Many organic compounds can exist in hydrated and anhydrous crystalline forms, each of which exhibits its own different set of physical properties. This makes dehydration–rehydration processes an important class of solid-state reactions; yet, the molecular-level mechanisms and cooperative motions which govern such transformation in molecular solids have been notoriously difficult to establish. Here using time-resolved synchrotron X-ray powder diffraction (sPXRD) and other methods, we identify a number of early subtle changes in thymine hydrate (TH) which set its trajectory for the formation of anhydrous products. An early cooperative “morning stretch” motion, characterized by a coordinated increase in the interlayer separation and angular rotation, was observed prior to the appearance of the first major anhydrous phase, Td1. Kinetic analyses indicated the overall solid-state reaction proceeds via a one-dimensional diffusion mechanism with an E a = 115–122 kJ/mol. At temperatures ≥45 °C, solid state dehydration yielded mixtures of Td1 and a second major anhydrous phase, Td2. Multiphase refinement of sPXRD data proved that Td2 is formed via two distinct routeseither directly due to water loss from TH or via the polymorphic transformation of Td1. Heating above ∼180 °C yielded Td2 as the major product. A limited number of weak diffraction peaks evidence the presence of a third transient form, Td*, which also converts to Td2. The time-resolved methods used here illustrate that solid-state dehydration even in a seemingly simple molecular hydrate system involves a significantly more complex set of coordinated molecular motions and solid–solid transformations than originally thought. The ability to glean a more complete picture of the cooperative motions that occur during water loss from soft crystalline hydrates is an important step in the development of a deeper understanding of this important class of materials.

Hydrogen bonding between urea groups is a widely used motif in crystal engineering and supramolecular chemistry studies. In an effort to discern how the steric and electronic properties of substituents affect the molecular conformation and crystal packing of ortho-substituted N,N′-diphenylureas (oPUs), herein we report the synthesis, characterization, and polymorph screening of eight members of this family. Of the 16 total oPU structures known (including nine structures from this study and seven previously reported), only two are isostructural. These 16 structures are sorted into three general architecture types based on their hydrogen bond topologies. In Type I, urea molecules related by translation form linear one-dimensional (1D) hydrogen bonded chains. In Type II, urea molecules rotate about a 1D hydrogen bond axis forming twisted chains. Urea groups do not hydrogen bond to one another in Type III. Energy calculations performed at the B3LYP/6-31G­(d,p) level show a higher rotational barrier about the amide bond in oPUs compared to meta-substituted diphenylureas (mPUs), which may explain the smaller range of torsion angles observed in oPUs compared to mPUs. Although ortho-substitution does not seem to limit the hydrogen bonding between urea groups in most cases, a notably higher percentage of oPU phases are polar compared to PUs with other substitution patterns. This suggests restricted conformations might offer some advantage in achieving acentric materials.

Monohydrate and anhydrate crystalline forms of the DNA nucleobase cytosine interconvert via a topotactic solid-state mechanism where water functions as a molecular switch. The solid-state dehydration mechanism and kinetics were elucidated using complementary time-resolved synchrotron powder X-ray diffraction and thermogravimetric methods. Results indicate the reaction initiates from the crystal surface, involves no other crystalline intermediates, and proceeds at rates that depend on the monohydrate processing. A molecular-level model, based on least-motion arguments and consistent with the totality of the experimental data, is proposed to account for the high degree of structure transfer associated with the transformation. Water loss on the monohydrate crystal surface activates the rotation of one-dimensional cytosine ribbons, which in turn alters the local environment of the neighboring unit cell, facilitating the release of additional water molecules and ribbon rotation. As the dehydration front progresses into the solid, this cooperative mechanism effectively converts two-dimensional layers of antiparallel π-offset stacked ribbons into orthogonal two-dimensional layers of parallel π-face–face stacked ribbons. Moisture sorption experiments performed under high-humidity conditions confirm the anhydrate product can be reversibly rehydrated back to the monohydrate and that repeated dehydration–rehydration cycles proceed at consistent rates. The ability to track both the structural and compositional changes in the sample throughout the course of the reaction makes this a powerful combination of techniques for characterizing cooperative rotational motions triggered by water loss and/or uptake from crystalline materials.

Many crystal engineering studies employ urea functionalities for their predictable association into one-dimensional hydrogen bonded chains. Previously, we showed (Cryst. Growth Des., 2015, 15 (10), 5068–5074) that the urea chain motif usually seen in structures of diphenylureas (PUs) with meta-substituents could be disrupted in several cases by cocrystallization with the strong hydrogen bond acceptor triphenylphosphine oxide (TPPO). Computed differences in the urea···urea and urea···TPPO dimer energies of ∼5.3–6 kcal/mol were a reasonably accurate indicator for cocrystallization success. The current study attempts to reassess the limits of this computational approach using a larger set of 16 ortho- and para-substituted PUs. Seven of the 10 PU systems predicted to cocrystallize on the basis of dimer energy calculations were experimentally realized, along with an eighth whose difference in homo/heterodimer energies fell below the threshold. The absence of cocrystallization in two of the predicted systems is likely due to preferred urea···substituent hydrogen bonding over both urea···urea and urea···TPPO interactions, a factor that was not considered in the homo/heterodimer energy comparisons. When taken in combination with the previous study, energy predictions were 87% accurate over the 30 systems investigated.

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.