Richard S. Glass

Honors

• Fellow of the American Association for the Advancement of Science, 1984
• Faculty of Science Career Teaching Award, 1990

Education and Appointments

• B.A. 1963, New York University
  
• Ph.D. 1967, Harvard University
  

Research Interests

• Organic
  
• Bioorganic and Natural Products
  
• Synthesis and Synthetic Methodology
  
• Catalysis and Reaction Dynamics
  
• Computational
  
• Organometallic and Coordination Chemistry
  

Research Summary

Electron transfer is of fundamental importance in such areas as biological redox reactions, organometals, superconductors, and photoconductors. We are interested in the factors that control electron transfer. One such factor is neighboring group participation. This is illustrated by electron transfer from dialkyl sulfides. Typical dialkyl sulfides oxidize electrochemically in acetonitrile with a peak potential in the range of 1.2-1.7 V (vs Ag/AgNO₃ in CH₃CN) but 1,5-dithiocane 1 oxidizes with a peak potential of 0.34 V because of neighboring group participation by the other sulfur atom to give 2. We are exploring participation in the oxidation by neighboring groups using not only nonbonding electrons but π-electrons as well.

Another factor is π-delocalization which has been addressed in the novel ring system 3 found in the naturally occurring thiarubrines. These compounds are typically orange to red in color which has been viewed as perplexing since 1,3-dienes and sulfides are typically colorless. An explanation of this color and evidence in support of this explanation has been obtained and the redox chemistry of this system, in which an unusually stable planar sulfur radical cation is formed from the nonplanar heterocycle, has been uncovered. The redox chemistry addresses the general question of coupling redox chemistry with geometry changes.

The active site of [NiFe]H₂ase, a bacterial enzyme that catalyzes the oxidation of dihydrogen to protons is shown in 4. It is unusual in that the iron bears the carbon ligands CO and CN. The source of these ligands is of interest because both CO and CN^- are highly toxic. Furthermore, these active sites involve new organometallic chemistry in biology (in addition to the well-known organometallic chemistry involving Vitamin B-12). We have found that the biological precursor of these ligands is carbamoyl phosphate, H₂NC(O)OPO₃⁼, which is a previously well-known biological intermediate. We have elucidated the unprecedented pathway by which carbamoyl phosphate is converted to the CN ligand.

Selenium is an essential mineral and is required in small amounts in the diet of humans. However, larger amounts are toxic. A number of mammalian and bacterial proteins containing selenium, have been found and typically the selenium occurs as selenocysteine and, if the protein is an enzyme, the selenocysteine is at the active site. Selenocysteine has been found to be the 21^st amino acid incorporated contranslationally. That is, there is a codon for it (UGA), a t-RNA that is charged with it and a special elongation factor for its incorporation. We have shown that the biosynthesis of selenocysteine involves the intermediacy of the novel monoselenophosphate which is the biological selenium donor formed from ingested selenite. High doses of selenite are toxic but, surprisingly, arsenite ameliorates its toxicity. We have shown that in vitro studies with the biological reductant GSH with selenite and arsenite gave rise to (GS)₂AsSe^- which was chemically characterized and subsequently identified in vivo. Identification of biological Se-containing species by Se-77 NMR spectroscopy is a powerful methodology which we are developing.

In duplex DNA the bases are π-stacked. This has led to the controversial suggestion that DNA might be a molecular wire. To test the conductivity through the π-stack we have synthesized redox-active adenine analogue 5 which incorporates a ferrocene ring. Electron-transfer between such a ferrocene ring and its ferrocenium analogue through the stack will be measured.

Selected Publications

• Glass, R. S. "Sulfur Radical Cations," Top Curr. Chem., 1999, 205, 1.

• Block, E.; Birringer, M.; DeOrazio, R.; Fabian, J.; Glass, R. S.; Guo, C.; He, C.; Lorance, E.; Qian, Q.; Schroeder, T.B.; Shan, Z.; Thiruvazhi, M.; Wilson, G.S.; Zhang, X. "Synthesis, Properties, Oxidation, and Electrochemistry of 1,2-Dichalcogenins," J. Am. Chem. Soc., 2000, 122, 5052.

