Direct evidence of polyamorphism in paracetamol

Abstract

While polymorphism is a common phenomenon in the crystallization processes of organic compounds, polyamorphism has gained importance only recently. Using sophisticated sample environments and applying in situ scattering methods and vibrational spectroscopy, the complete crystallization process of organic compounds from solution can be traced and characterized. Diffuse scattering from amorphous intermediates can be investigated by analyzing the atomic pair distribution function (PDF) to gain further insights into molecular pre-orientation. The crystallization behavior of paracetamol was studied exemplarily under defined, surface-free conditions. Based on the choice of the solvent, the formation of different polymorphs is promoted. The thermodynamically stable form I and the metastable orthorhombic form II could be isolated in pure form directly from solution. For both polymorphs, the crystallization from solution proceeds via a distinct amorphous precursor phase. PDF analyses of these different amorphous states indicate a specific pre-orientation of the analyte molecules introduced by the solvent. The resulting crystalline polymorph is already imprinted in these proto-crystalline precursors. Direct experimental evidence for the polyamorphism of paracetamol is provided.

Analyzing Raman spectral data without separabiliy assumption

“…Besides comparing time-step of phase change point observed in concentration curves with the experimental time-steps, another factor that validates the results are the peaks reported for metastable intermediate amorphous state closely matches with our calculated spectra. The peaks in red curve, for measured intermediate state, 1236 cm −1 ,1326 cm −1 ,1618 cm −1 to refer to few of many, match with calculated peaks at 1235 cm −1 , 1327 cm −1 ,1619 cm −1 [28]. Naturally, the peaks for Fig.…”

“…The spectral recoveries still show a reasonable agreement with the true spectra. The main traits of the reaction kinetics are recognizable as well structure of high order [28]. With our method, we were able to not only understand the kinetics of the intermediate phase, but were also able to calculate the spectra of the intermediate state.…”

Recent Advances in Mechanochromic Luminescence of Organic Crystalline Compounds

“…Specifically, the molten mixture of 40/41 (BD-M) exhibited green emission, which should be attributed to the energy transfer from 40 to 41 in perfectly amorphous phase 87 of 40. In the ground state of the mixture (BD-G), the fraction of 40 should exist as proto-crystalline amorphous state 88 and the emission color of 41 changes to orange owing to the more efficient intermolecular interactions of 41 molecules compared to that in BD-M state. Upon heating to 110°C, 40 and 41 independently crystallized and the blue emission from crystalline 40 should be observed for the resulting BD-C because of the low fluorescence quantum yield (Φ F ) of crystalline 41.…”

Selective polymorphism of α-glycine by acoustic levitation

“…Acoustic levitation has been also applied to study crystallisation, although only a very limited number of studies have been conducted up to now (see stateof-the-art table in ESI, † Section S1). 19,[21][22][23][24][25][26][27][28][29][30] To the best of our knowledge, there are no acoustic levitation studies conducted on glycine, the simplest amino acid, despite its wide use in crystallisation studies, [31][32][33][34][35] due to its simple molecular structure and well-known polymorphism. Glycine crystallises in three distinct polymorphic forms at ambient conditions, denoted as α, β and γ, with relative stabilities: γ > α > β at room temperature.…”