MR¼
(n^2 1)M
(n^2 þ2)r
(4:9)
wherenis the refractive index,Mthe relative mass andrthe density of the
compound. TheM/rterm is a measure of the molar volume whilst the refractive
index term is a measure of the polarizability of the compound. Although MR is
calculated for the whole molecule, it is an additive parameter, and so the MR
values for a molecule can be calculated by adding together the MR values for its
component parts (Table 4.7).
Table 4.7 Examples of calculated MR values. Reproduced by permission of John Wiley and Sons
Ltd. from Hansch C. and Leo A.J.Substituents Constants for Correlation Analysis in Chemistry and
Biology(1979)
Group MR Group MR Group MR
H– 1.03 F– 0.92 CH 3 O– 7.87
CH 3 – 5.65 Cl– 6.03 HO– 2.85
C 2 H 5 – 10.30 F 3 C– 5.02 CH 3 CONH– 14.93
(CH 3 ) 2 CH– 14.96 O 2 N– 7.63 CH 3 CO– 11.18
4. 4. 3. 3 Other parameters
These can be broadly divided into those that apply to sections of the molecule
and those that involve the whole molecule. The former include parameters such
as van der Waals’ radii, Charton’s steric constants and the Verloop steric
parameters. The latter range from relative molecular mass (RMM) and molar
volumes to surface area. They have all been used to correlate biological activity
to structure with varying degrees of success.
4.4.4 Hansch analysis
Hansch analysis attempts to mathematically relate drug activity to measurable
chemical properties. It is based on Hansch’s proposal that drug action could be
divided into two stages:
1. the transport of the drug to its site of action;
2. the binding of the drug to the target site.
QUANTITATIVE STRUCTURE–ACTIVITY RELATIONSHIPS (QSARS) 85