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					                                                               2009 IMSERC Annual Report


1. Integrated Molecular Structure Education and Research Center Mission:

 IMSERC’s mission is to further research at
Northwestern by providing access to and
educating students on the proper use of
instrumentation needed for molecular structure
characterization.     The Northwestern University
Integrated Molecular Structure Education and
Research Center (IMSERC) has been established
to educate Northwestern students to be scientific
leaders of 21st century, and support world-class
research. The synthesis of small molecules fuels
research of numerous core disciplines and
interdisciplinary activities, including chemistry,
molecular/cellular     biology,   drug    discovery,
chemical biology, translational medical research,
materials, catalysis, nanotechnology and energy
storage/conversion. All research at Northwestern
utilizing novel compounds relies on IMSERC to
characterize these molecules before application        Figure 1: IMSERC is located on the
testing can begin. As a “one stop shop” for            ground floor of the Technological
molecular       structure    characterization,   all   Institute.
instrumentation and staff scientist offices are
located on the ground floor of the Technological
Institute in rooms KG73-88 (see Figure 1).

2. Review of 2008:

IMSERC Officially open for business: In the last year, the conversion from the ASL to the
IMSERC moved to full speed. A $10M endowment enabled three new positions to be created
and resulted in the hiring of Dr. Jennifer Seymour, Dr. Amy Sarjeant and Dr. Josh Kurutz and a
dramatic reduction in user fees. In February, 2008, design started on the new showcase
facility to be located on the lowest two floors between the B and C wings of the Technological
Institute. This facility provides nearly double the space of the current lab and will provide
dedicated space for existing equipment, an advanced synthetic lab, a “smart classroom” and
meeting space. Plans for the new facility along and artist renditions of the NMR lab are shown
in Figure 2.

IMSERC also had a record year with over 25,000 individual experiments, by over 400 users in
62 research groups. For a detailed description of usage by faculty member, see Appendix 1.
In addition, over 600 undergraduate students analyzed over 2,000 samples using IMSERC
facilities through the labs in the Chem 101, 171, 102, 210, 212, 220 and 350 classes. IMSERC
users published 278 papers (see Appendix 2 for a complete list of publications). IMSERC
facilities provide support for over 100 externally funded research projects from the NIH, NSF,
DOE, DOD and other private groups.




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                                                                      2009 IMSERC Annual Report




 Figure 2: The new IMSERC site will be ready for occupancy in 2011.



Beyond providing critical resources for the daily
needs of synthetic chemists, IMSERC support
extends to all of the projects that depend on
carefully tailored new compounds.        IMSERC
supports faculty working in Weinberg college of
Arts and Sciences, McCormick School of
Engineering and the Feinberg School of
Medicine. Figure 3 illustrates the diversity of
projects that rely on IMSERC resources by
displaying the center usage by funding source.
                                                           3: Over 75% of FY2008 IMSERC use is
Over the last two years, a comprehensive plan to Figure by over 100 different sponsored projects
                                                    funded
improve both the technical capabilities of the funded by a wide variety of government, non-profit and
center and accessibility to staff expertise. Last for profit institutions.
year’s user survey indicates that most users
(>60%) are satisfied with IMSERC capabilities
and IMSERC services (see Appendix 3 for survey details). IMSERC continues to have active
programs to improve capabilities, educational opportunities and accessibility to data and staff
in 2009.

New Budget for IMSERC: The creation of IMSERC has enabled a new budget and fee
structure where fees are now competitive with peer institutions. In addition, fees are now set
with the goal of remaining constant over a three year interval to provide faculty members with
predictable analytical costs. IMSERC's operating costs are shown in Figure 4. Support for
staff dominates IMSERC’s budget. In addition to covering maintenance and operating costs
for equipment, a substantial portion of the budget is dedicated to improving equipment
capabilities and providing professional development for the staff. This investment in the future
of the lab will ensure the NU can continue to acquire and maintain state of the art
instrumentation. Operational funds for the IMSERC reflect the diversity of users of the center.
User fees for research groups and classes are subsidized through direct support from WCAS

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and the Central Administration. While IMSERC does perform work for outside industry, the
main focus of the staff is on education and conducting research. Therefore, external work, by
design, represents a small portion of IMSERC’s revenue.




 Figure 4: FY2008review of IMSERC expenses and revenue.




New Equipment for IMSERC: The IMSERC dramatically improved capabilities in all core
areas (mass spectrometry, NMR spectroscopy and X-Ray crystallography). As part of the
recruitment package of Prof. J Fraser Stoddart, IMSERC added a 600 MHz Bruker Avance
III NMR spectrometer which matches the highest field NMR instrument at Northwestern
University. In addition, the INOVA 500 MHz instrument was upgraded to a Bruker Avance II
system with a direct cryoprobe and 60 sample robot to enable automated sample analysis.
This system has nearly 20 times the 13C sensitivity compared to previous equipment.
Figure 5 shows the difference in spectral quality between the previously available
instruments and the Avance III system. This additional sensitivity means that experiments
that used to take 24 hours can be completed in less than 10 minutes. This capability is
critical in cases where sample quantities are limited, such as total natural product synthesis
schemes carried out in the Scheidt group. In addition, the sample changer has increased
utilization by almost 20%. When combined with the new 600 MHz instrument, NU has
tripled NMR instrumental capacity over the last year.

