Calculation of proton transfers in hydrogen bonding interactions with semi-empirical MNDO/H

A method for calculating proton transfer enthalpies by a proper modification of the recent H-bonding version of MNDO is presented. This method perceives the proton as being both “bonded” and “hydrogen bonded” to the two electronegative atoms involved in the hydrogen bond: as it moves from one potential minimum at X-H---Y to the other at X---H-Y, a hydrogen bonding function is attached to the proportion of the distance that is to be traversed. The method is applied to two proton transfers within anionic oxygen H-bonded complexes and is shown to reduce the previously calculated barriers which were too high. Gas phase results for the single step of proton transfer over a barrier are required to evaluate the results obtained by this method.     

Quantum-chemical investigation of the mechanism of nucleophilic addition in the HCNO molecule

Calculations by the MNDO, AM1, and MNDO/M methods were undertaken for the reaction of HCNO and CH₃OH. It was shown that the MNDO and AM1 methods overestimate the activation energy of the reaction involving proton transfer, and this leads to an incorrect conclusion about the mechanism of the process. It was concluded that the reaction of the HCNO molecule with nucleophiles takes place in a single stage by a concerted asynchronous mechanism. The product in the Z configuration is formed as a result of the stereospecific reaction.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 25, No. 6, pp. 719–722, November–December, 1989.     

3-羟基对氧萘酮分子内激发态质子转移反应位能面和机理的研究

用MNDO和INDO-SCF-CI法研究了3-羟基对氧萘酮分子内激发态质子转移反应基态和激发态的位能面,求得相应能垒△E₁、△E₂和荧光移位,并对光化学反应机理进行了探讨.     

Limitations on mndo and mndo/ci computations of activation barriers

The ability of MNDO and MNDO/CI for predicting activation barriers of unimolecular reactions is tested for decompositions of methane, ethane, nitromethane, and methyl nitrite. MNDO is not useful for this purpose; MNDO/CI gives energy barriers in agreement with experiment to about ±10 $\text{kcal}\text{mole}$ for the types of reactions considered.     

Theoretical studies on the acid hydrolysis of methyl carbamate

The mechanism of the A2 acid hydrolysis of methyl carbamate was investigated using MNDO method. The reaction was found to proceed in two steps: (1) the rate-determining nucleophilic attack of water on the carbonyl carbon of the N-protonated tautomer involving the tetrahedral TS; and (2) the fast subsequent proton abstraction by the leaving group, NH₃, to form products. The mechanism is similar to that involved in the A2 hydrolysis of acetamide. Effects of substituents, R¹, R², and R³ in R¹OCONR²R³, on rates can be predicted by the changes in electron densities on alkoxy oxygen and N, in complete agreement with the experimental results. We concluded that there is no need for invoking two different mechanisms for amides and carbamates since a common mechanism can easily accommodate all the experimental results.     

2，4-二硫基胸腺嘧啶的异构化和质子迁移的理论研究

采用密度泛函方法在B3LYP/6-31+G水平上研究了2，4-二硫基胸腺嘧啶孤立分 子和水合物的异构体的相对稳定性和可能的质子迁移反应，分析了水分子的参与对 2，4-二硫基胸腺嘧啶异构体的相对稳定性和质子迁移速率的影响。结果表 明，该分子在气相中只存在一种稳定构型，水分子的参与未改变2，4-二硫基胸腺 嘧啶各异构体的稳定性顺序，但大大降低了质子迁过程的活化能垒。     

Semiempirical study of compounds with O-H?O intramolecular hydrogen bond

Application of MNDO, AM1, PM3, MNDO/H, and MNDO/M methods to a set of compounds with intramolecular hydrogen bonds suggested that none of these methods accurately modeled the characteristics of the hydrogen bonds. Since the MNDO/H and MNDO/M methods work well for intermolecular hydrogen bonds, we followed their example and modified MNDO for intramolecular hydrogen bonds by altering the empirical core–core repulsion energy function for all pairs of atoms involved in intramolecular O-H? O bonds. The resulting modified method models the behavior of these bonds quite well, especially as regards their geometry and the barrier to proton transfer. © 1992 by John Wiley & Sons, Inc.     

