Mechanism of the α,α-diarylprolinol trimethylsilyl ether-catalyzed enantioselective C-C, C-N, C-F, C-S, and C-Br bond forming reactions

Theoretical calculations were employed to investigate the enantioselectivity of the α,α-diarylprolinol trimethylsilyl ether-catalyzed α-functionalization of aldehydes with various different electrophiles, via an enol intermediate. The reactions investigated were (i) Michael-aldol condensation, (ii) Michael addition, (iii) Mannich reaction, (iv) α-amination of an aldehyde, (v) α-fluorination of an aldehyde, (vi) α-sulfenylation of an aldehyde, and (vii) α-bromination of an aldehyde. In all seven cases, our proposed enol mechanism is able to account for the experimentally observed enantioselectivity of the products. Our calculations strongly suggest that these catalyzed reactions proceed via an enol intermediate and not via an enamine intermediate.     

2-巯基苯并咪唑及其类似物互变异构的理论研究

采用B3LYP/6-311G**方法, 计算了2-巯基苯并咪唑及其类似物(2-巯基苯并噁唑、2-巯基苯并噻唑、2-羟基苯并咪唑、2-羟基苯并噁唑、2-羟基苯并噻唑以及2-巯基咪唑、2-巯基噁唑、2-巯基噻唑、2-羟基咪唑、2-羟基噁唑、2-羟基噻唑)的(硫)醇式与(硫)酮式结构进行质子迁移的3种可能途径: (a)分子内质子迁移; (b)水助质子迁移; (c)甲醇助质子迁移．结果表明, 途经b和c所需要的活化能较小, 氢键在降低反应活化能方面起重要作用．采用PCM方法研究了反应体系的溶剂化效应．结果表明孤立分子、一水合物和一甲醇合物的最稳定异构体相同, 都为(硫)酮式, 与气相结论一致．溶剂化效应对异构化能垒的影响较小.     

A Theoretical Study on the Photochromic Mechanism of 1-Phenyl-3-methyl-4-（6-hydro-4-amino-5-sulfo-2,3-pyrazine）-pyrazole-5-one

The photochromic mechanism of 1-phenyl-3-methyl-4-（6-hydro-4-amino-5-sulfo-2,3- pyrazine）-pyrazole-5-one has been investigated using the density functional theory（DFT）. The solvent effect is simulated using the polarizable continuum model（PCM） of the self-consistent reaction field theory. According to the crystal structure of the title compound, an intramolecular proton transfer mechanism from enol to keto form was proposed to interpret its photochromism. Bader＇s atom-in-molecule（AIM） theory is used to investigate the nature of hydrogen bonds and ring structures. Time-dependent density functional theory（TDDFT） calculation results show that the photochromic process from enol to keto form is reasonable. The conformation and molecular orbital analysis of enol and keto forms explain why only intramolecular proton transfer is possible. The results from analyzing the energy and dipole moments of enol form, transition state and keto form in the gas phase and in different solvents have been used to assess the stability of the title compound.     

手性噁唑磷烷-硼烷催化还原苯乙酮对映选择性的理论研究

应用密度泛函理论BHandH/6-31G**计算方法研究新型手性非金属催化剂1,3,2-噁唑磷烷-硼烷催化还原苯乙酮的对映选择性反应机理, 确定了在反应途径上的反应物、络合物、过渡态, 中间体和对映体中间产物. 计算结果表明, 该对映选择性还原反应是两个平行的分步反应, 对映体产物主要是(R)构型. 采用同样的方法研究了对映选择性还原反应在甲苯中的溶剂化效应. SCRF计算显示, 甲苯溶剂不改变反应的机理, 但能降低各驻点的能量和(R)反应的位垒, 有利于催化还原反应朝生成(R)构型中间产物的方向进行.     

Electron stimulated reactions of methyl iodide coadsorbed with amorphous solid water

The electron stimulated reactions of methyl iodide (MeI) adsorbed on and suspended within amorphous solid water (ice) were studied using a combination of postirradiation temperature programmed desorption and reflection absorption infrared spectroscopy. For MeI adsorbed on top of amorphous solid water (ice), electron beam irradiation is responsible for both structural and chemical transformations within the overlayer. Electron stimulated reactions of MeI result principally in the formation of methyl radicals and solvated iodide anions. The cross section for electron stimulated decomposition of MeI is comparable to the gas phase value and is only weakly dependent upon the local environment. For both adsorbed MeI and suspended MeI, reactions of methyl radicals within MeI clusters lead to the formation of ethane, ethyl iodide, and diiodomethane. In contrast, reactions between the products of methyl iodide and water dissociation are responsible for the formation of methanol and carbon dioxide. Methane, formed as a result of reactions between methyl radicals and either parent MeI molecules or hydrogen atoms, is also observed. The product distribution is found to depend on the film's initial chemical composition as well as the electron fluence. Results from this study highlight the similarities in the carbon-containing products formed when monohalomethanes coadsorbed with amorphous solid water are irradiated by either electrons or photons.     

