OH hydrogen abstraction reactions from alanine and glycine: A quantum mechanical approach

Density functional theory (B3LYP and BHandHLYP) and unrestricted second‐order Møller–Plesset (MP2) calculations have been performed using 3‐21G, 6‐31G(d,p), and 6‐311 G(2d,2p) basis sets, to study the OH hydrogen abstraction reaction from alanine and glycine. The structures of the different stationary points are discussed. Ring‐like structures are found for all the transition states. Reaction profiles are modeled including the formation of prereactive complexes, and very low or negative net energy barriers are obtained depending on the method and on the reacting site. ZPE and thermal corrections to the energy for all the species, and BSSE corrections for B3LYP activation energies are included. A complex mechanism involving the formation of a prereactive complex is proposed, and the rate coefficients for the overall reactions are calculated using classical transition state theory. The predicted values of the rate coefficients are 3.54×10⁸ L?mol^?1?s^?1 for glycine and 1.38×10⁹ L?mol^?1?s^?1 for alanine. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1138–1153, 2001     

Molybdenum-mediated cleavage reactions of isoxazoline rings fused in bicyclic frameworks

The molybdenum-mediated cleavage reactions of isoxazoline rings fused in bicyclic frameworks were investigated. A tandem N-O bond cleavage-retro aldol reaction of an isoxazoline ring fused in a bicyclic framework led to the cleavage of the bicyclic framework. These reactions provide a novel stereoselective synthesis of substituted cyclopentene rings, cyclopentane rings, and attached-ring systems. [reaction: see text]     

Nonadiabatic transitions in chemical reactions: A quantum mechanical study

This work presents an exact quantum mechanical treatment of a reactive three-atom collinear model system incorporating nonadiabatic couplings. It was assumed that nonadiabatic transitions are induced by the vibrational motion only. The main findings are: (i) The reaction process can create conditions in which weak nonadiabatic couplings terms ( for which the Massey parameter was round 10) may cause large probabilities (～0.5) for transitions from one electronic surface to the other. In other words, the reaction process is able in certain cases to create a near resonance situation which makes the non-adiabatic transition almost independent of the magnitude of the coupling term. For this to happen the two surfaces need not be proximate, nor need they “almost” cross along a certain line (ii) In cases where the main nonadiabatic transitions take place outside the interaction region one may, at least qualitatively, decouple the reaction process from the nonadiabatic one. Thus, under the conditions specified one may first treat the reactive system on the ground state surface without including the excited interacting surface and then treat the nonadiabatic process independently.     

Synthesis of fused bicyclic glutarimides

We describe an efficient route towards the synthesis of fused bicyclic glutarimides using facile [3+3] reaction of α-sulfonylacetamides with different α,β-unsaturated esters as the key step. Intramolecular cyclization of 4-substituted 3-sulfonylglutarimide to form 5,6-, 6,6- or 6,7-fused bicyclic glutarimides was accomplished via alkylation, oxidative cyclization or ring-closing metathesis in modest yield.     

Synthesis of fused bicyclic imidazoles by sequential van Leusen/ring-closing metathesis reactions

[reaction: see text]. A new strategy employing the van Leusen three-component reaction and the ring-closing metathesis reaction in a sequential fashion to access fused bicyclic imidazole rings is reported. The two-step sequence generated compounds of significant molecular complexity from simple starting materials in an expedient fashion with excellent yields.     

A novel approach to bicyclic fused cyclopentenone derivatives

A new four-step reaction sequence leading to bicyclic fused cyclopentenone derivatives starting from cyclic ketones has been developed.     

A new strategy for construction of angularly fused tricyclic ring systems. Transannular bond formation of bicyclic enones via photochemical intramolecular hydrogen abstraction

Tricyclic ketones 3a, b and 7a–c having angularly fused 5-6-5 or 5-7-5 ring system have been efficiently prepared by irradiation of bicyclic enones 1 and 2.     

A computational study of the mechanisms of the photoisomerization reactions of monocyclic and bicyclic olefins

The mechanisms of the photochemical isomerization reactions were investigated theoretically using a model system of cyclohexene (1), cycloheptene (2), norbornene (3), and two bicyclic olefins (4 and 5) using the CASSCF (six-electron/six-orbital active space) and MP2-CAS methods with the 6-311(d,p) basis set. The structures of the conical intersections, which play a decisive role in such photoisomerizations, were obtained. The intermediates and transition structures of the ground state were also calculated to assist in providing a qualitative explanation of the reaction pathways. Two photoreaction pathways were examined in the present work. The first can produce a photoproduct with an extra ring. The other can yield a photoproduct with a smaller ring with an external double bond. Both pathways involve cyclic carbene intermediates. Also, our model investigations suggest that both reaction pathways follow a similar photochemical pattern as follows: reactant → Franck-Condon region → conical intersection → cyclic carbene intermediate → transition state → photoproduct. Moreover, these two reaction pathways can compete with each other since the energetics of their conical intersection points are quite similar. Our present theoretical results agree with the available experimental observations.     

