For Current Updates on COVID-19:

Jim Larrabee

Viola Ward Brinning & Elbert Calhoun Brinning Professor of Chemistry & Biochem

 work(802) 443-5453
 Spring 2020: Mon/Wed 9:00-11:00AM, Tues/Thurs 2:30 - 4:00PM, and by appointment
 McCardell Bicentennial Hall 547

Jim Larrabee obtained a B.S. degree from Trinity College and a Ph.D. degree from Princeton University. He worked for Exxon Research and Engineering Company as a Research Chemist before joining the Middlebury Faculty in 1986.

Research Interests

My area of research specialization is bioinorganic chemistry, which is the study of biological molecules that contain or react with metallic elements. My current research is in the application of magnetic circular dichroism (MCD) to the study of dimetallic hydrolase enzymes. Recently published studies include those  on three organo-phosphorous degrading enzymes (GpdQ, OpdA, and OPH), an N-terminal peptidase (methionine aminopeptidase), and model compound mimics of metallo-β-lactamases. Students in my research group use inorganic electronic spectroscopy (MCD, UV/VIS/NIR absorption and diffuse reflectance) and ligand field theory (angular overlap model) to help us understand the immediate coordination environment around the metal ions in these enzyme active sites. This information provides insight on the enzyme mechanism.



Course List: 

Courses offered in the past four years.
indicates offered in the current term
indicates offered in the upcoming term[s]

CHEM 0103 - General Chemistry I      

General Chemistry I
Major topics will include atomic theory and atomic structure; chemical bonding; stoichiometry; introduction to chemical thermodynamics. States of matter; solutions and nuclear chemistry. Laboratory work deals with testing of theories by various quantitative methods. Students with strong secondary school preparation are encouraged to consult the department chair for permission to elect CHEM 0104 or CHEM 0107 in place of this course. CHEM 0103 is also an appropriate course for a student with little or no prior preparation in chemistry who would like to learn about basic chemical principles while fulfilling the SCI or DED distribution requirement. 3 hrs. lect., 3 hrs. lab, 1 hr. disc. DED SCI

Fall 2019

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CHEM 0104 - General Chemistry II      

General Chemistry II
Major topics include chemical kinetics, chemical equilibrium, acid-base equilibria, chemical thermodynamics, electrochemistry, descriptive inorganic chemistry, and coordination chemistry. Lab work includes inorganic synthesis, qualitative analysis, and quantitative analysis in kinetics, acid-base and redox chemistry. (CHEM 0103 or by waiver) 3 hrs. lect., 3 hrs. lab, 1 hr. disc. DED SCI

Fall 2016, Spring 2017, Spring 2018, Fall 2018, Spring 2020

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CHEM 0230 - Bioinorganic Chemistry      

Bioinorganic Chemistry
Life depends on the proper functioning of proteins and nucleic acids that are often metalated. In this course we will study the structure and function of metalloproteins and other metallobiomolecules. We will begin with an overview of bioinorganic chemistry. Next, we will look at two classic questions in bioinorganic chemistry. (1) How does hemoglobin cooperatively bind dioxygen? and (2) Why is cis-platin an anti-cancer drug whereas trans-platin is not? We will then spend the rest of the first half of the course learning the inorganic chemistry that will allow us to answer these questions and many others: simple bonding, symmetry, transition metal chemistry, and ligand field theory. In the second half of the course, we will start with some biochemistry fundamentals and then move on to case studies of zinc, iron, copper proteins, and metals in medicine. The textbooks will be Inorganic Chemistry by Miessler, Fisher, and Tarr, and Biological Inorganic Chemistry by Crichton, both available on-line for free. (CHEM0104 or CHEM0107) 3hrs lect/disc SCI

Spring 2017, Spring 2018, Spring 2019, Spring 2020

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CHEM 0311 - Instrumental Analysis      

Instrumental Analysis
This course introduces fundamental concepts of analytical chemistry, instrumental analysis, and scientific writing. Lecture topics include experimental design and quality control; sample collection and preparation; calibration, error, and data analysis; statistics; and the theory and operation of chemical instrumentation. Multi-week laboratory projects provide hands-on experience in qualitative and quantitative analysis using a variety of research-quality instrumentation (e.g., graphite furnace atomic absorption spectroscopy, UV/Vis spectrometry, gas chromatography mass spectrometry, circular dichroism spectroscopy, high pressure liquid chromatography). Writing workshops promote professional scientific writing skills through guided practice in writing analysis, peer review, and revision. (CHEM 0204 or CHEM 0242) 3 hr. lect., 6 hrs. lab. CW

Fall 2017

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CHEM 0312 - Inorganic & Physical Chemistry      

