TSRI Facility Shoots for Crystal-Clear Results
By Mika Ono
Eight large crates marked “fragile” and "attention
Raj Chadha" arrived recently at The Scripps Research Institute
(TSRI). They contained what would soon be a boon to many scientists
on campus: a brand new x-ray crystallography machine.
"This instrument is fast," says Raj Chadha, who single-handedly
runs the X-Ray Crystallographic Facility, located on the ground
floor of the Beckman Building. "Data collection to determine
crystal structure takes five to ten hours instead of three
to seven days."
The equipment, a Bruker SMART APEX, has been put to use
by the TSRI researchers—mostly chemists—who work
with small molecules. Despite faster and easier methods to
ascertain structure, such as NMR and mass spectrometry, x-ray
crystallography still sets the standard for reliability in
the field, producing results that are rarely challenged.
Steven Brunette, research associate in the Boger lab, is
one of those on campus who has reaped the benefits of the
new technology. "I got results much faster than with the old
instrument—in one day versus one week," he says. "Raj
was also able to solve a structure [a non-natural alkylation
subunit of anti-tumor antibiotic CC-1065] he couldn’t
before. If those aren’t two big pluses for the new machine,
I don’t know what are."
Purchased with a grant to Professors Julius Rebek, Jr.,
and Reza Ghadiri, the x-ray crystallography machine sports
a 4K CCD detector—cutting-edge technology in such equipment.
Although the older Rigaku AFC6S machine is now used only occasionally,
it has been kept at the facility, serving as a back-up system
as well as the instrument of choice for absolute configuration
studies (which give the relative orientation of atoms in a
molecule).
Of Surprises and Solutions
Chadha solves some 50 structures a year for TSRI scientists.
Most of the time the sample turns out to be what the researchers
who synthesized it predicted. But, once in a while, there
is a surprise. "When my studies indicate a different substance
than expected, the researchers are forced to think about their
reactions in a new way," comments Chadha. "My knowledge of
chemistry comes in handy when I need to explain why we have
one compound and not another."
Chadha’s knowledge and experience also come in handy
when working with challenging structures. According to Chadha,
having good crystals and choosing the best crystal from the
flask are essential in difficult cases. One especially memorable
structure he determined came from the Ghadiri lab. The sample
consisted of nanotubes with free water molecules whose positions
were not defined.
Other projects Chadha has worked on in his nine years at
Scripps stand out for non-technical reasons. He remembers
well the project brought to him by the Nicolaou group: ascertaining
the structures of taxol—now approved by the Food and
Drug Administration for treatment of ovarian cancer—and
its precursors.
In addition to solving structures, Chadha writes reports,
archives data and submits findings to the Cambridge Crystallography
Database, the central depository for such information. He
also conducts elemental analysis (a technique used to determine
the amount of carbon, hydrogen and nitrogen in a sample),
maintains the equipment, and referees the journals "Inorganica
Chimica Acta" and "Journal of Chemical Crystallography."
His other duties help balance the cyclical nature of the
x-ray crystallography itself. "I can tell when the researchers
have been productive," Chadha laughs. "My workload has picked
up again now it’s March. The beginning of the year is
slow as a result of Christmas vacations."
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