Integrated Molecular Orbital+molecular Orbital Research Articles

Factors Governing Electron Capture by Small Disulfide Loops in Two-Cysteine Peptides

Integrated molecular orbital-molecular orbital (IMOMO) calculations on 17 short disulfide-bridged peptides (up to 16 residues, with at most five intraloop residues) were performed to elucidate some factors controlling their electron capture. These illustrative systems display contrasted behaviors, shedding light on several criteria of differentiation: size, shape, and rigidity of the disulfide-linking loop, intramolecular hydrogen bonds, etc. The geometrical malleability of disulfide radical anions, whose existence and role as intermediate have been evidenced, is discussed. The disulfide elongation (by ca. 0.7 A) upon electron capture induces "soft" structural damages for these turn structures, with a weakening or cleavage of vicinal hydrogen bond(s). On the basis of a series of six Cys-Alan-Cys peptides, it is proposed that electron affinity reflects the topological frustration of these short and highly constrained structures. Results for a series of amino acid mutations are analyzed for the Cys-Xxx-Yyy-Cys motif, common to redox enzymes of the thioredoxin superfamily.

Modified Carbon Pseudopotential for Use in ONIOM Calculations of Alkyl-Substituted Metallocenes

Nonrelativistic carbon 1s core pseudopotentials are optimized for substituted cyclopentadienide ring carbons for use in integrated molecular orbital molecular orbital (IMOMO) and integrated molecular orbital molecular mechanics (IMOMM) calculations where the Cp ring substituents are not included in the high-level IMOMO or IMOMM subsystem. Use of the optimized pseudopotential within the IMOMO framework leads to significant improvements in predicted carbonyl stretching frequencies for a series of Cp-ring-methylated zirconocenes compared to using a standard carbon pseudopotential. The technology is less successful in the IMOMM implementation.

DFT and ab initio calculations on two reactions between hydrogen atoms and the fire suppressants 2‐H heptafluoropropane and CF3Br

Reaction enthalpies and barrier heights of the reactions CF3Br+H-->CF3+HBr {reaction (1)} and CF3CHFCF3+H-->CF3CFCF3+H2 {reaction (2)} have been calculated at the near state-of-the-art ab initio level, and also by employing the B3LYP, BH&HLYP, BB1K, MPW1K, MPWB1K and TPSS1KCIS functionals. In addition, the integrated molecular orbital+molecular orbital (IMOMO) method has been used to study reaction (2). The ab initio benchmark values of the reaction enthalpy (298 K) and barrier height (0 K) of reaction (2) are reported for the first time {-(0.7+/-0.7) and 13.3+/-0.5 kcal/mole respectively}. When density functional theory (DFT) results are compared with ab initio benchmarks for both reactions (1) and (2), the MPWB1K functional is found to have the best performance of the six functionals used. The IMOMO method with the RCCSD/aug-cc-pVTZ and/or RCCSD(T)/aug-cc-pVTZ levels, as the high levels of calculation on the model system, gives reaction enthalpies and barrier heights of reaction (2), which agree with ab initio benchmark values to within 1 kcal/mole. Computed key geometrical parameters and imaginary vibrational frequencies of the transition state structures of reactions (1) and (2) obtained at different levels of calculation are compared. The magnitudes of the computed imaginary vibrational frequencies of the transition states of both reactions considered are found to be very sensitive to the levels of calculation used to obtain them. The heat of formation (298 K) of CF3CFCF3 calculated at the near state-of-the-art level has a value of -(318+/-3) kcal/mole.

Selenocysteine versus Cysteine Reactivity: A Theoretical Study of Their Oxidation by Hydrogen Peroxide

The cysteine and selenocysteine oxidation by H2O2 in vacuo and in aqueous solution was studied using the integrated molecular orbital + molecular orbital (IMOMO) method combining the quadratic configuration method QCISD(T) and the spin projection of second-order perturbation theory PMP2. It is shown that including in the model system of cysteine (selenocysteine) residue up to 20 atoms has significant consequences upon the calculated reaction energy barrier. On the other hand, it is demonstrated that free cysteine and selenocysteine have very similar reaction energy barriers, 77-79 kJ mol(-1) in aqueous solution. It is thus concluded that the high experimental reaction rate constant reported for the oxidation of the selenocysteine residue in the glutathione peroxidase (GPx) active center is due to an important interaction between selenocysteine and its molecular environment. The sensitivity of the calculated energy barrier to the dielectric constant of the molecular environment observed for both cysteine and selenocysteine as well as the catalytic effect of the NH group emphasized in the case of cysteine supports this hypothesis.