A Theoretical Investigation on N7(H)→N9(H)Tautomerization of Isolated and Monohydrated 2,6-Dithiopurine Combined with IPCM Solvent Model

The tautomerization reaction mechanism has been reported between N7(H) and N9(H) of isolated and monohydrated 2,6‐dithiopurine using B3LYP/6‐311+G(d,p). The isodensity polarized continuum model (IPCM) in the self‐consistent reaction field (SCRF) method is employed to account for the solvent effect of water on the tautomerization reaction activation energies. The results show that the two pathways P(1) (via the carbene intermediate I1) and P(2) (via the sp³‐hybrid intermediate I2) are found in intramolecular proton transfer, and each pathway is composed by two primary steps. The calculated activation energy barriers of the rate‐determining steps in isolated 2,6‐dithiopurine N7(H)→N9(H) tautomerism are 308.2 and 220.0 kJ·mol^?1 in the two pathways, respectively. Interestingly, in one‐water molecule catalyst, it dramatically lowers the N7(H)→N9(H) energy barriers by the concerted double proton transfer mechanism in P(1), favoring the formation of 2,6‐dithiopurine N9(H). However, the single proton transfer mechanism assisted with out‐of‐plane water in the first step of P(2) increases the activation energy barrier from 220.0 to 232.3 kJ·mol^?1, while the second step is the out‐of‐plane concerted double proton transfer mechanism, indicating that they will be less preferable for proton transfer. Additionally, the results also show that all the pathways are put into the aqueous solution, and the activation energy barriers have no significant changes. Therefore, the long‐range electrostatic effect of bulk solvent has no significant impact on proton transfer reactions and the interaction with explicit water molecules will significantly influence proton transfer reactions.     

Mechanism of proton exchange with water molecules by NH3 and HF molecules during the formation of ion pairs

The semiempirical quantum-chemical MNDO/VS-PD method has been used to investigate the mechanism of the formation and dissociation of quaternary ammonium salts in aqueous solution. It is shown that dissociation involving proton exchange with the H₂O molecules of the hydration shell has a considerably lower activation barrier than direct proton transfer. The energetic preference for the exchange mechanism arises because the transition state for the synchronous migration of two protons occurs earlier than in the reaction taking place in a single solvent cage.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 817–822, April, 1991.     

A semiempirical study of the reaction of the hemimercaptal of methylglyoxal and glutathione at the active center of glyoxalase I

An AM 1 and MNDO –PM 3 semiempirical study of the reaction mechanism of glyoxalase I is presented. According to some authors, this enzyme serves as a detoxifying agent, transforming ketoaldehydes to hydroxiacids. According to others, however, the enzyme serves as a growth-control agent, destroying 2-oxopropanal (MG), which might be involved in some, mostly unknown, biological pathways. Following a previous study on the conformation of the hemimercaptal of MG and glutathione (HSG) done using molecular mechanics, we study here the possible reaction path of this substrate at a model reaction site in the enzyme. First, the active center of the enzyme was modeled using a Zn²⁺ cation with several ligands. Second, its complex with the hemimercaptal of MG and HSG (SAG) was calculated using semiempirical methods. The reaction proceeds from the substrate to the enediol intermediate in two steps: In the first one, a proton from the activated carbon in SAG is captured by a base–which we model in this work by HO^?, CH3COO^?, and imidazole anion. Our calculations show that the likeliness of the reaction is enhanced if imidazole is used as the base instead of an acid conjugate base or a free hydroxide anion. Moreover, we found a stable intermediate carbanion–described for the first time as an intermediate in this mechanism–whose existence is supported by some of the available experimental evidence. In the second step of the mechanism, a proton is transferred from a Zn-bound water to the intermediate carbanion, giving the enediol species, originally postulated as the intermediate in this mechanism, and leaving a hydroxide anion bound to the Zn²⁺ complex. Comparing this reaction with the same process when no metal complex is present–as if the reaction occurred in aqueous solution–it is shown that the metal ion activates water, facilitating the proton transfer. Our calculations point out the existence of two potential energy barriers to be overcome in the process: the need of the metal center to be coordinated to water as a prerequisite for the second proton transfer to take place, and the fine tuning caused in the first proton transfer by the very nature of the base that initially captures the proton. No significant differences in the qualitative characteristics of the reaction were found in using AM 1 or PM 3 as the method of calculation. © 1992 John Wiley & Sons, Inc.     

