the exploration of biologically relevant heterocyclic compound indole. The QM/MM MD simulation underscores the dynamics of intermolecular hydrogen bonds as the driving force for the scalar ODNP in a long-living radical-substrate complex. Our work reconciles results obtained by DNP spectroscopy, paramagnetic NMR and computational chemistry and provides new mechanistic insights into the high-field scalar ODNP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carbon Isotopes / chemistry
Density Functional Theory
Hydrogen Bonding
Magnetic Fields
Molecular Dynamics Simulation
Nuclear Magnetic Resonance, Biomolecular / methods*
Temperature
Water / chemistry*

Substances

Carbon Isotopes
Water

Associated data

figshare/10.6084/m9.figshare.14774433
figshare/10.6084/m9.figshare.14774415