Mechanism of Cysteine Oxidation by a Hydroxyl Radical: A Theoretical Study

Cysteine oxidation by HO(.) was studied at a high level of ab initio theory in both gas phase and aqueous solution. Potential energy surface scans in the gas phase performed for the model system methanethiol+HO(.) indicate that the reactants can form two intermediate states: a sulfur-oxygen adduct and a hydrogen bound reactant complex. However these states appear to play a minor role in the reaction mechanism as long as they are fast dissociating states. Thus the main reaction channel predicted at the QCISD(T)/6-311+G(2df,2pd) level of theory is the direct hydrogen atom abstraction. The reaction mechanism is not perturbed by solvation which was found to induce only small variations in the Gibbs free energy of different reactant configurations. The larger size reactant system cysteine+HO* was treated by the integrated molecular orbital+molecular orbital (IMOMO) hybrid method mixing the QCISD(T)/6-311+G(2df,2pd) and the UMP2/6-311+G(d,p) levels of theory. The calculated potential energy, enthalpy, and Gibbs free energy barriers are slightly different from those of methanethiol. The method gave a rate constant for cysteine oxidation in aqueous solution, k=2.4 x 10(9) mol(-1) dm(3) s(-1), which is in good agreement with the experimental rate constant. Further analysis showed that the reaction is not very sensitive to hydrogen bonding and electrical polarity of the molecular environment.

DFT and ab initio calculations on the reaction between fluorine atoms and the fire suppressant, 2-H heptafluoropropane

Benchmark values for the reaction enthalpy (298 K) and the barrier height (0 K) of the reaction, CF 3CHFCF 3 + F → CF 3CFCF 3 + HF, have been calculated at state-of-the-art ab initio level to be −34.7 ± 1.0 and −0.9 ± 0.9 kcal/mole, respectively. The B3LYP, BH&HLYP, BB1K, MPW1K, MPWB1K and TPSS1KCIS functionals and the model method, the integrated molecular orbital + molecular orbital (IMOMO) method, have also been used to study this reaction.

An Integrated Molecular Orbital + Molecular Orbital (IMOMO) Study of the O + H−R → OH + R• Reaction Class

We investigate the O + H−R → OH + R• reaction class by employing the integrated molecular orbital + molecular orbital (IMOMO) methodology. The QCISD(T), MP4, and MP2 methods are employed as the high-level theories in the IMOMO method based on the geometries optimized at the BH&HLYP and MPW1K methods. The results show that the energies predicted from both QCISD(T) and MP4 calculations can reasonably be reproduced by the IMOMO method. In particular, the IMOMO method yields the mean absolute deviation of about 1 kcal/mol in reaction energies and less than 0.4 kcal/mol in classical barrier heights. The predicted thermal rate constants are in good agreement with the available experimental data. This approach has been further proven to be powerful tools for studying reactions involving large molecular systems.

On the application of the IMOMO (integrated molecular orbital + molecular orbital) method

On the application of the IMOMO (integrated molecular orbital + molecular orbital) method

On the application of the IMOMO (integrated molecular orbital + molecular orbital) method

Five years ago Morokuma and colleagues introduced the IMOMO method, which integrates two molecular orbital methods into one calculation. Since then, the method has been expanded in several ways; it has been generalized to consider up to three methods, and has been unified as the ONIOM method to include both MO and MM combinations. In this review we present the history of the method, a number of chemical problems that we have studied, how to assess IMOMO combinations and partitionings, and our latest efforts that take the method beyond the conventional investigation of ground state energy surfaces. In particular, we emphasize the importance of the S-value test for validation of the ONIOM method/model combinations. The method combination depends much on the properties and accuracies required. Generally speaking, however, if the target level is CCSD(T) or G2, the best choice of low level is MP2. If MP2 or DFT is the target level, HF or eventually semiempirical MO methods are good choices of low level. These methods can be further combined with an outer-most layer of the MM level. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 1419–1432, 2000

