Small molecules such as drugs and enzymatic
cofactors have been subjected to structural analysis using neutron powder and
single-crystal diffraction to provide information on ionization and hydration
states and bonding networks. Neutron experiments represent a valid analysis
additional to X-ray diffraction studies since they are able to provide hydrogen
atom anisotropic temperature factors and thus a more complete picture of the
molecular characteristics. A complete model of the thermal motional properties
of the molecule's constituent atoms permits the deconvolution of the thermal
motion in the molecule from the static electron density determined using X-rays.
Case study: the structure
of creatine monohydrate, (NH2)CN(CH3)CH2CO2.H2O
Creatine phosphate acts as
an energy reservoir in vertebrate muscle. Refinement of data from a
single-crystal neutron diffraction experiment using the diffractometer SXD
at RAL revealed the locations and
thermal properties of all atoms in the molecule. This permitted good definition
of the extensive network of hydrogen bonds present in the crystal. The thermal
parameter analysis revealed significant torsional motion of the methyl group
even at 20 K. J. Chem.
Soc. Faraday Trans. (1997) 93, 1875-1879.
Case study: the structures
of ibufrofen, acetylcholine and dopamine
Single-crystal analysis
of the analgesic ibuprofen and the neurotransmitter acetylcholine were carried
out using station SXD.
A powder diffraction structure determination for dopamine, another
neurotransmitter, using HPRD (the highest
resolution neutron powder diffractometer in the world) at RAL was also completed.
Case study: the structure
of paracetomol
The structure of the analgesic paracetomol, which
is structurally related to ibuprofen, was determined using single crystal
neutron diffraction. Anisotropic thermal parameters for all atoms were
determined, revealing gross positional variation due to thermal motion for the
methyl group hydrogens. J. Mol. Struct. (1997) 405, 207-217.
Case study: the structures
and interactions of Buckminsterfullerenes
Neutron experiments
have contributed to a better understanding of the structure and interactions of
spherical carbon (Nobel Prize in
Chemistry, 1996), for which a broad range of potential applications
including pharmaceutical products and industrial catalysts have been proposed.
The web page to the instruments
relevant to small-molecule structure determination at RAL give some further
examples, as does the D19 web page at the
ILL.