             A-500                                              I-400
             100mg/ml                                           100mg/ml
             16 scans                                           16 scans
             48 seconds                                         48 seconds
             S:N =1063:1                                        S:N= 64:1


   Figure 5: Sensitivity comparison between the recently upgraded Avance III 500 MHz NMR spectrometer and the
   previously existing IMSERC equipment.



In 2008, the Applied Biosystems Voyager DE-Pro MALDI system was replaced with a Bruker
Autoflex III MALDI system. The new mass spectrometer has approximately double the
resolution when compared to the Voyager system and is capable of accurate mass analysis,


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                                                                        2009 IMSERC Annual Report

protein identification experiments, analysis
of DNA and de novo peptide sequencing.
This instrument will eventually be equipped
to enable mass based tissue imaging for                                                       de novo peptide
                                                                                          Sequencing of YLEYALR
applications such has targeted drug delivery                                                 by MALDI MS/MS
and early cancer detection.

Finally, the X-Ray lab upgraded the SMART
1000 diffractometer to a KAPPA II detector
with almost 5 times the sensitivity and
IMSERC added a Cu source to dramatically
increase the ability to characterize crystals
with larger unit cells and weakly diffracting      Figure 6: Peptide sequencing experiment performed on
crystals with lighter atom constituents, such      Bruker Autoflex III MALDI mass spectrometer
as compounds with a large organic
component.       The addition of a second
wavelength        source     has       enabled
characterization and thereby publication of
many organic based samples for the Hupp
and Stoddart group when no signal was
present with the original Mo source. Figure 7
illustrates the signal enhancement using the
Cu source on a organic sample submitted by
the Stoddart group. This type of data is
required to publish new syntheses in the area
of macromolecular chemistry.

Outreach Activities: In keeping with the
collaborative model at NU, the IMSERC
actively partners with the research centers
and departments on campus to broaden
participation within the community.         All
instrumentation at the IMSERC is made
available to local industry for small projects
through the FastScience program which is
administered through the McCormick School
of Engineering in a pay-for-service mode.
This work provides funding for small upgrades
and helps to reduce fees for NU users, but is
not intended to be a major income-generating
activity. In addition, NU alumni working in
local industry can continue to use
instrumentation at a slightly higher rate than
users within NU pay. Several companies with
NU ties in the area advantage of this
relationship including Astellas, Nanotope,
PolyEra and OhmX. Finally, after a recent fire
at the University of Illinois, Chicago (UIC),
staff members were trained on the Agilent LC-        Figure7: Cu vs. Mo source diffraction pattern on
                                                     identical Stoddart group crystal collected with identical
TOF and UIC students were granted access             exposure times using the same display scale. In cases
                                                     of weakly diffracting crystals, the higher intensity source
                                                     is needed to obtain publication quality data.
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                                                                        2009 IMSERC Annual Report

to walk-up instruments in order continue their research during the recovery.

In order to broaden access
to scientific instruments to
the community in general,
the IMSERC also partners
with the CCNE, NU-
MRSEC and NSEC through
the Research Experience
for Undergraduates (REU)
and Research Experience
for      Teachers      (RET)
programs. Participants in
these programs work with
individual faculty members;
groups receive the same
training       that      the
Postdoctoral Fellows and          Figure 8: Chicago area Junior High School Students perform a protein
Graduate Students receive         identification experiment during Science Saturday using the Autoflex III
and are given the same            MALDI mass spectrometer.
level     of    access    to
instrumentation. Participants in the RET program are also encouraged to bring classes
back to the IMSERC for demonstrations to provide elementary through high school students
hands-on experience with state-of-the-art analytical equipment. While REU and RET
participant use is not specifically tracked, 41 participants in the program worked for faculty
who actively use IMSERC instrumentation (52% females and 33% underrepresented
minorities). The IMSERC also performs three to five hands-on demonstrations per year for
participants in CCNE, NU-MRSEC and NSEC on campus outreach activities. The most
recent such event was the Chicago Science Saturday event held January 19th focusing on
the “science of small” where students used mass spectrometry to identify a protein (see
above).

Goals for 2009: While IMSERC has seen dramatic improvements in 2008, active plans are
underway to improve support of research at NU, prepare for the move to the new site in
2011 and improve access to data and instrumentation. With the addition of the Scientists,
accessibility to staff for training, assistance with advanced experiments, and turnaround time
will be greatly improved. Finally, IMSERC will take ownership of the C411 graduate level
spectroscopy class in Fall 2009. The goal of this change will be to increase the level of
applications training for new students before they join research groups and make state of
the art NMR and mass spectrometry techniques available to all users, rather than a few
experts.

