Understanding and Evaluating Crystal Polymorphism by Second Harmonic Generation Microscopy
The crystalline form of a solid can profoundly affect its physical and chemical properties, with both potentially stable and metastable crystal polymorphs are accessible during crystal formation. Conventional methods limit the detection of rare nucleation and rapid phase transitioning events due to their lack of selectivity and sensitivity. Inkjet printing of a solution confines the nucleation event in a few micrometer volumes within the droplet, and furthermore rapid desolvation favors the kinetic factor to trap the rare metastable polymorphs. Second harmonic generation microscopy (SHG) possesses enough sensitivity to detect sub-micrometer size chiral crystals selectively and has the potential for use in crystal nucleation studies. The unfavored noncentrosymmetric crystal forms are observed by SHG microscopy in inkjet printed racemic solution of an amino acid. Polarization-dependent SHG measurement and synchrotron X-ray microdiffraction analysis of individual printed drops are consistent with formation of homochiral crystal production. Fundamentally, these results provide evidence supporting the ubiquity of Ostwald’s Rule of Stages, describing the hypothesized transitioning of crystals between metastable polymorphic forms in the early stages of crystal formation. In addition to the metastable polymorphs characterization, quantification of SHG signal is essential for definitive discrimination for the polymorphs with a certain confidence interval. In this regard, a microscopy approach is developed for quantifying (SHG) activity of powders that largely decouples linear and nonlinear optical interactions. Decoupling the linear and nonlinear optical effects provides a means to independently evaluate and optimize the role of each in crystal engineering efforts and facilitates direct comparisons between experimental and computational predictions of lattice hyperpolarizabilities. Using a focused fundamental beam places a controllable upper bound on the interaction length, given by the depth of field. An analytical model that includes scattering losses of a focused Gaussian beam reliably predicted several experimental observations. Specifically, the measured scattering length for SHG is in excellent agreement with the value predicted based on the particle size distribution. Additionally, histograms of the SHG intensities as functions of particle size and orientation agreed nicely with predictions from the model.
Simpson, Purdue University.
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