Oxidation-active flavin mimics. Chemical and redox properties of 7,14-diethyl-3,10-dimethylbenzo [1,2-g;4,5-g′]dipteridine-2,4,9,11-(3H,7H,10H,14H)-tetraone(benzo-dipteridine)

Abstract

The chemical and redox properties of benzo-dipteridine (BDP), an oxidation-active flavin mimic, were investigated. It was found that (i) BDP undergoes 2e-redox reaction under conventional conditions, (ii) pKa-values of 2e-reduced BDP (BDP,,) are 3.6 and 8.5, respectively, (iii) a mixture of BDP,, and BDP,, forms a charge-transfer complex in aqueous solution, (iv) BDP,, exhibits a remarkably high oxidation activity (ca. 1 07-fold) toward reactions involving nucleophilic attack at the C(4a) -position compared with 3,lO-dimethylisoalloxazine (DMI), and (v) the oxidation of an NADH model by BDP,, is acidcatalysed. As a new model reaction, BDP,, was found to oxidize sulphite ion via a BDP-SO,-adduct, which decomposes unimolecularly to give BDPH-and [SO,] in aqueous solution. This is the first example of an APS (adenosine 5'-phosphosulphate) reductase model.Flavin coenzymes exhibit diverse functions such as electron transfer, dehydrogenation, and activation of molecular oxygen in biological systems.2 For instance, flavoenzymes are able to oxidize various substrates such as amines, a-amino acids, ahydroxy acids, alcohols, dithiols, nitroalkanes, etc3 In model systems, however, the substrates oxidized by the conventional flavin models so far synthesized are very limited probably due to their lack of oxidizing power. Thus, for construction of artificial flavoenzymes, we thought that a first step would be exploitation of oxidation-active flavin mimics. Such flavin mimics would be quite useful not only for mechanistic studies of the oxidations mediated by flavin but also for exploitation of new model systems. From this point of view, we have continued to search for oxidation-active flavin mimics.Electron-deficient flavins such as 8-cyan0-~ and 7,8-dichloroflavins' are known to show high oxidizing activity. However, the substituent at the 6-position of the isoalloxazine ring, which is a peri-position from N(5), occasionally reduces the reactivity owing to steric hindrance6 To avoid this disadvantage, we employed the electron-withdrawing nature of ring nitrogen atom^,^ and found that 8 -~a -, ~ 6,8-diaza-,' and 6,89-triazaflavins" show remarkably high oxidizing activity. For example, the oxidation of thiols is facilitated by factors of ca. lo6 for 8azaflavin, ca. lo8 for 6,8-diazaflavin, and ca. 10" for 6,8,9-Paper 0/008861

Spectral and redox properties of benzodipteridine. A pulse radiolysis, laser flash photolysis and semi-empirical molecular orbital study

“…This agrees with the earlier suggestion that the observed red shift was due to the more extensive conjugated character of the 1,8-tautomer. 2 Upon deprotonation to give the monoanion, a small red shift is observed 2 (614-620 nm). This compares with the 76 nm red shift predicted for formation of the 1,8-monoanion and the very large red shift (ϩ287 nm) for formation of the 1,5-monoanion from the 1,5-neutral form.…”

“…Benzodipteridine (BDP) was synthesised as previously described. 2 All other chemicals were of AnalaR grade and were supplied by BDH. The solutions were typically 1-4 × 10 Ϫ5 mol dm Ϫ3 in BDP.…”

“…Recently, a benzodipteridine (BDP) flavin derivative was reported that more closely mimics flavoenzymes. 2 For example, thiols and phenylhydrazine were oxidised 10 7 -fold faster by BDP than with ordinary flavins. In contrast to the wealth of information on the chemical properties of natural flavins, little is known about the behaviour of benzodipteridines in their ground or excited states.…”