On the equipment horizon, three critical instruments supporting research at NU cannot be
moved to the new site in 2011. One 500 MHz and one 400 MHz NMR system are over 20
years old and are not likely to survive a move. Prof. Karl Scheidt is lead PI on an NIH
Shared Instrumentation (S10) proposal to replace the existing 500 MHz instrument. This
instrument will be sited in an IMSERC annex to be located in Silverman Hall. In addition,
the magnetic sector electron impact ionization mass spectrometer cannot be moved. Prof
Tobin Marks is lead PI on an NSF Major Research Instrumentation (MRI) program to replace
this instrument. Both of these instruments are needed to continue existing programs at NU


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                                                                   2009 IMSERC Annual Report

and will bring exciting new capabilities to NU. In addition, IMSERC is working to obtain a
higher flux X-Ray diffractometer to IMSERC’s fleet that will approach the flux of a first
generation synchrotron source and will ease congestion on the two existing systems.
Finally, 2009 will see the replacement of both a Raman and FTIR system that were each
over 15 years old.

With the procurement of modern instrumentation, users have already seen a dramatic
improvement in data accessibility. NMR systems now routinely email data to users for
offline processing. For 2009, NU Core Facilities funded a cyber infrastructure upgrade to
further improve access to data processing capabilities. IMSERC is adding a 14 TB RAID 10
data server to allow users to remotely access and process data from nearly all IMSERC
instrumentation. Users will have the choice of processing NMR data using iNMR or Topspin
on their own computers or can process data on IMSERC processing server which can
support simultaneous data processing by up to 25 users. In addition, the IMSERC web site
will be completely redesigned. These types of upgrades funded through the Vice President
of Research’s office are critical to ensuring that IMSERC can write competitive grants at a
time when ~70% of NSF funded instrumentation have a “cyber enabled” focus.

3. IMSERC Organizational Structure:

Oversight of IMSERC is performed by a six member committee that is reappointed on a yearly
basis. Table 1 shows the current advisory committee that includes Faculty representation of
each of the major user groups and also the technical expertise in the core characterization
techniques performed by the laboratory. Since much of the equipment in the IMSERC is
heavily utilized by the chemistry teaching laboratories, Dr. Frederick Northrup also serves on
the advisory committee to ensure that the undergraduate needs are fulfilled.
 Member                            Title
              A
 Karl Scheidt                      Irving Klotz Research Chair in Chemistry
 Andrew Ott                        IMSERC Director
 Mercouri Kanatzidis               Charles E and Emma H. Morrison Professor of Chemistry
 Frederick Northrup                Distinguished Senior Lecturer and Director of
                                   Undergraduate Studies
 Fraser Stoddart                   Trustees Professor of Chemistry
 Regan Thomson                     Assistant Professor of Chemistry
 Table 1: 2008/2009 IMSERC Advisory Committee
 A
   Chair of oversight committee



In the last year, the staffing model for IMSERC has been completely transformed to support
the broader education and research goals of the IMSERC. The new staffing model is shown
in Figure 9. The Specialists and Sr. Scientists all report to the Director. The key
differentiation between the titles is the expectation to be involved in active research projects
(either through improving IMSERC capabilities or collaboration with research groups) The
staffing level in the IMSERC has been designed to accomplish the following five goals:
     1. Ensure proper expertise and sufficient resources are available to support
        undergraduate classes in the current approved curriculum.
     2. Support the proposed in depth graduate level courses on modern instrumentation for
        molecular structure characterization and provide immediate assistance to students of
        all NU departments analyzing samples.


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                                                                2009 IMSERC Annual Report

   3. Provide expertise and resources to maintain the fleet of 6 NMR spectrometers, 8
      mass spectrometers, 2 X-Ray diffractometers, 2 trace metals analysis instruments,
      >10 optical spectrometers and 6 LC separations systems.
   4. Provide Ph.D. level support to educate both undergraduate and graduate users and
      assist groups with more difficult problems and support demonstrations of capabilities
      needed for grant proposals.
   5. Ensure that NU can pursue all external funding opportunities to maintain the entire
      instrument fleet.




  Figure 9: Current IMSERC organizational chart.



The goal of IMSERC is always to train users to perform measurements themselves. New
users are typically trained using a teaching assistant who has completed the graduate level
instrumentation class (C411) and then users receive access to instrumentation during
working hours when staff members are available to assist with routine problems.
Unrestricted access is granted after staff member certification. This certification process is
intended to both ensure users understand how to properly operate instruments and to
stimulate discussion between staff and users. Students are encouraged to work side by
side with IMSERC staff to perform more advanced experiments. In cases where extensive
expertise is required to analyze samples, such as in X-Ray crystallography and accurate
mass measurements, samples are submitted for analysis by staff members.

By integrating the education, research and maintenance roles into a single organization, the
IMSERC optimizes personnel numbers and capabilities to fuel the NU Chemistry
Department’s climb to among the very best research and educational programs in the world.
The doubling of the scientific staff now makes it possible to support research 52 weeks per
year and allows for both the Specialists and Research Associates to tackle difficult problems
(including cases where travel to alternate sites is required), while maintaining support for
day to day activities. Unless noted specifically below, all IMSERC staff work only on
IMSERC related projects.




