Dr L.C. Snoek
Physical & Theoretical Chemistry Laboratory
Telephone: 44 (0) 1865 275 469/447
Research Group Web Site
The
last few years have seen a very rapid growth of structural studies
of both free and hydrated biomolecules, isolated in the gas-phase.
The absolute structures of neutral (and partially
hydrated) systems including neurotransmitters, amides, nucleic acid
bases and amino acids have been determined, principally though laser-based
vibrational spectroscopic methods, in combination with high-level
ab-initio calculations. Hydration studies are particularly
important because, in addition to their intrinsic interest, they
provide a link between the gas phase and the solution phase. In
the gas phase, using mass-resolved detection, hydration interactions
can be studied essentially one water molecule at a time, and the
effects of the bound water on the conformation of the molecule can
be examined. Furthermore, by transferring a peptide or neurotransmitter
from the condensed phase into the gas phase, it is possible to separate
its hydration interactions and intramolecular interactions, and
examine them independently. Studies of secondary structure formation
in dehydrated (and partially hydrated) peptides for example, will
provide insight into the intramolecular (and solvent) interactions
that stabilise helices and sheets. Similarly, studies of "free"
and hydrated neurotransmitters and neurotransmitter models will
reveal the structural configuration associated with their optimum
pharmacological activity, while structural studies of "designed"
molecular complexes can be used to model the binding at specific
macromolecular receptor sites.
Under physiological conditions, important
molecular groups are generally charged: basic groups can be protonated,
acidic groups can be deprotonated, amino acids in neutral solution
are predominantly zwitterions, peptides and proteins can be highly
charged. Mass-spectrometric studies based on electrospray ionisation
(ESI) observe multiply protonated, charged ions, [M+nH]n+,
resulting from the addition of protons to basic sites of the biological
sample. In contrast, all laser-based spectroscopic gas-phase experiments
to date have only been able to focus on neutral species, or singly
charged ions of non-protonated character, because of
the nature and limitations of the sample evaporation techniques
necessarily employed.
Therefore a second, new direction in
our research involves the design and construction of a novel apparatus
incorporating sample evaporation techniques such as ESI and matrix
assisted laser desorption, MALDI.
Selected Recent Publications
- A spectroscopic and computational exploration
of tryprophan-water cluster structures in the gas phase, Lavina
C. Snoek, Romano T. Kroemer and John P. Simons, PhysChemChemPhys,
2002, 4, 2130.
- Conformational landscapes in amino
acids: infrared and ultraviolet ion dip spectroscopy of tryptophan,
L.C. Snoek, R.T. Kroemer, M.R. Hockridge and J.P. Simons, PhysChemChemPhys,
2001, 3, 1819-1826.
- Conformational landscapes in amino
acids: infrared and ultraviolet ion-dip spectroscopy of phenylalanine
in the gas phase, L.C. Snoek, E.G. Robertson, R.T. Kroemer
and J.P. Simons, Chem.Phys.Lett., 2000, 321, 49-56.
- Infrared ion-dip spectroscopy of a noradrenaline analogue:
hydrogen bonding in 2-amino-1-phenylethanol and its singly hydrated
complex, R.G. Graham, R.T. Kroemer, M. Mons, E.G. Robertson,
L.C. Snoek and J.P. Simons, J.Phys.Chem. A, 1999, 103,
9706-9711.
- Conformations of 2-phenyl ethanol and its singly hydrated
complexes: UV-UV and IR-UV ion-dip spectroscopy, M. Mons,
E.G. Robertson, L.C. Snoek and J.P. Simons, Chem.Phys.Lett.,
1999, 310, 423-432.
|
