Structure-molar refraction relationship

Kupchik, E.J. (1985) Structure-molar refraction relationships of alkylsilanes using molecular cormectivity. Quant. Struct. -Act Relat, 4,123-127. 

Jantschi, L. and Bolboaca, S. (2005) Molecular descriptors family on structure-activity relationships. 4. Molar refraction of cyclic organophosphorus compounds. Leonardo Electron. J. Pract. Technol, 7, 55-102. 

In addition to nonlinear lipophilicity relationships for the transport and distribution of drugs, nonlinear relationships on molar refractivity are frequently observed in QSAR studies of enzyme inhibition data (provided that MR values are scaled by a factor of 0.1, as usual) [60,63,64,66-68]. Two such examples are given in Eq. (63) (Escherichia coli DHFR) and Eq. (64) (Lactobacillus casei DHFR) [101]. The differences between both models could be explained after the 3D structure of the enzyme became known. Whereas all substituents of a benzyl ring contribute to biological activities in E. coli DHFR, only the 3- and 4-substituents show up in the QSAR model for L. casei DHFR but not the 5-substituents. This results from a narrower binding pocket in L. casei DHFR a (3-branched leucine hinders the accommodation of 5-substituents, whereas a more flexible methionine in the same position of E. coli DHFR opens a wider binding pocket [101] ... 

The simplest structural descriptors are just the number of carbon atoms, or molecular weight, that is linearly related to the increase in gas chromatographic retention among a homologous series of compounds. This simple relationship led to the development of the Kovits retention index scale. A linear relationship between Kovits retention index and carbon number for homo-logues has been shown to hold for a number of chemical groups. Molar volume, molar refractivity, and molecular polarizability are other simple descriptors of molecular bulk that have been used in QSRR studies. 

C = molar concentration of a drug CNS = central nervous system MR = molar refractivity P = partition coefficient PLS = partial least squares QSAR = quantitative structure-activity relationships. 

The alternatives to mathematical descriptors derived from molecular graphs or molecular geometry are the traditional QSAR (quantitative structure-activity relationship) descriptors and quantum chemically computed parameters. The former include the partition coefficient for oil/water (often octanol/water) (log P), the Hammet sigma value (electronic parameter that measures the electron withdrawal from and the electron release to the aromatic ring by a substituent, the Taft s parameters for the electronic effects of substituents in aliphatic compounds (a ), and a steric parameter for the proximity of substituents on reaction sites (Es)- Also selected molecular properties, such as molar refractivity (MR), polarizability (a), molecular weight (MW), and density (d), have been used. 

The principal refractive indices and and the birefringence A = - of 40 ne-matogenic compounds (A=589 nm) for a temperature T n-i -7 =10K, are listed in Table 1. It follows from Eq. (8) that at a constant reduced temperature the magnitude of the birefringence is mainly determined by the molecular polarizability anisotropy a,-0[, but also by the molar volume V=M/p. On the other hand, a, - (Zt depends strongly on the structural features of the molecules. As can be seen from Table 1 some general relationships between molecular structure and birefringence can be derived ... 

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