Self-association, reversible

Liu J, Nguyen MD, Andya JD, Shire SJ. Reversible self-association increases the viscosity of a concentrated monoclonal antibody in aqueous solution. J Pharm Sci 2005 94(9) 1928-19240 [Erratum in J Pharm Sci 2006 95(l) 234-235.]. 

Because of the potential effects on safety and activity, it is necessary to minimize the aggregate content in the final formulation. In the formulation screen for the recombinant humanized monoclonal antibody to vascular endothelial growth factor (rhuMAb VEGF), a reversible self-association of the protein was observed,... 

Esfandiary, R., Hayes, D.B., Parupudi, A., et al. (2013) A systematic multitechnique approach for detection and characterization of reversible self-association during formulation development of therapeutic antibodies. 7 Pharm Sci, 102 (9), 3089-3099. 

Gelling agents under appropriate conditions self-associate to produce a three-dimensional structure. Some gelling, as with gelatine, is thermo-reversible while others, such as with high methoxyl pectin, is irreversible. Apart from the effects on the texture of the product an irreversible gelling agent is more of a problem in the factory since it cannot readily be recycled. 

The mechanism of reversed-phase chromatography arises from the tendency of water molecules in the aqueous-organic mobile phase to self-associate by hydrogen bonding. This ordering is perturbed by the presence of nonpolar solute molecules. As a result, solute molecules tend to be excluded from the mobile phase and are bound by the hydrophobic stationary phase. This solvophobic... 

A similar approach is fruitful for investigating insulin mutants that may be under consideration as replacements for wild-type insulin in human therapy. For lispro insulin (in which positions P28 and K29 in human insulin are reversed), and for several other insulin mutants, PLIMSTEX clearly can distinguish the self-association properties and binding constants of lispro and r-human insulins [33]. 

Surfactants having an appropriate hydrophobic/hydrophilic balance (sodium bis(-2-ethylhexyl)sufosuccinate, or AOT, for example) undergo concentration-dependent self association in apolar solvents to form reversed or inverted micelles (Fig. 33) [256-262]. Reversed micelles are capable of solubilizing a large number of water molecules (AOT reversed micelles in hexane are able to take up 60 water molecules per surfactant molecule, for example). Reversed-micelle-entrapped water pools are unique they differ significantly from bulk water. At relatively small water-to-surfactant ratios (w = 8-10, where w = [H20]/[Surfactant]), all of the water molecules are strongly bound to the surfactant headgroups. Substrate solubilization in the restricted water pools of reversed micelles results in altered dissociation constants [256, 257, 263-265], reactivities [256, 258, 266], and reaction products [267]. 

In fact, even in pure block copolymer (say, diblock copolymer) solutions the self-association behavior of blocks of each type leads to very useful microstructures (see Fig. 1.7), analogous to association colloids formed by short-chain surfactants. The optical, electrical, and mechanical properties of such composites can be significantly different from those of conventional polymer blends (usually simple spherical dispersions). Conventional blends are formed by quenching processes and result in coarse composites in contrast, the above materials result from equilibrium structures and reversible phase transitions and therefore could lead to smart materials capable of responding to suitable external stimuli. 

For the particular case of 2- and 4-mercaptopyridines and 2-mercaptopyrimidines and by means of absorption UV-VIS spectroscopy, Stoyanov and collaborators122 have shown that polar solvents shift the thiol/thione tautomerism towards the thione form, while in dilute solutions of nonpolar solvents the thiol form predominates. However, one of the most significant contributions of this work122 is the observation of self-association. It also favors the thione forms and is followed by quantitative transformation of the thiol form into the corresponding symmetrical disulfides (see Scheme 6). More importantly thione-disulfide process is reversible in water, which can be of some relevance in biological systems. 

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