Faculty Directory

Eugene Mash

Professor
Degrees and Appointments: 
B.S. 1975, The University of California, Irvine
B.A. 1975, The University of California, Irvine
Ph.D. 1980, The University of Utah
NIH Postdoctoral Fellow 1981-1983, Harvard University
Awards and Honors: 
UA CoS Distinguished Career Teaching Award, 2009
UA CoS Innovation in Teaching Award, 1995
IBM Paul J Flory Fellow, 1990-1991
National Institutes of Health Postdoctoral Fellow, 1981-1983
Research Summary: 

1. Imaging and Drug Delivery to the Gastrointestinal Tract

We have developed untargeted molecules such as 1 based on a sucrose scaffold for use in magnetic resonance imaging of and drug delivery to the gastrointestinal tract (see Figure 1 below).  We are now working to develop targeted versions of these molecules for early detection and treatment of diseased tissues.


 

Figure 1.  T1-weighted GE3D images of the Gd-DOTA/sucrose construct 1 passing through the GI tract of a C3H mouse.  Arrows indicate points of bright CA-related contrast.  At 0.5 h post-gavage, bright contrast is observed in the esophagus and stomach; at 8.5 h contrast is observed in the small intestine; at 24.5 h contrast is observed in the large intestine; and by 47 h all contrast has cleared the GI tract.


 

2. Crystal Engineering with 1,4-Piperazine-2,5-diones

Non-covalent interactions are of universal importance in chemistry, materials science, and biology.  Using a family of piperazinedione-containing molecules, we have demonstrated that the three-dimensional order of an organic crystal can be controlled by incorporation of three linearly independent molecular recognition elements (see Figure 2).  In this way we have produced bulk materials that exhibit liquid crystal properties or non-linear optical properties.


Figure 2. A pentacyclic piperazinedione-containing scaffold incorporating three geometrically and chemically independent recognition elements might assemble predictably into a solid.

 

 

3. Polymers Containing Large Bicyclic Rings

Elasticity of polymeric materials is generally attributed to chain entanglement.  Materials with untangled, aligned chains make good fibers, but often have limited elasticity.  This research seeks to prepare polymers that can pack as untangled, aligned chains, but that do possess significant elasticity due to the conformational properties of one or both co-monomers incorporated during polymerization (see Figure 3).


Figure 3. Illustration of conformational compressibility and its possible effect on polymer elasticity.  Left: 1,10-Disubstituted bicyclo[8.8.8]hexacosane as a molecular spring.  Right: Stress response of polymers incorporating large bicyclo[m.m.m]alkane ring systems.

 

 

Publications: 

Dehigaspitiya, D. C.; Anglin, B. L.; Smith, K. R.; Weber, C. A.; Lynch, R. M.; Mash, E. A. Org. Biomol. Chem. 201513, 0000-0000. "Linear Scaffolds for Multivalent Targeting of Melanocortin Receptors."

Elshan, N. G. R. D.; Jayasundera, T.; Weber, C. A.; Lynch, R. M.; Mash, E. A. Bioorg. Med. Chem. 201523, 1841-1848. "Development of a Time-resolved Fluorescence Probe for Evaluation of Competitive Binding to the Cholecystokinin 2 Receptor."

Dehigaspitiya, D. C.; Navath, S.; Weber, C. A.; Lynch, R. M.; Mash, E. A. Tetrahedron. Lett. 2015, 56, 3060-3065. "Synthesis and Bioactivity of MSH4 Oligomers Prepared by an A2 + B2 Strategy."

Elshan, N. G. R. D.; Jayasundera, T.; Anglin, B. L.; Weber, C. A.; Lynch, R. M.; Mash, E. A. Org. Biomol. Chem. 201513, 1778-1791. "Trigonal Scaffolds for Multivalent Targeting of Melanocortin Receptors."

Elshan, N. G. R. D.; Patek, R.; Vagner, J.; Mash, E. A. Anal. Biochem. 2014464, 24-29. "Spectrophotometric Determination and Removal of Unchelated Europium Ions from Solutions Containing Eu-Diethylenetriaminepentaacetic Acid Chelate-Peptide Conjugates."

Jagadish, B.; Ozumerzifon, T. J.; Roberts, S. A.; Hall, G. B.; Mash, E. A.; Raghunand, N. Synthetic Communic. 201444, 441-449. "Improved Synthesis of 10-(2-Alkylamino-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic Acid Derivatives Bearing Acid-sensitive Linkers."

Jagadish, B.; Field, J. A.; Chorover, J.; Sierra-Alvarez, R.; Abrell, L.; Mash, E. A. J. Label. Compd. Radiopharm. 201457, 434-436. "Synthesis of 13C and 15N Labeled 2,4-Dinitroanisole."

Mash, E. A. CrystEngComm 201416, 8620-8637. "Crystal Engineering with 1,4-Piperazine-2,5-diones."