• Glass, R. S.; Gruhn, N.E.; Lichtenberger, D.L.; Lorance, E.; Pollard, J.R.; Birringer, M.; Block, E.; DeOrazio, R.; He, C.; Shan, Z.; Zhang, X. "Gas-Phase, Photoelectron Spectroscopic and Theoretical Studies of 1,2-Dichalcogenins: Ionization Energies, Orbital Assignments and an Explanation of Their Color," J. Am. Chem. Soc., 2000, 122, 5065.

• Glass, R.S.; Block, E.; Lorance, E.; Zakai, U.I.; Gruhn, N.E.; Jin, J.; Zhang, S.-Z. “The Si-Si Effect on Ionization of β-Disilanyl Sulfides and Selenides,” J. Am. Chem. Soc., 2006, 128, 12685-12692.

• Block, E.; Dikarev, E.V.; Glass, R.S.; Jin, J.; Li, B.; Li, X.; Zhang, S.-Z. “Synthesis, Structure and Chemistry of New Mixed Group 14 and 16 Heterocycles: Nucleophile–induced Ring Contraction of Mesocyclic Dications,” J. Am. Chem. Soc., 2006, 128,14949-14961.

• Paschos, A.; Glass, R. S.; Böck A. "Carbamoyl Phosphate Requirement for Synthesis of the Active Center for [NiFe]-Hydrogenases," FEBS Lett. 2001, 488, 9.

• Reissmann, S.; Hochleitner, E.; Wang, H.; Paschos, A.; Lottspeich, F.; Glass, R. S.; Böck A. "Taming of a Poison: Biosynthesis of the NiFe Hydrogenase Cyanide Ligands," Science, 2003, 299,1067.

• Glass, R.S.; Gruhn, N.E.; Lorance, E.; Singh, M.S.; Stessman, N.YT.; Zakai, U. “Synthesis, Gas-Phase Photoelectron Spectroscopic and Theoretical Studies of Stannylated Dinuclear Iron Dithiolates,” Inorg. Chem., 2005, 44, 5728-5737.

• Felton, G.A.; Glass, R.S.; Lichtenberger, D.L.; Evans, D.H. “Iron-Only Hydrogenase Mimics. Thermodynamic Aspects of the Use of Electrochemistry to Evaluate Catalytic Efficiency for Hydrogen Generation,” Inorg. Chem., 2006, 45, 9181-9184.

• Gailer, J.; George, G.N.; Pickering, I.J.; Prince, R.C.; Ringwald, S.C.; Pemberton, J.E.; Glass, R. S.; Younis, H.S.; DeYoung, D.W.; Aposhian, H.V. "A Metabolic Link Between Arsenite and Selenite: The Seleno bis (S-glutathionyl) Arsinium Ion," J. Am. Chem. Soc. 2000, 122, 4637.

• Block, E.; Glass, R. S.; Jacobsen, N. E.; Johnson, S.; Kahakachchi, C.; Kamiński, R.; Skowrońska, A.; Boakye, H. T.; Tyson, J. F.; Uden, P. C. “Identification and Synthesis of a Novel Selenium-Sulfur Amino Acid Found in Selenized Yeast: Rapid Indirect Detection NMR Methods for Characterizing Low-Level Organoselenium Compounds in Complex Matrices,” J. Agric. Food Chem., 2004, 52, 3761-3771.

• Xu, X.-M.; Carlson, B.A.; Mix, H.; Zhang, Y.; Saira, K. ; Glass, R.S.; Berry, M.J.; Gladyshev, V.N.; Hatfield, D.L. “Biosynthesis of Selenocysteine on its tRNA in Eukaryotes,” PLoS Biol., 2007, 5, 96-105.

• Glass, R. S.; Stessman, N.YT. "Synthesis of a Redox Active Analogue of Adenine," Tetrahedron Lett., 2000, 41, 9581.