Qualitative structure-activity relationships QSAR

Qualitative structure-activity relationship (QSAR) methods (see Sect. 5.2). 

It is important to consider the molecular interactions in liquids that are responsible for their physicochemical properties (such as boiling point, melting point, heat of vaporization, surface tension, etc.), which enables one to both describe and relate the different properties of matter in a more clear manner (both qualitatively and quantitatively). These ideas form the basis for quantitative structure activity relationship (QSAR Birdi, 2002). This approach toward analysis and application is becoming more common due to the enormous help available from computers. 

In contrast to the qualitative better and worse approach of traditional SAR, many researchers have sought to develop a method that is able to quantitatively link molecular structure changes to biological activity, a quantitative structure-activity relationship (QSAR). As a method, QSAR strives to develop a mathematical formula to relate biological activity as a function of molecular or substituent properties. 

In addition to using PMs, predictions of toxic hazard can also be made by using structure-activity relationships (SARs). A quantitative structure-activity relationship (QSAR) can be defined as any mathematical model for predicting biological activity from the structure or physicochemical properties of a chemical. In this chapter, the premodifer quantitative is used in accordance with the recommendation of Livingstone (1995) to indicate that a quantitative measure of chemical structure is used. In contrast, a SAR is simply a (qualitative) association between a specific molecular (sub)structure and biological activity. 

Structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs), referred to collectively as QSARs, can be used for the prediction of physicochemical properties, environmental fate parameters (e.g., accumulation and biodegradation), human health effects, and ecotoxicological effects. A SAR is a (qualitative) association between a chemical substructure and the potential of a chemical containing the substructure to exhibit a certain physical or biological effect. A QS AR is a mathematical model that relates a quantitative measure of chemical structure (e.g., a physicochemical property) to a physical property or to a biological effect (e.g., a toxicological endpoint). 

Roberts, D.W. 1989. Aquatic toxicity of linear alkyl benzene sulphonates (LAS) - a QSAR analysis. Communicaciones Presentadas a las Jomadas del Comite Espanol de la Detergencia, 20 (1989) 35-43. Also in J.E. Turner, M.W. England, T.W. Schultz and N.J. Kwaak (eds.) QSAR 88. Proc. Third International Workshop on Qualitative Structure-Activity Relationships in Environmental Toxicology, 22-26 May 1988, Knoxville, Tennessee, pp. 91-98. Available from the National Technical Information Service, US Dept, of Commerce, Springfield, VA... 

Qualitative stmcture-activity relationships (SAR) for binding affinity or ADME (absorption, distribution, metabolism, excretion) parameters can be developed within a particular compound series. Even more powerful though to guide the chemist in the design process are quantitative structure-activity relationships (QSAR), using various statistical and mathematical tools. 

As previously mentioned, the acronym QSAR stands for the quantitative structure-activity relationship. However, there may be some ambiguity associated with the attribute quantitative. It does not necessarily follows that results expressed or having numerical representation are necessarily quantitative. Qualitative results can equally be numerically represented. Strictly speaking, we define and view QSAR models as quantitative only when the numerically expressed models allow meaningful interpretation of the numerical results obtained for the structure-activity relationship within the basic concepts of the particular model. This means that the physicochemical models should allow quantitative interpretation of the numerical physicochemical descriptors used and that the structure-mathematical models should allow quantitative interpretation of the numerical structure-mathematical descriptors used. We will use the symbol qsar and QSAR as the abbreviation for qualitative structure-activity relationship. Such are the relationships that are non-numerical and the relationships that may be numerical but the variables used are interrelated and thus do not allow unique interpretation of the MRA equations. Because all molecular descriptors hitherto used in QSAR, whether they are based on physicochemical properties, quantum mechanical calculations, or molecular graphs, are all interrelated, it follows that all such hitherto reported results, without further elaboration, remain essentially qualitative, being qsar rather than QSAR. 

In this chapter, we have provided a critical view of the 3D-QSAR arena, some practical steps for modeling with CoMFA, and a set of criteria for assessing model validity. The need for quantitative models stems from the difficulty in discerning simple, intuitive (qualitative) structure-activity relationships. Although QSAR provides a rational framework for testing hypotheses, the QSAR models remain oversimplifications of the modeled process, and as such, are incomplete. The ultimate utility of any model rests with the scientist Is the model better than having no model at all ... 

SAR work can be classified into two categories QSAR (quantitative structure-activity relationships) and qSAR (qualitative structure-activity relationships). In QSAR analysis, biological activity is quantitatively expressed as a function of physico-chemical properties of molecules. QSAR involves modeling a continuous activity for quantitative prediction of the activity of new compounds. qSAR aims to separate the compounds into a number of discrete types, such as active and inactive or good and bad. It involves modeling a discrete activity for qualitative prediction of the activity of new compounds. 

A Structure-Activity Relationship (SAR) is the relationship of the molecular structure of a chemical with a physico-chemical property, environmental fate attribute, and/or specific effect on human health or an environmental species. These correlations may be qualitative (simple SAR) or quantitative (QSAR) (OECD 2002). 

Quantitative structure-activity relationship studies are of great importance in modern chemistry. From their origin in the study of organic chemistry dating back to the 19th century, these studies have relied on some empirical and qualitative rules about the reactivity similarities of compounds with similar structures. The most significant development in QSARs occurred with the work of Louis Hammett (1894-1987), who correlated some electronic properties of organic acids and bases with their equilibrium constants and reactivity (Johnson, 1973). Hammett postulated that the effect... 

---