A new method for the preparation of silyl enol ethers from carbonyl compounds and (trimethylsilyl)diazomethane in a regiospecific and highly stereoselective manner

The reaction of lithium (trimethylsilyl)diazomethane with aldehydes and ketones has been investigated, and it has been found that quenching at low temperature with MeOH followed by addition of Rh2(OAc)4 gave silyl enol ethers in high yields. Quenching with other electrophiles (e.g., deuterium, MeI) gave terminal and substituted silyl enol ethers with complete control over regio- and stereochemistry. The mechanism of this novel process has been mapped out through a combination of deuterium labeling, ReactIR, and isolation of reaction intermediates.     

Acid/base catalysis by pure water: the aldol reaction

[reaction: see text] The mechanism of aldol reactions in pure water has been studied with density functional calculations (B3LYP/6-311++G(3d,3p)//B3LYP/6-31G(d)). The reaction is a three-step process that involves: (1) water autoionization generates catalytic hydroxide and hydronium ions, (2) hydroxide and hydronium ions rapidly convert donor aldehyde or ketone into enol, and (3) C-C bond formation and proton transfer occur to give the aldol product. This study provides a general basis for understanding acid/base catalysis by pure water.     

An ab initio study of excited states of guanine in the gas phase and aqueous media: Electronic transitions and mechanism of spectral oscillations

Ground state geometries of the four tautomeric forms keto‐N9H, keto‐N7H, enol‐N9H, and enol‐N7H of guanine were optimized in the gas phase at the RHF level using a mixed basis set consisting of the 4‐31G basis set for all the atoms except the nitrogen atom of the amino group for which the 6‐311+G* basis set was used. These calculations were also extended to hydrogen‐bonded complexes of three water molecules with each of the keto‐N9H (G9‐3W) and keto‐N7H (G7‐3W) forms of guanine. Relative stabilities of the four above‐mentioned tautomers of guanine as well as those of G9‐3W and G7‐3W complexes in the ground state in the gas phase were studied employing the MP2 correlation correction. In aqueous solution, relative stabilities of these systems were studied using the MP2 correlation correction and polarized continuum model (PCM) or the isodensity surface polarized continuum model (IPCM) of the self‐consistent reaction field (SCRF) theory. Geometry optimization in the gas phase at the RHF level using the 6‐31+G* basis set for all atoms and the solvation calculations in water at the MP2 level using the same basis set were also carried out for the nonplanar keto‐N9H and keto‐N7H forms of guanine. Thus, it is shown that among the different tautomers of guanine, the keto‐N7H form is most stable in the gas phase, while the keto‐N9H form is most stable in aqueous solution. It appears that both the keto‐N9H and keto‐N7H forms of guanine would be present in the ground state, particularly near the aqueous solution–air interface. Vertical excitation and excited state geometry optimization calculations were performed using configuration interaction involving single electron excitation (CIS). It is found that the absorption spectrum of guanine would arise mainly due to its keto‐N9H form but the keto‐N7H form of the same would also make some contribution to it. The enol‐N9H and enol‐N7H forms of the molecule are not expected to occur in appreciable abundance in the gas phase or aqueous media. The normal fluorescence spectrum of guanine in aqueous solution with a peak near 332 nm seems to originate from the lowest singlet excited state of the keto‐N7H form of the molecule while the fluorescence of oxygen‐rich aqueous solutions of guanine with a peak near 450 nm appears to originate from the lowest singlet excited state of the keto‐N9H form of the molecule. The origin of the slow damped spectral oscillation observed in the absorption spectrum of guanine has been explained. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 826–846, 2000     

Excited state properties of 7-hydroxy-4-methylcoumarin in the gas phase and in solution. A theoretical study

TDDFT/B3LYP and RI-CC2 calculations with different basis sets have been performed for vertical and adiabatic excitations and emission properties of the lowest singlet states for the neutral (enol and keto), protonated and deprotonated forms of 7-hydroxy-4-methylcoumarin (7H4MC) in the gas phase and in solution. The effect of 7H4MC-solvent (water) interactions on the lowest excited and fluorescence states were computed using the Polarizable Continuum Method (PCM), 7H4MC-water clusters and a combination of both approaches. The calculations revealed that in aqueous solution the pi pi* energy is the lowest one for excitation and fluorescence transitions of all forms of 7H4MC studied. The calculated excitation and fluorescence energies in aqueous solution are in good agreement with experiment. It was found that, depending on the polarity of the medium, the solvent shifts vary, leading to a change in the character of the lowest excitation and fluorescence transition. The dipole-moment and electron-density changes of the excited states relative to the ground state correlate with the solvation effect on the singlet excited states and on transition energies, respectively. The calculations show that, in contrast to the ground state, the keto form has a lower energy in the pi pi* state as compared to enol, demonstrating from this point of view the energetic possibility of proton transfer from the enol to the keto form in the excited state.     

