Spinodal for the solution-to-crystal phase transformation

Area of Science:

• Physical Chemistry
• Materials Science
• Biophysics

Background:

• Crystallization from solution often involves intermediate disordered phases.
• Nucleation rates are influenced by free-energy barriers and kinetic factors.

Purpose of the Study:

• To experimentally determine the relative importance of free-energy barriers versus kinetics in protein crystal nucleation.
• To investigate the role of disordered intermediates in crystal formation.

Main Methods:

• Utilized a model protein system to study crystal nucleation from solution.
• Quantified nucleation rates and characterized intermediate phases.
• Investigated the effect of supersaturation on nucleus stability.

Main Results:

• Crystal nucleation is 8-10 orders of magnitude slower than disordered droplet nucleation, indicating the second step is rate-limiting.
• Significant nucleation barriers disappear below thermal energy (kBT), with nuclei transforming into single molecules.
• The slow growth of ordered clusters within disordered droplets is the main determinant of crystal nucleation rate.
• Defined a solution-to-crystal spinodal based on the transition to single-molecule nuclei.
• Heterogeneous nucleation centers accelerate nucleation by improving ordered embryo growth kinetics, not just lowering barriers.

Conclusions:

• The kinetics of ordered cluster growth within disordered intermediates are crucial for crystal nucleation.
• Classical nucleation theory's emphasis on barrier height alone is insufficient; kinetics play a vital role.
• Heterogeneous nucleation offers kinetic advantages beyond classical wetting effects.