Energy barriers of proton transfer reactions between amino acid side chain analogs and water from ab initio calculations

Proton transfer reactions were studied in all titratable pairs of amino acid side chains where, under physiologically reasonable conditions, one amino acid may function as a donor and the other one as an acceptor. Energy barriers for shifting the proton from donor to acceptor atom were calculated by electronic structure methods at the MP2/6-31++G(d,p) level, and the well-known double-well potentials were characterized. The energy difference between both minima can be expressed by a parabola using as argument the donor-acceptor distance R(DA). In this work, the fit parameters of the quadratic expression are determined for each donor-acceptor pair. Moreover, it was found previously that the energy barriers of the reactions can be expressed by an analytical expression depending on the distance between donor and acceptor and the energy difference between donor and acceptor bound states. The validity of this approach is supported by the extensive new data set. This new parameterization of proton transfer barriers between titratable amino acid side chains allows us to very efficiently estimate proton transfer probabilities in molecular modelling studies or during classical molecular dynamics simulation of biomolecular systems.     

A computational study of the reaction of methane with methyl radical

The activation energy and optimized transition-state geometry for the abstraction of a hydrogen atom from methane by methyl radical have been calculated by the semiempirical methods MINDO /3 and MNDO . These results are compared with other semiempirical and ab initio results. The MINDO /3 method, based upon accuracy of the computed energy of activation, appears to be the computational method of greatest reliability. A method of locating the transition state on semiempirical surfaces is demonstrated.     

甲苯-2,4-二异氰酸酯与仲胺类化合物反应中的质子转移过程

采用密度泛函理论B3LYP/6-31+G(d,p)方法研究了甲苯-2,4-二异氰酸酯(2,4-TDI)与仲胺类化合物反应过程中的质子转移效应. 研究发现甲醇分子对反应有显著的催化效应,可使反应能垒大幅降低,这表明含活泼氢的化合物会加速质子转移过程,从而加快反应速率. 2,4-TDI与甲基-N-甲基氨基甲酸酯的催化加成反应为一步反应,其反应过渡态呈六元环结构;而2,4-TDI与N-甲基对硝基苯胺、二苯胺、1,2-二氢-2,2,4-三甲基喹啉等芳香胺类化合物的催化加成反应经历了两步反应,其中第一步为速率控制步骤. 研究表明,在与2,4-TDI的反应中,芳胺化合物的活性高于甲基-N-甲基氨基甲酸酯的活性,计算的反应活性顺序与实验结果一致.     

Reaction of Free Methyl Cation with (Isobutylamino)trimethylsilane in the Gas Phase. A Radiochemical and Quantum-Chemical Study

The reaction of free methyl cation with (isobutylamino)trimethylsilane was studied by the radiochemical method. Like with organic amines and silazane, the reaction occurs by two channels: condensation and proton transfer. Proton transfer remains to be the major reaction channel, while its contribution is less that with amines and silazane. The radiochemical and quantum-chemical methods were used to show that the condensation and proton-transfer complexes decompose primarily via Si-N bond cleavage.     

