End Stations: Small Molecule Specifics
The huge potential for using synchrotron radiation for the determination of small
molecule structures, from crystals of a size that would formerly have been considered as single powder grains, was demonstrated by Harding in 1994 [42] with the
structure solution of the industrially important catalyst precursor material
aurichalcite. They used the SRS wiggler protein crystallography station, 9.6, at the
Daresbury Laboratory with an Enraf-Nonius FAST (electronic area detector) diffractometer (0.4
frames, exposure time 40 s per frame, covering 200
in φ with the
synchrotron ring current 20 mA (single-bunch mode)). Despite the low single-bunch
ring current and the very small crystal size (100 Â 40 Â 5 μm), they obtained
excellent results which demonstrated the need, and likely success, of a dedicated
small molecule single-crystal diffraction station at SRS. The work, in part, was a
precursor to the first beamline built at a synchrotron that was designed solely for the
support of small molecule crystallography, station 9.8 at SRS Daresbury [43], which
was built around a turn-key laboratory-based diffractometer system that was adapted
for the synchrotron environment.
Thereafter a number of dedicated small molecule crystallography beamlines at
synchrotrons also started out using commercial diffractometer and area detector
systems. This approach had the strong advantage that while almost all users had
no synchrotron experience, they were familiar with the software and operation of the
diffractometer system. Furthermore, the hardware and software were well tried and
tested by both the manufacturers and their customer base, with issues being found,
reported and fixed quickly. This combination of factors meant that a largely unfamiliar chemical crystallography community was able to rapidly and confidently
embrace the use of synchrotron radiation and quickly realise its benefits.
However, the rise of the third-generation synchrotrons with smaller source sizes
resulted in smaller, more intense beams, especially from undulator sources, and
flaws in this approach started to become evident. The diffractometers and detectors
were too slow to make the best use of the high intensity, resulting in the beam being
attenuated to get the diffracted intensities back into a range where they can be useful.
Furthermore, the smaller beams decrease the tolerance on the sphere of confusion of
the instrument and the alignment of the crystal. The manual goniometer head is then
no longer able to position the sample well enough, and mechanical wear becomes a
problem, as they were designed for a few crystals a day and not the 30 or 40 a day at
the synchrotron.
Not for the first time, the chemical crystallography community is looking to
protein crystallography beamlines to solve many of these problems. Air-bearing
diffractometers such as the SmarGON D6 [44] are capable of omega rotation at
speeds of 180
/s, compared with the 1
/s performance of traditional commercial
goniometers. Generally, the crystal positioning in all axes on this and the other
bespoke goniometers now in operation is motorised. Furthermore, detectors such as
the photon counting Dectris Eiger 1M are able to collect 3,000 frames per s, c.f. a
Bruker PHOTONII at 2 frames per s. Combining these technologies means a
standard dataset could take as little as 30 s.
Leading Edge Chemical Crystallography Service Provision and Its Impact on. . .
83
The huge potential for using synchrotron radiation for the determination of small
molecule structures, from crystals of a size that would formerly have been considered as single powder grains, was demonstrated by Harding in 1994 [42] with the
structure solution of the industrially important catalyst precursor material
aurichalcite. They used the SRS wiggler protein crystallography station, 9.6, at the
Daresbury Laboratory with an Enraf-Nonius FAST (electronic area detector) diffractometer (0.4
frames, exposure time 40 s per frame, covering 200
in φ with the
synchrotron ring current 20 mA (single-bunch mode)). Despite the low single-bunch
ring current and the very small crystal size (100 Â 40 Â 5 μm), they obtained
excellent results which demonstrated the need, and likely success, of a dedicated
small molecule single-crystal diffraction station at SRS. The work, in part, was a
precursor to the first beamline built at a synchrotron that was designed solely for the
support of small molecule crystallography, station 9.8 at SRS Daresbury [43], which
was built around a turn-key laboratory-based diffractometer system that was adapted
for the synchrotron environment.
Thereafter a number of dedicated small molecule crystallography beamlines at
synchrotrons also started out using commercial diffractometer and area detector
systems. This approach had the strong advantage that while almost all users had
no synchrotron experience, they were familiar with the software and operation of the
diffractometer system. Furthermore, the hardware and software were well tried and
tested by both the manufacturers and their customer base, with issues being found,
reported and fixed quickly. This combination of factors meant that a largely unfamiliar chemical crystallography community was able to rapidly and confidently
embrace the use of synchrotron radiation and quickly realise its benefits.
However, the rise of the third-generation synchrotrons with smaller source sizes
resulted in smaller, more intense beams, especially from undulator sources, and
flaws in this approach started to become evident. The diffractometers and detectors
were too slow to make the best use of the high intensity, resulting in the beam being
attenuated to get the diffracted intensities back into a range where they can be useful.
Furthermore, the smaller beams decrease the tolerance on the sphere of confusion of
the instrument and the alignment of the crystal. The manual goniometer head is then
no longer able to position the sample well enough, and mechanical wear becomes a
problem, as they were designed for a few crystals a day and not the 30 or 40 a day at
the synchrotron.
Not for the first time, the chemical crystallography community is looking to
protein crystallography beamlines to solve many of these problems. Air-bearing
diffractometers such as the SmarGON D6 [44] are capable of omega rotation at
speeds of 180
/s, compared with the 1
/s performance of traditional commercial
goniometers. Generally, the crystal positioning in all axes on this and the other
bespoke goniometers now in operation is motorised. Furthermore, detectors such as
the photon counting Dectris Eiger 1M are able to collect 3,000 frames per s, c.f. a
Bruker PHOTONII at 2 frames per s. Combining these technologies means a
standard dataset could take as little as 30 s.
Leading Edge Chemical Crystallography Service Provision and Its Impact on. . .
83