Crystallization labile region

In terms of the phase diagram, ideal crystal growth would begin with nuclei formed in the labile region, but just beyond the metastable. There, growth would occur slowly the solution, by depletion, would return to the metastable state where no more stable nuclei could form and the few nuclei that had established themselves would continue to grow to maturity at a pace free of defect formation. Thus in growing crystals for X-ray diffraction analysis, one attempts, by either dehydration or alteration of physical conditions, to transport... 

If the supersaturation generated during the cycle is not completely removed, the level of supersaturation attained during the following cycle is increased. This increase from cycle to cycle will continue until the supersaturation level of the solution exceeds the metastable region and enters the labile region, where spontaneous nucleation occurs. The occurrence of spontaneous nucleation means loss of control of crystal size. 

Usually the crystallization equipment is charged with a clear feed solution. As this solution is saturated, it is important to control the increase in supersaturation as the labile region is approached. This is important since the formation of an excessive number of nuclei will cause a continuous crystallizer system to have an extremely long period before desired crystal... 

Low suspension density. Since the solution cannot return to saturation before being resupersaturated in the circulation loop, the residual supersaturation builds up to the point that the solution is in the labile region. To remedy, increase the crystals in suspension to maintain the design density. 

As mentioned above, crystallization is possible when the concentration of the solute is larger than the equilibrium saturation, i.e. when the solution is supersaturated with the solute. The state of supersaturation can be easily achieved if the solution is cooled very slowly without agitation. Above a certain supersaturation (this state is also called supersolubility) spontaneous formation of crystals often, but not always, occurs. Spontaneous nucleation is less probable in the state between equilibrium saturation and supersolubility, although the presence of fine solid impurities, rough surfaces, or ultrashort radiation can cause this phenomenon to occur. The three regions (1) unsaturation (stable zone), where crystallization is impossible and only dissolution occurs, (2) metastable zone, extending between equilibrium saturation and supersolubility, and (3) labile zone, are shown in Fig. 5.3-20. 

The labile character of the Zn11— OR species 8b (although isolable as crystals, 8b is stable only at a limited alkaline pH region in aqueous solution) and the vulnerability of the acyl intermediate 10 in aqueous solution prevented more extensive, quantitative studies about the nature of Znn-bound alkoxide. 

The perplexing difficulties that arise in the crystallization of macromolecules, in comparison with conventional small molecules, stem from the greater complexity, lability, and dynamic properties of proteins and nucleic acids. The description offered above of labile and metastable regions of supersaturation are still applicable to macromolecules, but it must now be borne in mind that as conditions are adjusted to transport the solution away from equilibrium by alteration of its physical and chemical properties, the very nature of the solute molecules is changing as well. As temperature, pH, pressure, or solvation are changed, so may be the conformation, charge state, or size of the solute macromolecules. 

An additional problem with crystal structures that can give rise to a misleading model is the thermal motion and disorder within the crystalline lattice. Local regions of electron density can be poorly defined, even for structures with relatively good resolution if, for example, a protein residue is labile in the crystalline state. If undetected, a residue can be poorly modeled, misassigned, or omitted from the model. Even when detected and fully modeled, disorder implies flexibility, which may need specific handling in a docking study. 

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