Aqueous Polymorph and Morphology Control in ZIFs via 1‑Methylimidazole for Efficient Lipase Entrapment

Abstract

Controlling the phase and morphology of zeolitic imidazolate frameworks (ZIFs) is crucial for optimizing properties relevant to gas separation, adsorption, and, in particular, biocatalysis. In conventional synthesis, the formation of ZIF-8 often relies on organic solvents and a large ligand excess, which impairs sustainability and complicates in situ enzyme incorporation. Although aqueous synthesis is more environmentally friendly, it typically yields the ZIF-L phase, a sheet-like kinetic polymorph that competes with ZIF-8 formation in water. Here, we demonstrate that 1-methylimidazole (1-mIm) acts as a coordination modulator in water, enabling selective ZIF-8 formation without organic solvent and the large excess of imidazole ligands. By varying the 1-mIm:2-mIm (2-methylimidazole) ratio, we direct the phase selection from the 2D leaf-shaped ZIF-L (1-mIm:2-mIm = 0:1) to 3D SOD‑type ZIF‑8 (1-mIm:2-mIm = 2:1), obtaining well-controlled ZIF morphologies. Comprehensive materials characterization (HR-XRPD, FTIR, SEM, 1H NMR, BET, and TGA) confirms corresponding phase purity, crystallinity, and tunable surface properties across morphologies. Applying this control to Thermomyces Lanuginosus Lipase (TLL) entrapment, the lipase@ZIF composite with an intermediate ZIF morphology at 1‑mIm:2‑mIm = 1:1 delivers the highest enzymatic activity among all synthesized ZIF phases, that can be attributed to an increased enzyme loading capacity as well as an optimized substrate access to the enzyme. This water‑based, modulator‑assisted synthesis route provides a sustainable approach to designing a broader range of green MOFs, thereby enabling biocompatibility of materials such as ZIF polymorphs for enzymatic applications.