Lemont B. Kier

Molecular connectivity of phenols and their toxicity to fish

Reliable studies on the toxicity of a large number of compounds have recently become available to the scientific community from the Environmental Research Laboratory at Duluth, Minnesota, The Stanford Research Institute and the University of Wisconsin at Superior. This extensive database makes it possible to contact QSAR studies for the purpose of establishing structural relationships with toxicity in order to make predictions and possibly shed light on the mechanisms involved. One group of compounds, the phenols, are of particular interest due to their wide use and potential for environmental contamination. The purpose of this study is to relate the relative toxicity to the structure in an effort to make predictions about the toxic potentiality of other phenols.

Structure-activity studies on odor molecules using molecular connectivity

Abstract Several classes of odorants have been examined using a newly developed structural analysis known as molecular connectivity. Within each class significant correlations have been found between odor similarities to a reference standard and connectivity terms. In each case some interpretation is possible as to certain structure-activity relationships imparting odor.

A molecular connectivity study of electron density in alkanes

Abstract Molecular connectivity indices have been developed which characterize contributions of neighboring atoms to the CNDO/2 calculated electronic charge of a carbon atom. An analysis of these indices reveals their ability to predict this charge to 0.001 electron.

Structural influences and mechanisms of toxic effects of alcohols and their derivatives

ConclusionThe simple connectivity index1χ gives a reasonable account of the variation of potency with molecular structure for each of the cases presented here. The behavior of the alcohols is described better by the simple linear relationship than is the behavior of the xanthates, especially for inhibition of Tubifex worms and fish narcosis. Although a bilinear or nonlinear relationship may give improved description in these cases, lack of data in the region of higher monologs makes such equations difficult to justify on statistical grounds.The fact that the simple (nonvalence) index gives good correlation suggests that the heteroatoms (alcohol or xanthate group) plays a constant role in the biological processes. Variation in potency arises from variation in alkyl group structure.

Psychotomimetic phenalkylamines as serotonin agonists: An SAR analysis

Abstract The structure-activity relationships of a series of psychotomimetic phenethylamine and phenylisopropylamine analogs were examined using a molecular connectivity analysis. Greater than 90% of the variance in their activity as serotonin agonists in a model system can be explained on this basis.

Molecular connectivity and total response surface optimization

Abstract The relation between biological activity and molecular structure may be viewed mathematically as a surface. The maximum or minimum position on the surface is associated with optimum activity and structure parameters. A useful approach to QSAR is to identify the optimum structure and relate it to drug design. Such an approach has been applied to the neurotoxicity of 21 substituted phosphorus compounds using molecular connectivity indexes. Two-variable transformations are used. The first, not directly related to surface optimization, introduces the sum and difference of the first order chi indexes. These transformed variables are shown to represent size and electronic effects, respectively. Using these variables in the full five-variable quadratic expression, excellent statistics are achieved: r = 0.979, s = 0.18, F = 68, n = 21. The second transformation, moving the origin to the surface extremum, reduced the equation to three variables while retaining the high quality statistics. Detailed discussion of interpretation is presented.

Structure-activity studies on hallucinogenic amphetamines using model interaction calculations☆

Abstract In summary, we can briefly describe the model as developed at this time. We view the amphetamine receptor as possessing two principal features: one site provides anchoring for the onium group, whereas the other feature interacts with the phenyl ring and substitutents. In addition, there is implied the presence of a feature associated with the 3,4 region of the phenyl ring. The best model for the phenyl ring receptor is the methylindole molecule with the two rings, one directly above the other at a separation distance of 4·5 A. The correlation from these results [equation (2)] is better than that reported for any other SAR study to date, accounting for 74 % of the variation in the data. Further inclusion of a term relating to distribution or absorption improves the correlation so that 82Y. of the variation is accounted for. This provisional model can now be tested against data for other amphetamines, mescalines, tryptamines and other hallucinogenic agents.