Professor Emeritus & Arthur F. Thurnau University Professor
About
Curiosity and questions concerning molecular architecture and synthesis have been my abiding focus and direction. My group designed, constructed and studied a variety of diverse chemical frameworks so as to learn about molecular architecture, design, assembly and interactions. Each of these molecular architectures was applied to the understanding of chemical, biochemical and medicinal interactions and reactions.
Early in my career, a structure was designed and constructed to test whether double bond neighboring group participation might compete against direct nucleophilic displacement. The chemistry resulted in closure to a “non-classical” intermediate and the final formation of the bicyclic norbornyl system.
At Michigan my group first turned attention to the construction of the dibenzo[ghi, mno]fluoranthene [corannulene] structure. A particular challenge for synthetic organic chemistry continues to be the design and construction of molecules in which a compromise is forced between the factors of strain and aromaticity. The bowl shaped molecule corannulene uniquely embodies these special characteristics and was first designed and synthesized in our laboratories in 1966.
Our group designed, synthesized and studied the chemistry of molecular tools used in biochemistry, biotechnology and cell and molecular biology. Of most interest are cross-linking reagents, photo activated cross-link reagents and selective cleavage agents for proteins. Cross-linking reagents are bifunctional molecules that bridge between residues on a single protein or between residues on separate, but associated protein chains. The chemistry also provides pathways for the "tethering" of chemical identifiers to proteins and to assemble enzymes, proteins and antibodies on solid supports.
The research group has pioneered the chemistry of both mobile protein cross-link and unique photo-activatable cross-linking reagents. Equilibrium transfer alkylation cross-links [acronym:ETAC; pronounced EEE--tac] reagents allow the linking of residues on protein chains in either an intra- or inter-molecular fashion, yet the reagents still retain a mobile, transferable character. They can transfer from one protein residue to another or even to another protein through a cascade of consecutive Michael/retro-Michael reactions. Thus, the reagents have the ability to "walk", "skip", "jump" or "pivot" from one residue to another within the protein framework or protein aggregate architecture through a series of consecutive conjugate additions. The linked residues identify the distances and relationships of the sites in the proteins. By the incremental increase in the length of the bridging reagents, rigid molecular yardsticks are created that allow the measurement between different distant sites in proteins. Such yardstick-like molecules can also be used in the construction of unique large ring structures and in the construction of molecular architectures for the identification of molecular recognition elements.
Es passert einmal; es passert nur einmal-- und doch so wird es immer sine.
It happened one time; it happened just one time--and thus so it will be forever.
from the movie "Wings of Desire" by Wim Wenders 1985 in German with English subtitles.
....to be an essential part, however minor in retrospect, of something larger-- maybe even a watergap still swinging in the breeze after the worst of all spring floods. 1974 Richard D. Alexander; Professor of Zology & Evolutionary Biology, University of Michigan
see www.richarddalexander.com 1974 Commentary. "Creativity from the Scientist's Point of View" LS&A Diagonalia
Representative Publications
R. G. Lawton, "1,5-Participation in the Solvolysis of 2-(3-Cyclopentenyl)ethyl p-Nitrobenzenesulfonate", J. Am. Chem. Soc. 1961, 83, 2399.
Barth, W. E.; Lawton, R. G.; "Dibenzo(ghi,mno)fluoranthene", J. Am. Chem. Soc. 1966, 88, 380.
W. E. Barth & R. G. Lawton, "The Synthesis of Corannulene", J. Am. Chem. Soc. 1971, 93, 1730.
R. P. Nelson & R. G. Lawton, "On the a,a'-Annelation of Cyclic Ketones", J. Am. Chem. Soc. 1966, 88, 3884.
Nelson, R. P.; McEuen, J. M.; Lawton, R. G.; "The a,a'-Annelation of Cyclic Ketones. Synthesis of Bicyclo[3.2.1]octane Derivatives", J. Org. Chem. 1969, 34, 1225.
S. Mitra and R.G. Lawton "Reagents for the Cross-linking of Proteins by Equilibrium Transfer Alkylation," J. Am. Chem. Soc. (1979), 101, 3097.
V.S. Goodfellow, M. Setteneri and R.G. Lawton "p-Nitrophenyl 3-diazopyruvate and Diazopyruvamides. A New Family of Photoactivatable Cross-linking Bioprobes" Biochemistry 1989, 28, 6346.
F.A. Liberatore, R.D. Comeau, J. M. McKearin, D.A. Pearson, B.Q. Belonga, S.J. Brocchini, J. Kath, T. Phillips, K. Oswell and R.G. Lawton, "Site-Directed Modification and Cross-linking of a Monoclonal Antibody with Equilibrium Transfer Alkylating Cross-link Reagents" Bioconjugate Chemistry 1990,1, (Jan-Feb) 36.
Steve J. Brocchini, Martin Eberle & Richard Lawton "Molecular Yardsticks. Synthesis of Extended Equilibrium Transfer Alkylation Cross-link Reagents & their use in the Formation of Macrocycles." J. Am. Chem. Soc. 1988, 110, 5211-5212.
J.M. Taylor, G.G. Jacob-Mosier, R.G. Lawton,R.R. Neubig. " A new thiol specific photoactivatable crosslinking regent. Conjugation of an alpha 2-adrenergic receptor peptide to G-protein". Peptides, 1994, 15, 829-834.
J.M. Taylor, G.G. Jacob-Mosier, R.G. Lawton, A.E. Remmers, R. Neubig. "Binding of an alpha 2-adrenergic receptor third intercellular loop peptide to G beta and the amino terminus of G alpha ". J. Biol. Chem.1994, 45, 27618-27624.
Yaun-Shek Chen, Jeff W. Kampf and Richard G. Lawton. "Aromatic Stacking in Folded Architectures through Hydrogen Bonding." Tetrahedron Lett. 1997, 38, 5781-5184.
S.J. Brocchini, R.G. Lawton. "Titanium Chelation in Regioselective Michael Additions to Conjugated Dienones and Trienones". Tetrahedron Lett. 1997, 38, 6319-6323.
Y.S. Chen, J.W. Kampf, .G.Lawton. "Intramolecular Carboxylate Capture of an Intermediate in Aromatic Electrophilic Substitution. The 8,9,10,11-tetrahydro-7.11-methano-7H-cycloocta[de]naphthalene-9-endo-carboxylic acid System". Tetrahedron Lett. 1997, 38, 6831-6834.
Research Areas(s)
- Organic Chemistry
- Neighboring Group Participatiion
- Bioorganic Reagents & Chemistry as Probes of Molecular Architecture
Award(s)
- Arthur F. Thurnau Professor, 1993
- LS&A Excellence in Teaching Award, 1991, 1992, 1997
- University of Michigan Amoco Teaching Award, 1989
- International Academic Partnerships Fellow, Aachen Germany 1983
- John S. Guggenheim Foundation Fellow, Aachen Germany 1978
- Lilly Grantee, University of Michigan 1967
