Solution-phase small-molecule

Molecular exclusion chromatography is based on the inability of large molecules to enter small pores in the stationary phase. Small molecules enter these pores and therefore exhibit longer elution times than large molecules. Molecular exclusion is used for separations based on size and for molecular mass determinations of macromolecules. In affinity chromatography, the stationary phase retains one particular solute in a complex mixture. After all other components have been eluted, the desired species is liberated by a change in conditions. 

The thermodynamics of macromolecular solutions with small molecules is described in Sect. 7.1. A term frequently used to describe solutions of macromolecules is blend. The word is obviously derived from the mixing process and should only be used when the resulting system is not fully analyzed, i.e., one does not know if a dissolution occurred or the phases remained partially or fully separated. The term blend should best be used only if a phase-separated system has changed by vigorous mixing to a finer subdivision, containing micro- or nanophases. The differences between nanophase separation and solution can be rather subtle, as is seen, for example, in the thermodynamic description of block copolymers (see Sect. 7.1). Micro- and nanophase-separated systems can often be stabilized by compatibilizers that may be block copolymers of the two components. Their properties can be considerably different from macrophase separated systems or solutions and, thus, of considerable technical importance. 

In 1964, Merries thought of using micelles as the big objects not retained or excluded by a GPC polymer phase. Small molecules are retained by the pore of the stationary phase. They are less retained when solubilized inside an excluded micelle. The idea was to measure solute affinity for micelles through solute retention times. This was the first time a micellar phase was used in chromatography [16]. This part of MLC history was already exposed in Chapter 3. Terabe and Okada developed a slightly different approach to model the small molecule and ion retention in micellar GPC [ 17, 18]. The equation is ... 

Phase Diagrams. The phase diagrams reported so far in Figures 2, 3, and 5 refer to UCS behavior. These types of phase equilibria are those predicted on the basis of the Flory-Huggins theory and are observed experimentally for solutions of small molecules as well as polymer solutions. This situation implies that mixing is favored by heating and that it is accompanied by a decrease of the interaction parameter, while cooling may lead to a two-phase system. 

In SEC an analyte is, by definition, separated only according to its molecular size, not its molecular mass. This is important to remember since the same solute (with its specific molecular mass) can have a different structure, and therefore different sample size, in different solvents. If all other interactions (ionic interactions, adsorption, ect.) with the stationary phase are suppressed, the selectivity of the system depends entirely on the different accessibility of the pores of the matrix for the solutes. Very small molecules (usually solvent molecules) have access to the entire intra particle volume Vj of the stationary phase. In con-... 

We shall in section 4.2 deal with regular solutions of small-molecule substances. The construction of phase diagrams from the derived equations is demonstrated. The Flory—Huggins mean-field theory derived for mixtures of polymers and small-molecule solvents is dealt with in section 4.3. It turns out that the simple Flory—Huggins theory is inadequate in many cases. The scaling laws for dilute and semi-dilute solutions are briefly presented. The inadequacy of the Flory-Huggins approach has led to the development of the equation-of-state theories which is the fourth topic (section 4.6) Polymer-polymer mixtures are particularly complex and they are dealt with in section 4.7. 

At the time of writing this book, SPOS is in an area of reladve infancy but has considerable potential. One of the main difficulties in SPOS lies in the lack of techniques available to monitor reacdons carried out on polymer supports. Unlike reacdons in solution phase, reactions on solid support cannot be monitored with relative ease and this has hindered the progress as well as the efficacy of solid supported synthesis of small non-peptidic molecules. Despite these difficulties, a large body of studies is available for SPOS. Recent reviews incorporate... 

Elementary reactions are generally unimolecular or bimolecular, depending on whether they entail the reaction of one species or two. Occasionally a termolecular step occurs, particularly between atoms or small molecules in the gas phase. Solution reactions that might appear to be termolecular usually prove really to be a succession of two simpler ones. 

Molecularly motivated empiricisms, such as the solubility parameter concept, have been valuable in dealing with mixtures of weakly interacting small molecules where surface forces are small. However, they are completely inadequate for mixtures that involve macromolecules, associating entities like surfactants, and rod-like or plate-like species that can form ordered phases. New theories and models are needed to describe and understand these systems. This is an active research area where advances could lead to better understanding of the dynamics of polymers and colloids in solution, the rheological and mechanical properties of these solutions, and, more generally, the fluid mechaiucs of non-Newtonian liquids. 

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