Homologous series, quantitative approach

Most chemists still tend to think about the structure and reactivity of atomic and molecular species in qualitative terms that are related to electron pairs and to unpaired electrons. Concepts utilizing these terms such as, for example, the Lewis theory of valence, have had and still have a considerable impact on many areas of chemistry. They are particularly useful when it is necessary to highlight the qualitative similarities between the structure and reactivity of molecules containing identical functional groups, or within a homologous series. Many organic chemistry textbooks continue to use full and half-arrows to indicate the supposed movement of electron pairs or single electrons in the description of reaction mechanisms. Such concepts are closely related to classical valence-bond (VB) theory which, however, is unable to compete with advanced molecular orbital (MO) approaches in the accurate calculation of the quantitative features of the potential surface associated with a chemical reaction. 

In keeping with this method, several approaches have been developed to document methods and dose-response relationships for irritation in humans. This work suggests that, at least for nonreactive compounds such esters, aldehydes, ketones, alcohols, carboxylic acids, aromatic hydrocarbons, and pyridine, the percentage of vapor pressure saturation of a compound is a reasonable predictor of its irritant potency. Specific physical properties of molecules predict overall irritation potential. This work is based on the identification of irritant thresholds for homologous series of specific agents. Quantitative structure-activity relationships derived from such work suggests a reasonable model to explain mucosal irritation. 

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