Enhanced Detection Strategies Accomplished Through Metal Binding and Miniature Mass ...

180 Pages·2014·3.3 MB·English

by  Adam Graichen

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Open Access Dissertations
2-2013
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Adam Graichen
University of Massachusetts Amherst
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Graichen, Adam, "Enhanced Detection Strategies Accomplished Through Metal Binding and Miniature
Mass Spectrometry" (2013). Open Access Dissertations. 688.
https://doi.org/10.7275/78aj-nn03 https://scholarworks.umass.edu/open_access_dissertations/688
This Open Access Dissertation is brought to you for free and open access by ScholarWorks@UMass Amherst. It
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ENHANCED DETECTION STRATEGIES ACCOMPLISHED
THROUGH METAL BINDING AND MINIATURE MASS
SPECTROMETRY

A Dissertation Presented

by

ADAM GRAICHEN

Submitted to the Graduate School of the
University of Massachusetts Amherst in partial fulfillment
of the requirements for the degree of

DOCTOR OF PHILOSOPHY

February 2013

Department of Chemistry
© Copyright by Adam Graichen 2013

All Rights Reserved
ENHANCED DETECTION STRATEGIES ACCOMPLISHED
THROUGH METAL BINDING AND MINIATURIZED MASS
SPECTROMETRY

A Dissertation Presented

by

ADAM GRAICHEN

Approved as to style and content by:

________________________________
Richard W. Vachet, Chair

________________________________
Ricardo Metz, Member

________________________________
Michael Knapp, Member

________________________________
Stephen Eyles, Member

________________________________
Craig T. Martin, Department Head
Chemistry Department
DEDICATION

To my beautiful wife Allison and my family.
ACKNOWLEDGMENTS

Reflecting on the process of completing this degree, I remember many times
where I felt overwhelmed and defeated. With this in mind and for the few who read this
abstract and dissertation that are undergoing graduate studies, you’re not alone if you feel
like this too! My source of strength and power has continually come from my Lord and
Savior Jesus Christ. I have felt His hand in my life through the course of these studies,
and He has blessed me with the ability to get through the times when I have not felt
skilled enough to be here. Through His grace I have been given the opportunity to pursue
and complete these studies.
I must whole heartedly thank my wife and family for being beside me during my
time in this program. I think there are only two types of wives that a man can have if he
is in graduate school. The first choice is that you probably need to find someone that is
also in school and therefore is in lab a great deal of the time as well. The second type of
wife that you probably want to have, is one like mine. A woman that constantly supports
you, wants the best for you, is flexible enough to adjust to often weird hours, is
understanding/sympathizes with your struggles, helps whenever possible, and importantly
is your overall best friend. It’s also nice to have someone that cooks for you too when
you get home at 11:00 at night! My wife is just awesome and I appreciate her more than
she knows for the blessing and light she has been in my life. Maybe now that I’m done
with school our dates can progress past going to Wal-Mart together on Friday
nights…haha…even though I’ve been too busy for that lately!
v
My parents have also been there no matter what for me. So many times I have
borrowed the car to get into lab, or my dad has stopped by after work to pick up treasures
that I have found on campus that were being thrown out. Other times they have
split/delivered firewood when I haven’t had the time, helped to fix up our place (which
has been never ending!), and have just been there to sound off on. The support network
they have provided has been essential for my success.
There have only been a few professors that I thought have been above and beyond
the quality of others. One of which truly has been Richard. His personality and work
made UMASS appealing to me. I am thankful for his knowledge and teaching ability as
well as his personal values. Maybe if UMASS realized just how good of a professor he
really is, they would have him teaching 10 classes a semester! I well remember one of
our first meetings before I was a member of his group. It was during the time that
students have to pick research groups, which always seems to be stressful for advisers
and students alike. After concluding the meeting with a quick prayer, I knew that
Richard cared about me not only as a scientist, but also as an individual. So thank you
for caring about your students and wanting them to develop in all facets of their lives! I
have learned a lot from my advisor and appreciate his guidance through school. I believe
that his understanding of situations and life outside of school have been key to my
survival here along the years.
Lastly I would like to thank fellow labmates, classmates, my committee members
(Michael Knapp, Stephen Eyles, and Ricardo Metz), as well as the department in general
for everything that everyone has contributed to this experience. In particular I would like
to acknowledge the characters downstairs in the electronics/machine shop (by the way
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people should use that resource more). Both Bob and Ryan have been great to talk with
and have helped whenever possible with a number of different projects. If you need a
part, you should check with Bob because he probably has it!
I must also mention that I apologize for anyone that has to read or go through my
notebooks for future experiments. I changed styles and such over the years…so good
luck!