Theoretical investigation of the electrochemical mechanism of water splitting on a titanium oxide cluster model

The step-by-step electrochemical mechanism of water splitting by removal of protons and electrons is examined for the reaction of one and two water molecules on a Ti(2)O(4) cluster. Density functional theory (B3LYP) and coupled cluster single point calculations are employed to compute gas phase reaction energies. The polarizable continuum model (PCM) is utilized to calculate energies in the aqueous phase. Both neutral and alkaline media are considered. Proton and electron removal steps are generally found to be highly endothermic, with the exception of proton removal steps in alkaline medium. The effect of an external potential on reaction energies is considered. Oxygen-oxygen bonds form after the removal of only two electrons.     

Ter-body intermediates in the gas phase: reaction of ionized enols with tert-butanol

In the gas phase, the CH2CHOH.+ enol radical cation 1 as well as its higher homologues CH3CHCHOH.+ 2 and (CH3)2CCHOH.+ 3, undergo exactly the same sequence of reactions with tert-butanol, leading to the losses of isobutene, water and water plus alkene. Fourier transform ion cyclotron resonance (FT-ICR) experiments using labeled reactants as well as ab initio calculations show that independent pathways can be proposed to explain the observed reactivity. For ion 1, taken as the simplest model, the first step of the reaction is formation of a proton bound complex which gives, by a simple exothermic proton transfer, the ter-body intermediate [CH2CHO., H2O, C(CH3)3+]. This complex, which was shown to possess a significant lifetime, is the key intermediate which undergoes three reactions. First, it can collapse to yield tert-butylvinyl ether with elimination of water. Second, by a regiospecific proton transfer, this complex can isomerize into three different ter-body complexes formed of water, isobutene and ionized enol. Within one of these complexes, which does not interconvert with the others, elimination of isobutene leads to the formation of a solvated enol ion. Within the others, a cycloaddition-cycloreversion process can proceed to yield the ionized enol 3 (loss of water and ethylene channel).     

Density functional study on the reaction mechanism of proton transfer in 2-pyridone: effect of hydration and self-association

The proton-transfer mechanism in the isolated, mono, dehydrated forms and dimers of 2-pyridone and the effect of hydration or self-assistance on the transition state structures corresponding to proton transfer from the keto form to the enol form have been investigated using B3LYP and BH-LYP hybrid density functional methods at the 6-311++G (2d, 2p) basis set level. The barrier heights for both H2O-assisted and self-assisted reactions are significantly lower than that of the bare tautomerization reaction from 2-pyridone to 2-hydroxypyridine, implying the importance of the superior catalytic effect of H2O and (H2O)2 and the important role of 2-pyridone itself for the intramolecular proton transfer. Long-range solvent effects have also been taken into account by using the continuum model (Onsager model and polarizable continuum model (PCM)) of water. The tautomerization energies and the potential energy barriers are increased both for the water-assisted and for the self-assisted reaction because of the bulk solvent, which imply that the tautomerization of PY becomes less favorable in the polar solvent.     

H2O3 as a reactive oxygen species: formation of 8-oxoguanine from its reaction with guanine

Reaction of guanine with H2O3 in the absence and presence of a water molecule leading to the formation of 8-oxoguanine (8-oxoG) was investigated. Initial calculations were performed using imidazole (Im) as a model for the five-membered ring of guanine. The reactant, intermediate, and product complexes as well as transition states were obtained in gas phase at the B3LYP/6-31+G* and B3LYP/AUG-cc-pVDZ levels of theory. In all the cases, except for the reactions involving imidazole, single-point energy calculations were performed in gas phase at the MP2/AUG-cc-pVDZ level of theory. Solvation calculations in aqueous media were carried out using the polarizable continuum model (PCM) of the self-consistent reaction field (SCRF) theory. Vibrational frequency analysis and intrinsic reaction coordinate (IRC) calculations were performed to ensure that the transition states connected the reactant and product complexes properly. Zero-point energy (ZPE)-corrected total energies and Gibbs free energies at 298.15 K in gas phase and aqueous media were obtained. When a reaction of H2O3 in place of H2O2 with guanine is considered, the major barrier energy which is encountered at the first step is almost halved showing that H2O3 would be much more reactive than H2O2. Considering the reaction schemes investigated here and the observed fact that H2O3 is dissociated easily under ambient conditions, it appears that H2O3 would serve as an effective reactive oxygen species.     