A complete quantum mechanical study of chlorine photodissociation

A fully quantum mechanical dynamical calculation on the photodissociation of molecular chlorine is presented. The magnitudes and phases of all the relevant photofragment T-matrices have been calculated, making this study the computational equivalent of a "complete experiment," where all the possible parameters defining an experiment have been determined. The results are used to simulate cross-sections and angular momentum polarization information which may be compared with experimental data. The calculations rigorously confirm the currently accepted mechanism for the UV photodissociation of Cl(2), in which the majority of the products exit on the C(1)Π(1u) state, with non-adiabatic couplings to the A(3)Π(1u) and several other Ω = 1 states, and a small contribution from the B(3)Π state present at longer wavelengths.     

Synthesis of fused bicyclic imidazoles by ring-closing metathesis

The preparation of a number of dienylimidazole via chemoselective metal-halogen exchange and their utility in ring-closing metathesis is described. Essentially all regioisomeric permutations participate in metathesis with the notable exception of 4-vinyl-5-allylimidazoles, provided that the imidazole N3 atom is protonated.     

A stable fused bicyclic disilene as a model for silicon surface

We synthesized the first fused bicyclic disilene 1 representing topologically a partial structure of the Si(001) surface up to the third layer. In the solid state, the five-membered rings adopt the envelope conformation, and the Si=Si double bond in 1 exists in the slightly cis-bent form (bent angle theta is 3.6 degrees ) compared to that of the highly cis-bent dimer on the Si(001) surface. Highly symmetric 1H NMR spectral pattern of 1 remains even at -80 degrees C, indicating the facile ring flipping of the bicyclic skeleton in solution. While syn-adduct was obtained in the reaction of 1 with water, anti-addition of chlorine atoms across the Si=Si double bond in 1 was observed in the reaction with carbon tetrachloride. The structural characteristics of the 9,10-phenanthrenequinone adduct 7 are in good accord with those of the proposed structure of the 9,10-phenanthrenequinone molecule adsorbed on the Si(001) surface.     

State-to-state quantum dynamics of the H + HBr reaction: competition between the abstraction and exchange reactions

Quantum state-to-state dynamics for the H + HBr(υ(i) = 0, j(i) =0) reaction was studied on an accurate ab intio potential energy surface for the electronic ground state of BrH(2). Both the H + HBr → H(2) + Br abstraction reaction and the H' + HBr → H'Br + H exchange reaction were investigated up to a collision energy of 2.0 eV. It was found that the abstraction channel is dominant at lower collision energies, while the exchange channel becomes dominant at higher collision energies. The total integral cross section of the abstraction reaction at a collision energy of 1.6 eV was found to be 1.37 A?(2), which is larger than a recent quantum mechanical result (1.06 A?(2)) and still significantly smaller than the experimental value (3 ± 1 A?(2)). Meanwhile, similar to the previous theoretical study, our calculations also predicted much hotter product rotational state distributions than those from the experimental study. This suggests that further experimental investigations are highly desirable to elucidate the dynamic properties of the title reactions.     

Kinetics and mechanism of the gas‐phase OH hydrogen abstraction reaction from methionine: A quantum mechanical approach

Unrestricted density functional theory (BHandHLYP) calculations have been performed, using the 6‐311G(d,p) basis sets, to study the gas‐phase OH hydrogen abstraction reaction from methionine. The structures of the different stationary points are discussed. Ring‐like structures are found for all the transition states. Reaction profiles are modeled including the formation of prereactive complexes, and negative net activation energy is obtained for the gamma H‐abstraction channel. A complex mechanism is proposed, and the rate coefficients are calculated using transition state theory over the temperature range 250–350 K. The rate coefficients are proposed for the first time and it was found that in gas phase the hydrogen abstraction occurs almost exclusively from the gamma site. The large overall rate coefficient for the methionine + OH reaction compared to other free amino acids could explain the significant role of methionine in the oxidative processes. The following expressions in [L/(mol s)] are obtained for the alpha, beta, and gamma H‐abstraction channels, and for the overall temperature‐dependent rate constants, respectively: k_α = (3.42 ± 0.11) × 10⁸ exp[(?1118 ± 9)/T], k_β = (1.13 ± 0.03) × 10⁸ exp[(?1070 ± 8)/T], k_γ = (2.11 ± 0.26) × 10⁷ exp[(2049 ± 34)/T], and k_tot = (2.12 ± 0.26) × 10⁷ exp[(2047 ± 34)/T]. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 212–221, 2003     

Prediction of the mechanisms of enzyme-catalysed reactions using hybrid quantum mechanical/molecular mechanical methods

