Molar contributions, atom-based

Atom-based lipophilicity contributions and molar refractivity contributions have been derived for 3D QSAR studies [266 — 269]. Audry et ai defined molecular lipophilicity potentials [914—916] for the determination of lipophilic and hydrophilic regions of a molecule. 

Note The calculation of relative molecular mass, Mr, of organic molecules exceeding 2000 u is significantly influenced by the basis it is performed on. Both the atomic weights of the constituent elements and the natural variations in isotopic abundance contribute to the differences between monoisotopic- and relative atomic mass-based values. In addition, they tend to characteristically differ between major classes of biomolecules. This is primarily because of molar carbon content, e.g., the difference between polypeptides and nucleic acids is about 4 u at Mr = 25,000 u. Considering terrestrial sources alone, variations in the isotopic abundance of carbon lead to differences of about 10-25 ppm in Mr which is significant with respect to mass measurement accuracy in the region up to several 10 u. [41]... 

Three sets of molecular descriptors that can be computed from a molecular connection table are defined. The descriptors are based on the subdivision and classification of the molecular surface area according to atomic properties (such as contribution to logP, molar refractivity, and partial charge). The resulting 32 descriptors are shown (a) to be weakly correlated with each other (b) to encode many traditional molecular descriptors and (c) to be useful for QSAR, QSPAR, and compound classification. 

In the present work, we will use a relatively low level of theory to derive 32 weakly correlated molecular descriptors, each based on the subdivision and classification of the molecular surface area according to three fundamental properties contribution to ClogP, molar refractivity, and atomic partial charge. The resulting collection will be shown to have applicability in QSAR, QSPR, and compound classification. Moreover, the derived 32 descriptors linearly encode most of the information of a collection of traditional mathematical descriptors used in QSAR and QSPR. 

We have derived three sets of (easily calculated) molecular descriptors based on atomic contributions to logP, molar refractivity, and atomic partial charge. The individual descriptors were found to be weakly correlated with each other... 

The size parameter in such correlations can come from molecular weights, molar volumes, or other related parameters. One such parameter is the estimate of compound size based on the incremental contributions of the atoms involved. Such an approach is the basis for methods like those of McGowan (see Box 5.1 below). 

So the additive functions must be discovered the values of the atom group contributions or increments must be derived. This derivation of group contributions is relatively easy when the shape of the additive function is known and if sufficient experimental data for a fairly large number of substances are known. The derivation is mostly based on trial and error methods or linear programming in the latter case the program contains the desired group increments as adjustable parameters. The objective function aims at minimum differences between calculated and experimental molar quantities. 

As in the case of inorganic silica systems [Eqs. (8)-(ll)], both hydrolysis and condensation of alkoxides may be acid- or base-catalyzed [9,24,37]. The relative contributions of the four reactions—hydrolysis, olation, oxolation, and alcoxolation—determine the physical and chemical characteristics of the resulting oxide material. These contributions are in turn determined by the nature of the metal alkoxide (i.e., nature of the metal atom, nature of the alkyl groups) and the characteristics of the chosen experimental conditions (i.e., the water/alkoxide molar ratio, the nature and concentration of the catalyst, the nature of the solvent, and temperature). A major factor is the hydrolysis ratio, h, defined as the water/alkoxide molar ratio ... 

A useful method for estimating the molar heat capacity of an organic liquid is based on the additivity of the heat capaeity contributions [C] of the various atomic groupings in the moleeules (Johnson and Huang, 1955). Table 2.5 lists some [C] values, and the following examples illustrate the use of the method the molar capacity values (ealmoP °C ) in parentheses denote values obtained experimentally at 20 °C ... 

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. 

Molecular polarizability and molar refractivity are closely related properties that provide a measure of a molecule s susceptibility to becoming polarized. These descriptors are often useful in situations where dipole-induced dipole and dispersion interactions play an important role. They are readily calculated from refractive index and molar volume however, applications in QSAR and QSPR usually employ empirical estimates based on atomic, bond, or group contributions. A paper by Miller includes a review of techniques that have been used to estimate molecular polarizabilities. Methods for estimating molar refractivity may be found in the literature. ... 

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