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Definitions of kosmotropes and chaotropes
The terms 'kosmotrope' (order-maker) and 'chaotrope' (disorder-maker) originally denoted solutes that stabilized, or destabilized respectively, proteins and membranes; thus chaotropes unfold proteins, destabilize hydrophobic aggregates and increase the solubility of hydrophobes whereas kosmotropes stabilize proteins and hydrophobic aggregates in solution and reduce the solubility of hydrophobes. Later these terms referred to the apparently correlating property of increasing, or decreasing respectively, the structuring of water (a recent review of structure-making and structure-breaking ions has been presented [1567]). Although useful, the terminology may sometimes be misleading as such properties may vary dependent on the circumstances, method of determination or the solvation shell(s) investigated. For example a solute may not always act in the same way at different concentrations or in the presence of macromolecules or gels [276]. Also some solutes with less well-defined properties (for example, urea) are sometimes classified as kosmotropes [276] and sometimes as chaotropes [283]. An alternative term used for kosmotrope is 'compensatory solute' as they have been found to compensate for the deleterious effects of high salt contents (which destroy the natural hydrogen bonded network of water) in osmotically stressed cells, but again behavior as a kosmotrope in one system does not mean that a solute may behave as a 'compensatory solute' in another or even that it will stabilize the structuring of water in a third. Both the extent and strength of hydrogen bonding may be changed independently by the solute but either of these may be, and has been, used as measures of order making. It is, however, the effects on the extent of quality hydrogen bonding that is of overriding importance as true kosmotropes shift the local equilibrium



less dense water (for example, ES)  more dense water (for example, CS)



to the left and chaotropes shift it to the right. The ordering effects of kosmotropes may be confused by their diffusional rotation, which creates more extensive disorganized junction zones of greater disorder with the surrounding bulk water than less hydrated chaotropes. It seems clear that most kosmotropes do not cause a large scale net structuring in water [595].
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