Jean-Louis Rivail

A quantum chemical approach to dielectric solvent effects in molecular liquids

Abstract The SCF equations for a system of electrons and nuclei surrounded by a dielectric continuum are derived by using a multipolar expansion of the interaction energy The system is used as a model for the dielectric solvent effect. The case of a series of fluorinated is treated as an example in the CNDO/2 approximation. Ethyl fluoride and 1,1,1-trifluoroethane illustrate the importance of the moments other than the dipole one. The solvent effects on conformational equilibria of 1,2-difluoro, 1,1,2,2-tetrafluro, and 1,1,2-trifluoroethane are in reasonable agreement with other data owing to experimental incertainties.

Quantum mechanical computations on very large molecular systems: the local self-consistent field method

Quantum chemical computations on a subset of a large molecule can be performed, at the neglect of diatomic differential overlap (NDDO) level, without further approximation provided that the atomic orbitals of the frontier atoms are replaced by parametrized orthogonal hybrid orbitals. The electrostatic interaction with the rest of the molecule, treated classically by the usual molecular mechanical approximations, is included into the self‐consistent field (SCF) equations. The first and second derivatives of energy are obtained analytically, allowing the search for energy minima and transition states as well as the resolution of Newton equations in molecular dynamics simulations. The local self‐consistent field (LSCF) method based on these approximations is tested by studying the intramolecular proton transfer in a Gly‐Arg‐Glu‐Gly model tetrapeptide, which reveals an excellent agreement between a computation performed on the whole molecule and the results obtained by the present method, especially if the quantum subsystem includes the side chains and the peptidic unit in between. The merits of the LSCF method are examplified by a study of proton transfer in the Asp69—Arg71 salt bridge in dihydrofolate reductase. Simulations of large systems, involving local changes of electronic structure, are therefore possible at a good degree of approximation by introducing a quantum chemical part in molecular dynamics studies. This methodology is expected to be very useful for reactivity studies in biomolecules or at the surface of covalent solids.

Quantum chemical computations on parts of large molecules: the ab initio local self consistent field method

Abstract In this Letter we extend to the ab initio level the principles of the local self consistent field method (LSCF) developed earlier within the semiempirical approximations. It allows quantum electronic computations on a fragment of a large molecule mostly depicted by a classical force field. The bond separating the quantum subsystem from the classical one is assumed to be represented by localized orbitals introduced as data. The molecular orbitals of this subsystem are developed on a basis of functions, orthogonal to the localized orbitals, which derive from the atomic orbitals of the usual basis set by a simple linear transformation. The algorithm of the LSCF method is obtained by a simple modification of the standard Hartree-Fock or DFT codes.

Polarisabilites moléculaires et effet diélectrique de milieu à l'état liquide. Étude théorique de la molécule d'eau et de ses diméres

The model of Onsager in which a polar molecule undergoes a reaction field due to the polarization of the molecular surroundings is used to evaluate by a S.C.F. calculation (CNDO/2 approximation) the modifications of a molecular structure in the liquid state.Application to water molecule and to three polar dimers for values of the dielectric constant varying between 3 and 78, shows that most of geometric parameters and dipoles moments vary of few per cent when the molecule is inserted in a liquid. In the liquid state dipole moments do not depend very much on the dielectric constant but energies and relative stabilities of isomers are strongly dependent on the medium.[/p]

Ab initio SCF calculations on electrostatically solvated molecules using a deformable three axes ellipsoidal cavity

The analytical expression of the free energy of solvation of a molecule interacting with a dielectric continuum through a three axes ellipsoidal cavity is used to derive the SCF equations of such a solvated molecule. In this paper, the shape of the cavity is defined after the principal values of the electronic polarizability tensor. Applied to two sets of rotational isomers (trans and gauche 1,2 difluoroethane, and E and Z N methyl formamide), this method confirms that the electronic structure, the molecular geometry, and the equilibrium constant are influenced by the solvent. The energy of solvation depends strongly on the shape of the cavity although the electronic structure appears to be less influenced by a modification of the geometrical characteristics of the boundary surface at constant volume of cavity. Therefore, the computation of the electronic wave function of a molecule interacting with a solvent by electrostatic and induction forces appears to be quite feasible.

A COUPLED DENSITY FUNCTIONAL-MOLECULAR MECHANICS MONTE CARLO SIMULATION METHOD : THE WATER MOLECULE IN LIQUID WATER

A theoretical model to investigate chemical processes in solution is described. It is based on the use of a coupled density functional/molecular mechanics Hamiltonian. The most interesting feature of the method is that it allows a detailed study of the solutes electronic distribution and of its fluctuations. We present the results for isothermal‐isobaric constant‐NPT Monte Carlo simulation of a water molecule in liquid water. The quantum subsystem is described using a double‐zeta quality basis set with polarization orbitals and nonlocal exchange‐correlation corrections. The classical system is constituted by 128 classical TIP3P or Simple Point Charge (SPC) water molecules. The atom‐atom radial distribution functions present a good agreement with the experimental curves. Differences with respect to the classical simulation are discussed. The instantaneous and the averaged polarization of the quantum molecule are also analyzed.

