Congenerity

The Morgan Algorithm classifies all the congeneric atoms of a compound and selects invariant-labeled atoms (see Section 2.5.3.1). The classification uses the concept of considering the number of neighbors of an atom (connectivity), and does so in an iterative manner (extended connectivity, EC). On the basis of certain rules. 

Two approaches to quantify/fQ, i.e., to establish a quantitative relationship between the structural features of a compoimd and its properties, are described in this section quantitative structure-property relationships (QSPR) and linear free energy relationships (LFER) cf. Section 3.4.2.2). The LFER approach is important for historical reasons because it contributed the first attempt to predict the property of a compound from an analysis of its structure. LFERs can be established only for congeneric series of compounds, i.e., sets of compounds that share the same skeleton and only have variations in the substituents attached to this skeleton. As examples of a QSPR approach, currently available methods for the prediction of the octanol/water partition coefficient, log P, and of aqueous solubility, log S, of organic compoimds are described in Section 10.1.4 and Section 10.15, respectively. 

The hydrophobic constant r is a measure of the contribution of a substituent X to the lipophilidty of compound R-X compared with R-H. The constant representing the solvent/solvent system, analogously to Hammett s p constant for the reaction type, was arbitrarily set to 1 for octanol/water and thus does not appear in Eq. (7). The lipophilidty constant ti allows the estimation of log P values for congeneric series of compounds with various substituents (see Eq. (8)). 

The fundamental assumption of SAR and QSAR (Structure-Activity Relationships and Quantitative Structure-Activity Relationships) is that the activity of a compound is related to its structural and/or physicochemical properties. In a classic article Corwin Hansch formulated Eq. (15) as a linear frcc-cncrgy related model for the biological activity (e.g.. toxicity) of a group of congeneric chemicals [37, in which the inverse of C, the concentration effect of the toxicant, is related to a hy-drophobidty term, FI, an electronic term, a (the Hammett substituent constant). Stcric terms can be added to this equation (typically Taft s steric parameter, E,). 

Table 2. Congeneric Content of Various Distilled Alcoholic Beverages ...

Figure 4.2 Steam cycle path in WT boiler congeneration plant.

Their advantages are that they are simple to use and are transparent that is, the descriptors that best model the biological activity can be seen and— hopefully—understood. Their disadvantages are that they work best when restricted to congeneric series of compounds, they assume that the biological activity is a rectilinear function of each descriptor, and they can suffer from a high risk of chance correlations, especially when a large pool of descriptors is used. 

A key requirement of QSAR is that the compounds used in the modeling and prediction processes should have the same mechanism of action, and for this reason most QSAR studies are made with congeneric series of compounds. However, if a diverse set of compounds can reasonably be assumed to have the same mechanism of action, QSAR modeling can justihably be carried out. For example, Dearden et al. [43] developed a QSAR for the ratio of brain levels of 22 very diverse drugs in the wild-type mouse and the P-glycoprotein knockout mouse (R+/ ) ... 

Poroikov VV, Filimonov DA, Borodina YuV, Lagunin AA, Kos A. Robustness of biological activity spectra predicting by computer program PASS for non-congeneric sets of chemical compounds. J Chem Inf Comput Sci 2000 40 1349-55. 

The elements Zr and Hf are generally more similar in their chemistry than any other pair of congeneric elements as having nearly identical atomic or ionic radii, electronegativities, and elemental structures (actually, the similarities of Nb and Ta are nearly as close) however, their metal-rich chemistry is often surprising in its structural and physical aspects with fairly sharp distinctions emerging between the two elements [71]. 

Trone, M. D., Leonard, M. S., Khaledi, M. G. Congeneric behavior in estimations of octanol-water partition coefficients by micellar electrokinetic chromatography. Anal. Chem. 2000, 72, 1228-1235. 

Example of a Prey-Fish Indicator Yellow Perch Analyses of total mercnry in whole bodies or axial muscle tissue of age-1 yellow perch have provided a useful measure of MeHg concentrations in food webs of many North American lakes. This widely distributed species inhabits lakes and reservoirs across mnch of the north-central, northeastern, and eastern United States and across the central and eastern provinces of Canada (Scott and Crossman 1973 Becker 1983). An ecologically similar congeneric species, the Eurasian perch Perea fluvi-atilis), is distribnted across much of Europe and northern Asia (Thorpe 1977). 

The same assumptions apply to CoMFA as to ordinary Hansch analysis. These are additivity of effects and the availability of structurally similar (congeneric) molecules. The method does not account for pharmacokinetic effects, such as distribution, elimination, transport and metabolization. A prospective drug may appear to bind well to the receptor or enzyme, but may not reach the target site due to undesirable pharmacokinetic properties [8]. 

However, from our point of view, there remains a lack of sufficiently precise and reliable methods to compute thermodynamic water solubility. The majority of methods work only for congeneric series of compounds, and many have not been developed to function in areas of pharmaceutical research using drug-like molecules. Most of the methods do not use the three-dimensional structure of the compounds, while some depend on previous knowledge of certain experimental properties of the compounds of interest. Moreover, all of the methods are dependent upon the quality of solubility values in the training set used to develop the model indeed, this latter point is a critical limitation that has a major influence on solubility estimations. 

Hirono, S., Nakagome, I., Hirano, H. Matsuhita, Y., Yoshi, F., Moriguchi, I., Non-congeneric structure-pharmacokinetic property correlation studies using fuzzy adaptive least squared oral bioavailability, Biol. Pharm. Bull. 1994, 37, 306—309. 

Shiu, W.-Y., Gobas, F. A. P. C., Mackay, D. (1987) Physical-chemical properties of three congeneric series of chlorinated aromatic hydrocarbons. In QSAR in Environmental Toxicology II. Kaiser, K. L. E., Ed., pp. 347-362, D. Reidel Publishing, Dordrecht, The Netherlands. 

The existence of an evapotranspiration barrier in the upper soil horizon of Dry and Extra-Dry Desert ecosystems favors the accumulation of alkalinity and alkaline reaction of soil solution. In turn this accelerates the mineralization of organic matter and mobilization of finely dispersed mineral and organic suspensions. This fact provides a plausible explanation of the occurrence of some heavy metals, like Zr, Ti, Ga, Yt and their congeneric elements in the aqueous extracts from soil samples of Dry Desert ecosystems. 

The role of chemosignals in the maintenance of species isolation is supported by observations that the species L. jamesi, L. bellii, and L. lemniscatus, are able to discriminate between conspecifics and congeneric individuals (Labra et al. 2001 unpublished data). Moreover, these species do not discriminate between sympatric and allopatric congeneric species. In sympatry, the recognition of an individual as a non-conspecific reduces the possibility of hybridization among congeneric species. 

Basak, S. C., Mills, D., Gute, B. D., Hawkins, D. M. Predicting mutagenicity of congeneric and diverse sets of chemicals using computed molecular descriptors ... 

Cocchi, M., Menziani, M.C., Fanelli, F. and De Benedetti, P.G. (1995) Theoretical quantitative structure-activity relationship analysis of congeneric and non congeneric al-adrenoceptor antagonists a chemometric study. Journal of Molecular Structure (Theochem), 331, 79-93. 

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