Non-Classical Mechanisms of Nucleation of Crystals in Solution

Crystal nucleation is a central problem in numerous areas of science, technology, and medicine and one of the last scientific fields, in which theoretical predictions diverge from careful measurements by many orders of magnitude. Recent studies have demonstrated that the discrepancies between theory and experiment are due to behaviors that go beyond the assumptions of classical model structures. Three non-classical nucleation behaviors have received particular attention. Crystals of several substances were shown to nucleate form within pre-existing precursors, and not directly in the solution. The nucleation precursors are clusters consisting of dense liquid, which are metastable with respect to the host solution. Additional work has revealed that the shape of the nucleus is determined not by minimization of its free energy, but by the kinetics of aggregation. The non-equilibrium nucleus shape results in higher nucleation barriers and significantly slower nucleation. At high supersaturations, the size of the nucleus shrinks to just one molecule. In contrast to common beliefs , the nucleation rate in this spinodal regime is not infinite but is limited by the rate of protein association. The investigations of the non-classical nucleation behaviors are still in their infancy. Results on direct imaging of clusters and characterization of cluster mechanisms with a variety of compounds will soon lead to major breakthroughs in bottom-up design of new materials.