What can a crystal structure analysis do for you?

An X-ray crystal structure determination is almost the ultimate analysis. No other analytical technique currently available can deliver such complete and unambiguous information about the nature of the substance being investigated. The X-ray diffraction experiment provides a 3-dimensional map of electron density and therefore a complete 3-dimensional "picture" of the substance in question.

With the modern instrumentation now available, the diffraction experiment and initial solution of the structure can often be completed within just a few hours. Therefore, a crystal structure analysis has become the analytical method of choice when suitable crystals are available, because the speed of the analysis is approaching a similar timescale to that of other analytical methods (including interpretation of the spectra), and it provides unsurpassably detailed and unequivocal structural information.

An X-ray crystal structure determination is often used merely to confirm that the product of a chemical reaction or an isolated natural product is indeed the expected or predicted compound. In reality, the structure determination provides a wealth of information about the compound being investigated, much of which is often under-utilised.

Provided good quality crystals are available and there is no complex disorder present, the following information can be obtained from an analysis:

• The complete and precise 3-dimensional geometry of the molecule, including bond lengths, bond angles and torsion angles.
• The complete chemical composition and connectivity.
• The molecular conformation, which can be useful for understanding the reactivity of the compound.
• The relative configuration of chiral centres within the molecule.
• For an enantiomerically pure substance:
  • The absolute configuration can easily be deduced if one chiral centre is already known.
  • The absolute configuration can often be determined independently of any other knowledge. With high-quality crystals, an indication of absolute configuration might be possible with the heaviest element in the structure just being oxygen, but preferably a heavier element (silicon or heavier) is needed. The heavy atom does not have to be in the molecule of interest; it could be a counter-ion, or in a co-crystallised species such as a solvent molecule.
• Molecular motion / vibration
• Intermolecular interactions in the solid state, such as hydrogen bonding and non-bonding interactions.

• Good single crystals are required, and these are sometimes difficult to obtain without considerable effort.
• Decomposition of the compound during crystallisation attempts can be a difficulty with reactive compounds.
• The analysis is done on a single crystal, which may not be representative of the bulk material.
• The conformational results apply to the solid state and may be different to the molecular conformations present in solution, which is where most reactions take place.

Ideally, it would seem desirable to conduct an X-ray crystal structure determination for every substance that is synthesised or isolated, as this would quickly reveal the precise nature of the product and probably save hours of time evaluating and interpreting other spectra. This is particularly important if an unexpected and exciting new product has resulted, because the interpretation of other spectra may be very complicated and bothersome if the reaction has taken an unexpected and unknown course.

As the modern instrumentation has enabled the diffraction experiment to be completed within just a few hours, the above ideal can now be achieved quite readily. The biggest remaining hindrance to the application of this ideal is probably the effort required to grow single crystals of adequate quality within a reasonable timeframe.

While an X-ray structural analyses can usually be used to determine the molecular composition and connectivity of a compound without any prior knowledge, it is certainly useful to know, before commencing the analysis, what the compound is expected or likely to be. You should also try to ensure that you are not submitting an unexpected or unwanted product, simple side-product or unreacted reactant. In this way, you will save unnecessary analyses, as well as your own time and embarrassment. Therefore, whenever possible, at least preliminary MS, IR and NMR spectra should be recorded and evaluated before the crystals are submitted for an X-ray structure determination, so that the unnecessary determination of trivial or uninteresting structures can be avoided. However, if the spectra reveal that you have a product of interest, even if its structure cannot be deduced easily, you should not hesitate to request an X-ray crystal structure determination.

In the majority of cases, it is recommended that an X-ray crystal structure determination be carried out whenever one or more of the following situations arise:

• The confirmation of the product of a synthesis or isolation procedure is needed.
• Unresolved ambiguities remain after the initial evaluation of MS, IR and NMR spectra and the completion of a microanalysis.
• Precise geometrical or conformational information is required.
• There is interest in the topology, solid-state packing or intra- and intermolecular interactions.
• The absolute or relative configuration of stereocentres is needed.