X-ray Diffraction Applications – Small Molecules 

X-ray crystallography is used in a wide variety of applications, from routine structure analysis to highly specialised research in solid-state chemistry, geology and materials science.

Service crystallography

Many systems are installed in central facilities, and used by service crystallographers and research students for a wide array of both routine and specialist chemical structure determination. This requires system reliability and user-friendly, automated software approaches, such as those incorporated in Agilent’s CrysAlis^Pro and AutoChem packages.

 Absolute structure determination

X-ray crystallography is an extremely powerful tool for characterisation of the absolute configuration (or chirality) of a sample. Using the copper (Cu) X-ray wavelength to maximize the all-important anomalous scattering signal, this application relies on the quality of the sample and intensity of the X-ray source. With modern systems and techniques, it is possible to assign the absolute configuration of even very light atom-containing samples.

Macro-molecules

Large ‘small molecules’ can be very similar to proteins in their diffraction behaviour. The potential for structural disorder is high and such molecules often contain large solvent-containing cavities. The amount of solvent present in these cavities may vary throughout the crystal and this alone can kill diffraction intensity. High-intensity X-ray sources, such as the Nova (Cu) micro-focus X-ray source, enable high quality data to be obtained in-house from even the most challenging of samples.

Charge density

X-ray crystallography can do more than simply measure atomic resolution for structure determination. The collection of high resolution and high redundancy data using a molybdenum (Mo) X-ray source can yield detailed electron density maps. Multipole refinement methods are necessary, and the results are often used in conjunction with molecular modelling calculations in areas such as ligand screening for catalytic activity.

Twinning

Crystals can be twinned in a number of different ways. In non-merohedral twinning, multiple lattices are present in the diffraction pattern. This is caused by two or more inter-grown crystals, or simply where samples are small and inseparable multi-crystals and clusters. Cutting-edge and user-friendly twin deconvolution tools in CrysAlis^Pro  allow the user to resolve twin lattices, allowing for structure solution and refinement which is often as trivial as in a standard ‘single’ crystal.

Variable temperature – phase change experiments

Using an appropriate cryo- or heating device, data can be collected at a variety of temperatures in order to observe a phase change. With the helium cooled Helijet, temperatures as low as 10K can be reached, while the nitrogen cooled CryojetHT has a temperature range of 90-490K. CrysAlis^Pro enables the user to queue up experiments at a number of temperatures, which then run seamlessly with automatic cryo-device control.

High pressure

Samples can be exposed to large pressures using a Diamond anvil cell (DAC), a device which squeezes the crystal in a pressure medium between the faces of two diamonds. The DAC can be mounted on a diffractometer and data collected while the sample is subjected to a specific pressure. The DAC itself limits the amount of data which can be collected. However, Agilent’s CrysAlis^Pro  software can rapidly generate high pressure data collection strategies and also integrate data to account automatically for areas of diffraction images masked by gasket shadows.

Incommensurates and quasi-crystals

CrysAlis^Pro contains a number of user-friendly visual tools for describing and integrating modulated/quasi-crystalline samples. Up to three additional translation vectors can be defined for treatment of even the most complex of cases.

Extended inorganic materials

Inorganic materials often require the observation of weak sub-lattice peaks in a sea of strong parent-lattice reflections. The combination of Agilent’s CCD detectors, which have an 18-bit dynamic range, and software-controlled remeasurement of overloaded reflections, enables the measurement of very strong and extremely weak reflections on the same scale.

Absorbing samples

Samples containing heavy elements absorb X-rays, which means the detected signal changes significantly depending on how the orientation of the crystal within the X-ray beam. This absorption effect is exacerbated by the use of a copper source. By modelling the crystal shape within the software, an absorption correction can be applied to compensate for this effect, irrespective of the wavelength used.

Powder diffraction

The use of a single crystal diffractometer permits users to collect powder data using tiny amounts of sample. The powder is simply mounted in grease on the end of a glass fibre. The use of high intensity sources such as Agilent’s Nova micro-focus (Cu) source enables high quality powder data to be collected and exported to industry-standard powder software packages.

Diffuse Scattering

Diffuse scatter is defined as the intensity which is scattered by a crystal away from standard Bragg reflections. This is caused by long-range disorder within a crystal structure, resulting in a streaky diffraction pattern. The extent to which diffuse scatter can be observed is depends greatly on the intensity of the X-ray source, so Agilent’s Mova and Nova micro-focus X-ray sources are particularly useful for the observation of such effects.