structure factors. Crystal structure data, from the CSD, can be used to steer this
process. Its primary use is to reduce the search space, by the use of torsion angles
restraints using data from Mogul for the conformational preference or by providing a
starting geometry from a similar known single-crystal structure.
Probably the most important use of the CSD when using these techniques where
‘direct’ observation of the result is not possible is in the validation of the final
structural parameters. DASH provides an exemplary use of this approach [220–224].
4.2 How Far Can Single-Crystal Diffraction Structure
Analysis Be Developed?
4.2.1 Instrumentation
We consider first the future possibilities regarding synchrotron-based service crystallography and then go on to discuss what bearing these developments would have
on home laboratory facilities.
Essentially there is nothing stopping synchrotron-based service crystallography
being taken to the limit, which is the fully autonomous beamline. Such a facility
would operate in a service provision mode, acting in a similar philosophy to many
departmental institutional facilities. A user would send pre-mounted crystal and
receive back datasets, without having any interaction with the beamline. Macromolecular crystallography already uses optical recognition to find the mounting loop
and automatically centre it. If the crystal is essentially in the correct place, then it
would be automatically centred, or it would be possible to define a region in which
the crystal could be and search that region. A search could be performed optically, or
by diffraction, or starting with a large beam, or by fluorescence/absorption for
samples containing heavier elements. Once located, a second check could be run
by collecting some data and determining the unit cell. This would enable determination of the x,y,z positional errors, which can then be fed back through the
motorised positioner on the goniometer, further improving the centring. The next
question to be posed would then be ‘what are the data collection criteria for a crystal
and how would we code them for a machine to use?’ The first point to address would
be whether there are any diffraction peaks at all. If there are, then the following
would need to be assessed: Is it a diffraction pattern from a single crystal? What
resolution does it extend to? Are the peak shapes good? During the data collections,
are there, or will there be, signs of radiation damage?
Traditionally one would optically select the best crystal from a sample under the
microscope and collect data on solely that crystal – if it produces good enough data,
then the study is complete. However, there is often the situation where a screened
crystal produces an acceptable diffraction pattern but that would ideally be better, in
which case one has the dilemmas of: Are there any better crystals? Should the crystal
be switched and is there anything of worth left in the sample? If the crystal is
switched and subsequent attempts turn out worse, will the original crystal still be in a
Leading Edge Chemical Crystallography Service Provision and Its Impact on. . .
125
process. Its primary use is to reduce the search space, by the use of torsion angles
restraints using data from Mogul for the conformational preference or by providing a
starting geometry from a similar known single-crystal structure.
Probably the most important use of the CSD when using these techniques where
‘direct’ observation of the result is not possible is in the validation of the final
structural parameters. DASH provides an exemplary use of this approach [220–224].
4.2 How Far Can Single-Crystal Diffraction Structure
Analysis Be Developed?
4.2.1 Instrumentation
We consider first the future possibilities regarding synchrotron-based service crystallography and then go on to discuss what bearing these developments would have
on home laboratory facilities.
Essentially there is nothing stopping synchrotron-based service crystallography
being taken to the limit, which is the fully autonomous beamline. Such a facility
would operate in a service provision mode, acting in a similar philosophy to many
departmental institutional facilities. A user would send pre-mounted crystal and
receive back datasets, without having any interaction with the beamline. Macromolecular crystallography already uses optical recognition to find the mounting loop
and automatically centre it. If the crystal is essentially in the correct place, then it
would be automatically centred, or it would be possible to define a region in which
the crystal could be and search that region. A search could be performed optically, or
by diffraction, or starting with a large beam, or by fluorescence/absorption for
samples containing heavier elements. Once located, a second check could be run
by collecting some data and determining the unit cell. This would enable determination of the x,y,z positional errors, which can then be fed back through the
motorised positioner on the goniometer, further improving the centring. The next
question to be posed would then be ‘what are the data collection criteria for a crystal
and how would we code them for a machine to use?’ The first point to address would
be whether there are any diffraction peaks at all. If there are, then the following
would need to be assessed: Is it a diffraction pattern from a single crystal? What
resolution does it extend to? Are the peak shapes good? During the data collections,
are there, or will there be, signs of radiation damage?
Traditionally one would optically select the best crystal from a sample under the
microscope and collect data on solely that crystal – if it produces good enough data,
then the study is complete. However, there is often the situation where a screened
crystal produces an acceptable diffraction pattern but that would ideally be better, in
which case one has the dilemmas of: Are there any better crystals? Should the crystal
be switched and is there anything of worth left in the sample? If the crystal is
switched and subsequent attempts turn out worse, will the original crystal still be in a
Leading Edge Chemical Crystallography Service Provision and Its Impact on. . .
125