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Magnetic-Field Dependence of LC-Photo-CIDNP in the Presence of Target Molecules Carrying a Quasi-Isolated Spin Pair

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Abstract

NMR spectroscopy is well known for its high atomic-scale resolution, especially at high applied magnetic field. However, the sensitivity of this technique is marginal. Liquid-state low-concentration photo-chemically induced dynamic nuclear polarization (LC-photo-CIDNP) is a promising emerging technology capable of enhancing NMR sensitivity in solution. LC-photo-CIDNP works well on solvent-exposed Trp and Tyr residues, either in isolation or within proteins. This study explores the magnetic-field dependence of the LC-photo-CIDNP experienced by two tryptophan isotopologs in solution upon in situ LED-mediated optical irradiation. Out of the two uniformly 13C,15N-labeled Trp (Trp-U-13C,15N) and Trp-α-13C-β,β,2,4,5,6,7-d7 species employed here, only the latter bears a quasi-isolated 1Hα-13Cα spin pair. Computer simulations of the predicted polarization due to geminate recombination of both species display a roughly bell-shaped field dependence. Specifically, Trp-U-13C,15N is predicted to show a fairly weak field dependence with a maximum polarization at ca. 500 MHz (11.7 T). In contrast, Trp-α-13C-β,β,2,4,5,6,7-d7 is expected to show a much sharper field dependence with a polarization maximum at ca. 200 MHz (4.7 T). Experimental LC-photo-CIDNP studies on both Trp isotopologs (1 μM concentration) are consistent with the theoretical predictions. In summary, this study highlights the prominent field-dependence of LC-photo-CIDNP enhancements (ε) experienced by Trp isotopologs bearing a quasi-isolated spin pair.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Clayton Mickles, Clayton Thompson and Hung (Justin) Dang for preparing the enzymes and Trp isotopologs (see Methods). We are grateful to Charles G. Fry for technical assistance with NMR. Some of this research was carried out with the computer resources and assistance by the UW-Madison Center for High-Throughput Computing (CHTC) in the Department of Computer Sciences [29, 30].

Funding

This work was funded by the National Institutes of Health (grant R01GM125995 to S.C.). The Bruker Avance III 400 NMR spectrometer was supported by UW Madison Instructional Laboratory Modernization Award. The Bruker Avance III 600 NMR spectrometer was supported by NIH grant S10 OD012245. This study made use of the National Magnetic Resonance Facility at Madison (600 and 750 MHz spectrometers), which is supported by NIH grant R24GM141526. The CHTC is supported by UW-Madison, the Advanced Computing Initiative, the Wisconsin Alumni Research Foundation, the Wisconsin Institutes for Discovery, and the National Science Foundation, and is an active member of the OSG Consortium, which is supported by the National Science Foundation and the U.S. Department of Energy’s Office of Science.

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  1. Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, WI, 53706, USA

    Siyu Li, Hanming Yang, Heike Hofstetter & Silvia Cavagnero

  2. Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, 53706, USA

    Marco Tonelli

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Contributions

SL: performed all the spectroscopic measurements, the calculations, and prepared all the figures. SL and SC: wrote and reviewed the manuscript. HY: performed initial proof-of-concept calculations and experiments. HH: provided technical assistance. MT: contributed to T1 pulse-sequence writing and helped with the figure preparation of supplementary figure S1. All authors approved the manuscript.

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Correspondence to Silvia Cavagnero.

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Li, S., Yang, H., Hofstetter, H. et al. Magnetic-Field Dependence of LC-Photo-CIDNP in the Presence of Target Molecules Carrying a Quasi-Isolated Spin Pair. Appl Magn Reson 54, 59–75 (2023). https://doi.org/10.1007/s00723-022-01506-7

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