Energetics of proton transfer in liquid water. I. Ab initio study for origin of many-body interaction and potential energy surfaces

The energetics of proton transfer in liquid water investigated by using ab initio calculation. The molecular electronic interaction of hydrated proton clusters in classified into many-body interaction elements by a new energy decomposition method. It is found that up to three-body molecular interaction is essential to describe the potential energy surface. The three-body effect mainly arises from the (non-classical) charge transfer and strongly depends on their configuration. Higher than three-body effects are small enough to be neglected. To simulate the liquid state reactions, two cluster models including all water molecules up to the second shell in the proton transfer reactions are employed. It is shown that these proton transfer reactions only involve small potential energy barriers of a few kcal/mol or less when structural rearrangement of the solvent is induced along the proton movement.     

Improvement of the hydrogen bonding correction to MNDO for calculations of biochemical interest

Recent suggestions for correcting H? Acceptor interactions within MNDO, together with results of crystallographic analysis, were used to modify this SCF semiempirical calculation for multiple hydrogen bonded associations. Thermodynamic profiles for model systems of biochemical interest such as H₂O? H₂O, hydration of neutral and charged molecules, dimerizations and proton transfers show the advantages of this method. Its treatment of charges, bonding, geometries, energetics and vibrational frequencies is shown to be comparable to ab initio calculations with various basis sets. However, basic MNDO deficiencies and criteria applied for H-bonding result in some too high barriers for proton transfers.     

30-冠-10对生物极性客体的分子识别和分子开关

用AM1,MNDO和PM3方法对30-冠-10与苯衍生物及其生物活性物质脱氧核糖、核糖和呋喃果糖的超分子配合物进行理论研究,得到配合物的稳定化能,结果表明,冠醚对极性客体具有识别作用,尤其对脱氧核糖的识别效果较好。用INDO／SCI方法计算超分子配合物的电子吸收光谱,计算结果表明,配合物的光谱吸收峰与主体相比发生蓝移。探讨了冠醚和间二苯甲酸配合物的分子开关的形成机理。     

The reaction mechanism of the hydroamination of alkenes catalyzed by gold(I)-phosphine: the role of the counterion and the N-nucleophile substituents in the proton-transfer step

The reaction mechanism of the gold(I)-phosphine-catalyzed hydroamination of 1,3-dienes was analyzed by means of density functional methods combined with polarizable continuum models. Several mechanistic pathways for the reaction were considered and evaluated. It was found that the most favorable series of reaction steps include the ligand substitution reaction in the catalytically active Ph3PAuOTf species between the triflate and the substrate, subsequent nucleophile attack of the N-nucleophile (benzyl carbamate) on the activated double bond, which is followed by proton transfer from the NH2 group to the unsaturated carbon atom. The latter step, the most striking one, was analyzed in detail, and a novel pathway involving tautomerization of benzyl carbamate nucleophile assisted by triflate anion acting as a proton shuttle was characterized by the lowest barrier, which is consistent with experimental findings.     

Smooth solvation method for d-orbital semiempirical calculations of biological reactions. 1. Implementation

The present paper describes the extension of a recently developed smooth conductor-like screening model for solvation to a d-orbital semiempirical framework (MNDO/d-SCOSMO) with analytic gradients that can be used for geometry optimizations, transition state searches, and molecular dynamics simulations. The methodology is tested on the potential energy surfaces for separating ions and the dissociative phosphoryl transfer mechanism of methyl phosphate. The convergence behavior of the smooth COSMO method with respect to discretization level is examined and the numerical stability of the energy and gradient are compared to that from conventional COSMO calculations. The present method is further tested in applications to energy minimum and transition state geometry optimizations of neutral and charged metaphosphates, phosphates, and phosphoranes that are models for stationary points in transphosphorylation reaction pathways of enzymes and ribozymes. The results indicate that the smooth COSMO method greatly enhances the stability of quantum mechanical geometry optimization and transition state search calculations that would routinely fail with conventional solvation methods. The present MNDO/d-SCOSMO method has considerable computational advantages over hybrid quantum mechanical/molecular mechanical methods with explicit solvation, and represents a potentially useful tool in the arsenal of multi-scale quantum models used to study biochemical reactions.