Continuous flow synthesis of PCN-222 (MOF-545) with controlled size and morphology: a sustainable approach for efficient production

Zirconium-based MOFs, such as PCN-222 (MOF-545), have gained attention due to their regular porosity, tuneable pore size, versatile structure and exceptional thermal/chemical stability. However, the synthesis of PCN-222 using traditional batch processes suffers from limitations in productivity, scalability, and control over size and morphology. This study presents a paradigm shift from batch to continuous flow (c.f.) synthesis for the efficient production of PCN-222. The optimization of batch conditions and exploration of c.f. parameters enabled the synthesis of high-quality PCN-222 with Space-Time-Yield (STY) exceeding 950 kg m-3 day-1. The c.f. approach offered advantages including improved resource efficiency, safer chemical handling, and scalability. The integration of ultrasound-assisted technique into the c.f. facilitated the shaping of PCN-222 into prolate ellipsoids, making it suitable for applications in drug delivery and catalysis. The successful substitution of hazardous solvents with greener alternatives further enhanced the sustainability of the process. Finally, the loading of a thio-N-acetylgalactosamine-PEG-sulfate ligand on PCN-222 in tandem c.f., expanded the potentialities of the flow synthetic approach. This study not only advances the field of MOF synthesis but also paves the way for efficient and sustainable manufacturing processes in c.f. synthesis of nanoparticles and functionalized nanoparticles for active drug delivery. The first synthesis of Zirconium-based MOF PCN-222 with defined morphology using continuous flow chemistry is reported. The potential for biomedical applications is explored by loading a thio-N-acetyl galactosamine-PEG-sulfate ligand.