Arthur Greenberg
Professor
Organic Chemistry
Department of Chemistry
University of New Hampshire
Durham, NH 03824-3598 U.S.A.
Phone: 603-862-1180
Fax: 603-862-4278
art.greenberg@unh.edu
Education and Achievements
- B.S. 1967, Fairleigh Dickinson University
- A.M. 1970, Ph.D. 1971 Princeton University
Research Interests
Physical organic chemistry and environmental organic chemistry. Emphases include strained organic molecules such as bridgehead bicyclic lactams, having twisted amide linkages, and epoxyoxepins of possible relevance to benzene metabolism. Interests include airborne carcinogens such as polycyclic aromatic hydrocarbons (PAH) and their derivatives.
Current Research Interests
A. 2,3-Epoxyoxepins as Potential Benzene Metabolites
Benzene is a human carcinogen that is primarily metabolized in the liver. Although most absorbed benzene is metabolically functionalized to phenol which is further metabolized (Phase I) and conjugated (Phase II), a small but significant fraction is metabolically ring-opened to E,E-muconic acid (HOOC-CH=CH-CH=CH-COOH). At least two groups of researchers established some two decades ago that muconaldehyde (OHC-CH=CH-CH=CH-CHO) is the metabolic precursor. How is muconaldehyde formed metabolically. Follow the suggestion of Davies and Whitham in the 1970s we are the first to synthesize and spectroscopically observe epoxidation products of oxepins we term 2,3-epoxyoxepins. These compounds rapidly ring open supporting a logical pathway from benzene to muconaldehyde. Proposed studies will investigate the mechanism of ring opening of 2,3-epoxyoxepins to the corresponding dicarbonyl compounds. In addition, incubation with cytochrome P450 enzymes in collaborative studies will be investigated in order to test the biological significance of this pathway.
B. Bridgehead Bicyclic Lactams
The amide (or peptide) linkage (C-NR-CO-C) normally maintains planarity with a N-CO rotational barrier of about 20 kcal/mol (about one-third the rotational barrier of a C=C bond). Small bridgehead bicyclic lactams such as 1-azabicyclo[2.2.2]octan-2-one or 2-quinuclidone (see Chemical & Engineering News, June 12, 2006, p. 9) have substantially twisted and distorted amide linkages. The results include a loss (or partial loss) of classical resonance energy and changes in chemical properties such as changing the site of protonation or alkylation from oxygen, as in unstrained amides and lactams, to nitrogen in the highly twisted species. Our studies, both experimental and computational, examine the chemical consequences of such distortion upon the site of protonation and the possibility of producing an entirely new functional group: amide N-oxides. Our studies also focus on the potential syntheses of "hyperstable" bridgehead lactams.
C. Polycyclic Aromatic Hydrocarbons (PAH) and Derivatives on Air Particulates
Polycyclic aromatic hydrocarbons (PAH) are ubiquitous by-products of combustion or pyrolysis of organic substances. They are found on airborne particulate matter in concentrations typically on the order of ng per cubic meter. Nitro-derivatives of PAH, may be formed as primary pollutants (e.g. 1-nitropyrene) in the combustion of diesel fuel, or as secondary pollutants (e.g. 2-nitropyrene) from PAH reacting under atmospheric conditions. Nitro-PAH are usually found in pg per cubic meter concentrations but they are very strong mutagens. Our research employs HPLC with diode array UV and fluorescence to analyze PAH, nitro-PAH and other derivatives. One goal will be to assess the levels of these carcinogens and mutagens in airborne particulates obtained in downtown San Salvador (El Salvador) where very poorly maintained diesel buses are the primary mode of transportation. Such data will be employed in human risk assessment studies.
Group Members
Professor: Arthur Greenberg
New group forming!
Selected Recent Publications
Johnson, C., A. Greenberg and L. Sander, "Separation of Benzo[a]pyrene Sulfate Isomers by Reversed-Phase Liquid Chromatography," J. Chromatogr. A 753, 201-6 (1996)
Greenberg, A., D.T. Moore and T.D. DuBois, "Small and Medium Sized Bridgehead Bicyclic Lactams: A Systematic Ab Initio Molecular Orbital Study," J. Amer. Chem. Soc. 118, 8658-68 (1996)
Greenberg, A., and D.T. Moore, "Core Ionization Energies of Amides As a Probe of Structure and Bonding," J. Molec. Struct. 413/414, 477-85 (1997)
Greenberg, A, A. Ozari and C.M. Carlin, "Reactions of 2,7-Dimethyloxepin with Dimethyldioxirane and Methyl(trifluoromethyl)dioxirane: Ring Opening and Probable Observation of the Intermediate '2,3-Epoxyoxepin'," Struct. Chem. 9, 223-6 (1998)
Greenberg, A., and D.T. Moore, "Stabilization and Destabilization Energies of Distorted Amides," In Theoretical and Computational Chemistry, Vol. 6: Pauling's Legacy- Modern Modelling of the Chemical Bond," Z. Maksic and Orville-Chapman, Editors, Elsevier Science, Amsterdam, 1999, pp 321-46
Johnson, C., and A. Greenberg, "Extraction and High Performance Liquid Chromatographic Separation of Selected Pyrene and Benzo[a]pyrene Sulfates and Glucuronides: Preliminary Application to the Analysis of Smokers' Urine," J. Chromatograhy B728, 209-16 (1999)
Greenberg, A., and T.D. DuBois, "Amide N-Oxides: An Ab Initio Molecular Orbital Study," J. Molec. Struct. 567-568, 303-17 (2001).
Nauduri, D., and A. Greenberg, Direct Observation by 1H-NMR of 4,5-Benzoxepin-2,3-oxide and Its Surprisingly Rapid Ring-Opening Rearrangement to 1H-2-Benzopyran-1-carboxaldehyde, Tetrahedron Lett 45, 4789-93 (2004)
Recent Books
Greenberg, A., A Chemical History Tour, John Wiley & Sons, New York, 2000
Greenberg, A., The Art of Chemistry, John Wiley & Sons, New York, 2003
Greenberg, A., C.M. Breneman, and J.F. Liebman (Editors), The Amide Linkage: Structural Significance in Chemistry, Biochemistry, and Materials Science, John Wiley & Sons, New York, 2003 (This is softcover reissue of 2000 volume)
Greenberg, Arthur, From Alchemy to Chemistry in Picture and Story, John Wiley & Sons, New York, 2007.
Greenberg, Arthur, Twentieth Century Science: Chemistry - Decade by Decade, Facts on File, New York, 2007.