Structural Properties, Order–Disorder Phenomena, and Phase Stability of Orotic Acid Crystal Forms

Abstract

Orotic acid (OTA) is reported to exist in the anhydrous (AH), monohydrate (Hy1), and dimethyl sulfoxide monosolvate (SDMSO) forms. In this study we investigate the (de)hydration/desolvation behavior, aiming at an understanding of the elusive structural features of anhydrous OTA by a combination of experimental and computational techniques, namely, thermal analytical methods, gravimetric moisture (de)sorption studies, water activity measurements, X-ray powder diffraction, spectroscopy (vibrational, solid-state NMR), crystal energy landscape, and chemical shift calculations. The Hy1 is a highly stable hydrate, which dissociates above 135 °C and loses only a small part of the water when stored over desiccants (25 °C) for more than one year. In Hy1, orotic acid and water molecules are linked by strong hydrogen bonds in nearly perfectly planar arranged stacked layers. The layers are spaced by 3.1 Å and not linked via hydrogen bonds. Upon dehydration the X-ray powder diffraction and solid-state NMR peaks become broader, indicating some disorder in the anhydrous form. The Hy1 stacking reflection (122) is maintained, suggesting that the OTA molecules are still arranged in stacked layers in the dehydration product. Desolvation of SDMSO, a nonlayer structure, results in the same AH phase as observed upon dehydrating Hy1. Depending on the desolvation conditions, different levels of order–disorder of layers present in anhydrous OTA are observed, which is also suggested by the computed low energy crystal structures. These structures provide models for stacking faults as intergrowth of different layers is possible. The variability in anhydrate crystals is of practical concern as it affects the moisture dependent stability of AH with respect to hydration.

Insight into the role of bound water of a nucleating agent in polymer nucleation: a comparative study of anhydrous and monohydrated orotic acid on crystallization of poly(l-lactic acid)

“…A strong diffraction peak is observed at 2q ¼ 28.8 for both of the two samples, which corresponds to the stacking reection of layer structures. 45 In contrast to OA-m, a broadened diffraction peak appears at 2q around 20…”

“…In fact, there are two commercially available types for orotic acid, that is, anhydrous and monohydrated forms, which possess different structural features and properties, 45 and may result in discrepant nucleation ability on polymer crystallization. However, previous studies are mainly focused on the nucleation effects of monohydrated form.…”

“…Notably, this literature has also pointed out that OA-m loses the bound water and dissociates into OA-a when it is heated above 135 C under normal or hermetically sealed high-pressure atmospheric conditions. 45 In addition, it has been reported that an endothermic peak, which is attributed to the evaporation of the water associated with OA-m, appears at 144 C before the melting peak of poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) at 171 C in the rst heating DSC curve of PHBV solvent-cast lm containing 5 wt% OA-m. 44 In this work, considering the blended samples were prepared in the temperature range of 170-190 C for 6 min, it is reasonable to conclude that OA-m is transformed into OA-a during the melt extrusion processes, and nally, OAa acts as the true nucleating agent in PLLA/OA-m blends. Fig.…”

Computational and experimental study of reversible hydration/dehydration processes in molecular crystals of natural products – a case of catechin

“…In general, the 1 H isotropic shifts are regarded as more sensitive to structural changes. There are two structures that are close to fulfilling these requirements, namely, one 2.5-hydrate (16) and one dihydrate (11), which are both obtained by manual modification of the 4.5-hydrate structure. However, appropriate weights should be assigned to all of these features.…”

Capturing the Role of Temperature and Entropy in Crystal Polymorphs Through Molecular Simulations

“…A complicating factor in the search for commercially viable solid phases is that the stable forms of a material can change based on external factors such as temperature [18,46,[92][93][94][95][96][97][98][99][100][101][102][103], pressure [76][77][78][79][80][81] and humidity [47,82,83,200]. A complete experimental mapping of all possible solid forms for a given material would therefore require screening at every condition the material will encounter.…”