Chiral Separation By Ion Mobility Spectrometry

1
Department of Chemistry Hill Research Group Ion
Mobility Spectrometry
Chiral Separation By Ion Mobility
Spectrometry Herbert H. Hill Jr1., Prabha
Dwivedi1, and Ching Wu2 1 Department of
Chemistry Center for Multiphase Environmental
Research, Washington State University, Pullman,
WA 99164 2 Excellims Corporation 6 Westside
Drive Acton, MA 01720
RESULT SUMMARY
OVERVIEW
Purpose Gas Phase Separation of Chiral
Ions Method Ion Mobility Mass
Spectrometry Results Enantiomers interact
differently with added chiral modifiers in ion
mobility drift cell resulting in gas phase
chiral discrimination
Chiral analyte
Chiral Gas
A schematic illustration of 3-point-rule Pirkle
Rule required for chiral recognition. CIMS
separation utilizes stereo- chemically different
non-covalent interactions between the enantiomers
(pink shaded) and the chiral drift gas (blue
shaded).
Photograph and schematic diagram of the
ESI-APIMS-qMS. The IMS cell was divided into a
desolvation region (7.5 cm) and a drift region
(25 cm) by a Bradbury-Nielsen ion gate which was
used to pulse ion packets into the drift region
with a pulse width of 0.1 milliseconds. The qMS
was operated in the single ion monitoring mode to
monitor the arrival time distributions of mass
selected ions.
INTRODUCTION
Similarity of enantiomers in their chemical and
physical properties makes their separation and
detection difficult. Recently several MS methods
have been reported which produce rapid, universal
and reproducible enantiomer discrimination
without extensive sample preparation and method
development. However, these approaches often
require complex data analysis of fragmentation
patterns and ion-molecule reactions to occur
between a chiral selector and the ion of
interest. Ion mobility spectrometry separates
ions in gas phase within seconds based on
differences in ion-neutral collision dynamics.
Addition of chiral modifiers into the drift gas
provides an environment for preferential weak gas
phase interactions with the chiral modifier,
producing mobility differences between
enantiomeric ions and effecting their gas phase
separation.
Superimposed IM spectra of racemic mixtures of
valinol, threonine, penicillamine, tryptophan,
methyl-a-D-glucopyranoside and atenolol with
nitrogen as the drift gas. Single IMS peaks were
observed for each racemic mixture. Enantiomers
could not be separated in the pure nitrogen drift
gas.
CONCLUSIONS
Gas phase separation and resolution of
enantiomers is possible when the drift gas of an
ion mobility spectrometer is modified with a
chiral vapor. Selective interactions occur
between the enantiomers and the chiral modifier
such that the individual enantiomers have
different gas phase ion mobilities through the
spectrometer and can be separated in time. In
all cases the addition of the chiral modifier to
the drift gas reduced the mobilities of the
enantiomers but the one mobility of one
enantiomer was always reduced more than the
other. With a relative limited set of
experiments, un-optimized experimental parameters
and a single chiral drift gas modifier,
separations of multiple pairs of enantiomers from
four different classes of compounds were
achieved.
CIMS separation of atenolol enantiomers Top IMS
spectra of individual enantiomers Bottom IMS
spectra showing CIMS separation of enantiomers
from their racemic mixture
EXPERIMENTAL
IMS designed and constructed at WSU was
interfaced to a model 150-QC ABB Extrel
quadrupole MS via a 40-µm pinhole interface. The
IMS was operated at a temperature of 200oC and an
electric field of 432 V/cm (N number density
1.431019, E/N 3.02 Townsend) Nitrogen used as
the drift gas was doped with chiral modifiers and
arrival times of enantiomers monitored while
operating the IMS-qMS in single ion monitoring
mode. Chiral modifiers (S-()-2-butanol and
R-(-)-2-butanol) were infused by a syringe pump
into a silica capillary which was connected to
the heated nitrogen drift gas line using a
T-junction. Ions were produced by ESI at a
potential of 15.00 kV.
ACKNOWLEDGEMENTS
Effect of chiral modifier introduction rate on
arrival times of the methionine enantiomers.
Greater preferential shift in ion mobility of
enantiomers was observed with S-()-2-butanol
compared to R-(-)-2-butanol.
CIMS separation of sugar enantiomers Top IMS
spectra of individual enantiomers Bottom IMS
spectra showing CIMS separation of enantiomers
from their racemic mixture
The authors thank Dr. Issik Kanic of the Jet
Propulsion Laboratory (California Institute of
Technology, Pasadena, California 91109-8099 USA)
for providing initial funding for this project.
In addition this project was partially supported
by a Road Map Grant from the National Institutes
of Health (R21 DK 070274).