vii
ABSTRACT

ENHANCED DETECTION STRATEGIES ACCOMPLISHED THROUGH METAL
BINDING AND MINIATURE MASS SPECTROMETRY

FEBRUARY 2013

ADAM GRAICHEN

B.Sc., MESSIAH COLLEGE

Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST

Directed by: Richard W. Vachet, Ph. D.

A multiplexed method for performing MS/MS on multiple ions simultaneously in a
miniature rectilinear ion trap (RIT) mass spectrometer has been developed. This method
uses an ion encoding procedure that relies on the mass bias that exists when ions are
externally injected into an RIT operated with only a single phase RF applied to one pair
of electrodes. The ion injection profile under such conditions ions is Gaussian-like over a
wide range of RF amplitudes, or low mass cutoff (LMCO) values, during ion
accumulation. We show that this distribution is related to ion m/z and is likely caused by
ions having an optimal range of pseudo-potential well depths for efficient trapping.
Based on this observation, precursor ion intensity changes between two different
injection LMCO values can be predicted, and these ion intensity changes are found to be
carried through to their corresponding product ions, enabling multiplexed MS/MS spectra
to be deconvoluted.
The gas-phase reactions of a series of coordinatively unsaturated [Ni(L) ]y+
n
complexes, where L is a nitrogen-containing ligand, with chemical warfare agent (CWA)
simulants in a miniature rectilinear ion trap mass spectrometer were investigated as part
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of a new approach to detect CWA. Results show that the metal complex ions can react
with low concentrations of several CWA simulants, including dipropyl sulfide (simulant
for mustard gas), acetonitrile (simulant for the nerve agent tabun), and diethyl phosphite
(simulant for nerve agents sarin, soman, tabun, and VX), thereby providing a sensitive
means of detecting these compounds. The [Ni(L) ]2+ complexes are found to be
n
particularly reactive with the simulants of mustard gas and tabun, allowing their detection
at low parts-per-billion (ppb) levels. These detection limits are well below the median
lethal doses for these CWAs, which indicates the applicability of this new approach, and
are about two orders of magnitude lower than electron ionization detection limits on the
same mass spectrometer. The use of coordinatively unsaturated metal complexes as
reagent ions offers the possibility of further tuning the ion-molecule chemistry so that
desired compounds can be detected selectively or at even lower concentrations.
Mass spectrometry has become a tool for studying noncovalently bound
complexes. Specifically, electrospray ionization mass spectrometry (ESI-MS) has found
increasing use for the determination of affinity (K ) or dissociation (K ) constants. Direct
a d
measurement of the equilibrium components by ESI-MS is the most straightforward
approach for determining binding equilibrium constants, but this approach is prone to
error and has some inherent limitations. Transferring complexes from solution to the gas
phase may perturb the equilibrium concentrations and/or different ionization efficiencies
may cause the resulting ion signals not to reflect actual solution concentrations.
Furthermore, ESI only works under a limited range of solvent conditions (i.e. low ionic
strengths), which limits the broad applicability of this approach. We propose an
approach based on covalent labeling in the context of metal-catalyzed oxidation (MCO)
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