Confined liquid crystallization governed by electric field for API crystal polymorphism screening and massive preparation.

Active pharmaceutical ingredients (APIs) crystal preparation is a significant issue for the pharmaceutical development attributed to the effect on anti-inflammatory, anti-bacteria, and anti-viral, etc. While, the massive preparation of API crystal with high polymorphism selectivity is still a pendent challenge. Here, we firstly proposed a criterion according to the molecular aggregation, molecular orientation, and hydrogen bond energy between INA molecules from molecular dynamics (MD) simulations, which predicted the hydrogen bond architecture in crystal under different electric fields, hinting the recognition of crystal polymorphism. Then, an electric field governing confined liquid crystallization was constructed to achieve the INA crystal polymorphism screening relying on the criterion. Further, magnifying confined liquid volume by 5000 times from 1.0 µL to 5.0 mL realized the massive preparation of INA crystal with high polymorphic purity (>98.4%), giving a unique pathway for crystal engineering and pharmaceutical industry on the development of innovative and generic API based drugs.

Hydrogel Nanoparticles Enable Nucleation Barrier Regulation and Ion Anchoring as an Alternative Pathway for Monosodium Urate Monohydrate Crystallization Control.

Gout flare-up, commonly resulting from monosodium urate monohydrate (MSUM) crystallization, has led to painful inflammatory arthritis among hundreds of millions of people. Herein, a kind of hydrogel nanoparticles (HNPs) with specific properties was developed, aimed at providing a promising pathway for MSUM crystallization control. The experimental and molecular dynamics simulation results synchronously indicate that the fabricated HNPs achieve efficient inhibition of MSUM crystallization governed by the mechanism of "host-guest interaction" even under very low-dose administration. HNPs as the host dispersed in the hyperuricemic model effectively lift the relative heterogeneous nucleation barrier of the MSUM crystal and hinder solute aggregation with strong electronegativity and hydrophobicity. The initial appearance of MSUM crystals was then delayed from 94 to 334 h. HNPs as the guest on the surface of the formed crystal can decelerate the growth rate by anchoring ions and occupying the active sites on the surface, and the terminal yield of the MSUM crystal declined to less than 1% of the control group. The good biocompatibility of HNPs (cell viability > 94%) renders it possible for future clinical applications. This study can guide the rational design of inhibitory nanomaterials and the development of their application in the control of relevant pathological crystallization.

Tailored hydrogel composite membrane for the regulated crystallization of monosodium urate monohydrate within coffee's metabolites system.

Herein, a facile bionic research platform with fabricated hydrogel composite membrane (HCM) is constructed to uncover the effects of the main components of coffee's metabolites on MSUM crystallization. Tailored and biosafety polyethylene glycol diacrylate/N-isopropyl acrylamide (PEGDA/NIPAM) HCM allows the proper mass transfer of coffee's metabolites and can well simulate the process of coffee's metabolites acting in the joint system. With the validations of this platform, it is shown that chlorogenic acid (CGA) can hinder the MSUM crystals formation from 45 h (control group) to 122 h (2 mM CGA), which is the most likely reason that reduces the risk of gout after long-term coffee consumption. Molecular dynamics simulation further indicates that the high interaction energy (Eint) between CGA and MSUM crystal surface and the high electronegativity of CGA both contribute to the restraint of MSUM crystal formation. In conclusion, the fabricated HCM, as the core functional materials of the research platform, presents the understanding of the interaction between coffee consumption and gout control.

A Covalent Organic Framework Membrane with Homo Hierarchical Pores for Confined Reactive Crystallization.

Gas-liquid (G-L) reactive crystallization is a major technology for advanced materials construction, which requires a short diffusion path on the interface to ensure the reactant supply and stable crystal nucleation under ultrahigh supersaturation. Herein, a covalent organic framework (COF) membrane with homo hierarchical pore structures was proposed as an effective interfacial material for the regulation of confined reactive crystallization. By combining the ordered nanopores of COFs and micropores of anodic aluminum oxide (AAO), the COF membrane simultaneously provided an excellent nanoscale diffusion-reaction regulation network as the molecular-level confined G-L reactive interface and adjustable submicrometer gas mass transfer channels. The highly selective construction of CaCO3 superstructures was then achieved. When the submicrometer primary pore size rp of the constructed COF membrane ranged from 120 to 1.6 nm, the diffusion mechanism of CO2 varied from viscous flow diffusion to Knudsen diffusion. The growth orientation of CaCO3 crystals was well confined to obtain spindle-shaped crystals with high selectivity. Meanwhile, the crystal selectivity factor (cube/sphere) increased from 0 to 3.53 under the low interfacial nuclear barrier. Thus, the COF membrane with coupled micro-nanostructures successfully screened the directional preparation conditions for diverse CaCO3 superstructures, which also paved a meaningful path for the functional application of COFs in accurate mass transfer control and confined chemical reactions.