Jennifer A. Swift

Halogen/methyl exchange in a series of isostructural 1,3-bis(m-dihalophenyl)ureas

The solid state structures of a family of 1,3-bis(m-di-X-phenyl)ureas where X = Cl, Br, I and their mono- and di-tolyl analogues were determined. Crystal growth from a variety of solutions yielded isostructural and isomorphous P21212 phases for all compounds. The molecules associate into infinite [R12(6)] hydrogen bonded urea chains which are reinforced through π–π stacking interactions of neighboring phenyl rings within the chain. Short halogen–halogen contacts between anti-parallel urea chains are also observed. Ab initio calculations indicate that the rotational barrier about the amide bond is small, and that the molecular conformations observed in the crystal structures are close in energy to the calculated minima. These calculations suggest that a variety of low energy geometric conformations may be present in solution. Using a small scale conventional polymorph screening protocol (∼9 crystallization solvents and combinations thereof), analysis of the phase purity of powders obtained from a variety of solutions revealed the orthorhombic phase to be the predominant form for all compounds in all solvents. However, additional peaks were observed in select powder X-ray diffraction patterns, leaving open the possibility that concomitant polymorphism or solvate formation occurs for some compounds under particular crystallization conditions.

Step kinetics on monosodium urate monohydrate single crystal surfaces: an in situ AFM study

The deposition of monosodium urate (MSU) crystals in synovial fluid is a classic clinical symptom of the joint disease gout. In previous work (CrystEngComm, 2011, 13, 1111–1117), it was reported that crystal growth occurs by an island deposition mechanism in 2–10 mM urate solutions under simulated physiologic conditions (150 mM NaCl, 37 °C, pH = 7.4). The present work examines in greater detail the molecular-level growth occurring in the areas between deposited islands on two types of single crystal surfaces – (100) and (1–10) using in situ atomic force microscopy. The surface topography on both types of faces consisted of elementary (unit cell) steps and macrosteps (>45 nm) which showed significant quantifiable differences in their in-plane growth kinetics. All growing steps exhibited orientations corresponding to high Miller Index directions and showed a non-linear increase in lateral velocity over the supersaturation range σ = 2.5–3.4. Topographical imaging was additionally used to establish the preferred relative orientation of domains in these frequently twinned crystals.

Using solvent effects to guide the design of a CL-20 cocrystal

Co-crystallization of the high energy material CL-20 and triphenylphosphine oxide yields a 1 : 2 cocrystal in which CL-20 molecules adopt two different low energy conformations. Hydrogen bonding interactions between the H atoms on the isowurtzitane cage and phosphine oxide are consistent with solvent effects seen in previous crystal growth studies.

Adhesion Properties of Uric Acid Crystal Surfaces

Two key steps in kidney stone formation--crystal aggregation and attachment to renal tissues--depend on the surface adhesion properties of the crystalline components. Anhydrous uric acid (UA) is the most common organic crystalline phase found in human kidney stones. Using chemical force microscopy, the adhesion force between various functional groups and the largest (100) surface of UA single crystals was measured in both aqueous solution and model urine. Adhesion trends in the two solutions were identical, but were consistently lower in the latter. Changes in the solution ionic strength and pH were also found to affect the magnitude of the adhesion. UA surfaces showed the strongest adhesion to cationic functionalities, which is consistent with ionization of some surface uric acid molecules to urate. Although hydrogen-bonding and van der Waals interactions are usually considered to be dominant forces in the association between neutral organic compounds, this work demonstrates that electrostatic interactions can be important, particularly when dealing with weak acids under certain solution conditions.

