Steric parameters bioactive compounds

Bulk and Steric Parameters in Binding and Reactivity of Bioactive Compounds... 

Analysis of the Hansch descriptors illustrates that increasing the lipophilicity property for this series of compounds will increase the bioactivity in a more dramatic fashion than increasing the Tafts steric parameter. Increasing the water accessible surface area (MOE descriptor) will increase the bioactivity of the compounds. But there is more than just adding lipophilicity and water accessible surface area to the molecules to increase binding affinity. A comparison of the substituents to the bioactivities illustrates that the bulkier X and Y groups increase bioactivity in conjunction with atomic partial charge distribution of the substituents. 

In a parallel development, structural effects on the chemical reactivity and physical properties of organic compounds were modelled quantitatively by the Hammett equation 8). The topic is well reviewed by Shorter 9>. Hansen 10) attempted to apply the Hammett equation to biological activities, while Zahradnik U) suggested an analogous equation applicable to biological activities. The major step forward is due to the work of Hansch and Fujita12), who showed that a correlation equation which accounted for both electrical and hydrophobic effects could successfully model bioactivities. In later work, steric parameters were included 13). 

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. 

As exemplified above, various steric parameters can be properly utilized in QSAR studies depending upon the situation involved in the interaction between bioactive compounds and biomacromolecule. 

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