Inorganic and Physical Chemistry Laboratory
In this course students will carry out experiments in the field of inorganic and physical chemistry and write journal-style reports based on their results. In the first half of the semester students will conduct a multi-step synthesis and characterization of a Mo-Mo complex with a quadruple bond. Students will learn inert atmosphere synthetic techniques and how to use a glove box. The synthesized Mo-Mo complex will be characterized by UV-Vis, IR, 1H and 31P NMR spectroscopies, and cyclic voltammetry. In the second half of the semester students will conduct two physical chemistry experiments. First students will carry out a kinetic study of the isomerization of the Mo-Mo (alpha to beta or beta to alpha) complex by UV-Vis spectroscopy. Finally, students will obtain the high-resolution IR spectra of acetylene and deuterated acetylene and analyze the rotation-vibration spectra using statistical and quantum mechanics to obtain structural data and interpret the peak intensities. In addition to the laboratory activities, there will be lectures on metal quadruple bonds, principles of UV-Vis , IR, 1H and 31P NMR spectroscopies, cyclic voltammetry, and statistical mechanics. (CHEM 0311, CHEM 0351, and CHEM 0355. CHEM 0355 can be taken concurrently.) 3 hrs. lect. 3 hrs. lab

Spring 2019

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CHEM 0431 - Advanced Inorganic Chemistry      

Advanced Inorganic Chemistry
Atomic structure, bonding theories, and properties applicable to inorganic and organometallic compounds will be developed in depth. Specific topics will include valence bond theory, molecular orbital theory, ligand field theory, applications of group theory, and reaction mechanisms. (CHEM 0351) 3 hrs. lect.

Fall 2016, Fall 2017, Fall 2018, Fall 2019

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CHEM 0500 - Independent Study      

Independent Study Project
Individual study for qualified students. (Approval required)

Fall 2016, Winter 2017, Spring 2017, Fall 2017, Winter 2018, Spring 2018, Fall 2018, Winter 2019, Spring 2019, Fall 2019, Winter 2020, Spring 2020, Fall 2020, Spring 2021

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CHEM 0700 - Senior Research      

Senior Research
In this course students complete individual projects involving laboratory research on a topic chosen by the student and a faculty advisor. Prior to registering for CHEM 0700, a student must have discussed and agreed upon a project topic with a faculty member in the Chemistry and Biochemistry Department. Attendance at all Chemistry and Biochemistry Department seminars is expected. (Approval required; open only to seniors)

Fall 2016, Winter 2017, Spring 2017, Fall 2017, Winter 2018, Spring 2018, Fall 2018, Winter 2019, Spring 2019, Fall 2019, Winter 2020, Spring 2020, Fall 2020, Spring 2021

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CHEM 0701 - Senior Thesis      

Senior Thesis
Students who have initiated research projects in CHEM 0400 and who plan to complete a senior thesis should register for CHEM 0701. Students are required to write a thesis, give a public presentation, and defend their thesis before a committee of at least three faculty members. The final grade will be determined by the department. Attendance at all Chemistry and Biochemistry Department seminars is expected. (CHEM 0400; approval required)

Fall 2016, Winter 2017, Spring 2017, Fall 2017, Winter 2018, Spring 2018, Fall 2018, Winter 2019, Spring 2019, Fall 2019, Winter 2020, Spring 2020, Fall 2020, Spring 2021

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Recent Publications

* Denotes Middlebury College undergraduate co-authors.

Versantvoort, W.; Pol, A.; Daumann, L. J.; Larrabee, J. A.; *Strayer, A. H.; Jetten, M. S. M.; van Niftrik, L.; Reimann, J.; Op den Camp, H. J. M. “Characterization of a novel cytochrome cGJ as the electron acceptor of XoxFMDH in the thermoacidophilic methanotroph Methylacidiphilum fumariolicum SolV” BBA - Proteins and Proteomics 2019, 1867, 595–603, DOI: 10.1016/j.bbapap.2019.04.001.

Pedroso, M. M.; Selleck, C.; Bilyj, J.; Harmer, J. R.; Gahan, L. R.; Mitić, N.; Standish, A.; Tierney, D. L.; Larrabee, J. A.; Schenk, G. “Reaction mechanism of the metallohydrolase CpsB from Streptococcus pneumoniae, a promising target for novel antimicrobial agents” Dalton Transactions 2017, 46, 13194-13201, DOI: 10.1039/c7dt01350g.

Pedroso, M. M.; Selleck, C.; Enculescu, C.; Harmer, J.; Mitić, N.; Craig, W. A.; *Helweh, W.; Hugenholtz, P.; Tyson, G. W; David L. Tierney, D. L.; Larrabee, J. A.; Schenk, G. “An uncultured microbiome from a frozen environment harbours a highly efficient antibiotic-degrading metallo-β-lactamase” Metallomics 2017, 9, 1157-1168, DOI: 10.1039/c7mt00195a.

