Structural Studies of a Non‐Stoichiometric Channel Hydrate Using High Resolution X‐ray Powder Diffraction, Solid‐State Nuclear Magnetic Resonance, and Moisture Sorption Methods

One of the long-standing challenges in working with organic hydrates in general, and channel hydrates in particular, is their propensity to lose water over time and convert (either partially or fully) to anhydrous solid forms. In this work, we demonstrate the ability to rationally increase the thermal stability of a model channel hydrate, the DNA nucleobase thymine hydrate (TH), through the systematic creation of lattice substitutions with 5-aminouracil (AUr). Mixed crystals of TH−AUr with up to 17 mol % AUr were isomorphous with the pure hydrate, confirming our molecular-level design strategy which places 5-amino groups at the one-dimensional channel surfaces. The enhanced stabilization of the water molecules afforded by the proximal 5-amino substitutions resulted in mixed crystals with significantly higher thermal stability. The magnitude of the thermal stability enhancement scaled linearly with the included AUr concentration, yielding TH−AUr dehydration temperatures nearly double that of the pure hydrate. Kinetic analyses and time-resolved synchrotron structural studies of process-induced dehydration of the mixed composition hydrate indicated changes in both the solid-state mechanism and the resultant anhydrous products compared to those generated from the pure hydrate. The strategy adopted herein should be applicable to other hydrate systems to rationally tune their thermal stabilities.

Section: Introductionmentioning

confidence: 99%

Improving Channel Hydrate Stability via Localized Chemical Tuning of the Water Environment

Watts

Niederberger

Swift

2021

“…In other cases, crystallinity can be preserved after water loss even if significant structural changes result from the collapse of water channels (an effect that can be reversed by exposure of crystals to humidity) . When water molecules do not perform a major structure-sustaining role, the crystal structure can remain intact, with barely any structural alterations. − In metal-ion-associated hydrates, water molecules form strong interactions with transition metals or alkali metals . The resulting hydrated crystal form can show high stability against dehydration .…”

Section: Introductionmentioning

confidence: 99%

Toward an Understanding of the Propensity for Crystalline Hydrate Formation by Molecular Compounds. Part 2

Sanii

Patyk‐Kaźmierczak

Hua

et al. 2021

The propensity of molecular organic compounds to form stoichiometric or nonstoichiometric crystalline hydrates remains a challenging aspect of crystal engineering and is of practical relevance to fields such as pharmaceutical science. In this work, we address the propensity for hydrate formation of a library of eight compounds comprised of 5-and 6-membered Nheterocyclic aromatics classified into three subgroups: linear dipyridyls, substituted Schiff bases, and tripodal molecules. Each molecular compound studied possesses strong hydrogen bond acceptors and is devoid of strong hydrogen bond donors. Four methods were used to screen for hydrate propensity using the anhydrate forms of the molecular compounds in our library: water slurry under ambient conditions, exposure to humidity, aqueous solvent drop grinding (SDG), and dynamic water vapor sorption (DVS). In addition, crystallization from mixed solvents was studied. Water slurry, aqueous SDG, and exposure to humidity were found to be the most effective methods for hydrate screening. Our study also involved a structural analysis using the Cambridge Structural Database, electrostatic potential (ESP) maps, full interaction maps (FIMs), and crystal packing motifs. The hydrate propensity of each compound studied was compared to a compound of the same type known to form a hydrate through a previous study of ours. Out of the eight newly studied compounds (herein numbered 4−11), three Schiff bases were observed to form hydrates. Three crystal structures (two hydrates and one anhydrate) were determined. Compound 6 crystallized as an isolated site hydrate in the monoclinic space group P2 1 /a, while 7 and 10 crystallized in the monoclinic space group P2 1 /c as a channel tetrahydrate and an anhydrate, respectively. Whereas we did not find any direct correlation between the number of H−bond acceptors and either hydrate propensity or the stoichiometry of the resulting hydrates, analysis of FIMs suggested that hydrates tend to form when the corresponding anhydrate structure does not facilitate intermolecular interactions.

“…Organic molecular hydrates are a ubiquitous class of crystalline materials , encountered in the production of fine chemicals (e.g., active pharmaceutical ingredients), yet their thermal stabilities remain difficult to predict. − Often sensitive to environmental conditions (e.g., temperature and relative humidity), many molecular hydrates are susceptible to partial or complete water loss. Since the physical properties of a crystalline compound depend on its structure (e.g., solubility, mechanical strength), there is considerable interest in defining the structural factors − that dictate water loss from hydrated phases and the potential products that result from solid state dehydration reactions.…”

Section: Introductionmentioning

confidence: 99%

Steric Perturbation to a Channel Hydrate: The Limits of Isomorphism

Watts

Lee

Niederberger

et al. 2021

Thymine hydrate (TH) is a classic hydrate system in which water molecules are highly confined in linear one-dimensional channels. Here, we describe our efforts to tune the channel volume by preparing isomorphous mixed crystals with increasing concentrations of uracil (Ur) and 5-ethyluracil (EUr), molecular analogues with slightly smaller and larger volumes, respectively. Solutions with up to 20 mol % Ur successfully yielded isomorphous mixed crystals of TH-Ur x in phase-pure form, though analysis of the mixed crystal compositions indicated that only ∼46% of the Ur available in the initial growth solution was proportionately included in the host lattice. The thermal stability of the mixed TH-Ur x material was significantly altered, with a greater fraction of water loss occurring at low temperature compared to the pure hydrate phase. Isomorphous mixed crystals with EUr substitutions, TH-EUr x , were successfully prepared from solutions with 5–10 mol % EUr, although the fraction of EUr included was much lower (∼13–36%) than Ur. As the concentration of EUr in the growth solution increased to 15–20 mol %, an unexpected mixed composition anhydrate emerged as the dominant crystallization product. Although packing fraction estimates suggested that higher EUr substitution levels in the hydrate were theoretically possible, the formation of the mixed anhydrate presented a more favorable route to a dense material phase.