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

An acid-stable NADH model compound, 10-methyl-9,10-dihydroacridine (AcrH₂) (3), and cis-dialkylcobalt(III) complexes, cis-[R ₂Co(bipy)₂]⁺ (R = Me, Et; bipy = 2,2′-bipyridine), can reduce flavin analogues {Fl: 3-methyl-10- 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 (FlH ₂^+.). Essentially, no reaction occurs in the absence of HClO₄ under the same conditions. The radical cations (FlH ₂^+.) 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 FlH₂ ^+., indicating that hydride transfer from AcrH₂ to the protonated flavins (FlH⁺) to give the dihydroflavins (FlH ₂) is followed by fast comproportionation between FlH₂ and FlH⁺ to yield FlH₂^+. in the presence of HClO₄ in MeCN. The reaction mechanisms of hydride transfer from AcrH₂ to FlH⁺ are compared with the acid-catalysed electron-transfer reactions from cis-[R₂Co(bipy)₂] ⁺ to FlH⁺.