Selleck, C.; Larrabee, J. A.; Harmer, J.; Guddat, L. W.; Mitic, N.; *Helweh, W.; Ollis, D. L.; Craig, W. R.; Tierney, D. L.; Pedroso, M. M.; Schenk, G. “AIM-1: An antibiotic-degrading metallohydrolase that displays mechanistic flexibility” Chem. Eur. J. 2016, 22, 17704-17714, DOI: 10.1002/chem.201602762.

Tadrowski, S.; Pedroso, M. M.; Sieber, V.; Larrabee, J. A.; Guddat, L. W.; Schenk, G. “Metal ions play an essential catalytic role in the mechanism of ketol-acid reductoisomerase” Chem. Eur. J. 2016, 22, 7427-7436, DOI: 10.1002/chem.201600620.

Pedroso, M. M.; Larrabee, J. A.; Ely, F.; Gwee, S. E.; Mitic, N.; Ollis, D. L.; Gahan, L. R.; Schenk, G. “CaII binding regulates and dominates the reactivity of transition-metal-ion-dependent diesterase from Mycobacterium tuberculosisChem. Eur. J. 2016, 22, 999-1009, DOI: 10.1002/chem.201504001.

 Starus, A.; Nocek, B.; Bennett, B.; Larrabee, J. A.; *Shaw, D. L.; *Sae-Lee, W.; *Russo, M. T.; Gillner, D. M.; Makowska-Grzyska, M.; Joachimiak, A.; Holz, R. C. “Inhibition of the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Neisseria meningitides by L-captopril” Biochem. 2015, 54, 4834-4844, DOI: 10.1021/acs.biochem.5b00475.

Larrabee, J. A.; Schenk, G.; Mitic, N.; Riley, M. J. “Use of magnetic circular dichroism to study dinuclear metallohydrolases and the corresponding biomimetics” Eur. Biophys. J. 2015, 44, 393-415, DOI: 10.1007/s00249-015-1053-6.

Pedroso, M. M.; Ely, F.; Mitic, N.; Carpenter, M. C.; Gahan, L. R.; Wilcox, D. E.; Larrabee, J. A.; Ollis, D. L.; Schenk, G. “Comparative investigation of the reaction mechanisms of the organophosphate-degrading phosphotriesterases from Agrobacterium radiobacter (OpdA) and Pseudomonas diminuta (OPH)” J. Biol. Inorgan. Chem. 2014, 19, 1263-1275, DOI: 10.1007/s00775-014-1183-9.

Daumann, L. J.; Larrabee, J. A.; Ollis, D.; Schenk, G.; Gahan, L. R. “Immobilization of the enzyme GpdQ on magnetite nanoparticles for organophosphate pesticide bioremediation” J. Inorg. Biochem. 2014, 131, 1-7, DOI: 10.1016/j.jinorgbio.2013.10.007.

Daumann, L. J.; Larrabee, J. A.; Comba, P.; Schenk, G.; Gahan, L. R. “Dinuclear cobalt(II) complexes as metallo-β-lactamase mimics” Eur. J. Inorg. Chem. 2013, 2013, 3082-3089, DOI: 10.1002/ejic.201300280.

Daumann, L. J.; Comba, P., Larrabee, J. A.; Schenk, G.; Stranger, R.; Cavigliasso, G.; Gahan, L. R. “Synthesis, magnetic properties, and phosphoesterase activity of dinuclear cobalt(II) complexes” Inorg. Chem. 2013, 52, 2029-2043, DOI: 10.1021/ic302418x.

Daumann, L. J.; McCarthy, B. Y.; Hadler, K. S.; Murray, T. P.; Tracy, P.; Gahan, L. R.; Larrabee, J. A.; Ollis, D. L.; Schenk, G. “Promiscuity comes at a price: Catalytic versatility vs efficiency in different metal ion derivatives of the potential bioremediator GpdQ” Biochim. Biophys. Acta 2013, 1834, 424-432, DOI: 10.1016/j.bbapap.2012.02.004.

Ely, F.; Hadler, K. S.; Mitić, N.; Lawrence R Gahan, L. R.; David L. Ollis, D. L.; *Plugis, N. M.; *Russo, M. T.; Larrabee, J. A.; Schenk, G. “Electronic and geometric structure of the organophosphate-degrading enzyme from Agrobacterium radiobacter (OpdA)” J. Biol. Inorg. Chem.2011, 16, 777-787, DOI: 10.1007/s00775-011-0779-6.

