Regulation of Redox Potential of a Pterin Derivative Bound to a Ruthenium(II) Complex by Intermolecular Hydrogen Bonding with Nucleobases

摘要

Pterins are redox-active heteroaromatic coenzymes involved in a variety of redox-related reactions in biological systems to perform proton-coupled electron transfer (PCET). They originate from guanosine triphosphate and are fixed in the vicinity of metal ions by noncovalent interactions including hydrogen-bonding and π-π interactions to form active sites of metalloenzymes. To realize a required functionality in a certain enzyme, the redox potential of the pterin cofactor needs to be appropriately regulated. For example, in the active site of heme-containing induced nitric oxide synthase (iNOS), tetrahydrobiopterin (H4B) has π-π interaction with the indole ring of tryptophan 457 in the vicinity of the heme cofactor, which results in the stabilization of the radical intermediate of H4B to facilitate electron transfer from H4B to an Fe-O2 complex. Since the pterin cofactors are involved in extensive hydrogen-bonding networks in the active sites of pterin-dependent enzymes, hydrogen bonding should be an important factor to regulate the redox potential. Any clear evidence, however, has yet to be provided to support the notion that hydrogen-bonding interaction exerted to the pterins is the critical factor for the regulation of their redox behavior. This is because the direct determination of the redox potentials of pterins is generally difficult in biological systems. Thus, the lack of a sufficient dataset of redox potentials of pterins has precluded detailed discussion on the reactivity control of pterin-dependent enzymes by noncovalent interactions, which regulate the redox potentials of pterins in active sites of pterin-dependent enzymes.