Methylation of tin(II) by methyl iodide: influences of different environmental factors on the efficiency and reaction kinetics

The methylation reaction of Sn(II) with methyl iodide (MeI) in water has been studied using sensitive GC-QSIL-FPD technology. The pH value, amount of MeI and salinity (S) are the three important factors that influence the methylation reaction in an aquatic environment. In all experiments, monomethyltin (MMT) is the only methylation product of the tin(II) reacting with MeI observed. At the 95% confidence level, the pH, MeI and S are significant for the MMT yield. The concentration of MMT in the reactor increases with increase in pH within the selected pH range of 4–9 because four different species of Sn(II)–Sn²⁺, SnOH⁺, Sn(OH)₂⁰ and Sn(OH)₃⁻–have different reaction activities with MeI. The methylation activity of Sn(II) was found to be highest at a salinity of 0.1 M at three different pH levels: 5, 7 and 9. Higher concentration of Cl⁻ (as a relatively weak nucleophilic ion) will obstruct nucleophilic attack of Sn(II) on MeI. MMT production also increases with rising volume of MeI. Moreover, first-order reaction rates have been calculated at different pH, salinity and MeI, and found to be in the range 0.0018–0.0199 h⁻¹. The reaction rate also varies largely under different reaction conditions. One probable mechanism for the methylation reaction of Sn(II) with MeI is a S_N2 nucleophilic attack on the methyl group of MeI by Sn(II), via a process of oxidative methyl-transfer. Copyright © 2006 John Wiley & Sons, Ltd.     

Nucleophilic attack on phosphate diesters: a density functional study of in-line reactivity in dianionic, monoanionic, and neutral systems

A density functional study of the hydrolysis reaction of phosphodiesters with a series of attacking nucleophiles in the gas phase and in solution is presented. The nucleophiles HOH, HO-, CH3OH, and CH3O- were studied in reactions with ethylene phosphate, 2'3'-ribose cyclic phosphate and in their neutral (protonated) and monoanionic forms. Stationary-point geometries for the reactions were determined at the density functional B3LYP/6-31++G(d,p) level followed by energy refinement at the B3LYP/6-311++G(3df,2p) level. Solvation effects were estimated by using a dielectric approximation with the polarizable continuum model (PCM) at the gas-phase optimized geometries. This series of reactions characterizes factors that influence the intrinsic reactivity of the model phosphate compounds, including the effect of nucleophile, protonation state, cyclic structure, and solvent. The present study of the in-line mechanism for phosphodiester hydrolysis, a reaction of considerable biological importance, has implications for enzymatic mechanisms. The analysis generally supports the associative mechanism for phosphate ester hydrolysis. The results highlight the importance for the reaction barrier of charge neutralization resulting from the protonation of the nonbridging phosphoryl oxygens and the role of internal hydrogen transfer in the gas-phase mechanism. It also shows that solvent stabilization has a profound influence on the relative barrier heights for the dianionic, monoanionic, and neutral reactions. The calculations provide a comprehensive data set for the in-line hydrolysis mechanisms that can be used for the development of improved semiempirical quantum models for phosphate hydrolysis reactions.     

Formation of 8-nitroguanine and 8-oxoguanine due to reactions of peroxynitrite with guanine

Reactions of peroxynitrite with guanine were investigated using density functional theory (B3LYP) employing 6-31G** and AUG-cc-pVDZ basis sets. Single point energy calculations were performed at the MP2/AUG-cc-pVDZ level. Genuineness of the calculated transition states (TS) was tested by visually examining the vibrational modes corresponding to the imaginary vibrational frequencies and applying the criterion that the TS properly connected the reactant and product complexes (PC). Genuineness of all the calculated TS was further ensured by intrinsic reaction coordinate (IRC) calculations. Effects of aqueous media were investigated by solvating all the species involved in the reactions using the polarizable continuum model (PCM). The calculations reveal that the most stable nitro-product complex involving the anion of 8-nitroguanine and a water molecule i.e. 8NO(2)G(-) + H(2)O can be formed according to one reaction mechanism while there are two possible reaction mechanisms for the formation of the oxo-product complex involving 8-oxoguanine and anion of the NO(2) group i.e. 8OG + NO(2)(-). The calculated relative stabilities of the PC, barrier energies of the reactions and the corresponding enthalpy changes suggest that formation of the complex 8OG + NO(2)(-) would be somewhat preferred over that of the complex 8NO(2)G(-) + H(2)O. The possible biological implications of this result are discussed.     

