Quantitative Structure^retention Relationships (qsrr) Inchromatography

To relate structure and chromatographic retention an approach is needed that lacks the rigour of thermodynamics but which provides otherwise inaccessible information. Such an approach is a combination of detailed models with certain thermodynamic concepts. Linear free-energy relationships (LFER) may be regarded as linear relationships between the logarithms of the rate or equilibria constants for one reaction series and those for a second reaction series subjected to the same variation in reactant structure or reaction conditions. Retention parameters can be assumed to reSect the free-energy changes associated with the chromatographic distribution process. Accordingly, a chromatographic column can be treated as a ‘free-energy transducer’, translating differences in chemical potentials of analytes, arising from differences in their structure, into quantitative differences in retention parameters. Assuming LFER it is possible to determine relative inputs of individual structural groups, fragments or features, to a property measured for a series of compounds in various chemical, physical, physicochemical and biological experiments. Such structural parameters (descriptors) can then be related to retention parameters. The existence of LFER is normally proved statistically. The basic methodology of employing LFER to predict differences in pharmacological activity within a series of related agents was proposed in 1964 by Hansch and Fujita (QSAR, quantitative structure}activity relationships). Multiple regression analysis was applied in 1977 to chromatographic data (QSRR, quantitative structure}retention relationships). Other chemometric methods of data analysis have since been introduced to QSRR. QSRR are now one of the most extensively studied manifestations of LFER and, at the same time, the most common application of chemometrics. Methodology and Goals of QSRR Analysis