Thermodynamics context-based approaches

To circumvent the above problems with mass action schemes, it is necessary to use a more general thermodynamic formalism based on parameters known as interaction coefficients, also called Donnan coefficients in some contexts (Record et al, 1998). This approach is completely general it requires no assumptions about the types of interactions the ions may make with the RNA or the kinds of environments the ions may occupy. Although interaction parameters are a fundamental concept in thermodynamics and have been widely applied to biophysical problems, the literature on this topic can be difficult to access for anyone not already familiar with the formalism, and the application of interaction coefficients to the mixed monovalent-divalent cation solutions commonly used for RNA studies has received only limited attention (Grilley et al, 2006 Misra and Draper, 1999). For these reasons, the following theory section sets out the main concepts of the preferential interaction formalism in some detail, and outlines derivations of formulas relevant to monovalent ion-RNA interactions. Section 3 presents example analyses of experimental data, and extends the preferential interaction formalism to solutions of mixed salts (i.e., KC1 and MgCl2). The section includes discussions of potential sources of error and practical considerations in data analysis for experiments with both mono- and divalent ions. 

Recently, fragment based drug design (FBDD) has emerged as a popular structure based approach to lead discovery. Despite the success of FBDD for myriad proteins, the thermodynamic basis for its success remains elusive. Using stromelysin-1 (MMP-3) as a model system and two previously described ligands, we have characterized extensively the thermodynamic principles of additivity and cooperativity in the context of FBDD. The results of these studies and their implications for drug discovery will be discussed. 

It should be clear that any partially direct approach (e.g., the use of predetermined lists of compounds) is not consistent with the complete and comprehensive requirements of either the direct or the phased environmental assessment philosophy and therefore is not an alternative to either approach. Similarly, a priori judgments based on process chemistry, thermodynamics, etc. are not acceptable practices in this context. 

In the context of a chapter on plaque as a reservoir for active ingredients, plaque structure has an important influence on the penetration and clearance of such materials and also of various other species involved in the caries process. We have discussed in previous sections the thermodynamic approach to caries susceptibility adopted by Margolis et al. [1,4-5] that focuses on calculations of the DS of the plaque fluid with respect to dental enamel based on extensive chemical analyses of plaque samples. Dawes, Dibdin and their co-workers [12-19], on the other hand, have modelled essentially the kinetics of the saliva-plaque system to compute Stephan curves within plaque and at the enamel surface following sucrose exposure. Sucrose (and related highly water-soluble species such as glucose) strictly speaking are not retained in plaque, but are either rapidly cleared from the mouth by saliva or converted to other molecules by plaque bacteria. The H+ ions that determine pH are one product of such conversion processes and are retained to an extent. 

In this chapter we present a simple model calculation that demonstrates how this cooperative motion affects the scattering spectrum. Our approach is based on the Debye-Onsager treatment of ion transport (see Falkenhagen, 1934 Stephen, 1971). This is our first discussion of cooperative effects in light scattering. In Chapter 13 this problem is reconsidered in the context of the general theory of nonequilibrium thermodynamics. 

In real systems, nonrandom mixing effects, potentially caused by local polymer architecture and interchain forces, can have profound consequences on how intermolecular attractive potentials influence miscibility. Such nonideal effects can lead to large corrections, of both excess entropic and enthalpic origin, to the mean-field Flory-Huggins theory. As discussed in Section IV, for flexible chain blends of prime experimental interest the excess entropic contribution seems very small. Thus, attractive interactions, or enthalpy of mixing effects, are expected to often play a dominant role in determining blend miscibility. In this section we examine these enthalpic effects within the context of thermodynamic pertubation theory for atomistic, semiflexible, and Gaussian thread models. In addition, the validity of a Hildebrand-like molecular solubility parameter approach based on pure component properties is examined. 

---