Once a single-crystal structure has been obtained, its value cannot be underestimated. It is for this reason that we offer the structure determinations on a stand alone basis. We also realize the commercial sensitivity of this data and by performing these studies in-house we can ensure the confidentiality of your compounds which can often be at the pre-patent stage. We recognize that not everyone is an expert in this area, so we provide full reports and summaries of the data as well as full data tables and electronic .cif files. All of this data can be transferred, if required, using our 128bit encryption server and we will spend the required time explaining the data. The services we offer are shown below:
Determination of Structure and unambiguous phase ID:
In some cases NMR, although widely used, cannot unambiguously assign structure. Single-Crystal XRD can be used in these cases to confirm the suspected structure which gives a high level of confidence going forward. From this data, a calculated powder pattern may be generated to compare to that of the measure powder pattern from the bulk material. The calculated pattern may also be used to eliminate a phase from an X-ray powder pattern of polymorphic mixture.
Rigorous Determination of Absolute Stereochemistry:
 Proof of absolute stereochemistry of a homochiral active pharmaceutical ingredient is often a requirement as part of the regulatory submission data. At present the only reliable method available for proof of absolute stereochemistry is a single-crystal X-ray structure using the enantiomorph polarity estimation method developed by Flack. This methodology relies on the anomalous scattering effect. The reliability of the determination can be measured by the enantiomorph distinguishing power, which is the standard error on the Flack parameter. For a rigorous absolute stereochemistry determination, the Flack parameter should return a value of zero with an error of less than 0.1. Compounds that contain only first row light atoms i.e. C, H, N, O and F have very small anomalous contributions to the scattering factor when using Mo-Kα radiation. To enhance the enantiomorph distinguishing power it is essential to collect data at longer wavelength such as Cu-Kα.
Use of Synchrotron Radiation Methods:
Occasionally there may be instances where materials do not diffract with sufficient quality on laboratory based diffraction equipment, or crystals are simply too small. At these times it may be advantageous to collect a single crystal dataset at a synchrotron radiation facility. Use of the synchrotron is specialised and expertise in sample preparation and data collection techniques that are particular to pharmaceutical materials would be provided by our experience scientists. This process also ensures protection for the security of your data. For these services we would use the Synchrotron facility in Daresbury UK.
|
