Photoreduction of deazaflavin. Spectroscopic investigations

Bliese, Marianne; Launikonis, A.; Loder, JW; Mau, Albert W. H.; Sasse, W. H. F.

doi:10.1071/ch9831873

Cited by 14 publications

(8 citation statements)

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“…While NADH-reduced dRf gave only one product (H 2 dRf, as confirmed by its characteristic UV spectrum, Fig. S4.1) [56] EDTA-reduction of dRf yielded H 2 dRf and another product (most likely assigned to the dimeric, half-reduced semiquinone product) appearing simultaneously over time (Fig. S4.2).…”

Section: Resultsmentioning

confidence: 75%

“…Already in the 1970s, deazaflavins have been subject of extensive research efforts. Especially Massey, Hemmerich and coworkers have worked out the reactivity of deazaflavins revealing that the deazasemiquinone radical is significantly less stable compared to the 'normal' semiquinone [53][54][55][56][57][58][59][60]. This favours disproportionation and dimerization reactions leading to non-radical products exhibiting low(er) O 2 reactivity.…”

Section: Introductionmentioning

confidence: 99%

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Deazaflavins as photocatalysts for the direct reductive regeneration of flavoenzymes

Schie

Younes

Rauch

et al. 2018

Molecular Catalysis

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Deazaflavins are potentially useful redox mediators for the direct, nicotinamide-independent regeneration of oxidoreductases. Especially the O 2-stability of their reduced forms have attracted significant interest for the regeneration of monooxygenases. In this contribution we further investigate the photochemical properties of deazaflavins and investigate the scope and limitations of deazaflavin-based photoenzymatic reaction systems.

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Section: Resultsmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Deazaflavins as photocatalysts for the direct reductive regeneration of flavoenzymes

Schie

Younes

Rauch

et al. 2018

Molecular Catalysis

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“…It has been reported (Massey and Hemmerich, 1978;Duchstein et al, 1979;Goldberg et al, 1981;Bliese et al, 1983) that prolonged illumination of 3-methyl-5-deazaflavin l h and 3,7,8-trimethyl-5deazaflavin lj in the presence of the electron donor oxalate or EDTA leads to the formation of dimeric compounds 2h, 2j as final products of the photoreduction (Scheme 1). In our work we found that the photoreduction of dFloxs is strongly influenced by the substituent at position 8 and the electron donor used (Link et al, 1986b).…”

Section: Photoreduction Of 5-deazaflavinsmentioning

confidence: 97%

Spectroscopy and Photochemistry of 8‐substituted 5‐deazaflavins

Link

Plas

Müller

1987

Photochem & Photobiology

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Abstract— Absorption, fluorescence and phosphorescence spectra as well as fluorescence and phosphorescence quantum yields of 8‐X‐5‐deazaflavins (X = C1, NO2, p‐NO2‐C6H4, N(CH3)2, NH2, p‐NH2‐C6H4, p‐N(CH3)2‐C6H4‐N=N) were determined. It was found that all these data are highly influenced by the substituent at position 8 of the 5‐deazaisoalloxazine skeleton. Also the photoreduction of 8‐X‐5‐deazaflavins in the presence of electron donors was studied. It was established that the photoreduction leads to the formation of a 5,5‘‐dimer and/or a 6,7‐dihydro compound. Reduction of the C(6)‐C(7) bond is promoted by strong electron‐donating substituents and bulky electron donors. 5‐Deazaftavins with a reducible substituent at position 8 exhibit reduction of the substituent prior to the reduction of the 5‐deazaisoalloxazine skeleton.

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“…6. Here, the energy of the deazaflavin triplet, P Fe À 3 F*, E 0À0 = 2.58, was assumed to be equal to that of 3,10-dimethyl-5-deazaflavin [23] and that of the porphyrin triplet, 3 P Fe * À F, equal to that of tetraarylporphyrinatometals, E 0À0 = 1.50 [24].…”

Section: Cmentioning

confidence: 99%

Synthesis and Photophysical Properties of a Deazaflavin‐Bridged Porphyrinatoiron(III) That Mimics the Interaction of a Deazaflavin Inhibitor with the Heme‐Thiolate Cofactor of Cytochrome P450 3A4

Müller

Gáplovský

Wirz

et al. 2006

Helvetica Chimica Acta

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Cytochrome P450 3A4 metabolizes a majority of administered therapeutic agents in the human liver. We recently reported the synthesis of a new inhibitor, 1, whose binding to and displacement from the active site of CYP 3A4 can be conveniently followed by the associated changes in fluorescence intensity. Here we report the synthesis of a bichromophoric compound, 6, in which deazaflavin was strapped over the distal side of a porphyrinatoiron(III) complex to mimic the envisaged enzyme-inhibitor interaction within the active site. Femtosecond pump-probe and fluorescence spectroscopies were used to study the photophysical processes of 6. Rapid intramolecular energy transfer and enhanced intersystem-crossing processes induced by the high-spin Fe III central ion are responsible for the complete suppression of deazaflavin fluorescence in 6. Fluorescence quenching is less efficient in the iron-free analogue of 6, i.e., in 21.1. Introduction. -Cytochrome P450 3A4 (CYP 3A4), a heme-thiolate protein, is one of the most important P450s in the human liver [1]. The ability of CYP 3A4 to metabolize a majority of administered therapeutic agents accounts for the large number of documented drug-drug interactions associated with CYP 3A4 inhibition [2]. It is therefore of great importance to know the affinity of new drug candidates to CYP 3A4 at an early stage, in order to determine their potential as inhibitors, and to evaluate their influence on the metabolism of co-administered drugs. Some particular features of CYP 3A4 make it difficult to achieve this goal. Though X-ray structures are now available from truncated CYP 3A4 [3], these pictures provide no clues on how the enzyme accepts substrates as different as, e.g., erythromycin and nifedipine, how the active site accommodates more than one substrate [4], and why partial inhibition and even activation is observed when pairs of drugs are co-incubated [5].Our group has recently reported [6] the synthesis of a new inhibitor 1 that displayed favourable IC 50 values in the range of 1 -4 mM for three characteristic substrates of CYP 3A4 such as testosterone (2), midazolam (3), and nifedipine (4) (Fig. 1). The binding of 1 to the active site of CYP 3A4 and its displacement by other substrates can be followed by the associated change in the intensity of the deazaflavin fluorescence [7], such that a screening for drugs that might cause drug-drug interactions requires neither the determination of substrate turnover nor product analyses.From these experiments, it was suggested [6] that the fluorescence of 1 is quenched upon binding to CYP 3A4 due to an interaction such as that shown in structure 5 of the

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Photoreduction of deazaflavin. Spectroscopic investigations

Cited by 14 publications

References 0 publications

Deazaflavins as photocatalysts for the direct reductive regeneration of flavoenzymes

Deazaflavins as photocatalysts for the direct reductive regeneration of flavoenzymes

Spectroscopy and Photochemistry of 8‐substituted 5‐deazaflavins

Synthesis and Photophysical Properties of a Deazaflavin‐Bridged Porphyrinatoiron(III) That Mimics the Interaction of a Deazaflavin Inhibitor with the Heme‐Thiolate Cofactor of Cytochrome P450 3A4

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