Nanocrystallization: An Effective Approach to Enhance the Performance of Organic Molecules

Abstract

Organic nanocrystals have attracted great research interest in recent years due to their superior physical and chemical properties as compared to their amorphous counterparts. Higher photoluminescence intensity, steadier dissolution, and greater structural stability are a few examples of these properties, making nanocrystals an excellent choice for a wide range of applications, like electronics, bioimaging, and pharmaceuticals. Here, the principles of the most important nanocrystallization methods for organic compounds are elaborated. The discussion comprises the most important top‐down and bottom‐up approaches reported so far, explaining their advantages and limitations. To address the limitations of these methods, a new bottom‐up concept of stress‐induced seed‐assisted nanocrystallization is proved to be universally applicable to different organic molecules. To close, the future perspectives in the field are discussed.

General and Scalable Approach to Bright, Stable, and Functional AIE Fluorogen Colloidal Nanocrystals for in Vivo Imaging

“…The prevalent route to synthesize AIE-active FONs relies on the nanoprecipitation procedure. − This is a straightforward and easy-to-handle, bottom-up strategy based on supersaturation of the hydrophobic dyes (initially dissolved in a water-miscible solvent) upon addition of water (as the nonsolvent). ,,, However, the scope of this versatile solvent-shifting process remains limited in regard to biomedical applications by (i) the challenging control over the size and size distribution of the FONs, (ii) the usual formation of amorphous particles, where the fluorophore molecular arrangement may not be always optimal for promoting fluorescence emission, − and (iii) the fact that such metastable dispersions endure stability issues owing to uncontrolled crystallization upon storage or temperature fluctuations. , …”

“…33,34,42,43 However, the scope of this versatile solvent-shifting process remains limited in regard to biomedical applications by (i) the challenging control over the size and size distribution of the FONs, (ii) the usual formation of amorphous particles, where the fluorophore molecular arrangement may not be always optimal for promoting fluorescence emission, 44−46 and (iii) the fact that such metastable dispersions endure stability issues owing to uncontrolled crystallization upon storage or temperature fluctuations. 47,48 In this context, the establishment of simple, reproducible, and general methods toward the fabrication of thermodynamically stable aqueous dispersions of bright crystalline FONs with sub-200 nm diameters and a narrow size distribution holds great promise and is still actively sought worldwide for imaging purposes. Transposing methodologies exploited for the conception of crystalline drug delivery systems with enhanced bioavailability and dissolution rates 49 or semiconductor colloids, 50 Guldi and Bottari, 51 and more recently Tang and Liu, 52 described the rare examples of highly emissive AIEactive nanocrystals through sonochemical transformation of amorphous nanoprecipitated FONs.…”

Sonocrystallization of CMONS Needles and Nanocubes: Mechanistic Studies and Advanced Crystallinity Characterization by Combining X-ray and Electron Diffractions with DNP-Enhanced NMR

“…10 Nanosized organic dyes are also being intensively studied for application as tracers for in vivo fluorescence imaging. [11][12][13][14][15][16] In particular, the advent of aggregation-induced emission (AIE) has enabled the development of numerous nanoparticles (NPs) obtained by precipitation of a dye solution into water. [17][18][19] However, the fluorescence properties of the obtained colloids strongly depend on the ordering of the molecular packing and eventually on the polymorph that is formed when the NPs are crystalline.…”

Drug nanocrystals for cancer therapy

“…Such a higher structural stability in crystals also induces a steadier dissolution. When the size of drug NCs decreased, the solubility and dissolution rate of poorly water‐soluble drugs further increased …”