Synthesis and Characterization of Novel Flavin-Linked Porphyrins. Mechanism for Flavin-Catalyzed Inter- and Intramolecular 2e/1e Electron-Transfer Reactions

Article abstract of DOI:10.1021/ja00259a017

The synthesis of several flavin-linked porphyrins is described.The two moieties (Fl_oxC_n(TPP)M, M=H2 and Mn^IIICl) are covalently linked by an amide linkage with a methylene spacer group n, n=1-3> between the ortho position of (o-aminophenyl)triphenylporphyrin and the N3 or N10 positions of the flavin.The Fl_oxC_n(TPP)M (1a-e) were characterized by UV-visible, 1H NMR, and IR spectra.The proximity conformation of the flavin and porphyrin ring was demonstrated by 1H NMR studies of Fl_oxC_nTPPH2.The electrochemistry of Fl_oxC_n(TPP)M was investigated by cyclic voltammetry and differential-pulse polarography.Cyclic voltammetry demonstrated that the flavin reduction potentials, Fl_ox + e^- = Fl^.- and Fl^.- + e^- = Fl^2-, were positively shifted by the proximity of the linked porphyrin moiety.Flavin-catalyzed 2e/1e electron-transfer reactions from dihydropyridines to (TPP)Mn^IIICl have been investigated kinetically in intermolecular systems (PyH2 + Fl_ox + (TPP)Mn^IIICl) as well as in intramolecular systems (PyH2 + Fl_oxC_n(TPP)Mn^IIICl) in ethanol solution.In intermolecular systems, the presence of flavin enhances the apparent rates of electron transfer significantly.The kinetic behavior of the intermolecular system is zero order with respect to the (TPP)Mn^IIICl concentration and first order with respect to the PyH2 and Fl_ox concentrations, when PyH2 is in excess and Fl_ox is used in 0.25-1.5-fold to (TPP)Mn^IIICl.These observations indicate that the flavin acts as 2e/1e catalyst.In intramolecular systems, the kinetic behavior differs for the various Fl_oxC_n(TPP)Mn^IIICl systems.Whereas Fl_oxC1(TPP)Mn^IIICl shows clean first order, Fl_oxC2(TPP)Mn^IIICl and Fl_oxC3(TPP)Mn^IIICl exhibit a mixed-order behavior.The apparent second-order rate constants are increased for the intramolecular systems.The rate enhancements by the intramolecular effect are as follows: k_intra/k_inter = 8.0 (1a), 3.9 (1b), 2.1 (1c), 1.7 (1d), and 1.8 (1e).These results show that the k_intra/k_inter values are affected by the methylene spacer length and the linking position.Possible reasons for the rate enhancement are discussed by using electrochemical data, conformational data, and kinetic isotope effects.The proposed reaction mechanism for the intramolecular system, especially for Fl_oxC1(TPP)Mn^IIICl, involves a ternary complex such as ox...(TPP)Mn^IIICl>.The described systems are relavant models for biological electron-transfer processes requiring flavin 2e/1e catalysis and for flavin-heme interaction as in flavohemoproteins.