Water-accessible volume

The authors increased the quality of their correlation by replacing the molecular weight with the water-accessible volume, which gave a slightly higher correlation coefficient than did Eq. 23 ... 

Kaliszan and Markuszewski [23] Salminen et al. [41] Lipophilicity, size, and water-accessible volume log fciAM, molecular volume, and an ionization variable... 

BBB permeability increases with increasing lipophilicity and reducing size and water-accessible volume. 

For volume shell models, the free energy of hydration is assumed to be proportional to the water-accessible volume of a hydration layer surrounding the peptide. This can be represented in the form... 

The C5+, and smeta values were experimentally determined, and the ASA, vdW and logP (o/w) were determined in MOE. [7t = lipophilicity parameter o+ = Hammett constant for ben-zylic cations Esmeta = Tafts steric parameter ASA = water accessible surface area vol = van der Waals volume logP (o/w) = log of the octanol/water partition coefficient.]... 

In addition, the results of absorption studies for a series of (i-adrenoceptor blockers in vitro using Caco-2 monolayers and rat intestinal segments have been used to test new descriptors [55]. For this purpose, the authors calculated dynamic molecular surface properties considering all low-energy conformations. Molecular mechanics were used to consider the flexibility of the molecules, and the van der Waals volume (vdW) and water-accessible surface areas were also calculated (Table 4.18 and 4.19). When the dynamic polar vdW surface areas were used in regression analysis to describe cell permeability data obtained in Caco-2 cells and in rat ileum, excellent correlations were obtained (r2 = 0.99 and 0.92 respectively). 

Molecular volume represents the water-excluded volume (in A ), i.e. the volume enclosed by the water-accessible surface computed at a repulsive value of t-0.2kcalmoT. ... 

Use 90% DMSO/Water Consistent water content, volume and concentration Fast access as liquid Favor drug-Uke properties Instability for certain compounds... 

Water-exduded volume (in A ) at + 0.2 kcal/mol energy Accessible surface of the water interaction field at + 0.2 kcal/mol energy... 

Figure 13. Relationship between the initial rate of reaction and the volume of water accessible to molecules of different sizes...

One formulation of the second law states that, for a closed system, the entropy of the system can only increase or remain the same. In plain language, this says that nature favors having more accessible configurations or arrangements. It s why, for example, a drop of ink in water tends to spread out to fill its accessible volume but won t spontaneously reform a drop of ink. 

The respective atom and fragment values have been tabulated (e.g. Seydel and Schaper, 1979) the major disadvantage of these methods, however, is the neglect of the fact that volume and surface depend on the conformation of the molecule. The solvent-accessible volume and surface area depend on the size of the solvent molecule, generally water, and this is considered additionally. The solvent-accessible surface is defined as the locus of the centre of a spherical solvent rolled over the van der Waals surface of the solute. 

For not too large globular protein molecules, say, those with a molar mass M< 30,000Da, the volume V and the water-accessible surface (see Figure 13.5) may be approximated using the following empirical equations ... 

Brownian Motion When we place a blot of ink in still water, the colored region expands with time but the color fades, eventually filling the entire water in the container. The final state is a uniform concentration of the ink. Spreading of a substance throughout accessible volume is called diffusion. The phenomena is made possible by microscopic movement of water molecules. 

An additive relationship for the N individual atoms of the peptide is assumed, and (VHS,) represents the solvent-accessible volume of hydration shell for each atom i that is exposed to water. The (8,) parameters are empirically determined free energy of hydration densities for these atoms. 

We conclude that the beneficial effects of water are not necessarily limited to reactions that are characterised by a negative volume of activation. We infer that, apart from the retro Diels-Alder reaction also other reactions, in which no significant reduction or perhaps even an increase of solvent accessible surface area takes place, can be accelerated by water. A reduction of the nonpolar nature during the activation process is a prerequisite in these cases. 

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