The effect of substituting the intra-cyclic sulphur of thionine by oxygen (oxonine) and selenium (selenine) on the intersystem crossing (ISC) efficiency has been studied using high level quantum mechanical methods. The ISC rate constants are considerably increased when going from O towards Se while the fluorescence rate constants remain unchanged. For the three dyes, all accessible ISC channels are driven by vibronic spin-orbit coupling (SOC) between ππ* states. The interplay between the ground and low-lying excited states has been investigated in order to determine the dominant relaxation pathways. In oxonine the relaxation to the ground state after photoexcitation in water proceeds essentially via fluorescence from the S1(πHπL*) bright state (kF = 2.10 × 10(8) s(-1)), in agreement with the high experimental fluorescence quantum yield. In aqueous solution of thionine, the ISC rate constant (kISC ∼ 1 × 10(9) s(-1)) is one order of magnitude higher than fluorescence (kF = 1.66 × 10(8) s(-1)) which is consistent with its high triplet quantum yield observed in water (ϕT = 0.53). Due to a stronger vibronic SOC in selenine, the ISC rate is very high (kISC ∼ 10(10) s(-1)) and much faster than fluorescence (kF = 1.59 × 10(8) s(-1)). This suggests selenine-based dyes as very efficient triplet photosensitizers.

Mo ր ller-Plesset ͑MP2͒ and Becke-3-Lee-Yang-Parr ͑B3LYP͒ calculations have been used to compare the geometrical parameters, hydrogen-bonding properties, vibrational frequencies and relative energies for several X Ϫ and X ϩ hydrogen peroxide complexes. The geometries and interaction energies were corrected for the basis set superposition error ͑BSSE͒ in all the complexes ͑1-5͒, using the full counterpoise method, yielding small BSSE values for the 6-311 ϩG(3d f ,2p) basis set used. The interaction energies calculated ranged from medium to strong hydrogen-bonding systems ͑1-3͒ and strong electrostatic interactions ͑4 and 5͒. The molecular interactions have been characterized using the atoms in molecules theory ͑AIM͒, and by the analysis of the vibrational frequencies. The minima on the BSSE-counterpoise corrected potential-energy surface ͑PES͒ have been determined as described by S. Simón, M. Duran, and J. J. Dannenberg, and the results were compared with the uncorrected PES.

Classical molecular dynamics (MD) simulations and combined quantum mechanics/molecular mechanics (QM/MM) calculations were used to investigate the origin of the enantioselectivity of the Candida antarctica lipase B (CalB) catalyzed O-acetylation of (R,S)-propranolol. The reaction is a two-step process. The initial step is the formation of a reactive acyl enzyme (AcCalB) via a tetrahedral intermediate (TI-1). The stereoselectivity originates from the second step, when AcCalB reacts with the racemic substrate via a second tetrahedral intermediate (TI-2). Reaction barriers for the conversion of (R)- and (S)-propranolol to O-acetylpropranolol were computed for several distinct conformations of TI-2. In QM/MM geometry optimizations and reaction path calculations the QM region was described by density functional theory (B3LYP/TZVP) and the MM region by the CHARMM force field. The QM/MM calculations show that the formation of TI-2 is the rate-determining step. The energy barrier for transformation of (R)-propranolol to O-acetylpropranolol is 4.5 kcal/mol lower than that of the reaction of (S)-propranolol. Enzyme–substrate interactions were identified that play an important role in the enantioselectivity of the reaction. Our QM/MM calculations reproduce and rationalize the experimentally observed enantioselectivity in favor of (R)-propranolol. Furthermore, in contrast to what is commonly suggested for lipase-catalyzed reactions, our results indicate that the tetrahedral intermediate is not a good approximation of the corresponding transition states

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We have carried out a computational study on the reactivity of catechol (1,2-dihydroxybenzene) towards superoxide radical anion (O˙) in water, N,N-dimethylformamide (DMF), pentyl ethanoate (PEA) and vacuum using density functional theory and the coupled cluster method. Five reaction mechanisms were studied: (i) sequential proton transfer followed by hydrogen atom transfer (PT-HT), (ii) sequential hydrogen atom transfer followed by proton transfer (HT-PT), (iii) single electron transfer (SET), (iv) radical adduct formation (RAF) and (v) concerted double proton-transfer electron-transfer (denoted as global reaction, GR). Our results show that catechol and superoxide do not react via a sequential reaction mechanism (initial PT, initial HAT or SET). Instead, the reaction proceeds via a concerted double proton-transfer electron-transfer mechanism yielding hydrogen peroxide and catechol radical anion. The protons are transferred asynchronously between the σ orbitals of the catechol oxygen atoms to superoxide, while the electron is transferred between oxygen π orbitals in the same direction. The calculated rate constants in aqueous media agree with the experimental values reported in the literature. This suggests that the mechanism proposed in this work is adequate to describe this reaction. In addition, our results show that the reaction exhibits a large tunneling effect.

Flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD) are essential flavoprotein cofactors. A riboflavin kinase (RFK) activity catalyzes riboflavin phosphorylation to FMN, which can then be transformed into FAD by an FMN:adenylyltransferase (FMNAT) activity. Two enzymes are responsible for each one of these activities in eukaryotes, whereas prokaryotes have a single bifunctional enzyme, FAD synthase (FADS). FADS folds in two independent modules: the C-terminal with RFK activity and the N-terminal with FMNAT activity. Differences in structure and chemistry for the FMNAT catalysis among prokaryotic and eukaryotic enzymes pointed to the FMNAT activity of prokaryotic FADS as a potential antimicrobial target, making the structural model of the bacterial FMNAT module in complex with substrates relevant to understand the FADS catalytic mechanism and to the discovery of antimicrobial drugs. However, such a crystallographic complex remains elusive. Here, we have used molecular docking and molecular dynamics simulations to generate energetically stable interactions of the FMNAT module of FADS from Corynebacterium ammoniagenes with ATP/Mg and FMN in both the monomeric and dimer-of-trimers assemblies reported for this protein. For the monomer, we have identified the residues that accommodate the reactive phosphates in a conformation compatible with catalysis. Interestingly, for the dimer-of-trimers conformation, we have found that the RFK module negatively influences FMN binding at the interacting FMNAT module. These results agree with calorimetric data of purified samples containing nearly 100% monomer or nearly 100% dimer-of-trimers, indicating that FMN binds to the monomer but not to the dimer-of-trimers. Such observations support regulation of flavin homeostasis by quaternary C. ammoniagenes FADS assemblies.

We have examined the electronic and molecular structure of 1H-phenalen-1-one (phenalenone) in the electronic ground state and in the lowest excited states, as well as intersystem crossing. The electronic structure was calculated using a combination of density functional theory and multi-reference configuration interaction. Intersystem crossing rates were determined using Fermi's golden rule and taking direct and vibronic spin-orbit coupling into account. The required spin-orbit matrix elements were obtained applying a non-empirical spin-orbit mean-field approximation. Our calculated electronic energies are in good agreement with experimental data. We find the lowest excited singlet states to be of the npi* (S1) and pipi* (S2) type. Energetically accessible from S1 are two triplet states of the pipi* (T1) and npi* (T2) type, the latter being nearly degenerate to S1. This ordering of states is retained when the molecular structure in the electronically excited states is relaxed. We expect very efficient intersystem crossing between S1 and T1. Our calculated intersystem crossing rate is approximately 2 x 10(10) s(-1), which is in excellent agreement with the experimental value of 3.45 x 10(10) s(-1). Our estimated phosphorescence and fluorescence rates are many orders of magnitude smaller. Our results are in agreement with the experimentally observed behavior of phenalenone, including the high efficiency of 1O2 production.

A study of the possible intersystem crossing (ISC) mechanisms (S→T) in thionine (3,7-diamino-phenothiazin-5-ium), which is conducive to the efficient population of the triplet manifold, is presented. The radiationless deactivation channels {S(1),S(2)(π → π*) → T(1),T(2)(π → π*)} have been examined. Since the direct ISC does not explain the high triplet quantum yield in this system, attention has been centered on the vibronic spin-orbit coupling between the low-lying singlet and triplet (π → π*) states of interest. An efficient population transfer from the S(1)(π(H) → π(L)*) state to the T(2)(π(H-1) → π(L)*) state via this channel is confirmed. The calculated ISC rate constant for this channel is k(ISC) ≈ 3.35 × 10(8) s(-1), which can compete with the radiative depopulation of the S(1)(π(H) → π(L)*) state via fluorescence (k(F) ≈ 1.66 × 10(8) s(-1)) in a vacuum. The S(1)(π(H) → π(L)*) → T(1)(π(H) → π(L)*) and {S(2)(π(H-1) → π(L)*) → T(1),T(2)(π → π*)} ISC channels have been estimated to be less efficient (k(ISC) ≈ 10(5)-10(6) s(-1)). Based on the computed ISC rate constants and excited-state solvent shifts, it is suggested that the efficient triplet quantum yield of thionine in water is primarily due to the S(1)(π(H) → π(L)*) → T(2)(π(H-1) → π(L)*) channel with a computed rate constant of the order of 10(8)-10(9) s(-1) which is in accord with the experimental finding (k(ISC) = 2.8 × 10(9) s(-1)).