Polymorphic Behaviour of 3-Chloromandelic acid

For several years we have been making detailed comparisons of the crystal structures of large sets of related compounds in an attempt to understand the factors determining the adoption of particular molecular arrangements within crystal structures. In all these projects, the XPac program [1] was used to identify similarity between structures in 0-dimensions (0D) (discrete molecular arrangements e.g. dimers, trimers etc),1D (chains or stacks), 2D (sheets or planes) and 3D (frameworks or full isostructurality) as a preliminary to the detailed comparison of the similarities so identified. As part of a larger crystallographic project to investigate the relationship between structure and chirality, we have synthesized and determined crystal structures of families of monosubstituted racemic mandelic acids with fluoro, chloro, bromo, iodo, trifluoromethyl, methyl and methoxy substituents at the ortho, meta and para positions. The substituted mandelic acids are polymorphically prolific and with the inclusion of unsubstituted mandelic acid, 28 structures have been compared. Of special interest has been 3-chloromandelic acid (3-ClMA), for which so far five polymorphs have been discovered: three racemic, two of which are isostructural [2], and two enantiopure. A crystal structure prediction (CSP) study of 3-ClMA has been carried out using the CrystalPredictor [3] and CrystalOptimizer [3] algorithms to generate the crystal energy landscape which is exceptionally dense with 3050 structures within 20 kJ mol-1. Many of these are more stable than the known forms, which is consistent with the complex crystallisation behaviour observed. From our observations of the crystallisation behaviour of substituted chloromandelic acids in general and the CSP study of 3-ClMA, we expect to discover further polymorphs of 3-ClMA and to this end cross-seeding experiments using crystals from differently substituted mandelic acids and a comprehensive polymorph screen are at present being undertaken.

Charge density studies on 1:1 co-crystals of ethenzamide and saccharin

The study of multi-component crystals, as well as the phenomenon of polymorphism, both have relevance to crystal engineering. Obtaining a specific polymorph is crucial as different polymorphs usually exhibit different physical and chemical properties and often the origin of this behaviour is unknown. This is especially important in the pharmaceutical industry. Herein, we present results of comparative studies of an analgesic drug, ethenzamide and its co-crystals with saccharin. The co-crystalisation of ethenzamide (2-ethoxybenzamide, EA) with saccharin (1,1-dioxo-,1,2-benzothiazol-3-one, SAC) with a 1:1 stoichiometric ratio resulted in two polymorphic forms of the co-crystal. Form I crystallises in the triclinic P-1 space group, whereas form II crystallises in monoclinic space group P21/n. Previous crystal structure analyses on forms I and II revealed that in both polymorphs the primary carboxy-amide-imide heterosynthon is the same, however the secondary level of interactions which extends the hydrogen bond network is different. Form I consists of extended linear tapes via N-H···O hydrogen bonds, whereas form II is composed of stacks of tetrameric motifs including N-H···O hydrogen bonds and C-H···O interactions. These two forms of EA-SAC can be classified as synthon polymorphs at a secondary level of hydrogen bonding [1]. In our approach an accurate, high resolution charge density distribution analysis has been carried out to obtain greater insight into the electronic structures of both types of the EA-SAC co-crystals and relate differences in electronic distribution with their polymorphic behaviour. To describe the nature and role of inter and intra-molecular interactions in a quantitative manner, the Hansen-Coppens formalism [2] and Bader's AIM theory [3] approach have been applied.

Mixing and Quantifying Multi-Component Materials for Pyrotechnic Applications

This multidisciplinary research is looking at the relationship between components of a pyrotechnic product and how manufacturing, in particular the mixing method employed, affects its macroscopic structure and properties. For pyrotechnics to produce the desired effect the ingredients must be intimately mixed, however, the present physical mixing approach can lead to inconsistencies in performance between batches. X-ray computed tomography (CT) was used to investigate the distribution of components in a pyrotechnic mixture. Near-neighbour distances between particles were calculated and used to assess the homogeneity of the mixtures and the efficiency of combustion. Another strand of this research to overcome batch inconsistencies was by chemically binding pyrotechnic ingredients rather than physically mixing them together. One method of achieving this was through incorporating two or more components within the same crystalline lattice. This may be achieved through co-crystallisation or coordination in functional frameworks, thereby reducing the number of components in a physical mixture and minimising the variation between batches. Pang et al. have investigated using MOFs (metal-organic frameworks) to stabilise energetic materials [1]. The research presented here uses MOFs to bring together fuels and oxidisers into one framework to create a MOFirework. Numerous linkers and metal centres were investigated to build up a structural family to correlate structure with pyrotechnic function (e.g. changing burn colour; Sr = red, Ba = green). Both powder and single crystal X-ray diffraction were used to characterise the products. Differential scanning calorimetry was used to look at the thermal profiles to investigate their possible uses as pyrotechnics. Lastly, a burn test was carried out to determine their pyrotechnic effect (e.g. gas, smoke, gas, light, heat, colour, and sound) and quantitatively link this to structure.

