Photo-induced reduction of flavin mononucleotide in aqueous solutions

The photo-induced reduction of flavin mononucleotide (FMN) in aqueous solutions is studied by absorption spectra measurement under aerobic and anaerobic conditions. Samples without exogenous reducing agent and with the exogenous reducing agents ethylene-diamine-tetraacetic acid (EDTA) and dithiothreitol (DTT) are investigated. Under anaerobic conditions the photo-induced reduction with and without reducing agents is irreversible. Under aerobic conditions the photo-reduction without added reducing agent is small compared to the photo-degradation, and the photo-reduction of FMN by the reducing agents is reversible (re-oxidation in the dark). During photo-excitation of FMN the dissolved oxygen is consumed by singlet oxygen formation and subsequent chemical reaction. After light switch-off slow re-oxidation (slow absorption recovery) occurs due to air in-diffusion from surface. EDTA degradation by FMN excitation leads to oxygen scavenging. The quantum efficiencies of photo-reduction under aerobic and anaerobic conditions are determined. The re-oxidation of reduced FMN under aerobic conditions and due to air injection is investigated.     

Aerobic reduction of olefins by in situ generation of diimide with synthetic flavin catalysts

A versatile reducing agent, diimide, can be generated efficiently by the aerobic oxidation of hydrazine with neutral and cationic synthetic flavin catalysts 1 and 2. This technique provides a convenient and safe method for the aerobic reduction of olefins, which proceeds with 1 equiv of hydrazine under an atmosphere of O(2) or air. The synthetic advantage over the conventional gas-based method has been illustrated through high hydrazine efficiency, easy and safe handling, and characteristic chemoselectivity. Vitamin B(2) derivative 6 acts as a highly practical, robust catalyst for this purpose because of its high availability and recyclability. Association complexes of 1b with dendritic 2,5-bis(acylamino)pyridine 15 exhibit unprecedented catalytic activities, with the reduction of aromatic and hydroxy olefins proceeding significantly faster when a higher-generation dendrimer is used as a host pair for the association catalysts. Contrasting retardation is observed upon similar treatment of non-aromatic or non-hydroxy olefins with the dendrimer catalysts. Control experiments and kinetic studies revealed that these catalytic reactions include two independent, anaerobic and aerobic, processes for the generation of diimide from hydrazine. Positive and negative dendrimer effects on the catalytic reactions have been ascribed to the specific inclusion of hydrazine and olefinic substrates into the enzyme-like reaction cavities of the association complex catalysts.     

All-valence MO study of hydrogen bonding in water

Theoretical hydrogen bond energies and proton barriers for water dimer and trimer calculated by semiempirical all-valence MO methods have been compared. The results of CNDO/2 and INDO calculations are more adequate than those obtained by the MINDO/1 approach.     

A MINDO/3 MO study of oxidized flavins

The use of semi-empirical molecular orbital methods for the study of biologically important molecules has increased in recent years. The validity of well-known approximate Hartree-Fock molecular orbital methods such as MINDO/3 and MNDO still remains largely untested for biological molecules. Here we report its first application to the study of the electronic structures of isoalloxazines. Electronic charge distribution, variation of dipole moment, first ionization potential, electron affinity, orbital energies and electronic transitions are examined. Some of these results are compared with experiments. Good correlations with experiments were generally found in net atomic charge distributions, ionization potentials and electronic transitions. As a result of relatively good correlations with experiment application of the MINDO/3 method for extended study of biologically important coenzymes is promising.     

