Self-association aggregation

The conclusion of all these thermodynamic studies is the existence of thiazole-solvent and thiazole-thiazole associations. The most probable mode of association is of the n-rr type from the lone pair of the nitrogen of one molecule to the various other atoms of the other. These associations are confirmed by the results of viscosimetnc studies on thiazole and binary mixtures of thiazole and CCU or QHij. In the case of CCU, there is association of two thiazole molecules with one solvent molecule, whereas cyclohexane seems to destroy some thiazole self-associations (aggregates) existing in the pure liquid (312-314). The same conclusions are drawn from the study of the self-diffusion of thiazole (labeled with C) in thiazole-cyclohexane solutions (114). 

Certain surface-active compounds [499], when dissolved in water under conditions of saturation, form self-associated aggregates [39,486-488] or micelles [39,485], which can interfere with the determination of the true aqueous solubility and the pKa of the compound. When the compounds are very sparingly soluble in water, additives can be used to enhance the rate of dissolution [494,495], One can consider DMSO used in this sense. However, the presence of these solvents can in some cases interfere with the determination of the true aqueous solubility. If measurements are done in the presence of simple surfactants [500], bile salts [501], complexing agents such as cyclodextrins [489 191,493], or ion-pair-forming counterions [492], extensive considerations need to be applied in attempting to extract the true aqueous solubility from the data. Such corrective measures are described below. 

The nnfolding of lysozyme structure was reported to be induced by PEF (35 kV cm and 300 ps) this was accompanied by the cleavage of disulfide bonds and self association aggregation when the applied PEF dosage was higher than the critical level (Zhao et al., 2007). 

Insulin is composed of two peptide chains covalently linked by disulfide bonds (Figures 5.17 and 6.35). This monomer of insulin is the active form that binds to receptors in target cells. However, in solution, insulin spontaneously forms dimers, which themselves aggregate to form hexamers. The surface of the insulin molecule that self-associates to form hexamers is also the surface that binds to insulin receptors in target cells. Thus, hexamers of insulin are inactive. 

Coacervation occurs in tropoelastin solutions and is a precursor event in the assembly of elastin nanofibrils [42]. This phenomenon is thought to be mainly due to the interaction between hydro-phobic domains of tropoelastin. In scanning electron microscopy (SEM) picmres, nanofibril stmc-tures are visible in coacervate solutions of elastin-based peptides [37,43]. Indeed, Wright et al. [44] describe the self-association characteristics of multidomain proteins containing near-identical peptide repeat motifs. They suggest that this form of self-assembly occurs via specific intermolecular association, based on the repetition of identical or near-identical amino acid sequences. This specificity is consistent with the principle that ordered molecular assembhes are usually more stable than disordered ones, and with the idea that native-like interactions may be generally more favorable than nonnative ones in protein aggregates. 

In the case of the analytes able to participate in the self-associative lateral interactions (i.e., containing at least one AB functionality in their molecular structure), the negative impact of the interactions exerted on the separation performance depends on the number of the associated monomers per one H-bonded -meric unit, and the higher the number (n) of the self-associated analyte monomers in a given aggregate, the more crippled is the separation process. 

Loss of the native conformation of a protein generally exposes hydrophobic amino acid residues that are normally buried on the inside of the self-associated structure and are shielded from the aqueous environment. This leads to association between the exposed hydrophobic residues of neighboring proteins (aggregation) or between these exposed residues and hydrophobic surfaces that the protein may encounter either in the manufacturing process or in the primary package. 

Consider the case of a weak base, where the protonated, positively charged form self-associates to form aggregates, but the uncharged form does not. This may be the case with phenazopyridine (Fig. 6.12). Phenazopyridine is a base that consistently shows positive shifts in its apparent pKa, the opposite of what s expected... 

One inherent property of peptides that interact with membranes is that self-association or even aggregation will interfere with solubilization by organic solvents or micelles. The preparation, purification and sample preparation of extremely hydrophobic (often transmembrane) peptides is nontrivial and has been addressed by only a few papers [74—79]. 

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