Calculated molar refractivity

CMR Calculated molar refractivity of the whole molecule DNA Deoxyribonucleic acid... 

CMR represents the overall calculated molar refractivity. Its negative sign bring out a steric effect. It is interesting to note here that there is a high mutual correlation between ClogF and CMR (r= 0.966). Thus, it is very hard to predict for this data set if it is a negative hydrophobic or a polarizability effect. 

MRx is the calculated molar refractivity of X-substituents, whereas I is an indicator variable taking the value of 1 and 0 for the presence and absence of a phenyl ring in the X-substituents. The negative sign of MRx brings out a steric effect for the X-substituents that do not appear to reach a hydrophobic surface for ttx (calculated hydrophobicity of X-substituents), r = 0.470. The indicator variable (I) with positive coefficient suggests that the presence of a phenyl ring in the X-substituents would be favorable. 

This is a parabolic relation in terms of MRx (calculated molar refractivity of X-substituents), which suggests that the inhibitory activities of quinolones (XIX) against topo II first increases with an increase in the molar refractivity of X-substituents up to an optimiun MRx of 1.84 and then decreases. 

Effect of Ionization on the Refractive Index and Molar Refraction of Amino Acids and Proteins. Since the electrostriction produced by an amino acid does not affect its molar refraction, the ionization of an amino acid might be expected to produce no significant change in molar refraction. Table V indicates that this is the case, provided the large change in the volume of the amino acid as a result of ionization, found by Kauzmann, Bodanszky, and Rasper (23), is used in calculating molar refraction. The refractive index of an equivalent concentration of hy-... 

Table 9 Observed and Calculated Molar Refractions of 1,2,4-Trioxolanes...

The new diffusion models are successful in the description they provide, and are particularly useful because they require only the chemical structure as an input, no experimental data being necessary. Molecular size is described by the use of the calculated molar refractivity. A new model for the temperature dependence of the viscosity of water was required and developed. 

Keseru [35] used literature data on 55 compounds to train a QSAR model based on a number of calculated descriptors. Five descriptors were used clogP, calculated molar refractivity (CMR), partial negative surface area, and the VolSurf W2 (polarizability) and D3 (hydrophobicity) descriptors. A model of acceptable quality was obtained (f = 0.94, SSE = 0.82) and tested on a 13 compound holdout set (r2 = 0.56, SSE = 0.98). An HQSAR model was then created that made use of 2D fragment fingerprints (threshold hERG IC50 = lpM). The best HQSAR model was validated on a holdout set of 13 compounds (f = 0.81, SSE = 0.67). 

Plasma area under the concentration—time curves (AUCs) of 57 NCEs were determined following oral cassette administration (5—9 NCEs/cassette) to mice. Physicochemical properties [such as, molecular weight, calculated molar refractivity, and calculated lipophilicity (clogP)] and molecular descriptors [such as presence or absence of N-methylation, cyclobutyl moiety, or heteroatoms (non-C,H,0,N)] were calculated or estimated for these compounds. This structural data, along with the corresponding pharmacokinetic parameters (primarily AUC), were used to develop artificial neural network models [8]. These models were used to predict the AUCs of compounds under synthesis [10]. This approach demonstrates that predictive models could be developed which potentially predict in vivo pharmacokinetics of NCEs under synthesis. Similar examples have been reported elsewhere [11—13]. 

In this equation, MR-4 is the calculated molar refractivity of the substituents at position 4 whereas jt-1 is the calculated hydrophobic parameter of the substituents at position 1. This equation contains a positive correlation with Clog P and a negative correlation with n-1, so one should preserve a hydrophihc group at N1 while boosting the molecule s overall hydrophobic-ity. The parabohc nature of this equation in terms of MR-4 suggests that the value of MR-4 shotdd be 1.82 for the maximum cytotoxicity against B16 melanoma cells. 

MRx is the calculated molar refractivity of X-substituents and its negative coefficient suggests steric hindrance. 7 is an indicator variable, which acquired a value of 1 for amides and 0 for the esters. The negative coefficient of the indicator variable suggests an unfavorable cytotoxic effect for the amide derivatives against this cancer cell line. It is interesting to note here that there is a high mutual correlation between nx and MRx (r = 0.877). Thus, it is very hard to predict for this data set if it is a positive hydrophobic or polarizability effect of the X-substituents. We derived Eq. 17a with MRx and finally preferred Eq. 17 on the basis of their statistics, which are better than those of Eq. 17a ... 

Used three descriptors ClogP, calculated molar refractivity (CMR), and the pKa of the most basic nitrogen, to identify hERG blockers within an in-house data set. 

In inorganic crystals atoms have higher and, as follows from Table 11.3 and the polarizabilities of clusters (Table 11.6), their refractions must be lower than in the molecular state. Because the Lorentz-Lorenz function approaches 1 when n oo, and metals have very high RIs (at X = 10 (.im, Cu has n = 29.7, Ag 9.9, Au 8.2, Hg 14.0, V 12.8, Nb 16.0, Cr 21.2, etc [147]), we assumed that R = V foi solid metals [148], These refractions of metals, Rm (Table 11.5, lower lines) in some cases are close to the additive values [13,14]. Rm cannot be applied directly to calculate molar refractions of crystalline inorganic compounds because of the differences in Nc, but can be used [149] to calculate refractions of metals for such Nc as they have in the structures of their compounds, using the formula... 

The accuracy of calculated molar refractions of inorganic compounds has been much improved by taking into account the polarizing effect of atoms (g) and bond metallicity (m) [150], The former was described proceeding from the van der Waals interactions, g = [(Ra — b)/ a] where Ra < Rb (see Eq. 4.24). If the smaller ion (A) is the cation, this will lower the refraction, otherwise will increase it. The bond metallicity m, i.e. the delocalized fraction of covalent electrons of A—A bonds in AB... 

Bl, B5 L Verloop s sterimol parameters for substituent width and length CMR calculated molar refractivity... 

Distinct differences between saturated and unsaturated compounds were observed on the polar columns (ii) and (iii), and average values of retention index divided by molecular weight increased with two exceptions, as the refractive index increased. A correlation of increasing retention index with increasing calculated molar refraction applied without exception to (i) and with a few exceptions to (ii) and (iii). The retention indices of the 14 compounds mentioned by these workers are tabulated in Table 105. 

The molecular descriptors used are as follows CMR (Calculated molar refractivity), pZ (Z component of the dipole moment), HOMO (Energy of the highest occupied molecular orbital), FZ (9), FY (6) and FY (11) (Z and Y are the components of the electric field at specified grid points), VDWE (4) (The van der Waal s energy of the interaction of a carbon atom at a specified grid point), ALP (3) (The self atom polarizability of the specified atom). 

---