Solvation COSMO

Having recognized the theoretical inadequacy of the dielectric theory for polar solvents, I started to reconsider the entire problem of solvation models. Because the good performance of dielectric continuum solvation models for water cannot be a result of pure chance, in some way there must be an internal relationship between these models and the physical reality. Therefore I decided to reconsider the problem from the north pole of the globe, i.e., from the state of molecules swimming in a virtual perfect conductor. I was probably the first to enjoy this really novel perspective, and this led me to a perfectly novel, efficient, and accurate solvation model based upon, but going far beyond, the dielectric continuum solvation models such as COSMO. This COSMO for realistic solvation (COSMO-RS) model will be described in the remainder of this book. 

Continuum Solvation COSMO and COSMO-RS Peri-cyclic Reactions The Diels-Alder Reaction Reaction Path Following Solvation Modeling Transition States in Organic Chemistry Ab Initio. 

Continuum Solvation COSMO and COSMO-RS Free Energy Changes in Solution Hydrophobic Effect Molecular Surface and Volume Molecular Surfaces and Solubility Monte Carlo Simulations for Liquids Scaled Particle Theory Self-consistent Reaction Field Methods Solvation Modeling. 

A number of types of calculations can be performed. These include optimization of geometry, transition structure optimization, frequency calculation, and IRC calculation. It is also possible to compute electronic excited states using the TDDFT method. Solvation effects can be included using the COSMO method. Electric fields and point charges may be included in the calculation. Relativistic density functional calculations can be run using the ZORA method or the Pauli Hamiltonian. The program authors recommend using the ZORA method. 

COSMO (conductor-like screening model) a method for including solvation effects in orbital-based calculations... 

COSMO-RS conductor-like screening model for realistic solvation... 

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]. 

A. Schiiurmann, G. COSMO a new approach to dielectric screening in solvents with explicit expressions for the screening energy and its gradient. J. Chem. Soc., Perkins Trans. 1993, 799-805. (c) Klamt, A. Jonas, V. Burger, T. Lohrenz, J. C. W. Refinement and parametrization of COSMO-RS. J. Phys. Chem. A 1998, 102, 5074—5085. (d) For a more comprehensive treatment of solvation models, see Cramer, C. J. Truhlar, D. G. Implicit solvation models equilibria, structure, spectra, and dynamics. Chem. Rev. 1999, 99, 2161— 2200. 

Smooth COSMO solvation model. We have recently extended our smooth COSMO solvation model with analytical gradients [71] to work with semiempirical QM and QM/MM methods within the CHARMM and MNDO programs [72, 73], The method is a considerably more stable implementation of the conventional COSMO method for geometry optimizations, transition state searches and potential energy surfaces [72], The method was applied to study dissociative phosphoryl transfer reactions [40], and native and thio-substituted transphosphorylation reactions [73] and compared with density-functional and hybrid QM/MM calculation results. The smooth COSMO method can be formulated as a linear-scaling Green s function approach [72] and was applied to ascertain the contribution of phosphate-phosphate repulsions in linear and bent-form DNA models based on the crystallographic structure of a full turn of DNA in a nucleosome core particle [74],... 

Fig. 2.6 Comparison of the calculated structures for glycine in the gas-phase and in water (COSMO solvation model). Note that the central bond angle in the zwitterionic form 1 is distorted by the hydrogen bond length of 1.96A computed for this structure in the gas phase. When solvation effects are included in the calculation using COSMO, the electrostatic interaction is reduced in magnitude due to charge screening by water, and the bond angle distortion is no longer present.

An alternative to the GB, COSMO, and Poisson electrostatic calculations is to model the solution to the Poisson equation in terms of pair potentials between solute atoms this procedure is based on the physical picture that the solvent screens the intra-solute Coulombic interactions of the solute, except for the critical descreening of one part of the solute from the solvent by another part of this solute. This descreening can be modeled in an average way to a certain level of accuracy by pairwise functions of atomic positions.18, M 65 One can obtain quite accurate solvation energies in this way, and it has recently been shown that this algorithm provides a satisfactory alternative to more expensive explicit-solvent simulations even for the demanding cases of 10-base-pair duplexes of DNA and RNA in water.66... 

FIGURE 3.25. Potential energy profiles (from B3LYP/6-13G calculations) for the clevage of 3- and 4-nitrobenzyl chloride anion radicals (a and b, respectively) in the gas phase (top) and in a solvent (middle and bottom) (from COSMO solvation calculations with a dielectric constant of 36.6 and 78.4, respectively). Dotted and solid lines best-fitting Morse and dissociative Morse curves, respectively. Adapted from Figure 3 of reference 43, with permission from the American Chemical Society. 

FIGURE 3.31. Reaction of alkyl chlorides with NO as a function of steric hindrance at carbon. Central line reactant state Left-hand lines ET transition and product states. Right-hand lines 5 2 transition and product states. Numbers above and below the lines are the standard free energies (in eV) numbers in parentheses are the entropies in meV/K. The numbers on the structures are bond lengths in A. From MP2/6-31G //UHF/6-31G and COSMO (solvation) calculations. 

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. 

The insight provided by studying 8-oxo-guanine, and the ability to substitute DNA with a nucleobase that could be selectively oxidized by a low-potential complex, prompted us to search for other minimally substituted, redox-active nucleobases [92]. We therefore developed a library of nucleobases that were investigated using density functional theory (DFT) [93, 94] calculations self-consistently coupled to the conductorlike solvation model (COSMO) [95, 96]. The case of oxidation of nucleobases, particularly guanine. 

The calculated reaction profile for H abstraction for the TauD Fe(IV)=0 model is shown in Fig. 2 (23). The calculations were carried out with the ORCA package (24), using the B3LYP density functional (25,26) and Karlsruhe basis sets for all atoms (27—29) in combination with the RIJONX (30) or RIJCOSX approximations (31) and appropriate auxiliary basis sets (32—34). The protein environment was modeled by the COSMO solvation model with a dielectric constant of... 

CoiTelation. (see also Electron correlation), 110 CoiTelation energy density. 259. 263 COSMO, (see Solvation)... 

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