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Chemical and Dynamical Processes in Solution; Polymers, Glasses, and Soft Matter
Flavin Adenine Dinucleotide Photochemistry Is Magnetic Field Sensitive at Physiological pH Lewis Martyn Antill, and Jonathan Roger Woodward J. Phys. Chem. Lett., Just Accepted Manuscript • DOI: 10.1021/acs.jpclett.8b01088 • Publication Date (Web): 03 May 2018 Downloaded from http://pubs.acs.org on May 5, 2018
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The Journal of Physical Chemistry Letters
Flavin Adenine Dinucleotide Photochemistry is Magnetic Field Sensitive at Physiological pH Lewis M. Antill and Jonathan R. Woodward* Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, Japan AUTHOR INFORMATION Corresponding Author *Jonathan R. Woodward, E-mail:
[email protected] ABSTRACT We present time-resolved optical absorption and magnetic field effect data on the photochemistry following blue light excitation of flavin adenine dinucleotide (FAD) in aqueous solution in the pH range 2.3 to 8.0. Effects of closed form conformations of FAD in ground, excited singlet and radical pair states exhibit significant influence on the observed kinetics and magnetic field dependence and remarkably, magnetic field effects are observed even at physiological pH where the FAD radical pairs are only 75% less magnetic field sensitive than at pH 2.3.
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Flavins are found throughout nature and participate in a wide range of biochemical reactions as coenzymes and photoreceptors.1 They are broadly distributed as both free cellular flavins,2 and bound in flavoproteins, mainly in the forms of FAD and flavin mononucleotide (FMN). Mechanisms involving UV-/blue-light absorbing flavoproteins include DNA repair by DNA photolyase3 and the entrainment of circadian rhythms by cryptochrome,4 both of which utilize a FAD chromophore. A growing body of evidence suggests that cryptochromes might have a role in the ability of flora and fauna to sense the geomagnetic field.5,6 This chemical magnetoreception hypothesis operates through spin correlated radical pairs (RPs) generated by a photoinduced electron transfer from a nearby protein residue to a bound FAD cofactor molecule. The process by which these cryptochrome RPs respond to an external magnetic field (MF) is via the radical pair mechanism (RPM), and low field effects (LFEs, the name given to the effect of very weak magnetic fields on RP reactions due to the unlocking of zero quantum coherences) may allow plants and animals to detect fields as weak as the geomagnetic field (~30-50 µT).7 Furthermore, epidemiological studies suggest a weak correlation between the development of cancer and teratological effects and exposure to 50/60 Hz extremely low frequency- (ELF)
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The Journal of Physical Chemistry Letters
MFs.8-11 The cryptochrome RPM hypothesis is considered a plausible mechanism for explaining the biological effects of ELF-MFs.12,13 In isolation the key cryptochrome cofactor, FAD, has also been shown, on blue light excitation in aqueous solution, to generate RPs through intramolecular electron transfer from the adenine to the isoalloxazine moiety, which undergo spin-selective recombination, yielding both chemically induced dynamic nuclear polarization14 (CIDNP) and magnetic field effects15,16 (MFEs). The original CIDNP studies showed the strong dependence of the CIDNP signal on pH and argued that the primary pH dependence was due to the conformation of ground state FAD. At low pH (3.6) the excited triplet state and RP are both electrically neutral and that the RP formed under such conditions produces no CIDNP due to stacking analogous to that in the ground state, which in this case leads to a very large exchange interaction and thus the removal of any coherent spin effects. This explanation suggests that FAD should demonstrate no magnetic field sensitivity at neutral and physiological pH. Subsequently, MFE studies of FAD photochemistry revealed that the photochemistry at low pH (