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                                                                2009 IMSERC Annual Report



Current Personnel:

Dr. Andrew Ott (IMSERC Director / Research Professor):
Dr. Ott has been the full time Director of the Analytical
Services Lab (ASL) and then the IMSERC since 2007 when
the full time position was created. Dr. Ott rejoined NU after
spending eight years as a Sr. Process Engineer and Group
Leader in the Logic Technology Development Division of Intel.
Dr. Ott has extensive experience building and maintaining
vacuum, plasma, RF and chemical vapor deposition systems
through his work at Intel, his post-doctoral position in the
R.P.H. Chang lab at NU and his doctoral work with Prof.
Steven George at the University of Colorado. In less than 10%
role, Dr. Ott serves as the Director of the Masters of Quality
and Regulatory Science Program through the School of
Continuing Studies. Dr. Ott’s focus in the lab has been in
improving the education of the users through undergraduate
and graduate level classes, incorporating automation and advanced equipment to give hands-
on access to state of the art instrumental analysis techniques to all user and providing off line
analysis capabilities to ensure NU gets full use from IMSERC equipment.

Dr. Joseph (Josh) Kurutz (Senior Research Associate –
NMR Spectroscopy): Josh Kurutz, Ph.D., is a Senior
Scientist for NMR who started in March, 2009. He has applied
NMR to the study of a wide variety of chemical species with
biological relevance. Until recently, he was the Technical
Director of the Biological NMR Facility at the University of
Chicago, where he collaborated on projects such as 1)
Determining monomer conformation in Prof. Steve Meredith’s
self-assembling cyclic peptide project (Bioconj. Chem. 20,
231; 2009), 2) Verifying capsular polysaccharide identity and
determining sites of natural covalent modifications for Prof.
Olaf Schneewind’s program developing a vaccine for drug-
resistant Staphylococcus aureus infections., 3) Determining ligand binding locations on Raf
kinase inhibitor protein (RKIP) for Prof. Marsha Rosner. As an undergraduate Chemistry
major at Caltech, he examined DNA oligomer structures by NMR with Prof. John D. Roberts,
then developed hardware and software for in vivo imaging and localized 1H and 31P
spectroscopy at Huntington Medical Research Institutes in Pasadena, CA, with Dr. Hunter
Sheldon and Dr. Brian D. Ross. He earned his Ph.D. in Biophysics with Prof. Laura Kiessling
at the University of Wisconsin, elucidating structures of synthetic trisaccharides involved in
cell adhesion. His postdoctoral work at the University of Chicago with Prof. Ka Yee Lee
focused on elucidating structures and biophysical activities of peptide fragments associated
with human lung surfactant.




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                                                              2009 IMSERC Annual Report




Dr. Amy Sarjeant (Research Associate – X-Ray
Crystallography): Dr. Amy Sarjeant joined the
IMSERC facility in early March 2009 as an X-Ray
Crystallography specialist. Most recently, Dr.
Sarjeant implemented and managed the small-
molecule, single crystal X-Ray facility at Johns
Hopkins University in Baltimore, Maryland. In
addition to working with 11 diverse research
groups and over 60 students, post-docs and
visiting scholars at Johns Hopkins University, Dr.
Sarjeant also performed data collections and
structural analyses for several external academic
and industrial users, and ran a small lecture on
crystallography as part of a larger analytical
course. Dr. Sarjeant received her B.S. from the College of William and Mary, doing
undergraduate research on the magnetic properties of solid-state materials. She received
her Ph.D. at Northwestern University under the direction of Prof. Jim Ibers. She has 60
publications in major research journals, including 49 from her work at Johns Hopkins. Amy’s
primary roles are centered around improving turnaround time for routine samples,
expanding single crystal X-Ray capabilities at NU and forming a relationship with the
Advanced Photon Source at Argonne National Laboratory that enables NU samples needed
high intensity sources to be seamlessly analyzed using the DND or ChemMatCARS
beamlines.

Dr. Jennifer Seymour (Research
Associate - Mass Spectrometry):
Jennifer L. Seymour joined NU in
October 2008 as part of the creation of
the IMSERC.         Dr. Seymour has a
background in small molecule mass
spectrometry that began by studying the
gas-phase ion chemistry of bioinorganic
complexes at         the University of
Washington under the guidance of
František Tureček. She then moved to
a postdoctoral position in Catherine
Costello’s lab at Boston University
School of Medicine to study the ion
energetics      and    fragmentation   of
oligosaccharides. Most recently, she spent three years at GlaxoSmithKline in the structural
identification group of Drug Metabolism and Pharmacokinetics using mass spectrometry to
elucidate structures of drug candidates and their metabolites.          In her position at
Northwestern, Jennifer performs accurate mass analyses, develops new techniques, and
consults with users from various departments of the university, to provide them with mass
spectrometric options for solving chemical and biological problems. Her goals are to provide
fast turnaround time for submitted samples, improve the working knowledge of mass
spectrometry within the chemistry department and provide state of the art instrumentation
and mass spectrometry methodologies for scientists to apply to their own research. Dr.

