Self-reproduction of chirality in carbon-carbon bond formation via dipolar intermediates generated in situ by [1,5] hydrogen transfer (original) (raw)
Related papers
2012
There has been a tremendous interest in the study of flavins and their derivatives in order to gain information valuable for designing model compounds that can mimic the functions of flavoenzymes. This thesis aims a) to explore and enhance the knowledge about the behavior of the flavin cofactors in its different redox states b) to further study and develop the mechanism of BLUF domain protein. To achieve a better understanding of flavin behavior, we conducted a comparative study of excited state dynamics of different redox states of flavin cofactors in both aqueous solutions and protein. In this thesis, we present the systematic study of excited-state dynamics of the common flavin molecule: FAD and its fully reduced hydroquinones: FADH2 and FADH- together with its radical semiquinones: FADH● and FAD●- with the visible to mid-IR transient absorption spectroscopy. Ground and excited state frequencies of the characteristic carbonyl modes are observed and assigned with the aid of DFT ca...
Journal of the American Chemical Society, 2016
The spread of the absorbance of the stable FADH • radical (300−700 nm) allows CPD photolyase to highly efficiently form FADH − , making it functional for DNA repair. In this study, FTIR spectroscopy detected a strong hydrogen bond, from FAD N 5 −H to the carbonyl group of the Asn378 side chain, that is modulated by the redox state of FAD. The observed characteristic frequency shifts were reproduced in quantum-mechanical models of the flavin binding site, which were then employed to elucidate redox tuning governed by Asn378. We demonstrate that enhanced hydrogen bonding of the Asn378 side chain with the FADH • radical increases thermodynamic stabilization of the radical state, and further ensures kinetic stabilization and accumulation of the fully reduced FADH − state.
Photochemistry and Photobiology, 1981
The quenching of flavin excited states and the production of radical intermediates by aliphatic a-substituted acetic acids have been investigated using fluorescence and laser photolysis measurements. Stern-Volmer quenching constants for the flavin triplet are 2-4 orders of magnitude smaller than those found previously for aromatic acids. At the high substrate concentrations required to obtain triplet quenching, singlet quenching, probably via exciplex formation, is also observed. When triplet and radical yields are quantitated, it is found that, for pyruvate, glyoxylate and lactate, quenching occurs virtually exclusively by a one-electron transfer mechanism. This supports the contention that the flavin-sensitized photodecarboxylation of these acids proceeds via a radical mechanism.
(Photo)chemistry of 5-deazaflavin. A clue to the mechanism of flavin-dependent (de)hydrogenation
European journal of biochemistry / FEBS, 1979
The catalytic action of 5-deazaflavin in the photochemical reduction of flavin and iron proteins [Massey, V. and Hemmerich, P. (1978) Biochemistry, 17, 9--17] is shown to be due to the highly reactive 5-deazaflavosemiquinone. This radical is generated in a complex sequence of reactions, which involves (a) covalent photoaddition of the substrate residue to the deazaflavin, (b) fast secondary photoreaction of this adduct with starting deazaflavin to yield a covalent radical dimer, accompanied by the liberation of the oxidized substrate, and (c) deazaflavin-sensitized cleavage of the radical dimer to the monomers. The structure and properties of this radical (redimerisation or dismutation) and the precursor intermediates as well as the mechanism of the photoreaction are described. Deazaflavins and their natural parent compounds are compared with respect to their different redox behavior and radical stability. The syntheses of 5-deuterated deazaflavins are described and their redox reac...
Flavins as Organocatalysts for Environmentally Benign Molecular Transformations
Chemical Record, 2007
Recent progress in the development of fl avin-catalyzed oxidations and related reactions is described with respect to scope, limitation, and reaction mechanism. The 4a-hydroperoxyfl avins, which are the most simplifi ed model compounds of fl avoenzymes, act as catalytically active species for the oxidation of organic substrates with the help of H 2 O 2 or O 2 as a mild oxidant. This principle behind the simulation of fl avoenzymes led to the discovery of a variety of environmentally benign, oxidative transformations of secondary amines to nitrones, tertiary amines to N-oxides, sulfi des to sulfoxides, and Baeyer-Villiger oxidations of ketones. Asymmetric oxidation of sulfi des can also be performed with several chiral fl avin catalysts. One of the fortunate outcomes of this study is the development of an environmentally friendly ("green") method for the "aerobic hydrogenation" of olefi ns, which is achieved by in situ generation of diimide with the aid of the fl avin-catalyzed oxidation of hydrazine under an O 2 atmosphere.
