P, calculation

Thus, a list of 1 5 descriptors was calculated for these purposes, as described below. The partition coefficient log P (calculated by a method based on the Gho.sc/Crip-pen approach [11]) (see also Chapter X, Section 1.1 in the Handbook) was calculated because it affects the solubility dramatically [17, 18]. All the other descriptors were calculated with the program PETRA (Parameter Estimation for the Treatment of Reactivity Applications) [28. ... 

Figure 7.9 Fractions of iso, syndio, and hetero triads as a function of p, calculated assuming zero-order Markov (Bernoulli) statistics in Example 7.7.

The rectangular structure is calculated to be strongly destabilized (antiaromatic) with respect to a polyene model. With 6-3IG calculations, for example, cyclobutadiene is found to have a negative resonance energy of—54.7 kcal/mol, relative to 1,3-butadiene. In addition, 30.7 kcal of strain is found, giving a total destabilization of 85.4 kcal/mol. G2 and MP4/G-31(d,p) calculations arrive at an antiaromatic destabilization energy of about 42kcal/mol. ... 

TABLE 12.4 Specific Resolution (R,p) Calculations for PLgel Mixed Gel Columns... 

MP4(SDQ)/6-31+(d,p) calculation is used to approximate higher order contributions. This model also includes some additional empirical corrections. 

The calculation usually proceeds along the traditional lines of HF-LCAO theory. We make an initial estimate of the electron density matrix P, calculate a revised h and iterate until the electron density and the HP matrix are self-consistent. 

Figure 4.2-3 contains the DFT (B3LYP) structure of [NMIM][PFg] obtained with a 6-31G(d,p) basis set. Here one observes C-H-F hydrogen bonds shorter than those obtained from the MP2/6-31G(d,p) calculation shown in Figure 4.2-2. 

Fig. 48 a, b. Distribution of the degree of polymerization P, calculated with the empirical technique, for a polymer sample degraded at strain rate e(0) = 1.5 x 105 s 1 (a) and at strain rate e(0) = 3.5 x 105 s"1 (b) (I) before degradation (II) part of polymer undegraded after passage through the orifice (III) part of polymer with one broken bond per molecule (IV) part of polymer with two broken bonds per molecule... 

Clog P Calculated hydrophobicity of the whole molecule (calculated logarithm of partition coefficient (P) in M-octanol/water) ji Calculated hydrophobicity of the substituent... 

Fig. 1.7 Correlation between virtual log P (calculated with the molecular lipophilicity potential) and the dipole moment (f = 0.76) as obtained from MD simulation of acetylcholine in water. Reproduced from Ref [16] with kind permission of American Chemical Society 2005.

With only few exceptions, most log P programs refer to the octanol-water system. Based on Rekker s fragmental constant approach, a log P calculation for aliphatic hydrocarbon-water partitioning has been reported [96]. Another more recent approach to alkane-water log P and log D is based on the program VolSurf [97]. It is believed that these values may offer a better predictor for uptake in the brain. 

Clog P calculated octanol-water partition coefficient... 

Ertl, P., Rohde, B., Selzer, P. Calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. In Rational Approaches to Drug Design, Holtje, H.-D., Sippl, W. (eds.), Prous, Barcelona, 2001, pp. 4514 55. 

Regression analyses revealed systematic differences between experimental log P and log P calculations based on the summation of fragment values. These differences could be attributed to chemical characteristics of the molecules, which in turn allowed the definition of correction rules such as chain conjugation, electronegativity facing bulk or the proximity effect, which describes the presence of electronegative centers in a molecule separated by one or two carbons. Correction values needed for log P calculation were shown to represent multiples of a constant value of 0.289, which is known as the magic constant (CM). 

The actual 2/ system [34] lists 13 correction rules and 169 fragment values, including 14 new heterocyclic fragments as well as doubly and triply halogenated methyls. A typical calculation is depicted in Fig. 14.1 for quinidine. The 2/system is the only fragment method allowing manual log P calculation. Computerized... 

Log P calculation for quinidine with the atom contribution method according to Ghose and Crippen. R group connected to C X heteroatom = double bond aromatic bond aromatic single bond (e.g. C=N in pyrrole) subscripts give the hybridization state and superscripts the formal oxidization number. For the quinidine structure see Fig. 14.1. 

Klopman, G., U,). W., Wang, S., Dimayuga, M. Computer automated log P calculations based on an extended group contribution approach. 

Ruskin, Richard P., Calculating Line Sizes for Flashing Steam-Condensate, Chemical Engineering, Aug. 18, 1975. 

Huron, M.J. Claverie, P., Calculation of the interaction energy of one molecule with its whole surroundings. I. Method and application to pure nonpolar compounds., J. Phys. Chem. 1972, 76, 2123-2133... 

Maccallum, J. L. Tieleman, D. P., Calculation of the water-cyclohexane transfer free energies of neutral amino acid side-chain analogs using the OPLS all-atom force held, J. Comput. Chem. 2003, 24, 1930-1935. 

To verify the mechanism presented, the quantum-chemical calculations of proton affinity, Aa, were carried out for modifiers, since the corresponding experimental data are quite rare. The calculations were performed for isolated molecules, since the properties of species in the interlayer space are probably closer to the gas phase rather than the liquid. The values of Ah were calculated as a difference in the total energy between the initial and protonated forms of the modifier. Energies were calculated using the TZV(2df, 2p) basis and MP2 electron correlation correction. Preliminarily, geometries were fully optimized in the framework of the MP2/6-31G(d, p) calculation. The GAMESS suite of ah initio programs was employed [10]. Comparison between the calculated at 0 K proton affinities for water (7.46 eV) and dioxane (8.50 eV) and the experimental data 7.50 eV and 8.42 eV at 298 K, respectively (see [11]), demonstrates a sufficient accuracy of the calculation. 

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