Delivering practical crystallography experience to undergraduate students

Teaching of laboratory-based chemistry in universities has barely evolved since its inception. Practical work is generally conducted in a highly structured, dedicated teaching laboratory environment or on a `student-as-apprentice' basis in an active research laboratory. Exposure to crystallography as an undergraduate is generally limited to theoretical lecture-based courses, with little or no practical experience, despite the fact that training in the use of expensive research-based instruments is becoming a necessity of modern science. We present a course based around the solid-state structural chemistry of a molecular polymorphic system, delivered to third year undergraduates (70 students) at the University of Southampton which contains numerous novel features: 1) Students work in pairs (maximum group size of 8). 2) It is a `hands-on' experience for every participant, involving single crystal and powder diffractometers (Rigaku XtaLab mini and MiniFlex benchtop systems) dedicated to educational activities. 3) It is a student-led activity, designed as an `advanced practical' providing a taste of the research experience. 4) Laboratory manuals are available to students via an Electronic Laboratory Notebook (ELN) system. 5) Plans, experimental enactments, observations and conclusions are recorded by students in the ELN (directly linked to the manual sections). 6) Feedback and assessment is delivered through the ELN by directly linking instructor comments to the student ELN record. The experiment comprises about 15 manual sections in the LabTrove ELN system, which has a similar design to a blog, enabling student comments and assessor feedback to be linked to these sections. This talk will outline the design of the experiment and instruments involved, the mode and logistics of delivery, and will discuss the evaluation of its impact on student learning by analysis of feedback questionnaires.

Experimental Charge Density studies of Ge(II) complexes using beamline I19

Interest in the p-block elements has recently been stimulated by the need for new reagents for materials and electronics applications, as well as the intrinsic interest in the unprecedented structures and properties observed. For germanium the development of low-valent compounds, organometallics, multiply bonded species, radicals and clusters is of significant importance. We have probed the coordination chemistry of Ge(II) with a range of neutral ligands, few examples of which were reported until recently. They exhibit many striking features including diverse structural motifs and highly variable coordination numbers (between 3 and 8) [1] suggesting the Ge centre does not to have a strong stereochemical preference and small differences in steric and electronic properties of the donor ligands have a significant role. Bonding models have been used to rationalise the observed structures with a Ge-based lone pair occupying the stabilised Ge 4s orbital. However these models are not entirely satisfactory and experimental charge density studies could provide valuable insights into the structures and chemistry of these compounds. [GeCl2(2,2'-bipyridine)], 1, and [GeCl2(1,2-bis(dimethylphosphino)benzene], 2, were selected as targets for initial experimental charge density studies and data have been collected using 3 different experimental configurations of the small molecule single-crystal diffraction beamline I19 [2] at Diamond Light Source. Using a Rigaku Saturn 724+ CCD detector on a 4-circle kappa-geometry CrystalLogic goniometer, data for 1 were collected at λ=0.6889Å without bimorph focussing mirrors in place, and for 2 data were collected at both λ=0.6889Å with bimorph mirrors and λ=0.4859Å without mirrors giving data to 0.48 and 0.38 Å resolution respectively. Details of the analysis of the topology of the electron density will be presented with the insights gained into the bonding in these unusual complexes.

Opening up the Lab Notebook: Publishing Experimental & Supplementary Information

Supplementary Information supporting publications is not uniform across journals, is generally not 100% representative of the work undertaken, is not structured or comprehensive and therefore is often not fully considered in review. In chemistry articles where characterisation techniques are applied widely, crystallography is the exception in that there are universally agreed processes and protocols for presenting the scientific findings and the supporting data. Crystallography can therefore lead the way! Our approach to solving the broader problem of availability of supporting information is to expose the observations of the researchers who conducted the work when it was performed. By combining these observations with related data (eg in information management systems) and linking these with the article there is the potential for a much richer system for data supporting a publication. The Electronic Laboratory Notebook (ELN) plays a key role by establishing authenticity, adding structure to the record and having the capacity to be made open. We present a formal publication in Chemistry Central Journal (http://journal.chemistrycentral.com/content/7/1/182) which is a collaborative piece of work between the UK National Crystallography Service (University of Southampton) and the University of Greenwich, where the data supporting the article is not contained within it, but is openly exposed at source by an ELN and a crystal structure repository. We draw on the experience of crystallographic publishing and aligning that with the other characterisation techniques alongside which crystal structures are routinely published and related. The article presents all the supplementary information (some 35 or so data sources) in a single graphical approach, which permits examination of synthesis, spectra & structures in-line and provides a link to the original ELN record. All records are assigned a Digital Object Identifier (DOI) by a system established within the University.

Radiation Damage in Chemical Crystallography

Although crystals suffering radiation damage is a well-known and studied phenomena for macromolecular crystallography[1], as far as we are aware there appears to be no such published work relating to chemical crystallography. However, there are numerous anecdotal accounts of disintegrating crystals and resolution progressively dropping off that have been ascribed to radiation damage. Since the start of operations on the small molecule synchrotron beamline I19[2] at Diamond Light Source, there have been multiple comments from several users observing sample damage in the beam. The UK National Crystallography Service[3] handles a wide variety of samples and a number of these have experienced radiation damage. In order to understand the causes and symptoms of this effect in greater detail some controlled experiments were performed. A series of experiments were conducted on crystals that were known to undergo radiation damage in order to determine some quantification of the effect. Additionally the aim is to understand what one might be able to do to mitigate against the damage caused and determine whether the effects observed are similar to those of macromolecular crystallography. The effects of varying the collection temperature, overall dose, dose rate and wavelength of X-ray used were all tested and normalised for each sample. Samples where radiation damage has been observed were chosen and were also required to be air stable and preferably not suffer from solvent loss, in order to minimize problems of non-reproducibility. Those chosen to probe this effect were: 1. A gold complex - has potential to suffer heavily from absorption effects. 2. A nickel complex with significant solvent water - this could to some extent mimic the behaviour exhibited by proteins. 3. A small organic compound - an example of unexpected decay. The poster will summarise the results of these experiments and contrast them with data collected on a high intensity rotating anode laboratory source.