Environment- and Conformation-Induced Frequency Shifts of C–D Vibrational Stark Probes in NAD(P)H Cofactors

26 August 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

NAD(P)H cofactors are found in all forms of life and are essential for electron and hydrogen atom transfer. The linear response of a carbon-deuterium (C–D) vibration based on the vibrational Stark effect can facilitate measurements of electric fields for critical biological reactions including cofactor-mediated hydride transfer. We find both inter- and intramolecular electric fields influence the C–D frequency in NAD(P)H and nicotinamide-like models where the reactive C4-hydrogen has been deuterated. Hence, the C–D frequency can report both environmental electrostatics and conformational changes of the nicotinamide ring. Conformation-dependent effects are mediated through space as electrostatic effects, rather than through-bond. A Stark tuning rate of ~0.57 cm-1/(MV/cm) was determined using both experimental and computational approaches, including vibrational solvatochromism, molecular dynamics simulations, and in-silico Stark calculations. The vibrational probe’s Stark tuning rate is shown to be robust and suitable for measuring fields along hydride transfer reaction coordinates in enzymes

Keywords

NADH
NADPH
Nicotinamide
Cofactor
Coenzyme
Enzyme
Vibrational Spectroscopy
Vibrational Stark Effect
Carbon-deuterium bond
Electrostatics
Electric Field

Supplementary materials

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Supplementary Information
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Supplementary methods and data, figures S1-S26, tables S1-S6, and supplementary references
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