STERIMOL method

The results of the studies will be summarized. Details of the QSAR analyses are or will be published elsewhere, including intercorrelation matrices of the steric parameters mentioned. But relevant conclusions from e.g. intercorrelations will be dicussed. At this moment the STERIMOL method has been applied successfully in about 50 publications often with better results than other steric approaches, including MTD and MTD, especially in series with few substituent positions. A recent example is our study of DDT analogs. Brown et al. (9J analysed a series of 21 derivatives using the van de Waals (Vw) volumes as steric parameters. In Table I the equations are given in which the steric parameters are compared. 

STERIMOL and MTD (Minimum Topological Difference) steric parameters to account for steric influences in QSAR of pesticides have been described and applied in the literature. We have recently developed an improved version of the Simon MTD method, i.e. MTD parameters. The MTD and MTD methods will be described. The scope and limitations of the STERIMOL,... 

When less substituent positions are present STERIMOL can be used but in those cases there is often hardly any difference in results if compared with the MTD method. This is illustrated by our version of the QSAR of the insecticidal activity against American cockroaches of 36 substituted benzyl chrysanthemates. 

These results give some insight in the scope and limitations of the MTD, MTD and STERIMOL parameters. Let us first compare the MTD and MTD methods. In the example of the benzyl chrysanthemates the regression equations have only steric terms, sothat there is no difference between the two methods in principle. In the case of the benzoylphenyl ureas the intercorrelation between the MTD values and the other parameters is very low, so it is understandable that there is hardly any difference. But in the four other studies there was much more intercorrelation between the MTD values on the one hand and the electronic and/or hydrophobic parameters on the other hand, and in these cases the MTD method gives slightly better results. Our preliminary conclusion from the examples discussed, is that the MTD is the preferable one, both from fundamental and... 

The compounds were synthesized according to known methods. The Sterimol parameters by Verloop et al. (16.17) proved very useful in the QSAR work. CNDO/2 calculations were carried out by using a QCPE program ( ) which was modified inhouse. studies were made in... 

Sigma-rho corrections were assigned equally to the substituents at positions 6 and 7. Revised STERIMOL (L, B1 and B5) parameters were calculated following established methods.f27.28l The data matrices consist of lipophilicity (F), molar refractivity (MR), STERIMOL (L, Bl, B5) parameters and de novo indicator variables for substituents in positions 1, 6 and 7. The contribution to the partition coefficient by the substituents at positions 6 and 7 were summed, 2F(6,7), as were the molar refractivity contributions, 2MR(6,7). These two sets of summed variables paralleled a similar approach used by Koga in his QSAR analysis of a set of quinoline derivatives. (231 At the same time, the limitations that apply to summed n values, particularly where there is a significant a-p interaction were kept in mind.f22.29.301 The latter is represented as API in the data tables and its significance was evaluated in some of the regression models. In order to check for parabolic relationships, squared terms for the partition coefficient, molar refraction, and STERIMOL parameters were evaluated. 

Turning to a series of larvicides, the Dutch workers obtained the best correlation by combining partition and Hammett-sigma values with two sterimol terms (Z) and (- 4). In subsequent work, the Verloop method was subtly refined to increase predictive powers a new table of substituent values was issued, and the arithmetical correspondence between B and was noted (Verloop, 1981, 1983). 

---