Hadler, K. S.; Mitić, N.; Gahan, L. R.; Ollis, D. L.; Schenk, G.; Larrabee, J. A. “Electronic structure analysis of the dinuclear metal center in the bioremediator glycerophosphodiesterase (GpdQ) from Enterobacter aerogenesInorg. Chem. 2010, 49, 2727-2734, DOI: 10.1021/ic901950c.

Larrabee, J. A.; *Johnson, W. R.; *Volwiler, A. S. “Magnetic circular dichroism study of a complex with mixed 5- and 6-coordination: A spectroscopic model for dicobalt(II) hydrolases” Inorg. Chem. 2009, 48, 8822-8829, DOI: 10.1021/ic901000d.

Hadler, K. S.; Mitić, N.; Ely, F.; Hanson, G. R.; Gahan, L. R.; Larrabee, J. A.; Ollis, D. L.; Schenk, G. “Structural flexibility enhances the reactivity of the bioremediator glycerophosphodiesterase by fine tuning its mechanism of hydrolysis” J. Am. Chem. Soc. 2009, 131, 11900-11908, DOI: 10.1021/ja903534f.

Larrabee, J. A.; *Chyun, S-A.; *Volwiler, A. S. “Magnetic circular dichroism study of a methionine aminopeptidase/fumagillin complex and dicobalt II-II and II-III model complexes” Inorg. Chem. 2008, 47, 10499-10508, DOI: 10.1021/ic8011553.

Hadler, K. S.; Tanifum, E.; Yip, S. H-C.; Mitić, N.; Guddat, L. W.; Jackson, C. J.; Gahan, L. R.; Carr, P.; Ollis, D. L.; Hengge, A. C.; Larrabee, J. A.; Schenk, G. “Substrate-promoted formation of a catalytically competent binuclear center and regulation of reactivity in glycerophosphodiesterase from Enterobacter aerogenesJ. Am. Chem. Soc. 2008, 130, 14129-14138, DOI: 10.1021/ja803346w.

Johansson, F. B.; Bond, A. D.; Nielsen, U. G.; Moubaraki, B.; Murray, K. S.; Berry, K. J.; Larrabee, J. A.; McKenzie, C. J. “Dicobalt II–II, II–III and III–III complexes as spectroscopic models for dicobalt enzyme active sites” Inorg. Chem. 2008, 47, 5079-5092, DOI: 10.1021/ic7020534.

Choi, S.; *Vastag, L.; *Leung, C-H.; *Beard, A. M.; *Knowles, D. E.; Larrabee, J. A. “Kinetics and mechanism of the oxidation of guanosine derivatives by Pt(IV) complexes” Inorg. Chem. 2006, 45, 10108-10114, DOI: 10.1021/ic061243g.

Larrabee, J. A.; *Leung, C-H.; *Moore, R. L.; *Thamrong-nawasawat, T.; *Wessler, B. S. H. “Magnetic circular dichroism and cobalt(II) binding equilibrium studies of Escherichia coli methionyl aminopeptidase” J. Am. Chem. Soc. 2004, 126, 12316-12324, DOI: 10.1021/ja0485006.

Larrabee, J. A.; *Thamrong-nawasawat, T.; *Mon, S. Y. “An HPLC method for the assay of methionine aminopeptidase activity: Application to the study of enzymatic inactivation” Anal. Biochem. 1999, 269, 194-198, DOI: 10.1006/abio.1998.3086.

Larrabee, J. A.; *Alessi, C. M.; *Asiedu, E. T.; *Cook, J. O.; *Hoerning, K. R.; *Klingler, L. J.; *Okin, G. S.; *Santee, S. G.; *Volkert, T. L. “Magnetic circular dichroism spectroscopy as a probe of geometric and electronic structure of cobalt(II)-substituted proteins: Ground state zero field splitting as a coordination number indicator” J. Am. Chem. Soc. 1997, 119, 4182-4196, DOI: 10.1021/ja963555w.

Recent Grants

NSF/RUI, CHE-1904005 “RUI: Magnetic circular dichroism of dicobalt(II) enzymes" August 1, 2019-July 31, 2022, $213,000.

NSF/RUI, CHE-1303852 “RUI: Magnetic circular dichroism of dicobalt(II) enzymes” 2013-2017, $201,000.

NSF/RUI, CHE-0848433 “RUI: Magnetic circular dichroism of dicobalt(II) enzymes and complexes” 2009-2013, $300,000.

NSF/MRI, CHE-0820965 “Acquisition of spectropolarimeter for circular dichroism and magnetic circular dichroism” 2008-2009, $76,748.

Department of Chemistry & Biochemistry

McCardell Bicentennial Hall
276 Bicentennial Way
Middlebury College
Middlebury, VT 05753