A combined reaction class approach with integrated molecular orbital+molecular orbital (IMOMO) methodology: A practical tool for kinetic modeling

We present a new practical computational methodology for predicting thermal rate constants of reactions involving large molecules or a large number of elementary reactions in the same class. This methodology combines the integrated molecular orbital+molecular orbital (IMOMO) approach with our recently proposed reaction class models for tunneling. With the new methodology, we show that it is possible to significantly reduce the computational cost by several orders of magnitude while compromising the accuracy in the predicted rate constants by less than 40% over a wide range of temperatures. Another important result is that the computational cost increases only slightly as the system size increases.

The accurate calculation and prediction of the bond dissociation energies in a series of hydrocarbons using the IMOMO (integrated molecular orbital+molecular orbital) methods

The IMOMO (integrated molecular orbital+molecular orbital) method was used to accurately calculate and compare with the experiment for the single-bond C–H and C–C bond dissociation energies of a series of hydrocarbons, R1−R2→R1+R2, where R1 is H or CH3, while the largest R2 considered is 1,1-diphenylethyl, C(C6H5)2(CH3). While the geometries and zero point vibrational energies were obtained at the hybrid density function (B3LYP/6-31G) level for the real system, a small system, H–CH3 or CH3–CH3, was used as the “model” in the IMOMO energy calculation, for which a high level method is used. Of a large number of IMOMO combinations tested, the combination of the modified Gaussian-2 method (G2MSr) with the restricted open-shell second-order Møller–Plesset perturbation method (ROMP2), the IMOMO(G2MSr:ROMP2/6-31G(d)) method, yields the best results, and can be used for bond dissociation energy predictions of very large molecules. Finally, the IMOMO(G2MSr:ROMP2/6-31G(d)) method was used to predict the C–H bond dissociation energy in H–C(C6H5)3 and the C–C bond dissociation energy in CH3–C(C6H5)3, neither of which is available experimentally. These predicted values are 75.9 and 64.1 kcal/mol, respectively, which are smaller than any other C–H and C–CH3 BDE studied in this paper.

Integrated molecular orbital+molecular orbital (IMOMO) treatment of single electron transfer (SET) via a two-center three-electron (2c–3e) bonded complex: substituted carbonyl–ammonia example

Abstract An application of the `IMOMO' method is presented on single electron transfer (SET) via two-center three-electron (2c–3e) bonded complexes. The IMOMO method allows one to calculate locally the correlation effects and saves much computational time on the calculation of substituent effects. This work concerns the ability of a carbonyl to form a 2c–3e stable complex with the ammonia radical cation. The stability of this intermediate is found to be ca. 30 kcal/mol. Three substituents are studied here for these R–HCO systems: R=CH3, NH2, C2H3 (vinyl substituent). The choice of these substituents was made in order to study different kinds of electronic effects (σ, π donating effects) from the outer part to the model. In some cases, quite important spin contamination was encountered. The IMOMO scheme is found to be an interesting tool in spin contaminated cases. In these cases the coupled cluster method should be chosen instead of the heavily spin contaminated MP4 calculations. The IMOMO method reproduces the coupled cluster method results for a significantly smaller computational effort. For the low level, projected methods such as PUHF or PMP2 are then required. The accuracy of the integrated level (CCSD:PMP2) is estimated to be ca. 1 kcal/mol from the high level benchmark calculations (CCSD). Using PUHF as the low level may lead to results differing from the benchmark by ca. 3 kcal/mol.

