Quantitative structure-physical property applications

When the property being described is a physical property, such as the boiling point, this is referred to as a quantitative structure-property relationship (QSPR). When the property being described is a type of biological activity, such as drug activity, this is referred to as a quantitative structure-activity relationship (QSAR). Our discussion will first address QSPR. All the points covered in the QSPR section are also applicable to QSAR, which is discussed next. 

In this review recent theoretical developments which enable quantitative measures of molecular orientation in polymers to be obtained from infra-red and Raman spectroscopy and nuclear magnetic resonance have been discussed in some detail. Although this is clearly a subject of some complexity, it has been possible to show that the systematic application of these techniques to polyethylene terephthalate and polytetramethylene terephthalate can provide unique information of considerable value. This information can be used on the one hand to gain an understanding of the mechanisms of deformation, and on the other to provide a structural understanding of physical properties, especially mechanical properties. 

The final physical properties of thermoset polymers depend primarily on the network structure that is developed during cure. Development of improved thermosets has been hampered by the lack of quantitative relationships between polymer variables and final physical properties. The development of a mathematical relationship between formulation and final cure properties is a formidable task requiring detailed characterization of the polymer components, an understanding of the cure chemistry and a model of the cure kinetics, determination of cure process variables (air temperature, heat transfer etc.), a relationship between cure chemistry and network structure, and the existence of a network structure parameter that correlates with physical properties. The lack of availability of easy-to-use network structure models which are applicable to the complex crosslinking systems typical of "real-world" thermosets makes it difficult to develop such correlations. 

In a study by Andersson et al. [30], the possibilities to use quantitative structure-activity relationship (QSAR) models to predict physical chemical and ecotoxico-logical properties of approximately 200 different plastic additives have been assessed. Physical chemical properties were predicted with the U.S. Environmental Protection Agency Estimation Program Interface (EPI) Suite, Version 3.20. Aquatic ecotoxicity data were calculated by QSAR models in the Toxicity Estimation Software Tool (T.E.S.T.), version 3.3, from U.S. Environmental Protection Agency, as described by Rahmberg et al. [31]. To evaluate the applicability of the QSAR-based characterization factors, they were compared to experiment-based characterization factors for the same substances taken from the USEtox organics database [32], This was done for 39 plastic additives for which experiment-based characterization factors were already available. 

From the physics point of view, the system that we deal with here—a semiflexible polyelectrolyte that is packaged by protein complexes regularly spaced along its contour—is of a complexity that still allows the application of analytical and numerical models. For quantitative prediction of chromatin properties from such models, certain physical parameters must be known such as the dimensions of the nucleosomes and DNA, their surface charge, interactions, and mechanical flexibility. Current structural research on chromatin, oligonucleosomes, and DNA has brought us into a position where many such elementary physical parameters are known. Thus, our understanding of the components of the chromatin fiber is now at a level where predictions of physical properties of the fiber are possible and can be experimentally tested. 

In a parallel development, structural effects on the chemical reactivity and physical properties of organic compounds were modelled quantitatively by the Hammett equation 8). The topic is well reviewed by Shorter 9>. Hansen 10) attempted to apply the Hammett equation to biological activities, while Zahradnik U) suggested an analogous equation applicable to biological activities. The major step forward is due to the work of Hansch and Fujita12), who showed that a correlation equation which accounted for both electrical and hydrophobic effects could successfully model bioactivities. In later work, steric parameters were included 13). 

At the end of this volume the application of separation techniques in quantitative structure retention relationship studies and measurement of physical properties are discussed. This represents a special field of separation science where the results can be used directly in drug research and optimisation of the lead compound or can be fed back to method development for other separation problems, characterising not only the solutes but also the stationary phases. 

Phase-solubility analysis17 (sometimes referred to as phase equilibrium purification) is the quantitative determination of the purity of a substance through the application of precise solubility measurements. At a given temperature, a definite amount of a pure substance is soluble in a definite quantity of solvent. The resulting solution is saturated with respect to the particular substance, but the solution remains unsaturated with respect to other substances even though such substances may be closely related in chemical structure and physical properties to the particular substance being tested. There are examples of the use of this technique in HPLC methods development18 and in the characterization of reference standards,19 but the... 

The dissociations described above have mostly been identified as interface advance reactions for which the nucleation step occurs relatively readily. The dominant kinetic feature is the progress of the reaction zone inwards to the particle centres. The Polanyi-Wigner reaction model (Chapter 7) was developed to account for the rates of such processes. Shannon [83] identified 29 different chemical changes of this type and found that only one-third of the reported kinetic parameters were within an order of magnitude of the theoretically expected values. From these, the dissociations of CaCO, and MgCOj were selected for more quantitative application of the absolute reaction rate theory. The known crystal structure and physical properties of the participating bonds were used to represent the transition state as follows ... 

Biinz, A.P., Braun, B. and Janowsky, R. (1998) Application of quantitative structure-performance relationship and neural network models for the prediction of physical properties from molecular structure. Ind. Eng. Chem. Res., 37, 3044—3051. 

Mid-infrared (IR) spectroscopy is a well-established technique for the identification and structural analysis of chemical compounds. The peaks in the IR spectrum of a sample represent the excitation of vibrational modes of the molecules in the sample and thus are associated with the various chemical bonds and functional groups present in the molecules. Thus, the IR spectrum of a compound is one of its most characteristic physical properties and can be regarded as its "fingerprint." Infrared spectroscopy is also a powerful tool for quantitative analysis as the amount of infrared energy absorbed by a compound is proportional to its concentration. However, until recently, IR spectroscopy has seen fairly limited application in both the qualitative and the quantitative analysis of food systems, largely owing to experimental limitations. 

Quantitative infrared spectroscopy suffers certain disadvantages when compared with other analytical techniques and thus it tends to be confined to specialist applications. However, there are certain applications where it is used because it is cheaper or faster. The technique is often used for the analysis of one component of a mixture, particularly when the compounds in the mixture are alike chemically or haye very similar physical properties, e.g. structural isomers. In these cases, analysis by using ultraviolet/visible spectroscopy is difficult because the spectra of the components will be almost identical Chromatographic analysis may be of limited use because the separation of isomers, for example, is difficult to achieve. The infrared spectra of isomers are usually quite different in the fingerprint region. Another advantage of the infrared technique is that it is non-destructive and requires only a relatively small amount of sample. 

Epoxy thermosets are typical densely cross-linked polymer materials. They are used in a wide variety of practical applications and thus have been studied extensively. However, the quantitative dependence of physical properties, such as strength, stiffness, and fracture toughness, on network microstructure are largely undetermined. This can be attributed, in part, to the lack of adequate techniques for characterizing densely cross-linked network structure. Several microstructiu e variables that have been studied with some success are (1) cross-link density,... 

Althou, in principle, the general theory is superior to the band theory, the appropriate techniques for its application are not yet developed sufficiently well and a unified approach to a quantitative description of the structures and the physical properties of crystals is still lacking. The less generally valid band theory can at present give clearer and more convincing explanations of changes in the physical properties of crystals caused by variations in the temperature, pressure, magnetic and electric fields intensities, impurity concentrations, etc. However, many problems encoimtered in the study of chemical bonds in crystals cannot be considered within the framework of the standard band theory. They include, for example, determination of the elastic, thermal, and thermodynamic properties of solids, as well as the structure and properties of liquid and amorphous semiconductors. 

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