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                                                                2009 IMSERC Annual Report

Seymour will be assisting with the instruction of C411, Organic Spectroscopy, in the fall
quarter of 2009 and also looks forward to offering a seminar series on mass spectrometry
for interested members of the chemistry department.

Mr.     Saman        Shafaie      (Mass
Spectrometry Specialist):            Mr.
Shafaie is primarily responsible for
mass spectrometry sample analysis,
instrument upkeep, trace metals
analysis and the optical equipment in
the IMSERC. Mr. Shafaie holds as
B.S. in Zoology from the University of
Wisconsin. He joined NU in 1989 as
the small instrument specialist after
working as a Mass Spectrometrist at
the Wisconsin State Laboratory of
Hygiene. Mr. Shafaie was promoted
to the Mass Spectrometry Specialist
position in 2006 as a reflection of his performance at the time. Mr. Shafaie’s strengths are
both the ability to maintain and train users on a wide variety of equipment and develop training
plans that teach users concepts need to properly use instrumentation based on users past
education and experience.

Ms. Charlotte Stern (Single Crystal X-Ray
Crystallographer): Charlotte Stern has
operated the x-ray crystallographic facility
since May 1990. This includes consulting
and performing data collection and full
structural analysis on crystals for university
faculty and outside academic and industrial
clients. She maintains and trouble shoots
the x-ray diffractometer, and associated
computer software packages. She teaches a
graduate       level     course      in     x-ray
crystallography,       including       laboratory
instruction (Chem 435). She trains and supervises students in crystallographic analysis.
Charlotte received her Bachelor’s degree from the University of Illinois, Champaign, Il in 1985.
She worked as an assistant research chemist at the University of Illinois from 1986-1990. In
the year 2008 she had 7 peer reviewed journal articles and 1 meeting abstract. She has
participated in a total of 215 peer reviewed journal articles and 27 meeting abstracts.




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                                                              2009 IMSERC Annual Report




Dr. Yuyang Wu (NMR Specialist): Dr. Wu started as
ASL’s NMR specialist in 1999 and is 100% dedicated to
IMSERC activities. Dr. Wu received his Ph.D. from the
University of Western Ontario in 1994 before
completing a Post doc at UC-Davis and then joining the
staff at NU. Dr. Wu has a background in heteronuclear
NMR at UWO, paramaganetic protein NMR at UC-
Davis, and saccharide NMR at NRC-IBS. When Dr. Wu
was coming to NU, he primarily operated all the liquid
NMR facility work to support NU research and
education, and meanwhile he learned some solid NMR
techniques at NU. Now Dr. Wu’s primary research
interests are in the areas of heteronuclear NMR and
Solid state NMR.

Mr. Kevin Gilmore (Engineer): Mr. Kevin Gilmore has
been with NU since 1991 and transitioned to support the
then ASL upon the official closing of the electronics shop
in 2004. Mr. Gilmore provides 20% support for the
Physics computer labs and 80% support for IMSERC
activities. Mr. Gilmore’s primary role is servicing and
repairing all different kinds of electronic and computer
equipment. This includes very sophisticated analytical
instruments such as NMR spectrometers. Through the
employment of Mr. Gilmore, the IMSERC is able to avoid
over $150,000/year in service contracts and dramatically
reduce downtime by addressing issues either
preventatively or typically in less than 24 hours. In
addition, Mr. Gilmore has been integral in the installation
of the new data sever that will allow all users to access
and process data remotely.

4. Equipment and Services: The IMSERC is divided roughly into five sections; NMR
Spectroscopy, Mass Spectrometry, Single Crystal X-Ray Crystallography, Trace Metals
Analysis and Optical Spectroscopy. The goal of the lab is to provide 24X7 access to all
instrumentation needed to provide feedback to synthetic groups so that the IMSERC facilitates
research rather than acting as a bottleneck. In the cases of accurate mass analysis and single
crystal X-Ray diffraction, a high level of training is required both to operate the equipment
properly and to interpret the data. In these cases, users submit samples for analysis by staff
member. The IMSERC provides training through the use of TA’s and staff members to any
member of NU with a valid Café account. The current fee structure for equipment use is
shown in Table 2. The IMSERC will perform work for academic institutions and local industry
affiliated with NU research groups at twice the internal rate and unaffiliated industry are
charged at a flat rate of $100/hr for equipment time and $200 / hr for staff time.