The Reduction of Flavins by Borohydride: 3,4-Dihydroflavin. Structure, Absorption and Luminescence
European Journal of Biochemistry, 1969
The reduction of flavins by BH4is slow, but strongly catalyzed by light. The main product of the reaction is 1,5-dihydroflavin, i. e. normal leucoflavin, which is rapidly reoxidized upon admission of air. Under continuous aeration, however, a second reaction, irreversible by oxygen in the dark, becomes dominant yielding a tetrahydroflavin which, upon exhaustive reaction of BH,-, is autoxidized to give a new dihydroflavin of structure I. This compound is stable toward further oxidation in the crystalline state and in solution with organic solvents. Compound I has to be considered as a formal 3,4-dihydroflavin. It is photooxidizable to give starting flavin, reacts very slowly with S,O,compared to flavoquinone (II), but is easily reduced by EDTA in the presence of light. The compound was also synthesized by an unequivocal route and found identical with the product obtained by BH,-reduction of lurniffavin. The light absorption spectrum of I shows absorption maxima a t about 405, 320, 270, and 220 nm and is practically identical with that of the BH,-reduction product of the flavoproteins D-and L-amino acid oxidase. The BH,-reduction products of the amino acid oxidases are catalytically active. From this it follows that position 4 of the flavocoenzyme is not involved in enzymatic dehydrogenation. The first photo-excited triplet state of I has been investigated by optical and electron paramagnetic resonance spectroscopy. The structure of I was elucidated by means of infrared and nuclear magnetic resonance spectroscopy. Although flavins are well known to be ubiquitous redoxcoenzymes, much remains to be investigated in the chemistry of flavin oxido-reduction. It was recently shown by Massey et al. [l] that the flavoproteins D-and L-amiuo acid oxidase are readily reduced by BH,to give a product absorbing a t 410nm. The products thus obtained showed enzymatic activity. Hence the natural redox function of the active group was left undisturbed by the action of BH,-. Therefore, establishment of the chemical background of this reaction is of great enzymological interest. Obviously, action of BH4must result primarily in a hydride-transfer, i. e. two-electron
Tetrahedron: Asymmetry, 2017
A series of chiral non-racemic N 1 ,N 10-ethylene bridged flavinium salts 4 was prepared using enantiomerically pure 2-substituted 2-aminoethanols (R = isopropyl, phenyl, benzyl, 4-methoxybenzyl, 4-benzyloxybenzyl) derived from amino acids as the sole source of chirality. The flavinium salts were shown to form 10a-hydroperoxy-and 10a-methoxy-adducts with moderate to high diastereoselectivity depending on the ethylene bridge substituent originating from the starting amino acid. High diastereoselectivities (dr values from 80:20 to >95:5) were observed for flavinium salts bearing benzyl substituents attached to the ethylene bridge. The benzyl group preferred the face-to-face (syn) orientation relative to the flavinium unit; thereby effectively preventing nucleophilic attack from one side. This conformation was found to be the most stable according to the DFT calculations. Consequently, the presence of benzyl groups causes intermolecular fluorescence quenching resulting in a significant decrease in the fluorescence quantum yield from 11% for 4a bearing an isopropyl substituent to 0.3% for 4c containing a benzyl group and to a value lower than 0.1% for the benzyloxybenzyl derivative 4e.
Photochemistry of Flavothione and Hydroxyflavothiones: Mechanisms and Kinetics¶
Photochemistry and Photobiology, 2003
In this work we present a detailed study of the mechanism of photochemistry and thermal reactions, as well as of the kinetics of flavothione (FLT) in ethanol. Furthermore, we analyzed how the hydroxysubstitution pattern of FLT influenced both the kinetics and the mechanism relative to the parent FLT. We show that the primary photochemical reaction of FLT in the absence of oxygen is hydrogen (H)-atom abstraction from the solvent by way of the excited triplet state of FLT. Several products result from thermal reactions of the resulting semireduced FLTH radical, including more than one dimer. A full mechanism is proposed, and the relevant rate constants are evaluated. On the other hand, in the presence of oxygen and a low concentration of FLT, we found that the principal photoproduct is the parent flavone (FL). The reaction leading to photoxidation is not via 1 O 2 attacking a thione, but instead, it is via a reaction of the FLTH radical with ground state oxygen. The kinetic data also demonstrate that the relative values of concentrations of reactants and the rate constants of the reactions can control the dominance of one mechanism over others. We also have examined the photochemical mechanisms and kinetics for several hydroxyflavothiones (n-OHFLT) and compared them with FLT itself. We have found that the photochemical mechanism radically changes depending on the positions of substitution. These differences are directly related to the ordering of the excited states of the n-OHFLT. Specifically, FLT with lowest 3 n,p* states (FLT, 6-hydroxyflavothione, 7-hydroxyflavothione and 7,8-dihydroxyflavothione) efficiently abstract H atoms to give the semireduced radical of the thione. The radical can (1) dimerize to form two different dimers; (2) react with oxygen to produce the parent FL; and (3) recombine with the solvent radical to yield the original FLT. In contrast, FLT with lowest 3 p,p* states (3-hydroxyflavothione, 3,6-dihydroxyflavothione and 3,7-dihydroxyflavothione) behave as photosensitizers of oxygen to form singlet oxygen, which then reacts with the ground state of the substituted FLT. Finally, when T 2