Steric constant Sterimol

For years, we have been studying QSAR (quantitative structure-activity relationship) analyses of pesticides and other bioactive compounds. In many examples, we have found a decisive role of the steric effect in determining the activity variation. In this chapter, applications of various steric constants such as E E°, Vw and STERIMOL parameters to QSAR studies mostly from our own laboratory are reviewed. 

Other parameters (molar refractivity of the molecules/substituents, molar volume, Taft s steric constant, and Verio op s sterimol parameters) also appear in several QSAR. In some cases, these parameters correlate all of the observed variations in activity, but they do not seem to play as important a role as hydrophobicity for the data sets that we have examined. 

The Sterimol Steric constants were developed by Verloop (30)... 

The use of the QSAR technique known as the Hansch Approach in the investigation of odor intensity and odorant physico-chemical properties has indicated that hydrophobic properties of homologous series of compounds, not steric or polar properties, are highly correlated to the level of odor intensity. This was shown to be the case for literature odor threshold and suprathreshold data determined at different laboratories using various media. The poor correlation between odor intensity and the steric properties of molecules (Taft Steric Constant) which had been reported earlier by this author (11) have been further verified by the use of Charton and Verloop Sterimol steric parameters. 

While the development of the Taft parameter is similar to that of Hammett and Hansch, / )-val ucs are based on rate constants instead of equilibrium constants. The Taft parameter is a measure of changes in activation energy, not standard free energy. Of the Hammett, Hansch, and Taft parameters, the Taft parameter is utilized the least in QSAR studies. Other steric parameters have been developed over time, and like the Taft parameter, all have shortcomings. One alternative steric parameter was developed by Marvin Charton of Pratt Institute in New York. Charton s parameter is based on the van der Waal radius of a substituent.6 Another alternative steric model is the STERIMOL parameter set developed by Arie Verloop of Philips-Duphar in Holland.7 Unlike Taft and Charton, Verloop... 

The major electronic factor influencing the activity has been Hammett s constant a. In some cases, the steric factors were also found to be important, e.g., Bs the Sterimol parameter for the largest width of substituents and L the Sterimol parameter for the length of the substituents. The positive coef-Acients of these parameters give an important positive contribution of width and length of substituents to the inhibition. The values of Taft steric param-... 

MR molar refractivity it hydrophobic substituent constant and Op overall electronic constants for meta- and para-position K and p Swain-Lupton resonance and field constants L Sterimol length parameter B1 and B5 Sterimol B parameters SD Dash-Behera steric density parameter. 

Hydrophobic parameters are mostly experimentally obtained log P or calculated log P (C log P), where P is the octanol-water partition coefficient. n is the hydrophobic constant of the substituents. The electronic parameters (Hammett constants) a, a and appHes to substituent effects on aromatic systems and Taft s a appHes to ahphatic systems. Steric parameters are Tafts steric parameter Es, McGowan volume MgVol, van der Waals volume Vw, molecular weight MW. Verloop s sterimol parameters Bl, B5 and L... 

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