Artificial Flavin Receptors: Effects of Hydrogen Bonding on Redox Properties of a Flavin Mimic

Abstract

This review describes the roles of hydrogen bonding on the redox properties of a flavin mimic by using artificial flavin receptors. The receptors exploited are melamine derivatives bearing guanidinium ion(s) that strongly bind 6-azaflavin through five or seven hydrogen bonds involving N(1), C(2)=O, N(3)-H, C(4)=O, N(5), and N(6) positions in CHCl3 and CHCl3-acetonitrile. It has been shown that receptors are quite useful for examination of the hydrogen bonding effects on the redox potential, stability of the anionic semiquinone radical, and the oxidation activity of 6-azaflavin. The functionalized receptors have a substrate- or a metal-binding site have been shown to facilitate the reactions by forming the noncovalent assemblies. A possibility as an apoprotein model of the receptors has been mentioned also.

In silico structure–function analysis of E. cloacae nitroreductase

“…A molecule of FMN cofactor is bound noncovalently in the interior of the EcNR domain by a network of hydrogen bonds and van der Waals and electrostatic interactions. Flavin cofactor–protein interactions play a major role in the “tuning” of the redox potentials and activities of flavoproteins through the differential stabilization of each redox state 54–57. A positively charged amino acid positioned near the flavin ring stabilizes the anionic reduced states of the cofactor through favorable electrostatic interactions.…”

Machine Learning for Efficient Prediction of Protein Redox Potential: The Flavoproteins Case

“…Furthermore, residues accepting/donating H-bonds found in close proximity to the flavin may also be involved in direct interactions with the isoalloxazine ring. This would cause a shift of redox potential in the positive direction by lowering flavin’s lowest unoccupied molecular orbital energy levels, as indicated previously. ,− …”