Coenzyme models. Part 39. Synthesis and properties of a flavin with a fused phenolate moiety which serves as a metal chelation site

Abstract

A new flavin, sodium 7,9,10,11-tetrahydro-1-hydroxy-7-methyl-9,11-dioxonaphtho[l,2-g]pteridine-3-sulphonate (‘sodium 1’-hydroxy-l0-methylbenzo[2′,3′-h]isoalloxazine-5′-sulphonate,OHFI), which has a fused phenol within the molecular structure, has been synthesized. Measurement of absorption spectra revealed that in contrast to the non-affinity of conventional flavinsfor most heavy metal ions, OHFI can form complexes with several heavy metal ions in aqueous solution;in particular, Cu^II shows very strong affinity. It has been demonstrated through oxidation of 1-benzyl-3-carbamoyl-1,4-dihydroquinoline (BCQH), an acid-stable NADH model compound, that several metal ions (Cu^II, Hg^II, Mg^II, etc.) can ‘activate’ OHFI as an oxidising agent; Cu^II shows the highest co-catalytic effect. Spectroscopic examination established that OHFI forms 1:1 complexes with Cu^IIand Ni^II with K(association constant) 26 300 and 806 I mol^–1, respectively. The OHFI–Cu^II complex in aqueous solution has been found to have square-bipyramidal co-ordination about copper from e.s.r. spectra. In methanol, many heavy metal ions could bind to OHFI and the rate constants for the oxidation of BCQH by OHFI·Mⁿ⁺ complexes (Mⁿ⁺= Zn^II, Ni^II, and Cr^III) were enhanced by more than three orders of magnitude. These results suggest that the metal-OHFI complexes are not only useful as biomimetic oxidation catalysts but also may provide a clue to understanding metal–flavin interactions in metalloflavoproteins.