Combined analysis of structural data from several different techniques

Every structural method has its limitations. Using data from just one experimental technique can render accurate structure determination impossible for some molecules. The larger and less symmetric the molecule, the bigger the problem can be.

Combining data from different experimental methods

Both electron diffraction and rotational spectroscopy give information about gas-phase molecules. Electron diffraction provides information about individual interatomic distances, whereas each rotation constant is a property of the whole structure. Using both sets of data together, otherwise intractable structural problems can be solved, and accuracy improved.

Direct coupling constants measured by NMR spectroscopy in liquid-crystal solvents provide information about structures in solution, which is complementary to that obtained by electron diffraction. So long as there are no strong solvent-solute interactions, these data can be used in a combined analysis, which can give unprecedented accuracy for structures of molecules with about 10 to 12 atoms.

We can now analyse simultaneously data from all techniques that provide structural information, in what has become known as the STRADIVARIUS method - STRuctural Analysis using DIffraction and VARIoUS other data.

Combining experimental and theoretical data

SARACEN

Even using all available experimental data, there are many structures which are too complex to solve. We need more information. So we have developed a method of using flexible restraints derived from ab initio or density functional theory calculations as if they were additional experimental observations - the SARACEN (Structure Analysis Restrained by Ab initio Calculations for Electron diffractioN) method. Using this method enables us to remove symmetry assumptions and to refine all parameters. This has revolutionised our structural studies, and nothing is too big or complex to be studied. If it is volatile, its structure can be determined. The resulting structure is based on both theory and experiment, using the best of both worlds.

The SARACEN method is described in references 1996/2 and 1996/5. Examples of its application can be found in almost all of our papers published since then.

DYNAMITE

The application of the SARACEN method has revolutionised gas-phase structure determination. Larger, more complex, molecules can now be studied. However, although all parameters describing the heavy-atom skeleton of molecules can now be refined, assumptions are generally made about the positions of light atoms to reduce the overall number of parameters required. Although a distance, bond angle and bond torsion may be used to describe hydrogen positions in a methyl group, local C3 symmetry will still be assumed. When considering sterically crowded molecules, for example containing t-butyl or trimethylsilyl groups, this lack of flexibility within the methyl groups could lead to the heavy-atom positions compensating for the light-atom interactions. The use of the DYNAMic Interaction of Theory and Experiment (DYNAMITE) method removes these problems. The procedure involves refining the heavy-atom skeleton of the molecule using the GED data while continually updating the light-atom positions during the refinement using computational methods (currently molecular mechanics). This removes errors associated with the assumption of local symmetry for the light-atom groups, which can affect the final values of the heavy-atom parameters.

Thus DYNAMITE is a method for total structure determination and is described in references 2004/2 and 2005/9.

SEMTEX

As mentioned above, DYNAMITE uses molecular mechanics (MM) to determine positions of peripheral light atoms. However, MM is based on a set of empirical parameters, so light atoms are not completely free to find their optimal geometries. Ideally, an ab initio computational method would be used for the dynamic updating of the light-atom positions, but limitations of computing time mean that such methods cannot be implemented directly. For this reason we developed the SEMTEX (Structure Enhancement Methodology for Theory and Experiment) method. SEMTEX indirectly includes the results of MP2 calculations in the refinement process in the form of a calculated set of differences between these parameters and those from MM. The differences may be recalculated several times during the refinements, to ensure that the final structure is effectively constrained entirely by the high-level, ab initio calculations. SEMTEX is described in greater detail in references 2007/8 and 2010/11.

For information about structures determined world-wide by electron diffraction (with or without data from other methods), see the Gas Electron Diffraction Information Service.