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                                                                           2009 IMSERC Annual Report




           Instrument                                            Rate
           NMR                                                   $8-15 / hr
           Mass Spec (MSD1100)                                   $4 / sample
           Mass Spec (other walk up)                             $32.50 / hr
           Mass Spec (low res / staff run)                       $26 / sample ($60/hr staff rate)
           Mass Spec (High Res / User Prepared LCMS)             $32.50 / sample
           Mass Spec (Neat / EI / additional prep required)      $60 / sample
           ICP AES                                               $26 / hr
           ICP MS                                                $32.50 / hr
           X-Ray Diffraction structure solution                  $400 / sample
           X-Ray Diffraction data collection                     $150/sample
           X-Ray unit cell                                       $35/ sample
           Staff time                                            $60 / hr

Table 2: FY2009 User Rates Rates



NMR Spectroscopy Resources:              High Resolution Nuclear Magnetic Resonance
Spectroscopy is a heavily utilized technique for determining atomic connectivity within a
molecule or extended solid, and can be used to assess 3D molecular structure, molecular
dynamics, reaction kinetics, ligand binding and docking, and other applications. Before
compounds can be tested for biological activity, used in an electronic device, or employed in
any other application, synthetic chemists must confirm the exact structure, including chirality,
of newly synthesized compounds. NMR is a non-destructive technique that provides critical
structural information about new compounds. Figure 10 shows an example where NMR is
used to assign a chemical structure for a model compound used to improve MRI sensitivity
and enable early cancer detection [Urbanczyk-Pearson et. al., Mechanistic Investigation of
b-Galactosidase-Activated MR Contrast Agents. 2008 Inorganic Chemistry, 47, 56-68].




Figure 10: Example from Prof. Tom Meade’s group using complimentary NMR techniques to determine the
structure of model Magnetic Resonance Imaging (MRI) contrast agent to be used to enable earlier detection
                               1
of cancer. A) High resolution H NMR of β-EgadMe Eu(III) B)DQF-COSY of β-EgadMe Eu(III) . Spectra
shown were critical in assigning the draw structure.



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                                                                                      2009 IMSERC Annual Report




The magnetic field of an NMR instrument is typically described by the resonance frequency
of hydrogen atoms within the magnet; thus, a 14 Tesla magnet is part of a 600 MHz NMR
system. Increasing the magnetic field of an instrument increases its sensitivity, reduces the
time required to acquire data, enhances the ability to analyze complex compounds, and
raises the cost of operation. IMSERC employs multiple instruments with different field
strengths to allow simple or crude mixtures to be analyzed immediately on lower cost
instruments while more complex experiments are performed on higher field instruments.
Analyses can be performed on as little as 0.5 mg of sample and are typically performed
using >10 mg. Further, the range of NMR experiments available to IMSERC users is
determined by the types of probes available to them. Certain probes are optimized for
particular sorts of work; for example, a "broadband" probe is best for detecting non-
hydrogen nuclei, whereas an "inverse" probe is best for detecting hydrogens. IMSERC's
size allows it to maintain instruments with different types of probes, which enables users to
walk in and use the best spectrometer for their needs without reconfiguring hardware.

  Console /Magnet                   Probe                 Primary Experiment                       Funding Source
  AVANCE III 600 MHz            Broadband and        Macromolecular Chemistry                      NU / Int. Institute of
                                   Inverse           Variable Temperature                           Nanotechnology
                                                     Experiments
  AVANCE III 500 MHz               Direct CH         Final Products Characterization                     NSF / NU
                                   cryoprobe                           13
                                                     Low concentration C
    INOVA 500 MHz                 Inverse HC         Walk up 1H / COSY                               Pfizer Donation

      “Mercury 400”               Broadband          Variable Temperature                         NSF /Pfizer Donation
                                                                                                   (INOVA console)

     INOVA 400MHz                 Broadband          Education / Walkup HCX 1D                              NSF

     Solids-400 Mhz              5 mm pencil         Solids                                                 NSF
Table 3. List of NU open access NMR spectrometers with configuration and age of critical components. Broadband probes are
used for multiple nuclei and are optimized for best 13C sensitivity. Inverse probes are used when the best 1H sensitivity is needed.




The entire fleet of NMR instruments available for open-access use is housed in IMSERC.
The Structural Biology core facility maintains a 600 MHz instrument with an HCX cryoprobe
and is also located in IMSERC space. IMSERC maintains a fleet of five liquids probe-
equipped NMR systems at a variety of field strengths and a single 400 MHz wide-bore
instrument dedicated to solid-state studies.         An overview of open-access NMR
instrumentation is shown in Table 3. IMSERC has actively invested in upgrades to the small
molecule capabilities through the recent purchase of a Bruker Avance III 600 MHz system
and upgrade of an existing 500 MHz magnet with an Avance III console and a direct CH
cryoprobe, and upgrades to the probe fleet for the other spectrometers. These advanced
capabilities have dramatically improved the data quality and accessibility of more advanced
pulse sequences, such as solvent suppression experiments combined with pulsed-field
gradient NOESY or ROESY and selective excitation experiments such as 1D NOE which
are now carried out routinely on IMSERC systems.




