Coenzyme models. Part 43. New metal-stabilised radicals of a flavin with a fused pyridine moiety which serves also as a metal chelation site in the oxidised state

Abstract

A new flavin, 2,4,7-trimethyl-10-benzylquino[8,7,-g]pteridine-9,11(7H,10H)-dione (PyFl) has been synthesised which has within the molecule a flavin as a catalytic site and a fused pyridine as an additional metal-chelation site. Unlike conventional oxidised flavins lacking affinity with most metal ions, PyFl could associate with a variety of metal ions in acetonitrile. PyFl forms 1:1 complexes with Zn^II, Cd^II, and Co^II ions, the association constants being (1.4–4.4)× 10⁵M^–1. These are the largest association constants reported for oxidised flavin–d-metal complexes. The oxidation of 1-benzyl-1,4-dihydronicotinamide (BNAH) by PyFl in acetonitrile, which did not take place in the absence of metal ion, was efficiently catalysed by several metal ions: [Mg^II, Zn^II, Cd^II, and Sb^III]. Furthermore, the reaction with BNAH in the presence of Mg^II, Zn^II, and Cd^II resulted in the formation of the flavosemiquinone which could be detected by absorption and e.s.r. spectroscopy. The e.s.r. spectral pattern is identical to that prepared by mixing equimolar amounts of oxidised and reduced PyFl. These results suggest that PyFl becomes even more electron-deficient than flavin owing to a PyFl → metal charge transfer while the semiquinone is stabilised through the interaction with these metal ions. These flavin-metal interactions serve as a model system possibly relevant to the action of metalloflavoenzymes. Such reactions cannot be provided by using conventional flavins.