Abstract
There is mounting evidence that crystal nucleation from supersaturated solution involves the formation and reorganization of prenucleation clusters, contradicting classical nucleation theory. One of the key unresolved issues pertains to the origin, composition, and structure of these clusters. Here, a range of amino acids and peptides is investigated using light scattering, mass spectrometry, and in situ terahertz Raman spectroscopy, showing that the presence of amorphous aggregates is a general phenomenon in supersaturated solutions. Significantly, these aggregates are found on a vast range of length scales from dimers to 30-mers to the nanometre and even micrometre scale, implying a continuous distribution throughout this range. Larger amorphous aggregates are sites of spontaneous crystal nucleation and act as intermediates for laser-induced crystal nucleation. These results are shown to be consistent with a nonclassical nucleation model in which barrierless (homogeneous) nucleation of amorphous aggregates is followed by the nucleation of crystals from solute-enriched aggregates. This provides a novel perspective on crystal nucleation and the role of nonclassical pathways.