Alleti, R.; Vagner, J.; Dehigaspitiya, D. C.; Moberg, V. E.; Elshan, N. G. R. D.; Tafreshi, N. K.; Brabez, N.; Weber, C. S.; Lynch, R. M.; Hruby, V. J.; Gillies, R. J.; Morse, D. L.; Mash, E. A. Bioorg. Med. Chem. 2013, 21, 5029-5038. "Synthesis and Characterization of Time-resolved Fluorescence Probes for Evaluation of Competitive Binding to Melanocortin Receptors."

Martinez, G. V.; Navath, S.; Sewda, K.; Rao, V.; Foroutan, P.; Alleti, R.; Moberg, V. E.; Ahad, A. M.; Coppola, D.; Lloyd, M. C.; Gillies, R. J.; Morse, D. L.; Mash, E. A. Bioorg. Med. Chem. Lett. 2013, 23, 2061-2064. "Demonstration of a Sucrose-derived Contrast Agent for Magnetic Resonance Imaging of the GI Tract."

Navath, S.; Rao, V.; Woodford, R. T.; Midura-Kiela, M. T.; Ahad, A. M.; Alleti, R.; Kiela, P. R.; Mash, E. A. ACS Med. Chem. Lett. 2012, 3, 710-714. "Design, Synthesis, and Testing of a Molecular Truck for Colonic Delivery of 5-Aminosalicylic Acid."

Mash, E. A. (2012) "Synthetically Derived Chiral Auxiliaries: Uses of Derivatives of Non-Carbohydrate Aldehydes and Ketones in Asymmetric Synthesis." In: Carreira E.M. and Yamamoto H. (eds.) Comprehensive Chirality, Volume 3, pp. 377-407; Amsterdam: Elsevier.

Wells, K.E.; Weatherhead, R. A.; Murigi, F. N.; Nichol, G. S.; Carducci, M. D.; Selby, H. D.; Mash, E. A. Cryst. Growth Des. 201212, 5056-5068. "Organic Crystal Engineering with 1,4-Piperazine-2,5-diones. 8. Synthesis, Crystal Packing, and Thermochemistry of Piperazinediones Derived from 2-Amino-4,7-dialkoxyindan-2-carboxylic Acids."

Jagadish, B.; Guntle, G. P.; Zhao, D.; Gokhale, V.; Ozumerzifon, T. J.; Ahad, A. M.; Mash, E. A.; Raghunand, N. J. Med. Chem. 2012, 55, 10378-10386. "Redox-active Magnetic Imaging Contrast Agents: Studies with Thiol-bearing 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetracetic Acid Derivatives."

Jagadish, B.; Brickert-Albrecht, G. L.; Nichol, G. S.; Mash, E. A.; Raghunand, N. Tetrahedron Lett. 2011, 52, 2058-2061. "On the Synthesis of 1,4,7-Tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane."

Rao, V.; Alleti, R.; Xu, L.; Tafreshi, N. K.; Morse, D. L.; Gillies, R. J.; Mash, E. A. Bioorg. Med. Chem. 201119, 6474-6482. "A Sucrose-Derived Scaffold for Multimerization of Bioactive Peptides."

Alleti, R.; Rao, V.; Xu, L.; Gillies, R. J.; Mash, E. A. J. Org. Chem. 201075, 5895-5903. "A Solanesol-Derived Scaffold for Multimerization of Bioactive Peptides."

Raghunand, N.; Guntle, G. P.; Gokhale, V.; Nichol, G. S.; Mash, E. A.; Jagadish, B. J. Med. Chem. 2010, 53, 6747-6757. "Design, Synthesis, and Evaluation of 1,4,7,10-Tetraazacyclododecane-1,4,7-triacetic Acid-Derived, Redox-Sensitive Contrast Agents for Magnetic Resonance Imaging."

Murigi, F. N.; Nichol, G. S.; Mash, E. A. J. Org. Chem. 2010, 75, 1293-1296. "Synthesis of the Conformationally Constrained Tyrosine Analogs, (R)- and (S)-5-Hydroxy-2-aminoindan-2-carboxylic Acids."

Weatherhead, R. A.; Carducci, M. D.; Mash, E. A. J. Org. Chem. 2009, 74, 8773-8778. "Synthesis of Conformationally Constrained Diaminodicarboxylic Acid Derivatives."

Jones, I. W.; Lynn, M. A.; Mash, E. A. Tetrahedron 2009, 65, 10317-10322. "Conformational Analysis of Bridgehead-substituted Bicyclo[m.m.m]alkanes and Bicyclo[8.8.n]alkanes."

Ntirampebura, D.; Jagadish, B.; Nichol, G. S.; Carducci, M. D.; Dawson, A.; Rajapakshe, A.; Oliver, A. G.; Clegg, W.; Harrington, R. W.; Layne Jr., L.; Margolis, J. I.; Mash, E. A. Crystal Growth & Design 20088, 3257-3270. "Organic Crystal Engineering with Piperazine-2,5-diones. 7. Crystal Packing of Piperazinediones Derived from 2-Amino-7-nitro-4-methoxyindan-2-carboxylic Acid."