Solution-mediated phase transformation of uric acid dihydrate

Various crystalline phases of uric acid are frequently identified components of human kidney stones, including anhydrous uric acid (UA) and uric acid dihydrate (UAD). Herein we report a quantitative study of the solution-mediated phase transformation of metastable UAD to UA as a function of pH as well as in model urine solution. Using a combination of X-ray diffraction, thermal analysis, and optical microscopy techniques, the UAD to UA transformation was found to go to completion within 48 hours at 37 °C in buffered solutions with pH between 4.0–6.5 with no evidence for intermediate crystalline phases. In solutions with pH > 6.8, UAD transformation to a different monosodium urate monohydrate phase becomes dominant. In artificial urine solution, the transformation occurs on a slightly faster timescale and results in smaller UA crystals. Seeding and saturation experiments indicate that the rate-limiting step in the overall transformation is the dissolution of UAD. The kinetics of these transformation processes suggest that interconversions between various solid state forms of uric acid are relevant under the physiologic conditions which lead to stone formation.

Structure of a lead urate complex and its effect on the nucleation of monosodium urate monohydrate

Lead diurate monohydrate (PbU22·H22O), the crystal structure of which is reported herein, induces the nucleation of monosodium urate from otherwise stable uric acid solutions.

Directed Nucleation of Molecular Crystals on Self-Assembled Monolayer Surfaces

The nucleation and growth of four types of molecular crystals (4,4′-diiodobiphenyl, 2-methyl-4-nitroaniline, 3-nitroaniline, and 2-amino-5-nitropyridine) on gold-thiol self-assembled monolayers (SAMs) of 4′-X- and 3′-X-4-mercaptobiphenyl (X = I and NO2) is described herein. In each case, crystals were found to nucleate heterogeneously on the SAM template and adopt specific growth orientations with respect to the underlying monolayer surface. The preferred orientations observed in these and other systems can be rationalized on the basis of coincident epitaxy and complementary NO…I interactions across the SAM/crystal interface.

Uric Acid Dye Inclusion Crystals

ABSTRACT Crystallization in the presence of molecular dye probes has been used as a means of discerning surface recognition events that occur during the growth of uric acid (UA) and uric acid dihydrate (UAD), which are known components of some human kidney stones. The growth of synthetic UA and UAD crystals from supersaturated aqueous solutions containing seven different cationic dyes (Thionin, New Methylene Blue, Neutral Red, Acridine Yellow G, Safranine O, Bismarck Brown Y, and Bismarck Brown R) yielded dye-included crystals in all cases. Herein we describe the specific inclusion patterns and/or habit modification resulting from these growth conditions.

Concomitant polymorphs of 1,3-bis(3-fluorophenyl)urea.

Hydrogen bonding between urea functionalities is a common structural motif employed in crystal-engineering studies. Crystallization of 1,3-bis(3-fluorophenyl)urea, C13H10F2N2O, from many solvents yielded concomitant mixtures of at least two polymorphs. In the monoclinic form, one-dimensional chains of hydrogen-bonded urea molecules align in an antiparallel orientation, as is typical of many diphenylureas. In the orthorhombic form, one-dimensional chains of hydrogen-bonded urea molecules have a parallel orientation rarely observed in symmetrically substituted diphenylureas.

Two tautomeric forms of 2-amino-5,6-dimethylpyrimidin-4-one.

Derivatives of 4-hydroxypyrimidine are an important class of biomolecules. These compounds can undergo keto-enol tautomerization in solution, though a search of the Cambridge Structural Database shows a strong bias toward the 3H-keto tautomer in the solid state. Recrystallization of 2-amino-5,6-dimethyl-4-hydroxypyrimidine, C6H9N3O, from aqueous solution yielded triclinic crystals of the 1H-keto tautomer, denoted form (I). Though not apparent in the X-ray data, the IR spectrum suggests that small amounts of the 4-hydroxy tautomer are also present in the crystal. Monoclinic crystals of form (II), comprised of a 1:1 ratio of both the 1H-keto and the 3H-keto tautomers, were obtained from aqueous solutions containing uric acid. Forms (I) and (II) exhibit one-dimensional and three-dimensional hydrogen-bonding motifs, respectively.