HYBRID CLASSICAL QUANTUM FORCE FIELD FOR MODELING VERY LARGE MOLECULES

A coherent computational scheme on a very large molecule in which the subsystem that undergoes the most important electronic changes is treated by a semiempirical quantum chemical method, though the rest of the molecule is described by a classical force field, has been proposed recently. The continuity between the two subsystems is obtained by a strictly localized bond orbital, which is assumed to have transferable properties determined on model molecules. The computation of the forces acting on the atoms is now operating, giving rise to a hybrid classical quantum force field (CQFF) which allows full energy minimization and modeling chemical changes in large biomolecules. As an illustrative example, we study the short hydrogen bonds and the proton-exchange process in the histidine-aspartic acid system of the catalytic triad of human neutrophil elastase. The CQFF approach reproduces the crystallographic data quite well, in opposition to a classical force field. The method also offers the possibility of switching off the electrostatic interaction between the quantum and the classical subsystems, allowing us to analyze the various components of the perturbation exerted by the macromolecule in the reactive part. Molecular dynamics confirm a fast proton exchange between the three possible energy wells. The method appears to be quite powerful and applicable to other cases of chemical interest such as surface reactivity of nonmetallic solids.

Specific force field parameters determination for the hybrid ab initio QM/MM LSCF method.

The pure quantum mechanics method, called Local Self‐Consistent Field (LSCF), that allows to optimize a wave function within the constraint that some predefined spinorbitals are kept frozen, is discussed. These spinorbitals can be of any shape, and their occupation numbers can be 0 or 1. Any post‐Hartree–Fock method, based on the restricted or unrestricted Hartree–Fock Slater determinant, and Kohn–Sham‐based DFT method are available. The LSCF method is easily applied to hybrid quantum mechanics/molecular mechanics (QM/MM) procedure where the quantum and the classical parts are covalently bonded. The complete methodology of our hybrid QM/MM scheme is detailed for studies of macromolecular systems. Not only the energy but also the gradients are derived; thus, the full geometry optimization of the whole system is feasible. We show that only specific force field parameters are needed for a correct description of the molecule, they are given for some general chemical bonds. A careful analysis of the errors induced by the use of molecular mechanics in hybrid computation show that a general procedure can be derived to obtain accurate results at low computation effort. The methodology is applied to the structure determination of the crambin protein and to Menshutkin reactions between primary amines and chloromethane.

Theoretical modeling of large molecular systems. Advances in the local self consistent field method for mixed quantum mechanics/molecular mechanics calculations.

Molecular mechanics methods can efficiently compute the macroscopic properties of a large molecular system but cannot represent the electronic changes that occur during a chemical reaction or an electronic transition. Quantum mechanical methods can accurately simulate these processes, but they require considerably greater computational resources. Because electronic changes typically occur in a limited part of the system, such as the solute in a molecular solution or the substrate within the active site of enzymatic reactions, researchers can limit the quantum computation to this part of the system. Researchers take into account the influence of the surroundings by embedding this quantum computation into a calculation of the whole system described at the molecular mechanical level, a strategy known as the mixed quantum mechanics/molecular mechanics (QM/MM) approach. The accuracy of this embedding varies according to the types of interactions included, whether they are purely mechanical or classically electrostatic. This embedding can also introduce the induced polarization of the surroundings. The difficulty in QM/MM calculations comes from the splitting of the system into two parts, which requires severing the chemical bonds that link the quantum mechanical subsystem to the classical subsystem. Typically, researchers replace the quantoclassical atoms, those at the boundary between the subsystems, with a monovalent link atom. For example, researchers might add a hydrogen atom when a C-C bond is cut. This Account describes another approach, the Local Self Consistent Field (LSCF), which was developed in our laboratory. LSCF links the quantum mechanical portion of the molecule to the classical portion using a strictly localized bond orbital extracted from a small model molecule for each bond. In this scenario, the quantoclassical atom has an apparent nuclear charge of +1. To achieve correct bond lengths and force constants, we must take into account the inner shell of the atom: for an sp(3) carbon atom, we consider the two core 1s electrons and treat that carbon as an atom with three electrons. This results in an LSCF+3 model. Similarly, a nitrogen atom with a lone pair of electrons available for conjugation is treated as an atom with five electrons (LSCF+5). This approach is particularly well suited to splitting peptide bonds and other bonds that include carbon or nitrogen atoms. To embed the induced polarization within the calculation, researchers must use a polarizable force field. However, because the parameters of the usual force fields include an average of the induction effects, researchers typically can obtain satisfactory results without explicitly introducing the polarization. When considering electronic transitions, researchers must take into account the changes in the electronic polarization. One approach is to simulate the electronic cloud of the surroundings by a continuum whose dielectric constant is equal to the square of the refractive index. This Electronic Response of the Surroundings (ERS) methodology allows researchers to model the changes in induced polarization easily. We illustrate this approach by modeling the electronic absorption of tryptophan in human serum albumin (HSA).

Reaction field factors for a multipole distribution in a cavity surrounded by a continuum

Abstract The reaction field factors appear in the generalization of the Kirkwood model of solvation for a molecule imbedded in a cavity surrounded by a dielectric continuum. A general algorithm is proposed to compute these factors for a distributed multipole analysis of the charge distribution of the solute.