Acid-catalysed reduction of flavin analogues by an NADH model compound, 10-methyl-9,10-dihydroacridine and cis-dialkylcobalt(III) complexes

Abstract

An acid-stable NADH model compound, 10-methyl-9,10-dihydroacridine (AcrH₂)(3), and cis-dialkylcobalt(III) complexes, cis-[R₂Co(bipy)₂]⁺(R = Me, Et; bipy = 2,2′-bipyridine), can reduce flavin analogues {Fl: 3-methyl-l0-phenylbenzo[g]pteridine-2(1H),4(3H)-dione (1) and riboflavin (2)}, efficiently in the presence of perchloric acid (HClO₄) in acetonitrile (MeCN) at 298 K to yield the corresponding dihydroflavin radical cations (FIH₂⁺˙). Essentially, no reaction occurs in the absence of HClO₄ under the same conditions. The radical cations (FIH₂⁺˙) formed are very stable to oxygen in the presence of HClO₄ in MeCN. Large primary kinetic isotope effects [k_H/k_D 9.6 ± 0.8 and 9.9 ± 0.8 for (1) and (2), respectively] have been observed for the formation of FIH₂⁺˙, indicating that hydride transfer from AcrH₂ to the protonated flavins (FIH⁺) to give the dihydroflavins (FIH₂) is followed by fast comproportionation between FIH₂ and FIH⁺ to yield FIH₂⁺˙ in the presence of HClO₄ in MeCN. The reaction mechanisms of hydride transfer from AcrH₂ to FIH⁺ are compared with the acid-catalysed electron-transfer reactions from cis-[R₂Co(bipy)₂]⁺ to FIH⁺.