Charlotte K. Leech

Control and prediction of packing motifs: a rare occurrence of carbamazepine in a catemeric configuration

A predicted orthorhombic crystal structure of carbamazepine is isostructural with an experimentally determined dihydrocarbamazepine crystal structure, providing a rationale for synthesising a novel 1 : 1 solid solution that has carbamazepine in a rare catemeric configuration.

A catemer-to-dimer structural transformation in cyheptamide

A catemeric crystal structure of cyheptamide undergoes a transformation in the solid-state upon heating to produce a dimer-based form whose structure has been determined from laboratory X-ray powder diffraction (XRPD) data, thereby providing the first conclusive evidence of a carbamazepine analogue crystallising in both hydrogen bonded motifs.

Discovery of three polymorphs of 7-fluoroisatin reveals challenges in using computational crystal structure prediction as a complement to experimental screening

A combined computational and experimental polymorph search was undertaken to establish the crystal forms of 7-fluoroisatin, a simple molecule with no reported crystal structures, to evaluate the value of crystal structure prediction studies as an aid to solid form discovery. Three polymorphs were found in a manual crystallisation screen, as well as two solvates. Form I (P21/c, Z′ = 1), found from the majority of solvent evaporation experiments, corresponded to the most stable form in the computational search of Z′ = 1 structures. Form III (P21/a, Z′ = 2) is probably a metastable form, which was only found concomitantly with form I, and has the same dimeric R22(8) hydrogen bonding motif as form I and the majority of the computed low energy structures. However, the most thermodynamically stable polymorph, form II (P, Z′ = 2), has an expanded four molecule R44(18) hydrogen bonding motif, which could not have been found within the routine computational study. The computed relative energies of the three forms are not in accord with experimental results. Thus, the experimental finding of three crystalline polymorphs of 7-fluoroisatin illustrates the many challenges for computational screening to be a tool for the experimental crystal engineer, in contrast to the results for an analogous investigation of 5-fluoroisatin.

Solid Phases of Cyclopentane: Combined Experimental and Simulation Study

The phase diagram of cyclopentane has been studied by powder neutron diffraction, providing diffraction patterns for phases I, II, and III, over a range of temperatures and pressures. The putative phase IV was not observed. The structure of the ordered phase III has been solved by single-crystal diffraction. Computational modeling reveals that there are many equienergetic ordered structures for cyclopentane within a small energy range. Molecular dynamics simulations reproduce the structures and diffraction patterns for phases I and III and also show an intermediate disordered phase, which is used to interpret phase II.

Engineering short, strong hydrogen bonds in urea di-carboxylic acid complexes

A series of seven 2 : 1 molecular complexes of urea (U) and methyl ureas with di-carboxylic acids (A) are reported, along with the results of their study by variable temperature diffraction. These all contain short, strong O–H⋯O hydrogen bonds and a recurring acid⋯amide heterodimer forming U–A–U synthons. Despite differences in the degree of saturation of the linking C–C groups of the di-carboxylic acids and the single or double methyl substitution of one of the N atoms of the urea, the packing arrangements are remarkably similar in five of the complexes; the exceptions being N-methylurea oxalic acid and N,N-dimethylurea fumaric acid. The five similar molecular complexes all show contraction of one unit cell parameter on increasing temperature due to rearrangements of the weaker interactions which hold together the U–A–U units. The strength of the short, strong O–H⋯O hydrogen bond is shown to be linked both to the length of the connecting bridge between the carboxylic acid groups of the acid, and to the ΔpKa values between the two components.

Stability and cooperativity of hydrogen bonds in dihydroxybenzoic acids

Multiple temperature single crystal neutron diffraction studies of a new polymorphic form of 2,4-dihydroxybenzoic acid, and of the isomer 2,5-dihydroxybenzoic acid, are presented, together with static and dynamic solid-state density functional theory calculations. The studies present an unambiguous analysis of the potential for cooperativity and hydrogen atom disorder in the hydrogen bond network of both materials. The neutron diffraction experiments establish clearly that there is no disorder, and hence that no hydrogen bond cooperativity is present in either system at temperatures up to 150 K. The findings are supported by DFT calculations, from which lattice and hydrogen bond configuration energies are also obtained, together with computed vibrational spectra.

Accurate molecular structures of chlorothiazide and hydrochlorothiazide by joint refinement against powder neutron and X-ray diffraction data

The compounds chlorothiazide and hydrochlorothiazide (crystalline form II) have been studied in their fully hydrogenous forms by powder neutron diffraction on the GEM diffractometer. The results of joint Rietveld refinement of the structures against multi-bank neutron and single-bank X-ray powder data are reported and show that accurate and precise structural information can be obtained from polycrystalline molecular organic materials by this route.

Hirshfeld surface analysis of two bendroflumethiazide solvates.

Bendroflumethiazide, or 3-benzyl-6-(trifluoromethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, is reported to crystallize as 1:1 solvates with acetone, C(15)H(14)F(3)N(3)O(4)S(2).C(3)H(6)O, and N,N-dimethylformamide, C(15)H(14)F(3)N(3)O(4)S(2).C(3)H(7)NO. A detailed investigation of the crystal packing and intermolecular interactions is presented by means of Hirshfeld surface analysis. This analysis confirms the atomic positions of methyl H atoms of the solvent molecules that were inferred from the X-ray data and provides a useful tool for structure validation.

7-Fluoroisatin–1,4-dioxane (1/1)

The title 1,4-dioxane solvate, C 8H4FNO2 center dot C4H8O2, was isolated during a manual crystallization screen on 7-fluoroisatin (7-fluoroindoline-2,3-dione). The 7-fluoroisatin molecule occupies a general position and each of the independent molecules of 1,4-dioxane is disposed about a centre of inversion, with half of each in the asymmetric unit. Hydrogen-bonded ribbons of 7-fluoroisatin are linked by 1,4-dioxane to form sheets parallel to (30 (1) over bar). Whilst one solvent molecule has an active role in the sheet formation, the other simply fills the cavity formed within the sheet.

Accurate molecular structures and hydrogen bonding in two polymorphs of ortho-acetamidobenzamide by single-crystal neutron diffraction

The structures of both known forms of the polymorphic material ortho-acetamidobenzamide, C(9)H(10)N(2)O(2), have been determined by low-temperature neutron single-crystal diffraction. Neutron diffraction allows the full description of the H-atom positions in this molecular material, which is vital in benchmarking related crystal-structure predictions. Significant conformational differences are indicated by a number of the torsion angles involving H atoms when compared with previous X-ray studies. A comprehensive description of the hydrogen-bonding scheme in both polymorphs is given.