McGowan volume

MgVol Calculated molar volume of the whole molecule (McGowan volume)... 

H-bonding is an important, but not the sole, interatomic interaction. Thus, total energy is usually calculated as the sum of steric, electrostatic, H-bonding and other components of interatomic interactions. A similar situation holds with QSAR studies of any property (activity) where H-bond parameters are used in combination with other descriptors. For example, five molecular descriptors are applied in the solvation equation of Kamlet-Taft-Abraham excess of molecular refraction (Rj), which models dispersion force interactions arising from the polarizability of n- and n-electrons the solute polarity/polarizability (ir ) due to solute-solvent interactions between bond dipoles and induced dipoles overall or summation H-bond acidity (2a ) overall or summation H-bond basicity (2(3 ) and McGowan volume (VJ [53] ... 

Bromocriptine, erythromycin and terfenadine had to be omitted from this correlation because Absolv does not calculate the water solubilities of compounds with McGowan volumes, V, greater than 4.0. This is because the solubility training set used in Absolv, Eq. (6), does not contain compounds with V values greater than 4 hence predictive power for such compounds are not reliable. 

In an excellent paper, Zhao et al. [29] assembled a carefully reviewed literature set of human absorption data on 241 drugs. They showed that a linear regression model built with 5 Abraham descriptors could fit percent human absorption data reasonably well (r2 = 0.83, RMSE = 14%). The descriptors are excess molar refraction (E), polarizability (S), hydrogen bond acidity (A), hydrogen bond basicity (B), and McGowan volume (V), all related to lipophilicity, hydrophilicity, and size. In a follow-on paper, data on rat absorption for 151 drugs was collected from the literature and modeled using the Abraham descriptors [30]. A model with only descriptors A and B had r2 = 0.66, RMSE = 15%. 

Abraham et at. [2], [3], [4] Solubility, excess molar refraction, polarizability, hydrogen-bond acidity/basicity, and McGowan volume... 

Increase in polarity, polarizability, and hydrogen-bonding ability leads to a decrease in BBB permeation rate. Compound size as measured by the McGowan volume leads to an increase in the permeation rate. 

Abraham et al. (1999) generated a QSAR equation for the permeation of 47 aqueous solutes across human skin. This demonstrated that dermal permeability increased with increasing molar refraction and McGowan volume and decreased as hydrogen bond acidity, basicity, and dipolar-ity/polarizability increased. 

In Eq. [19], Vxi is the McGowan volume that models the energy needed to make a solute molecule-sized cavity in the solvent. Again, the subscript 2 denotes a solute molecule. The parameters ti and 82 account for dipolarity/ polarizability, and ai and pi model hydrogen bond (HB) acidity and basicity, respectively. This parameter set was used to correlate more than 250 biological, chemical, and physical properties successfully. ... 

Zhao, Y.H., Abraham, M.H. and Zissimos, A.M. (2003a) Determination of McGowan volumes for ions and correlation with van der Waals volumes. /. Chem. Inf. Comput. Sci., 43, 1848-1854. 

FIGURE 15.3. Distribution data between water and sodium dodecyl sulfate micelles as a function of the solute McGowan volume for the entire database (a) and for categorized classes of solutes (b), data from Reference 25. Database labels in (a) as in Figure 15.2. (A) hexadecane-water partition data for alkanes, from Reference 16. Labels in (b) ( ) alkyl benzenes (O) alkyl phenyl ketones (A) alkyl phenols ( ) halo benzenes and ( ) halo phenols. 

Here Rs is the excess molar refraction of the solute over that of an alkane with the same characteristic volume (Abraham et al. 1990) (not further specified). The Kamlet-Taft solvatochromic parameters of the solute (Kamlet et al. 1983) are n, the polarity/polarizibility, a the HB donation (electron pair acceptance) ability, and P the HB acceptance (electron pair donation) ability. The volume of the solute is represented by the Abraham-McGowan volumes Vx (Abraham and McGowan 1987), based on invariant atom and bond contributions. The parameters a and /9 pertain to the monomeric solutes (measured in dilute solutions thereof). The correlation coefficient for Eq. (1.21) for 408 solutes is 0.998 and the standard deviation is 0.15. 

Hydrophobic parameters are mostly experimentally obtained log P or calculated log P (C log P), where P is the octanol-water partition coefficient. n is the hydrophobic constant of the substituents. The electronic parameters (Hammett constants) a, a and appHes to substituent effects on aromatic systems and Taft s a appHes to ahphatic systems. Steric parameters are Tafts steric parameter Es, McGowan volume MgVol, van der Waals volume Vw, molecular weight MW. Verloop s sterimol parameters Bl, B5 and L... 

However, the quantities already include the interactions of the solutes with water, but properties foreign to such interactions are preferable for predictive purposes. Two such properties have been proposed and tested by Marcus [65] the Kamlet-Taft polarity/polarizability index a (Section 3.3.2.1) and the Hildebrand solubility parameter (Section 3.2.2). These as well as the intrinsic volumes of the solutes, expressed as their McGowan volumes are independent of interactions with water, hence true predictive parameters that are known or calculable from group contributions for a large number of solutes. The predictive expression (for ambient temperatures) is ... 

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