Multiple cluster model (MCM) for surface reaction systems

Multiple cluster model (MCM) for investigating surface reactions is formulated. In this model the reaction center, where electron correlation effects often play a key role, is described by an accurate high-level approximation, and bulk effects such as the lattice distortion energy are evaluated using a simple low-level approximation. Therefore, the MCM can properly simulate the potential energy hypersurface of the surface reaction system with a feasible computational cost. Since there exists no fixed atom in the MCM, we can rigorously characterize the stationary point (the minimum energy point or the transition state) on the potential energy hypersurface by vibrational frequency analysis. The MCM can be applied not only to surface systems, but also to various large systems. A detailed comparison of the MCM with the integrated molecular orbital+molecular mechanics (IMOMM), the integrated molecular orbital+molecular orbital (IMOMO), and ONIOM developed by Morokuma and co-workers is also presented. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 71: 403–413, 1999

Systematic Analysis of Bond Energies Calculated by the Integrated Molecular Orbital−Molecular Orbital Method

This paper tests the ability of the integrated molecular orbital−molecular orbital (IMOMO) method to include the effects of extended basis sets and higher-order electron correlation on bond energies by treating only a capped subsystem of a large molecule at a high level and integrating this with a lower-level calculation on the entire system. First, our results show that improving the basis on the capped subsystem is an excellent way to improve the bond energy without the expense of using a large basis set for the whole system. In a second study, we show that correlated calculations on a capped subsystem with the Hartree−Fock (HF) approximation for the entire system yield results that are within 1 kcal/mol of CCSD(T)/6-31G(d,p) accuracy for a set of molecules involving first-row atoms. For chloroethane, though, the HF level is inadequate for such a treatment, and the calculations have an error of about 3 kcal/mol with respect to a full CCSD(T)/6-31G(d,p) calculation. However, for this case, using even a low level of electron correlation, such as Møller−Plesset second-order perturbation theory (MP2), for the entire system makes it possible to achieve high accuracy. A final set of results show how well we can get an accuracy comparable to MP2/6-31G(d,p) by using only Hartree−Fock calculations for the entire system. Such an integrated strategy, using a double-zeta basis set, is good enough for obtaining MP2/6-31G(d,p) accuracy within 1 kcal/mol for all the molecules investigated except difluoroethane and chloroethane.

Energetics using the single point IMOMO (integrated molecular orbital+molecular orbital) calculations: Choices of computational levels and model system

The integrated MO+MO (IMOMO) method, recently proposed for geometry optimization, is tested for accurate single point calculations. The principle idea of the IMOMO method is to reproduce results of a high level MO calculation for a large ‘‘real’’ system by dividing it into a small ‘‘model’’ system and the rest and applying different levels of MO theory for the two parts. Test examples are the activation barrier of the SN2 reaction of Cl−+alkyl chlorides, the C=C double bond dissociation of olefins and the energy of reaction for epoxidation of benzene. The effects of basis set and method in the lower level calculation as well as the effects of the choice of model system are investigated in detail. The IMOMO method gives an approximation to the high level MO energetics on the real system, in most cases with very small errors, with a small additional cost over the low level calculation. For instance, when the MP2 (Mo/ller–Plesset second-order perturbation) method is used as the lower level method, the IMOMO method reproduces the results of very high level MO method within 2 kcal/mol, with less than 50% of additional computer time, for the first two test examples. When the HF (Hartree–Fock) method is used as the lower level method, it is less accurate and depends more on the choice of model system, though the improvement over the HF energy is still very significant. Thus the IMOMO single point calculation provides a method for obtaining reliable local energetics such as bond energies and activation barriers for a large molecular system.

The IMOMO method: Integration of different levels of molecular orbital approximations for geometry optimization of large systems: Test for n-butane conformation and S N2 reaction: RCl+Cl−

A new theoretical method, called IMOMO (integrated MO (molecular orbital)+MO), for integration of two different levels of MO approximation is presented. Only the active or more difficult part of a molecule is treated at a higher level of approximation and the rest of the molecule at a lower level of approximation. The integrated total energy and energy derivatives are defined from three different calculations, and the structure of transition state as well as the equilibrium structure can be optimized using the integrated energy. Any combination of any molecular orbital approximations (ab initio, density functional to semi-empirical) can be used. Test calculations in the IMOMO method have been performed and compared with normal MO calculations for the conformation energy of ethane and n-butane and the SN2 reaction of ethyl, propyl, isobutyl, and neopentyl chloride with Cl−. The results indicate that these methods have a tremendous potential for theoretical study of larger molecules, in particular for transition states.