Computer Automated Structure Evaluation Methodology Research Articles

Application of the multiple computer automated structure evaluation methodology to a quantitative structure–activity relationship study of acidity

AbstractWe applied the Multiple Computer Automated Structure Evaluation (Multi‐CASE) program to the analysis of the relationship between the structure of 2464 organic acids and their (first) pKa values. By using the self‐created expert dictionary of molecular attributes pertinent to acidity, the program could make successful a priori prediction of the acidity of new organic compounds. © 1994 by John Wiley & Sons, Inc.

Multiple Computer Automated Structure Evaluation Methodology as an Alternative toIn VivoEye Irritation Testing

The Multiple Computer Automated Structure Evaluation (Multi-CASE) methodology was applied to the semi-quantitative analysis of eye irritation potential of 186 organic chemicals. The resulting expert dictionary of substructural attributes indicates that the following functionalities are linked to eye irritation potential: carboxylate and sulphonate groups in anionic surfactants, phenolic moieties in non-ionic surfactants, amino groups, halogenated and unsaturated structures, anhydrides and epoxides. Ester groups were recognised as having a low irritation potential. The Multi-CASE program successfully predicted a priori the eye irritation potential of: 1) 21 individual chemicals; 2) chemical mixtures such as coconut oil, hydrogenated castor oil, rice bran, eucalyptus oils and potassium alginate; and 3) polymers,’ including polyvinyl alcohols, polyvinyl butyral, polyvinyl pyrrolidone, corn starch and nylon. It was found that the structure of the repeat units together, and not that of the individual monomers, is the best predictor of the eye irritation potential of the corresponding polymers. It appears that the repeat units of polymers dilute out the irritation potential of terminal groups normally expected to contribute significant irritation potential to chemicals of lower molecular weight.The Multi-CASE eye irritation model can be used for: 1) in vitro prescreening for eye irritation potential; and 2) design and modification of chemicals when low eye irritation potential is important.

Application of the computer automated structure evaluation methodology to a QSAR study of chemoreception. Aromatic musky odorants

Eighty-seven nitro-free aromatic musks and 65 of their odorless structural analogs were studied using the computer automated structure evaluation (CASE) methodology. A QSAR equation relating the strength of musky odor to 23 structural descriptors and (Log f12 was obtained. Lipophilicity appears to be less important than structural features for the strength of musky odor. A hierarchical MultiCASE analysis identified nine structural determinants responsible for the musky smell as well as seven dearomatizing fragments. This allowed speculations about the spatial requirements for interaction between a musk molecule and a hypothetical musky odor receptor. In random testing the (Multi-)CASE model was able to predict a priori 9 of 10 musky odorants and 8 of 9 odorless chemicals correctly. Forty-six nitrated musks were analyzed. Overlap was found between the structural requirements for musky odor in nitrated and nitro-free musks.