Quantum chemical calculation continuum solvation models

QuantlogP, developed by Quantum Pharmaceuticals, uses another quantum-chemical model to calculate the solvation energy. As in COSMO-RS, the authors do not explicitly consider water molecules but use a continuum solvation model. However, while the COSMO-RS model simpUfies solvation to interaction of molecular surfaces, the new vector-field model of polar Uquids accounts for short-range (H-bond formation) and long-range dipole-dipole interactions of target and solute molecules [40]. The application of QuantlogP to calculate log P for over 900 molecules resulted in an RMSE of 0.7 and a correlation coefficient r of 0.94 [41]. 

Recently, Wichmann et al. [47] applied several COSMO-RS cr-moments as descriptors to model BBB permeability. The performance of the log BB model was reasonable given only four descriptors were applied n — 103, r2 = 0.71, RMSE = 0.4, LOO q2 — 0.68, RMSEtest = 0.42. The COSMO-RS cr-moments were obtained from quantum chemical calculations using the continuum solvation model COSMO and a subsequent statistical decomposition of the resulting polarization charge densities. 

Most of the quantum chemical calculations of the nuclear shielding constants have involved two classes of solvation models, which belong to the second group of models (n), namely, the continuum group (i) the apparent surface charge technique (ASC) in formulation C-PCM and IEF-PCM, and (ii) models based on a multipolar expansion of the reaction filed (MPE). The PCM formalism with its representation of the solvent field through an ASC approach is more flexible as far as the cavity shape is concerned, which permits solvent effects to be taken into account in a more accurate manner. 

The second chapter ends with two overviews by Stephens Devlin and by Hug on the theoretical and the physical aspects of two vibrational optical activity spectroscopies (VCD and VROA, respectively). In both overviews the emphasis is more on their basic formalism and the gas-phase quantum chemical calculations than on the analysis of solvent effects. For these spectroscopies, in fact, both the formulation of continuum solvation models and their applications to realistic solvated systems are still in their infancy. 

Solvent effects can significantly influence the function and reactivity of organic molecules.1 Because of the complexity and size of the molecular system, it presents a great challenge in theoretical chemistry to accurately calculate the rates for complex reactions in solution. Although continuum solvation models that treat the solvent as a structureless medium with a characteristic dielectric constant have been successfully used for studying solvent effects,2,3 these methods do not provide detailed information on specific intermolecular interactions. An alternative approach is to use statistical mechanical Monte Carlo and molecular dynamics simulation to model solute-solvent interactions explicitly.4 8 In this article, we review a combined quantum mechanical and molecular mechanical (QM/MM) method that couples molecular orbital and valence bond theories, called the MOVB method, to determine the free energy reaction profiles, or potentials of mean force (PMF), for chemical reactions in solution. We apply the combined QM-MOVB/MM method to... 

Combined QM/MM methods, pioneered by Warshel and Levitt, [10] can be introduced either from the point of view of conventional molecular simulation methods or from the viewpoint of quantum chemical calculations. To clarify the latter case we recall that in computational Quantum Chemistry the calculations are carried out in vacuum and at OK, which, of course, does not always correspond to the most desirable conditions. Quantum chemists early adopted the continuum models [11] to develop their solvation models, hoping to bring the solvent medium into their calculations. Therefore, the combined QM/MM simulations... 

Briefly, the PSP approach heavily resides on the quantum mechanics-based COSMO-RS theory of solutions [17-22], The COSMO model belongs to the class of continuum solvation models (CSM) of quantum mechanics. For the solvation picture, it considers the molecule embedded in a conductor of infinite permittivity that screens perfectly the molecular charges on the surface of its molecular cavity. This molecular cavity is characterized by a volume, Fcogni, and a molecular surface area, The crucial information is contained in the so-called COSMO tile of each compound obtained from quantum chemical calculations at various levels of theory. COSMO tiles give the detailed surface charge distribution or the o-protile of each molecule. The o-protile may be analyzed into its moments of various orders, known as COSMOments, out of which a large number of properties may be calculated, among them the molecular descriptors of Abraham s QSPR/LSER model [23,24]. 

Recent years have shown significant progress in the use of computation-based approaches for predicting surface energies and wettability. Continuum solvation models, in particular, the conductQr-Uke screening model (COSMO), are well-established methods to incorporate solvation effects into quantum chemical calculations. COSMO takes into account the detailed atomic structure of the interface interacting with the dielectric liquid. 

Summary of the continuum model. The method described in this section is the first application to calculating a solvated molecule s properties in a quantum chemical manner. Qualitative considerations seem to be reasonable in spite of their considerable simplicity. PCM can be regarded as a final achievement amongst the series of ab initio MO-dielectric continuum combined methods, since all the method is based on the Poisson-Laplace equation. However, it is important to pay much attention to the serious disadvantage in all these... 

Proper inclusion of the solvent into the calculations is unfortunately quite difficult [46]. One can use classical molecular dynamics or Monte Carlo simulations, classical continuum models based on the Poisson-Boltzman equation, and quantum-chemical studies using various variants of the Self Consistent Reaction Field (SCRF) approach at the semiempirical or ab initio level. There are serious approximations associated with these methods. Continuous models neglect the specific solute-solvent interactions which are very important for polar solvent. Classical methods neglect the changes in the electronic structure of the solute due to the solvent effects. These uncertainties can be illustrated using the predicted solvation energy of adenine treated by various modem approaches. The calculated values vary from -8 to -20 kcal/mol [68]. 

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