Controlled microcrystallization for in situ photocrystallography: optimizing crystal size and habit

Abstract

While advanced crystallization methods controlling microcrystal size and shape are common for pharmaceutical targets, there are few examples where such methods are applied to inorganic functional materials. This is surprising, considering the impact of particle size on numerous useful properties. As an archetypal photoswitch exhibiting photoinduced linkage isomerism (PLI), sodium nitroprusside dihydrate (SNP·2H₂O) is an ideal prototype for the design of advanced inorganic microcrystallization approaches. Slow evaporation in water characteristically gives long (>1 mm) lath-like crystals with a broad size distribution. These samples are undesirable for in situ photocrystallography, where small crystals of ideally plate habit are preferred to maximize light penetration. This article explores the influence of solvent, temperature and crystallization method on the formation of homogeneous microcrystal batches of SNP·2H₂O at small (ca. 5 mL) scale, targeting a plate-like habit and an average size of (50 ± 10) μm in the two dimensions parallel to the plate. Successful experiments utilize an acetonitrile antisolvent methodology, delivering a narrow crystal size distribution in the correct range. Steady-state photocrystallography measurements on crystals grown by controlled vs. uncontrolled methodologies showcase how regulating crystal particle attributes can minimise variability in the excited state population, reinforcing the importance of these parameters for real photoswitching applications where achieving a reproducible response is often key. A previously unknown mixed methanol : water solvate of SNP is also reported that is metastable in air.