Jim Larrabee
Emeritus Viola Ward Brinning & Elbert Calhoun Brinning Professor of Chemistry and Biochem
- Office
- McCardell Bicentennial Hall 547
- Tel
- (802) 443-5453
- larrabee@middlebury.edu
- Office Hours
- On leave
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.
Courses Taught
CHEM 0103
General Chemistry I
Course Description
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.
Terms Taught
Requirements
CHEM 0104
General Chemistry II
Course Description
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 equivalent) 3 hrs. lect., 3 hrs. lab, 1 hr. disc.
Terms Taught
Requirements
CHEM 0230
Bioinorganic Chemistry
Course Description
Bioinorganic Chemistry
Bioinorganic chemistry focuses on the role of metals and metal ions in many biological contexts. Whether it is calcium in cell signaling and muscle contraction or iron for the transport and storage of O2 molecules in the blood, metals are engraved in bioorganic systems in different states and concentrations. In this course, we will first familiarize ourselves with the basics of inorganic chemistry needed for understanding bioinorganic chemistry. We will learn the nature of chemical bonding in bioinorganic systems with the theories and examples associated with them. We will then move toward the biochemistry of molecules - the building blocks of proteins: amino acids, followed by processes of RNA, DNA, and protein synthesis. We will conclude the course with a broad discussion on the role of metals in biological systems and their applications with possibly a few specific examples in detail.
Terms Taught
Requirements
CHEM 0431
Advanced Inorganic Chemistry
Course Description
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.
Terms Taught
CHEM 0500
Upcoming
Independent Study
Course Description
Independent Study Project
Individual study for qualified students. (Approval required)
Terms Taught
CHEM 0700
Upcoming
Senior Research
Course Description
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)
Terms Taught
CHEM 0701
Upcoming
Senior Thesis
Course Description
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)
Terms Taught
Academic Degrees
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.
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 tuberculosis” Chem. 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 aerogenes” Inorg. 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 aerogenes” J. 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.