Ring-opening reactions of cyclic acetals and 1,3-oxazolidines with halosilane equivalents

Reactions of acetal and 1,3-oxazolidine rings were examined using two kinds of iodosilane equivalent reagents, a 1:2 mixture of Me3SiNEt2 and MeI (reagent 1a) and a 1:1 mixture of Et3SiH and MeI containing a catalytic amount of PdCl2 (reagent 1b). In the reactions of alkanone ethylene acetals with reagent 1a, a C-O bond in the acetal ring readily cleaved to give 2-(trimethylsiloxy)ethyl enol ethers. Similarly, the C-O bond of 1,3-oxazolidine rings cleaved to give ring-opened imine or enamine derivatives. The reactions of aromatic ketone ethylene acetals and cyclohexanone trimethylene acetal led to deprotection of the acetal unit to liberate free ketones. With reagent 1b, cycloalkanone ethylene acetal afforded a dimeric product with 2-iodoethyl alkenoate moieties, while aromatic ketone ethylene or trimethylene acetals produced deprotected ketones.     

The Effect of Solvation on the Radiation Damage Rate Constants for Adenine

It is well known that water plays an important part in almost all biological systems and that inclusion of solvation effects might therefore be of utmost importance in studies of radiation damage to DNA. In the present investigation, we have studied the effect of different solvation models in calculations of Gibbs free energies and reaction rates for the reaction between the OH radical and the DNA nucleobase adenine by conducting density functional theory calculations at the ωB97X‐D/6‐311++G(2df,2pd) level with the Eckart tunnelling correction. The solvent, water, was included through either the implicit polarizable continuum model (PCM) or through explicit modelling of micro‐solvation by a single water molecule at the site of reaction as well as by the combination of both. Scrutiny of the thermodynamics and kinetics of the individual sub‐reactions suggests that the qualitative differences introduced by the solvation models do not significantly alter the conclusions made based solely on simple gas‐phase calculations. Abstraction of the amine hydrogen atoms H₆₁ and H₆₂ and addition onto C₈ remain the most likely reaction pathways.     

A theoretical and spectroscopic study of conformational structures of piroxicam

Piroxicam (PRX) has been widely studied in an attempt to elucidate the causes and mechanisms of its side effects, mainly the photo-toxicity. In this paper fluorescence spectra in non-protic solvents and different polarities were carried out along with theoretical calculations. Preliminary potential surfaces of the keto and enol forms were obtained at AM1 level of theory providing the most stable conformers, which had their structure re-optimized through the B3LYP/CEP-31G(d,p) method. From the optimized structures, the electronic spectra were calculated using the TD-DFT method in vacuum and including the solvent effect through the PCM method and a single water molecule near PRX. A new potential surface was constructed to the enol tautomer at DFT level and the most stable conformers were submitted to the QST2 calculations. The experimental data showed that in apolar media, the solution fluorescence is raised. Based on conformational analysis for the two tautomers, keto and enol, the results indicated that the PRX-enol is the main tautomer related to the drug fluorescence, which is reinforced by the spectra results, as well as the interconvertion barrier obtained from the QST2 calculations. The results suggest that the PRX one of the enol conformers presents great possibility of involvement in the photo-toxicity mechanisms.     

Molecular and computational structure characterizations of (E)-2-ethoxy-6-[(4-fluorophenylimino)methyl]phenol

The (E)-2-ethoxy-6-[(4-fluorophenylimino)methyl]phenol compound was synthesized and characterized by X-ray Diffraction, IR and Electronic spectroscopy. X-Ray and IR results showed that the title compound preferred the enol form in solid state. UV-Vis absorption spectra of the title compound were recorded in different solvents. The results showed that the molecule existed only in enol form even in the solvent media. Electronic structure and spectroscopic properties of the title compound were investigated from calculative point of view. The gas phase geometry optimization was obtained based on X-ray geometry by DFT method with B3LYP applying 6-311G(d,p) basis set. Geometry optimizations in the solvent media were obtained with the same level of theory by the polarizable continuum model (PCM). TD-DFT calculations starting from the optimized geometry were made in both gas and solution phase to measure the excitation energies of enol and keto tautomers. Vibrational frequency and natural bond orbital analysis (NBO) were performed and the thermodynamic properties of the title compound were obtained at the optimized geometry with the same level of theory.