Linear free energy relationship methodology

Computational chemistry methodology is finding increasing application to the design of new flavoring agents. This chapter surveys several useful techniques linear free energy relationships, quantitative structure-activity relationships, conformational analysis, electronic structure calculations, and statistical methods. Applications to the study of artificial sweeteners are described. 

However equally important is the availability of physically grounded models that can provide understanding of chemical reactivity. In the past, theories of reactivity have been based on empirical structure-reactivity relationships (viz. linear free energy relationships) or qualitative theoretical concepts (viz. Woodward-Hoffmann approach or the frontier orbital method)[4-ll]. However, there is a different approach, which is potentially more fruitful. In this approach one uses physically grounded models that can be obtained from the best state of the art methodology of quantum chemistry. These physically grounded models must be both quantitative and qualitative. On the one hand, any model used should reproduce the numerically computed quantities exactly, on the... 

The surface tension component method assumes that surface tension can be partitioned into different components, which address different intermolecular interactions individually. The overall surface tension will be the sum of all the components according to the linear free energy relationship. In the original Fowkes method [14], only the dispersion interaction is considered. The component method has been subsequentiy extended to include polar component and later divided the polar component into dipolar interaction and H-bonding interaction. The vOCG model appeared as a refined version of the surface tension component methodology. It assumes the existence of both additive and nonadditive components. The Lifshitz-van der Waals component (/ ) is additive, and the electron donor and acceptor components (7 and 7" ) are nonadditive. The solid surface tension (7sv) can be calculated by using three Uquids with known y, y and y values. Since this is a semiempirical approach, the calcu-... 

Iwamura(51) has investigated the structure-sweetness relationship in four classes of L-aspartyl dipeptides using linear free energy descriptors and multi-dimensional regression analysis. In essence, the Hansch methodology was employed. The four classes of compounds are - ... 

Before analyzing concrete cases, a theoretical introduction with respect to some basic methodological issues will be provided in the next section. The methods to be applied are quantum mechanical calculations, which are different from the use of the linear solvation free energy relationships for predicting the equilibrium constant, as described in Chapter 12 of [1]. It is to be mentioned here that the forthcoming discussion of the theoretical results for the prototropic tautomerism always refers to ground-state processes. 

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