The process of self-assembly transitioning from chaos to order represents a complex and stochastic process that poses a significant experimental challenge in chemistry. Crystallization, creating solid structures from molecular assembly, is a subject of extensive investigation spanning both fundamental and applied contexts. However, grasping transition moments and transient intermediates during self-assembly remains constrained due to the limitations in measurement techniques. In light of these challenges, there has been a recent surge of interest in delving into nucleation, the pivotal initial phase of crystallization, operating at the molecular level. This commentary places emphasis on employing cutting-edge methodologies like Atomic-Resolution Transmission Electron Microscopy (AR-TEM) in vacuum environments. It become s evident that the dynamics of intermediate clusters consisting of dozens of atoms are more intricate than the conventional non-classical two-step nucleation mechanism. These meticulous investigations provide us with atomic atomic-scale and milli-second insights, substantially propelling our comprehension of these complex processes.

  Classical nucleation theory is well known for its inability to explain experimental results. The development of an advanced nucleation theory is essential to predict and discuss bottom-up crystal synthesis from atoms/molecules, and natural phenomena such as the formation of clouds and cosmic dust. The major challenge lies in the fact that we do not know the reason why experiment and theory do not match. To clarify the reason, we have conducted nucleation experiments from the gas phase, where ideal homogeneous nucleation experiments can be performed, in parallel with in situ observations of the nucleation process using transmission electron microscopy in liquid, which can directly visualize individual nuclei on a nanoscale. The results show that the final products are the result of diverse and multi-step nucleation pathways. I believe that the nucleation theory can be made to fit experiment by considering the singularity of nanoparticles and resulting diversity of nucleation pathways. Here, I mainly present multi-step nucleation as captured by in-situ observation using transmission electron microscopy in liquid.

  Multistep nucleation can be broadly classified into several types, in each of which the occurrence of precursor phenomenon is observed. However, the true nature and role of the precursor phenomenon are controversial. In this report, molecular dynamics simulations are performed for the nematic (N) to smectic (Sm) phase transition of uniaxial liquid crystals induced by supercooling. In the N-Sm transition, a precursor phenomenon, known experimentally as “pre-transition fluctuation,” in which the X-ray diffraction intensity increases at temperatures higher than the phase transition temperature, has been believed to be the generation of molecular clusters with Sm-like short-range order, although no direct evidence exists. To visualize the pre-transition fluctuation, appropriate local order parameters are introduced by applying machine learning. The development of the N-Sm transition through multistep nucleation is demonstrated, suggesting the true nature and role of pre-transition fluctuation.

  Although crystallization is expected below the triple point temperature, it has often been observed, in nature and experiments, that nuclei formed from vapor are supercooled liquid droplets. This is an example of Ostwald’s step rule, where a metastable phase appears first before a stable phase. Though the transition from vapor to solid is a familiar process, it is not yet fully understood even for simple homogeneous nucleation. We present multistep homogeneous nucleation in vapor-to-solid transitions as revealed by molecular dynamics simulations on Lennard-Jones molecules. The nuclei of liquid first appeared even at temperatures lower than the triple point. In the MD simulations, the crystallization in many large, supercooled nanoclusters is observed once the liquid clusters grow to a certain size (∼1000 molecules). The clusters crystallized quickly and completely except at surface layers. However, they did not have stable crystal structures, rather they had metastable structures such as icosahedral, decahedral, face-centered-cubic–rich (fcc-rich), and hexagonal-close-packed–rich (hcp-rich). We also investigated the multi-step nucleation of water vapor by using a theoretical model, taking into account the condensation nucleation from the water gas phase and the crystallization process in supercooled water droplets. Our results imply that multistep nucleation is a common first stage of condensation from vapor to solid.

  This paper presents an overview of the formation, growth, and dissolution behavior of a plate-like L-phenylalanine (L-Phe) crystal induced by laser trapping in its unsaturated solutions. By focusing the near-infrared laser onto the air/solution interface of the sample solution, a single crystal of L-Phe is formed at the focal spot. The generated crystal exhibits continuous two-dimensional growth while being trapped at the laser focus. The apparent crystal growth is paused by decreasing the laser power. This equilibrium state is kept for a certain period, and then the crystal begins to dissolve. Through the analysis of the temporal changes in the crystal surface area, it is suggested that the crystal is surrounded by a highly concentrated domain consisting of liquid-like clusters (pre-nucleation clusters). Thus, laser trapping-induced crystallization of L-Phe proceeds in two steps, where initially liquid nucleation leads to the domain formation and the following solid nucleation generates an L-Phe crystal.