Mechanism of Crystalline Self‐Assembly in Aqueous Medium: A Combined Cryo‐TEM/Kinetic Study

Abstract

Understanding the crystallization of organic molecules is a long-standing challenge. Herein, a mechanistic study on the self-assembly of crystalline arrays in aqueous solution is presented. The crystalline arrays are assembled from perylene diimide (PDI) amphiphiles bearing a chiral N-acetyltyrosine side group connected to the PDI aromatic core. A kinetic study of the crystallization process was performed using circular dichroism spectroscopy combined with time-resolved cryogenic transmission electron microscopy (cryo-TEM) imaging of key points along the reaction coordinate, and molecular dynamics simulation of the initial stages of the assembly. The study reveals a complex self-assembly process starting from the formation of amorphous aggregates that are transformed into crystalline material through a nucleation-growth process. Activation parameters indicate the key role of desolvation along the assembly pathway. The insights from the kinetic study correlate well with the structural data from cryo-TEM imaging. Overall, the study reveals four stages of crystalline self-assembly: 1) collapse into amorphous aggregates; 2) nucleation as partial ordering; 3) crystal growth; and 4) fusion of smaller crystalline aggregates into large crystals. These studies indicate that the assembly process proceeds according to a two-step crystallization model, whereby initially formed amorphous material is reorganized into an ordered system. This process follows Ostwald's rule of stages, evolving through a series of intermediate phases prior to forming the final structure, thus providing an insight into the crystalline self-assembly process in aqueous medium.

Self‐Assembly of Perylenediimide–Single‐Strand‐DNA Conjugates: Employing Hydrophobic Interactions and DNA Base‐Pairing To Create a Diverse Structural Space

“…In the case of TA5 , the most notable features are parallel high‐contrast structures tens to hundreds of nm long, having a thickness of 1.3±0.2 nm enclosing a light contrast domain of 1.5 nm. These imaged structures are consistent with the formation of bilayers formed by hydrophobic association of the N ‐alkyl groups from each layer (Scheme b) . Expectedly, only a relatively small number of cross‐sections is observed, because the large bilayer structures tend to orient perpendicularly to the optical axis due to the shear forces induced during sample preparation.…”

“…The cryo-TEM images of TA4-5 (Figure 3b and c) show the formation of linear fibers with diameters similart ot hose for TA1-3 ( Table S3 in the formation of bilayers formed by hydrophobic association of the N-alkyl groups from each layer (Scheme 3b). [26] Expectedly,o nly ar elativelys mall number of cross-sections is observed, because the large bilayer structures tend to orientp erpendicularly to the opticala xis due to the shear forces induced during sample preparation.…”

Two types of amorphous protein particles facilitate crystal nucleation

“…It is likely that the large size and related flexibility of these molecules may invoke in their solutions behaviors similar to those observed with proteins, including the complex nucleation pathways reported here. Such a complex pathway has also been observed using cryo-TEM in organic materials, where the amorphous material that is initially formed is reorganized into an ordered system (27).…”

Observation of crystallisation dynamics by crystal-structure-sensitive room-temperature phosphorescence from Au(I) complexes

“…Numerous theoretical and experimental studies have attempted to reveal the dynamics of crystallisation processes using methods such as electron microscopy, IR spectroscopy, and Raman spectroscopy; however, it is difficult to observe the crystallisation processes directly in situ and in real time during the early stage, which hinders the elucidation of the crystallisation and polymorphic behaviour during crystal growth [7][8][9][10][11][12] . A more powerful method is the in situ observation of luminescence changes during the crystallisation process 12 .…”