Atomic molar refractivity contribution

Atomic molar refractivity contributions have been defined [267 — 269]. The MEDCHEM software [253] also contains a routine for the calculation of MR... 

This formula represents the two components in this parameter the term - l)/ ri + 2) indicates the delocalizability of the electrons in the molecule (i.e. the aptness of the electron system to be polarized). The relation MW/d reveals MR to depend on the molar volume. The larger the polar part of a molecule, the larger is its MR value. Atomic molar refractivity contributions are assumed to be additive and can be retrieved from tabulations (e.g. Hansch, 1975 Seydel and Schaper, 1979). The closely related parachor, the product of the molar volume and a surface tension term, is of negligible relevance for QSAR studies and cannot be recommended for use, except for the empirical estimation of boiling points (section 4.5). 

Values for the atomic molar refractivity were also estimated by - group contribution methods [Ghose and Crippen, 1987],... 

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. 

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... 

Viswanadhan, V. N., et al., An Estimation of the Atomic Contribution to Octanol-Water Partition Coefficient and Molar Refractivity from Fundamental Atomic and Structural Properties Its Uses in Computer Aided Drug Design. Math. Comput. Model., 1990 14, 505-510. 

The refractive index of a compound is a property of some significance in regard to molecular constitution. The molar refraction, defined by Eq. (29-14), is a constitutive and additive property for a given compound it may be approximated by the sum of contributions of individual atoms, double bonds, aromatic rings, and other structural features. 

Table L4 Ghose-Crippen atomic contributions to logP and molar refractivity (MR).

Properties relate to measures of molecular size in various ways. Some properties depend heavily on the atom count. Molar volume, heat of atomization, and molar refraction are approximately proportional to atom count contributions can be summed to give an estimate of the total property value. Generally, properties require additional information about the immediate bonding environment of atoms for useful estimation models. Water solubility depends on the branching in the molecular skeleton. Molecular fragments larger than individual atoms are required to estimate most property values. This additive-constitutive nature of properties has been amply demonstrated by many additive property schemes. 

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. 

The static average electric dipole polarizability a = 4.84 was derived [1] from older data [2] for the dielectric constant, the molar refraction, and the dipole moment. A vibrational contribution avib=0.086 (0.096x10" ° C2-m2-j- formerly called atomic polarization ) was obtained... 

The CLOGP and CMR modules of the Daylight system (see entry under database software) calculate log P by the Hansch and Leo fragment system, and molar refractivity by an atom contribution scheme. 

Polar interactions, which result from dispersion forces (van der Waals interactions) are best described by molar refractiv-ity MR, which is a refractive index-corrected molar volume. Thus, it has also been used to describe steric features of substituents. Like log P, MR is an additive constitutive molecular property which can be calculated from atom and group contributions. " ... 

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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