Theoretical study on the lowest-frequency mode of the flavin ring

The dynamic aspects along the normal vibrational motions of the lowest frequencies in the oxidized, radical, and reduced states of flavin (isoalloxazine) have been studied. In comparison with the twist motions in the oxidized state, the butterfly motions in the radical and reduced states turned out to bring more significant variations to the frontier molecular orbital energies and to the charge distributions on the atoms of the pyrazine ring in isoalloxazine. It can be considered that the electron transfers from and to the isoalloxazine ring can be adjusted or controlled by these variations. In the reduced states the electron release from the molecule, and in the radical states the electron release from or acceptance by the molecule, could be impelled by the butterfly motions, while in the oxidized state the electron acceptance by the molecule could be accelerated slightly by the twist motion. Received: 30 September 1998 / Accepted: 20 January 1999 / Published online: 7 June 1999     

A comparative study of approximate SCF MO treatments of hydrides

A comparative study of approximate and exact ab initio treatments of H₂O, NH₃ and CH₄ has been carried out. Three approximate schemes based on the NDDO approach are introduced. The results compare well with best results obtained by other authors.

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Zusammenfassung Die angenäherte und exakte ab initio Behandlung von H₂O, NH₃ and CH₄ wird verglichen. Drei Verfahren, die auf die NDDO-Näherung zurückgehen, werden eingeführt. Die Resultate sind von vergleichbarer Qualität wie die besten Ergebnisse anderer Autoren.

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The work was partly supported by the Institute of Low Temperatures of the Polish Academy of Sciences, Wrocaw.     

Correlated MO study of the low-barrier intramolecular motions in donor-acceptor ethenes

Correlated MP2 and MCSCF MO calculations of several model push-pull ethenes in most cases indicate no great participation of excited singlet and triplet electronic configurations in either the minima or the transition structures for the suggested facilitated intramolecular rotation about the polarized C=C bond. This situation changes significantly only in molecules with sulfur atoms in the molecule as either donors or acceptors. The outstanding contribution of sulfur atoms as either donors or acceptors is a significant increase of push-pull ethene molecular polarizabilities. Thus, within the studied small series of mostly planar push-pull ethenes, polarizability appears a better indicator of rapid intramolecular motions about the C=C bond than straight polarity. Substituents with larger steric demands around the C=C bond are shown to likely preclude its complete turnaround, thus prompting a ramification of the interpretations of dynamic NMR phenomena in sterically constrained push-pull ethenes as large-amplitude librations resulting from strong rovibrational and relatively weak electronic coupling. These librations, as shown by complete vibrational mode analysis of corresponding rotational transition structures, cover in fact certain sectors of the intuitively suggested full rotations similar to those about C-C single bonds.     

Trinitromethyl anion. An ab initio MO study of its structure

Several conformers of nitroform anion are studied with ab initio MO methods.     

Babysitting flavin for biosynthesis

Enzymes involved in natural product biosynthesis employ a variety of cofactors, reaction mechanisms, and substrate preferences to achieve remarkable chemical diversity found in nature. In this issue of Chemistry & Biology, Goldman and colleagues show how cofactor (FAD) binding affinity impacts the reaction mechanism and outcome of two related proteins, RebC and StaC, involved in indolocarbazoles biosynthesis.     

A lag-phase in the reduction of flavin dependent thymidylate synthase (FDTS) revealed a mechanistic missing link

An unexpected substrate-dependent lag-phase, found in the single turnover reduction of FDTS bound flavin, sheds light on the molecular mechanism of this alternative thymidylate synthase.     

Femtosecond dynamics of flavin cofactor in DNA photolyase: radical reduction, local solvation, and charge recombination

We report here our femtosecond studies of the photoreduction dynamics of the neutral radical flavin (FADH) cofactor in E. coli photolyase, a process converting the inactive form to the biologically active one, a fully reduced deprotonated flavin FADH(-). The observed temporal absorption evolution revealed two initial electron-transfer reactions, occurring in 11 and 42 ps with the neighboring aromatic residues of W382 and F366, respectively. The new transient absorption, observed at 550 nm previously in photolyase, was found from the excited-state neutral radical and is probably caused by strong interactions with the adenine moiety through the flavin U-shaped configuration and the highly polar/charged surrounding residues. The solvation dynamics from the locally ordered water molecules in the active site was observed to occur in approximately 2 ps. These ultrafast ordered-water motions are critical to stabilizing the photoreduction product FADH(-) instantaneously to prevent fast charge recombination. The back electron-transfer reaction was found to occur in approximately 3 ns. This slow process, consistent with ultrafast stabilization of the catalytic cofactor, favors photoreduction in photolyase.     