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                                                                         2009 IMSERC Annual Report

Mass Spectrometry Resources: Mass Spectrometry is used to determine molecular weight ,
provide structural information on compounds, monitor reaction progress, determine sample
purity, and quantify sample concentration and can be used to gain structural information. .
Analysis can be performed using sample volumes of less than 1 uL and concentrations of <1
uM. This typically corresponds to 10-9 to 10-15 grams of material. Using low resolution mass
spectrometry, groups can quickly gauge reaction progress. Figure 11 shows a reaction
sequence developed in the Thomson lab. In this case, 0.5 Da accuracy is more than sufficient
to monitor reaction progress using mass spectrometry. By improving the accuracy and
resolution of the mass spectrometer, users can take advantage of the difference between the




 Figure 11: Thomson group example of a three step synthesis. Each compound has a very different
 molecular weight so reaction progress can be monitored using 1uL of reaction mixture.

nominal mass of a compound and the
theoretical monoisotopic mass. For instance,
the monoisotopic mass of CO is 27.994 Da
vs. N2 is 28.006, thus uniquely distinguishing
the two compounds from one another.
Modern mass spectrometers are capable of
measuring this difference and so many
Journals and reviewers frequently require
accurate mass analysis with agreement
between the measured mass and theoretical
mass to be better than 0.5 ppm (0.0025 Da
for a 500 Da compound). Figure 12 shows
an example from the Silverman group of a
possible treatment for neurodegenerative
diseases analyzed on the Agilent 6210 LC-
TOF mass spectrometer. The synthesis of
these novel compounds based on rational                Figure 12: The Silverman group uses accurate
models has lead to many successful                     mass analysis to confirm the molecular formula of a
treatments, including the development of               compound possible treatments for
                                                       neurodegenerative deseases.
pregabalin, better known by the trade name
LyricaTM, for the treatment of fibromyalga.

Due to the complexity of instrumentation
required to perform accurate mass analysis
and the incredible diversity of compounds
synthesized at NU on a regular basis,
IMSERC maintains a suite of instruments to
meet NU research needs.           IMSERC
provides walk-up access to an instruments              Figure 13: Chemical structure of pregabalin
                                                              TM
with <0.5 Da accuracy for nearly any                   (Lyrica ) which was developed at NU.
molecular compound 24 hrs / day and 7
days / week and also provides staff run

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                                                                          2009 IMSERC Annual Report

accurate mass analysis for all compounds with less than two day turnaround time. IMSERC
provides access to multiple ionization techniques for both walk-up and staff-supported analysis
to ensure that the proper instrument is readily available to analyze nearly every sample.

The IMSERC provides three classes of ionization techniques. Atmospheric pressure ionization
(API) includes electrospray (ESI), atmospheric pressure chemical ionization (APCI) and
atmospheric pressure photo ionization (APPI) and is primarily used for analysis of polar
molecules and biological materials, such as proteins and oligosacharides. Electron Impact (EI)
and chemical ionization (CI) are primarily used for small (<1000 Da) non-polar compounds that
do not ionize using API. Matrix Assisted Laser Ionization (MALDI) is primarily utilized for
higher molecular weight compounds with vapor pressures that are too low for EI/CI, and do not
ionize well using API techniques. In addition, IMSERC provides four introduction techniques.
Direct injection probe (DIP) can be used with neat samples that are volatile when heated. Gas
Chromatography (GC) introduction is used to separate volatile compounds before analysis and
provides a user friendly introduction method fo EI analysis. Liquid Chromatography (LC) can
be performed on samples with higher molecular weight or polarity and is typically combined
with API techniques. MALDI is typically used for proteins, polymers and other samples that
have poor volatility, but cannot be ionized using API. Table 4 shows a list of the current mass
spectrometers and the main use of each. This group of instruments allows users to analyze
80-90% of synthesized compounds using walk-up instrumentation with the remainder needing
staff-run instruments.


         Instrument                   Inlet /        Staff /    Primary Sample Type           Funding Source
                                    Ionization       Walkup
                                      Type
Agilent MSD 5792                      GC / EI        Walkup    m/z < 800 / nonpolar        NSF
Agilent 1100 MSD                      LC / ESI       Walkup    m/z <1500 / polar solvent   Pfizer donation
Thermo Finnegan LCQ                   LC / ESI       Walkup    m/z < 2000 / nonpolar       NSF
                                                               solvent
Applied Biosystems API3000            LC/ ESI        Walkup    m/z <3000, quantitation     Pfizer Donation
Bruker Apex III MALDI                 MALDI          Walkup    m/z <100,000, protein,      NU / State of Illinois /
                                                               polymer, small molecule     NSF
Agilent 6210 LC-TOF               ESI/APCI/APPI      Staff     m/z <20,000 / accurate      State of Illinois
                                                               mass
Thermo Finnegan MAT900              DIP / EI (CI)    Staff     m/z < 850 / accurate mass   NSF
Table 4: IMSERC mass spectrometers with configuration.




