Homologous series, quantitative

Blakey GE, Nestorov lA, Arundel PA, Aarons LJ, Rowland M. Quantitative structure-pharmacokinetics relationships I. Development of a whole-body physiologically based model to characterize changes in pharmacokinetics across a homologous series of barbiturates in the rat. J Pharmacokinet Biopharm 1997 Jun 25(3) 277-312. Erratum in J Pharmacokinet Biopharm 1998 Feb 26(l) 131. 

Although cSFC shows relatively poor figures of merit (speed, sensitivity, detection dynamic range and sample capacity) as well as a limited application area, its applications tend to be unique. These include solutes that can be solvated with pure SCCO2 and quantified with FID. Linear density programs typical in cSFC are ideal for homologous series found in surfactants, many prepolymers, etc. Selectivity in cSFC, which can be achieved by mobile phase density and temperature programming, relies on selective interactions with the stationary phase. Quantitative analysis in cSFC may be rendered difficult by small injected volumes the use of internal standards is recommended. 

SN2 reactions of primary organolithium compounds on PMMA in dilute homogeneous solution may be considered as a model system where all the important reaction parameters may be controlled they allow both a quantitative analysis of PMMA chain reactivity and the synthesis of well defined ketonic copolymers within a wide range of possible structural variations. The two homologous series of organolithium compounds and the corresponding reaction conditions we selected are given below ... 

To understand micelle formation quantitatively, critical micelle concentrations (cmc) have to be determined for a large number of surf actants ( 5 ). When the cmc values of the surfactants with the same hydrophilic group (a homologous series) are examined, a nearly 3-fold decrease in cmc is observed for nonlonlc and zwitterionlc surfactants (1,2) upon the addition of a methylene group into the hydrocarbon chain, whereas, a 2-fold or only 1.8-fold reduction in cmc can be observed for univalent (1,2) and blvalent( ) ionic surfactants,respectively. 

Bassette and Keeney (1960) ascribed the cereal-type flavor in dry skim milk to a homologous series of saturated aldehydes resulting from lipid oxidation in conjunction with products of the browning reaction. The results of Parks and Patton (1961) suggest that saturated and unsaturated aldehydes at levels near threshold may impart an off-flavor suggestive of staleness in dry whole milk. Wishner and Keeney (1963) concluded from studies on milk exposed to sunlight that C6 to Cn alk-2-enals are important contributors to the oxidized flavor in this product. Parks et al. (1963) concluded, as a result of quantitative carbonyl analysis and flavor studies, that alk-2-4-dienals, especially... 

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. 

The effectiveness of heterogeneous defoaming is determined mainly by two factors the antifoam solubility and its ability to prevent adsorption of the surfactant at the aqueous film/antifoam interface, thus, destabilising the asymmetric aqueous films. The solubility of saturated alcohols in water and in aqueous surfactant solutions decreases with the increase in the molecular mass within the homologous series. The ability of alcohols to prevent adsorption change in the same direction. The difference between the interfacial tensions water/alcohol and aqueous surfactant solution/alcohol can serve as a quantitative measure for the change in the surfactant adsorption at the aqueous solution/alcohol interface... 

In summary the results observed in these studies [160] of poly(Sty-co-DVB) swelling in aromatic liquids serve to show that the method of measuring a is so sensitive that it can detect an effect caused by even the smallest modification in the molecular geometry of attached substituents, and that these differences correlate qualitatively with expectation based on the known principles of physico-organic chemistry of aromatic compounds. Since the observed a is the net effect of electronic attraction and steric hindrance between the sorbed molecule and the adsorption site, i.e. the monomer unit of the polymer, it would be impossible to separate quantitatively the electronic and steric contributions of a particular substituent. The ability to make such a differentiation, however, appears to be more promising with liquids that comprise homologous series of the type Z(CH2)nH (where Z is a phenyl, chloro, bromo or iodo substituent), since the added electronic contribution to Z by each additional methylene group is well known to be extremely small when n becomes >3 [165],... 

It has been shown that gas-Hquid chromatographic methods are particularly suitable for a quantitative characterization of the polarity of solvents. In gas-liquid chromatography it is possible to determine the solvent power of the stationary liquid phase very accurately for a large number of substances [98, 99, 259, 260]. Many groups of substances exhibit a certain dependence of their relative retention parameters on the solvation characteristics of the stationary phase or of the separable components. In determining universal gas-chromatographic characteristics, the so-called retention index, I, introduced by Kovats [100], is frequently used. The elution maxima of individual members of the homologous series of n-alkanes (C H2 +2) form the fixed points of the system of retention indices. The retention index is defined by means of Eq. (7-41),... 

Evans and Polanyi- have noted that in a homologous series of exothermic abstraction reactions (A + BC AB + C), the change in activation energy is related to the change in heat of reaction by the relation AAact = ofA act where a is a constant for a given series. The more recent and more accurate results on methyl radical abstractions would seem, however, to place limits on the quantitative value of the rule. Voevodskii has pro-... 

On closer investigation, however, it is found that rules II and III in particular are only in qualitative agreement with experimental results and fail to account for the latter quantitatively. In connexion with rule II we first notice that the moment is not constant for members of the same homologous series, but invariably depends on the hydrocarbon also, as Table I shows in the case of one or two substances. 

To strike a balance, structural information will be presented only for those cases of direct relevance to the photoinitiated reactions, namely (i) a few examples of CO2-HX and N2O-HX spectra in which large, qualitative differences can be seen, (ii) a compilation of all experimentally derived distances and angles, and (iii) comparisons to calculated values, when a combination of experiment and theory is needed to draw conclusions. What has been rather absent so far in studies of weakly bonded complexes, is information about systems involving heavy atoms. It is true that species like iodine and bromine do not necessarily bring joy to the lives of electronic structure theorists, but these are the systems most amenable to the experimental photoinitiated reaction studies. Also, the possibility of marked differences for seemingly homologous series makes quantitative evaluations imperative. Our discovery of the qualitative structural difference between CO2-HCI and C02-HBr underscores this point [34]. As pragmatists, we were able to quickly exploit this difference, but more importantly, it may be possible in the future to systematically use such differences to examine different photochemical entrance channels. 

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. 

S. Nestorov, S. T. Hadjitodorov, I. Petrov, and M. Rowland, Empirical versns mechanistic modelling comparison of an artificial nenral network to a mechanistically based model for quantitative structure pharmacokinetic relationships of a homologous series of barbiturates. AAPS Pharm Sci 1 E17 (1999). 

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