Thomas W. Bell

Professor

Organic and Bioorganic Chemistry

B.S. (1974), California Institute of Technology; Ph.D. (1980), University College, University of London (F. Sondheimer); NIH Postdoctoral Fellow (1980-1982), Cornell University (J. Meinwald); Fellow of the American Association for the Advancement of Science (1995-present)

E-mail: twb [at] unr.edu
Phone: 775-784-1842
FAX: 775-784-6804
Office: CB 334

Thomas W. Bell

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Research Interests

Our research projects draw upon concepts and methods in synthetic and physical organic chemistry, coordination chemistry, spectroscopy and structural chemistry. The unifying theme is molecular devices: molecules that are tailored to bind and sense other molecules, to act as switches or motors, or to act as drugs interfering with biochemical processes.

We have made artificial receptors by fusing rings, particularly pyridine, that can bind guest molecules by forming hydrogen bonds. These “hexagonal lattice receptors” can be tailored to bind analytes of medical interest and report their concentrations by an optical response. Two examples are a chromogenic reagent for measuring blood creatinine, which is an indicator of kidney function, and a fluorescent sensor for bicarbonate ion.

Our third research area is aimed at novel antiviral drugs. We have synthesized a series of compounds, called CADA analogs, that are active against several viruses, including HIV. Our approach to new drugs for AIDS is to synthesize and test compounds designed on the basis of proposed mechanisms of action.

A Hexagonal Lattice Receptor for Guanidines
A Hexagonal Lattice Receptor for Guanidines

A Chemionic Switch
A Chemionic Switch

X-Ray Crystal Structure of CADA (Free Base Form)
CADA

Selected Publications

“Design and cellular kinetics of dansyl-labeled CADA derivatives with anti-HIV and CD4 receptor down-modulating activity,” Vermeire, K.; Lisco, A.; Grivel, J.-C.; Scarbrough, E.; Dey, K.; Duffy, N.; Margolis, L.; Bell, T.W.; Schols, D. Biochemical Pharmacology 2007, 74, 566-578.

“A D2 symmetric tetraamide macrocycle based on 1,10,4,40-tetrahydro[3,30(2H,20H)-spirobiquinoline]-2,20-dione: Synthesis and selectivity for lithium oer sodium and alkaline earth ions,” Choi, H.-J.; Park, Y.S.; Kim, M.G.; Park, Y.J.; Yoon, N.S.; Bell, T.W. Tetrahedron 2006, 8696-8701.

“CD4-targeted HIV inhibitors,” Vermeire, K.; Schols, D.; Bell, T.W. Curr. Med. Chem. 2006, 13, 731-743.

“Synthesis and structure-activity relationship studies of CD4 down-modulating cyclotriazadisulfonamide (CADA) analogs,” Bell, T.W.; Anugu, S.; Bailey, P.; Catalano, V.J.; Dey, K.; Drew, M.G.B.; Duffy, N.H.; Jin, Q.; Samala, M.F.; Sodoma, A.; Welch, W.H.; Schols, D.; Vermeire, K. J. Med. Chem. 2006, 49, 1291-1312.

“Syntheses, structures, and photoisomerization of (E)- and (Z)-2-tert-butyl-9-(2,2,2)-triphenyethylidenefluorene,” Barr, J.W.; Bell, T.W.; Catalano, V.J.; Cline, J.I.; Phillips, D.J.; Procupez, R. J. Phys. Chem. 2005, A 109, 11650-11654.

“CD4 down-modulating compounds with potent anti-HIV activity,” Vermeire, K.; Schols, D.; Bell, T.W. Curr. Pharmaceut. Design 2004, 10, 1795-1803.

“Torands,” Bell, T.W., in Encyclopedia of Supramolecular Chemistry, J. Atwood and J. Steed, Eds.; M. Dekker: New York, 2004, pp. 1508-1515.

“Supramolecular optical chemosensors for organic analytes,” Bell, T.W.; Hext, N.M. Chem. Soc. Rev. 2004, 33, 589-598.

“CADA, a novel CD4-targeted HIV inhibitor, is synergistic with various anti-HIV drugs in vitro,” Vermeire, K.; Princen, K.; Hatse, S.; De Clerq, E.; Dey, K.; Bell, T.W.; Schols, D. AIDS 2004, 18, 2115-2125.

“Syntheses, conformations, and basicities of bicyclic triamines,” Bell, T.W.; Choi, H.-J.; Harte, W.; Drew, M.G.B. J. Am. Chem. Soc. 2003, 125, 12196-12210.

“The anti-HIV potency of CADA analogues is directly correlated with their ability to down-modulate the CD4 receptor,” Vermeire, K.; Bell, T.W.; Choi, H.-J.; Jin, Q.; Samala, M.F.; Sodoma, A.; de Clercq, E.; Schols, D. Mol. Pharmacol. 2003, 63, 203-210.

“Bond angle vs. torsional deformation in an overcrowded alkene: 9-(2,2,2)-Triphenylethylidenefluorene,” Bell, T.W.; Catalano, V.J.; Drew, M.G.B.; Phillips, D.J. Chem. Eur. J. 2002, 8, 5001-5006.

“CADA inhibits human immunodeficiency virus and human herpesvirus type 7 replication by down-modulation of the cellular CD4 receptor,” Vermeire, K.; Zhang, Y.; Samala, M.; Dey, K.; Choi, H.; Ahn, Y.; Snoeck, R.; Andrei, G.; Princen, K.; de Clercq, E.; Bell, T.W.; Schols, D. Virology 2002, 302, 342-353.

“Reversible photoinsertion of ferrocene into a hydrophobic semiconductor surface: A chemionic switch,” Muraoka, M.; Gillett, S.L.; Bell, T.W. Angew. Chem. Int. Ed. Engl. 2002, 41, 3653-3656.

“Artificial receptors for chemosensors,” Bell, T.W.; Hext, N.M., in Optical Biosensors: Present and Past, F.S. Ligler and C. Rowe-Taitt, Eds.; Elsevier Science: Amsterdam, The Netherlands, 2002, Ch. 11, pp. 331-368.

“Circular dichroism readout of sugar recognition in the cleft of a fused-pyridine receptor,” Tamaru, S.; Shinkai, S.; Khasanov, A.B.; Bell, T.W. Proc. Natl. Acad. Sci. USA 2002, 99, 4972-4976.

“A hydrogen-bonding receptor that binds cationic monosaccharides with high affinity in methanol,” Tamaru, S.; Yamamoto, M.; Shinkai, S.; Khasanov, A.B.; Bell, T.W. Chem. Eur. J. 2001, 7, 5270-5276.

“Synthesis of 1,2,3,4,5,6,7,8-octahydroacridine via condensation of cyclohexanone with formaldehyde,” Pilato, M.L.; Catalano, V.J.; Bell, T.W. J. Org. Chem. 2001, 66, 1525-1527.

“A small-molecule guanidinium receptor: The arginine cork,” Bell, T.W.; Khasanov, A.B.; Drew, M.G.B.; Filikov, A.; James, T.L. Angew. Chem., Int. Ed. 1999, 38, 2543-2547.