Crystallography Resources: Diffraction patterns from a single crystal as small as 100 μm in
size can be used to determine relative positions of atoms in a repeating unit cell. Figure 14
shows a diffraction pattern and solved crystal structure from a Mirkin group sample showing
the arrangement of atoms in a metal oxide framework (MOF) compound [Spokoyny, A. M.;
Kim, D.; Sumrein, A.; Mirkin, C. A. Chem. Soc. Rev. 2009, in press]. This goal of this research
is to develop high surface area materials with uniform pores for applications such as hydrogen
storage or selective adsorption. This type of research is critical in the national program to
develop energy alternatives to burning fossil fuels and also for catalysis applications.

IMSERC currently maintains two X-Ray diffractometers to support research at NU. The Bruker
Platform diffractometer, funding provided by the NSF, is equipped with an APEXII CCD

                                                         15
                                                                                       2009 IMSERC Annual Report

detector and a 3kW MoKα source. This instrument is primarily used for inorganic compounds
with smaller unit cells and heavy atoms which can be high x-ray absorbers. The Bruker
KAPPA instrument, funding provided by the State of Illinois, utilizes a 3kW CuKα source and is
used for more weakly diffracting organic compounds with larger unit cells, such as the MOF
compound, below. Both instruments are staff-run, and users may analyze the data themselves
or have staff members create publication quality reports. Most users who refine their own
structures take a graduate level crystallography class in order to learn how to solve and refine
crystal structures.




   Figure 14. Diffraction pattern (left) for a Mirkin group MOF structure. These diffraction patterns are used to model a
   crystal structure (right).




Trace        Metals        Analysis
Resources:               Inductively
Coupled Plasmas (ICP) can be
used        to      create       gas
temperatures over 5000 oC. At
these temperatures, nearly all
metals exists as atomic gases
as ions or in highly excited
electronic                   states.
Concentrations of the metals
can be accurately determined
by monitoring the light emission
from the metals using optical Figure 15. Mercury concentration in drinking water is shown to be
                                                   safe levels after                      chalcogonide compounds
emission spectroscopy (OES) absorbed to in the Kanatzidisexposure to layered Adv. Funct. Mater. 2009, 19,
                                       synthesized                   group (Manos et al.,
or by monitoring the ions 1-6).
directly         using        mass
spectrometry. Trace metals analysis can be used to measure metal levels in the parts per
trillion (ppt) to parts per million range. These instruments are used for applications ranging
from monitoring environmental contaminants, to determining stoichiometry of solids to
research involving mechanisms of metal transport across cellular membranes. In the last
year, ICP measurements enabled the Kanatzidis group to quantify the removal of Cs, Hg, U
and other hazardous materials by layered chalocogenide compounds in the range of the
EPA’s acceptable limits [Manos et al., Adv. Funct. Mater. 2009, 19, 1-6].



                                                             16
                                                                                  2009 IMSERC Annual Report

While the sensitivity of each instrument is dependent on the element of interest, Table 5 shows
the distribution of concentrations that can be measured on each instrument. Each instrument
requires approximately 10 ml of sample for analysis. Samples are typically prepared by
digesting samples in nitric acid, diluting to 5% nitric acid and then filtering. Organic
compounds may polymerize in the ICP, so a staff member must be contacted before
performing analyses on boilogical samples. The ICP-AES is an open access instrument that is
available 24 hrs/day and 7 days/week. Due to the much higher sensitivity and increased
complexity of the ICP-MS, super users must be trained for each group for ICP-MS analyses.

           Instrument                           Sensitivity                 Funding Source            Notes
   Varian Vista MPX ICP-OES                   1 ppb to 100 ppm                    NSF                   user
                                                                                                    staff / super
      VG PQ Excell ICP-MS                      1 ppt to 100 ppb            Department of Energy
                                                                                                        user
Table 5. List of NU mass spectrometers spectrometers with configuration




Optical Characterization Resources: IMSERC houses all of the spectrometers used in the
undergraduate teaching laboratories. These instruments have primarily been purchased to
support the undergraduate classes, but are typically used heavily for only 4-5 weeks out of the
year. The instruments are made available to the NU community when not in use for the
classes. Last year, Keck Biophysics (KBP) purchased a new UV-Vis spectrometer using core
facilities funding. Due to the high time requirement needed to keep the IMSERC instrument
running, new users are directed to KBP’s instrument.


           Instrument                Wavelength            Sample Type           Information             Notes
                                                                                Electronic        Absorption and
    PTI Spectrofluorimeter            100-900 nm        liquid/solution
                                                                                Structure         Emission
                                                                                Electronic        Use new instrument
    Cary 1EUV-Vis                    200 – 900 nm       liquids
                                                                                Structure         in Keck Biophysics
                                                   -1
    Bruker Tensor 37 FTIR            400-8000 cm        KBr pellet / liquid /   Bonding           Arriving June 2009
                                                        Solid                   Structure
    Delta Nu Raman                 685nm excitation     solid / solution        Bonding           Arrived March 2009
                                                                                Structure

    Table 6. Optical Spectrometers in IMSERC




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                                                   2009 IMSERC Annual Report




Many appendices are for internal use only. If you need access to this data,
please contact the IMSERC Director.




                                     18
                                            2009 IMSERC Annual Report


Appendix 3: 2008 User Survey Results




                                       19

				
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