NDDO MO calculations

The Roby version of the NDDO MO method has been analysed by performing extensive calculations on several molecular systems employing a minimum basis set of STO-3G functions. The effect of using uniform scale factors and those derived from theS-expansion technique, for electron repulsion integrals has also been studied. At the all-electron level, the method, with all its refinements, does not appear promising. The all-valence NDDO MO method after correction byS-expansion, however, yields results which are in good agreement withab initio results. The performance of this scheme is comparable to that of the simplifiedab initio method of Brown and Roby.     

NDDO MO Calculations

Siegbahn's potential model as extended by Ellison et al. is used with density matrix elements calculated by the NDDO/2 procedure, to correlate the K-shell binding energy shifts of C, N and O atoms in a few molecules containing only the first-row atoms. The correlation is not superior to that obtained with the CNDO/2 method when only the monopole term is retained in calculating the Madelung potential energy. However, the results are in excellent agreement with experiment when the two-parameters model including the dipole and quadrupole terms is used.     

NDDO MO calculations

Three valence-only schemes based on the Roby version of NDDO MO theory, which differ only in the core-valence treatment and the choice of the basis set, have been applied to the study of molecules containing first-row atoms. Orbital energies, charge distribution, dipole moments, field gradients, and a few other one-electron molecular properties are calculated to satisfactory accuracy. The schemes appear unreliable in the prediction of barriers to internal rotation in molecules, presumably due to errors in the core contribution to the total energy. An alternative treatment is suggested.     

Ab initio MO study of dipole—dipole interactions in acetonitrile dimers

MO STO-3G ab initio calculations have been carried out for the antiparallel dipole and the head-to-tail dipole model of acetonitrile dimers. The optimized interaction enthalpy is about half of the lowest experimental estimate. The calculated interaction distance for the antiparallel dipole model is very close to the sum of intermolecular radii of N and C; the distance for the head-to-tail model is about 20% higher than the sum of N and H intermolecular radii. The discussion of the interaction in terms of the supermolecule MO's suggests for both models a bonding of mainly electrostatic character. The shortcomings of the STO-3G basis set in dealing with this problem are compared with those reported in the literature. The influence of the basis set on the calculated electron distribution in acetonitrile monomer was examined as a preliminary part of the present study, and is also reported in the paper.     

An ab initio MO study of allene episulfide, cyclopropanethione and thioxyallyl

The electronic structures of allene episulfide, cyclopropanethione and thioxyallyl were examined by ab initio MO calculations and were compared with those of the corresponding oxygen compounds, allene oxide, cyclopropanone and oxyallyl. The difference in reactivities of allene episulfide and allene oxide was also speculatively estimated from the calculated electronic structures. The lowest singlet state of thioxyallyl was predicted to be the B₂ state, which corresponds to the σ, π-diradical. A small activation energy is required for the cyclization of the B₂ state to give allene episulfide. The A₁ singlet state lies 11 kcal mol⁻¹ higher than the B₂ singlet state and undergoes the disrotatory rotation of methylene groups to give cyclopropanethione with no activation energy.     

Analytical MO study of the singlet–triplet coupling in xylylenes

The singlet–triplet energy difference in para-, meta-, and ortho-xylylenes is studied as the interaction of two radical centers through the benzene ring. An SCF perturbative procedure adapted to open-shell systems leads to two benzyl-like nonbonding molecular orbitals (NBMOS ) and to benzene-like occupied and vacant MOS whatever the xylylene isomer. The superposition of these NBMOS in para-, meta-, and ortho-positions and their interaction with the benzene-like MOS lead, at the configuration interaction level, to the following results: The exchange energy (which favors the triplet state) and the charge transfer energy (which favors the singlet state) are important only in the meta-xylylene; the dynamic (or double) spin polarization favors the triplet in meta and the singlet in para and ortho-isomers; the super-exchange energy (which favors the singlet) is important only in para- and ortho-isomers. The above results are independent of the chosen geometry.