The use of hybrid methods, involving both quantum mechanics and molecular mechanics, to model the mechanism of enzyme-catalysed reactions, is discussed. Two alternative approaches to treating the electrostatic interactions between the quantum mechanical and molecular mechanical regions are studied, involving either the inclusion of this term in the electronic Hamiltonian (QM/MM), or evaluating it purely classically (MO + MM). In the latter scheme, possible problems of using force fields that are standard for macromolecular modelling are identified. The use of QM/MM schemes to investigate the mechanism of the enzymes thymidine phosphorylase (ThdPase) and protein tyrosine phosphatase (PTP) is described. For both systems, transition states have been identified using a PM3 Hamiltonian. For ThdPase, concerted motion of the enzyme during the course of the reaction is suggested and, for PTP, a two-step dephosphorylation reaction is indicated, both with quite low barriers.     

Hydrogen atom abstraction reactions of the sugar moiety of 2′‐deoxyguanosine with an OH radical: A quantum chemical study

Mechanisms of hydrogen atom abstraction reactions of the sugar moiety of 2′‐deoxyguanosine with an OH radical were investigated using the B3LYP and BHandHLYP functionals of density functional theory and the second order Møller–Plesset Perturbation (MP2) theory in gas phase and aqueous media. The 6‐31+G* and AUG‐cc‐pVDZ basis sets were used. Gibbs free barrier energies and rate constants of the reactions in aqueous media suggest that an OH radical would abstract the hydrogen atoms of the sugar moiety of 2′‐deoxyguanosine in the following order of preference: H5′ ≈ H5″ > H3′ > H4′ > H1′ ≈ H2′ > H2″, the rate constant for H5′ abstraction being 10³–10⁵ times greater than that for H2″ at the different levels of theory. Relative stabilities of the different deoxyribose radicals are also discussed. The most and least favored hydrogen abstraction reactions found here are in agreement with experimental observation. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Theoretical study of the addition and abstraction reactions of hydroxyl radical with uracil

The addition as well as abstraction reactions of hydroxyl radical (OH) with the nucleic acid base, uracil (U), in the gas phase has been explored at the B3LYP/6-31+G(d,p) level of density functional theory (DFT). The energy barrier of the OH addition to both the C5 and C6 positions of the uracil is less than 1 kcal/mol while the hydrogen abstractions (H-abstractions) from either the N1 or the N3 positions are ∼9.5 kcal/mol. Further the energetics of these reactions are assessed by applying the effect of aqueous medium through the polarizable continuum model (PCM). Both the gas and the solution phase data established that the thermodynamic and kinetic factors are more favorable for the OH addition to either C5 or C6 positions of the uracil than the H-abstraction reactions. Moreover, calculations at the MPW1K/6-31+G(d,p), CCSD(T)/6-31+G(d,p)//B3LYP/6-31+G(d,p) and CCSD(T)/6-31+G(d,p)//MPW1K/6-31+G(d,p) levels of theoretical methods qualitatively supported the B3LYP/6-31+G(d,p) results.     

Diels-Alder reactions of three fused nitrogen-containing bicyclic enones: an efficient method toward novel nitrogen-containing angular tricyclic skeletons

The syntheses of three fused bicyclic enones, including 1,2,6,6a-tetrahydro-1-tosyl-cyclopenta[b]pyrrol-3(5H)-one, 1,2,3,6,7,7a-hexahydro-4H-1-tosyl-cyclopenta[b]pyridin-4-one and 1,2,5,6,7,7a-hexahydro-3H-1-tosyl-indol-3-one, via anionic cyclization and Diels-Alder reactions with various dienes to construct novel nitrogen-containing angular tricyclic skeletons are described.     

Theoretical study of the mechanism of the abstraction reactions of heavy cyclopropenes by alcohol

The potential energy surfaces for the abstraction reactions of heavy cyclopropenes with alcohol have been characterized in detail using density functional theory (B3LYP/LANL2DZdp), including zero-point corrections. Five heavy cyclopropene species including cyclopropene, cyclotrisilene, cyclotrigermene, cyclotritinene, and cyclotrileadene, have been chosen in this work as model reactants. All the interactions involve a hydrogen shift via a two-center transition state. The activation barriers and enthalpies of the reactions were compared in order to determine the relative reactivity of the heavy cyclopropenes. The present theoretical investigations suggest that the relative heavy cyclopropene reactivity increases in the order cyclopropene < cyclotrisilene < cyclotrigermene < cyclotritinene < cyclotrileadene. That is, for alcohol dehydrogenations there is a very clear trend toward lower activation barriers and less endothermic reactions on going from C to Pb. Besides this, our theoretical findings indicate that the final abstraction-addition products should adopt the anti geometry, rather than the syn geometry, from a thermodynamic viewpoint. Furthermore, a configuration mixing model based on the work of Pross and Shaik is used to rationalize the computational results. The results obtained allow a number of predictions to be made.