Professor Gokel attended Tulane University, New Orleans, LA, B.S. chemistry, 1968, University of Southern California, Los Angeles, CA, Ph.D. chemistry with I. K. Ugi, 1971 and UCLA, where he did a postdoctoral fellowship with D.J. Cram, 1972-1974. He served on the faculty at Penn State, Maryland and Miami prior to heading the Program in Chemical Biology, Washington University School of Medicine, St. Louis. He joined UM-St. Louis as Distinguished Professor in 2006.
Phone: (314) 516-5321
Fax: (314) 516-5342
Professor Gokel's Research Home Page
Synthetic cation and anion channels
During the past decade, our lab has developed and elaborated a class of synthetic ion channels called hydraphiles. We use diaza-18-crown-6 macrocycles as head groups and entry portals for ion conduction. Hydrophobic spacer chains connect the headgroups and impart the appropriate length for the hydraphile to span the bilayer. A third, central macrocycle acts as an "ion relay". This subunit serves the same purpose as the recently discovered "water and ion-filled capsule" identified in the solid state structure of KcsA channel of Streptomyces lividans. A side arm of varying identity extends from the distal crown, providing anchoring and stabilization in the bilayer. These ion channels show antibacterial activity and we are currently developing this important aspect of their chemistry.
Anion, particularly chloride, permeability is essential for volume, pH, and membrane potential regulation in all cells. We have developed a chloride-selective channel in an attempt to model anion transport and explore these cellular requirements. Using known protein chloride channels as a guide, we have synthesized a chloride-selective transporter that is active in phospholipid bilayers. We use a broad range of biophysical methods to characterize the behavior of channels. These include dynamic light scattering, fluorescence techniques, ion selective electrodes, calorimetry, NMR, the Langmuir trough, and Brewster angle microscopy. The cation (left) and anion (right) channels are shown in the figure below.
Molecular Capsules and Nanotubes
It has been known for more than a century that phenols and aldehydes react to form macrocycles. We have been developing the chemistry of amphiphilic nanocapsules and nanotubes for drug delivery. The pyrogallolarene compounds have a unique and nearly unexplored chemistry. We have found that they form ion channels and exhibit very unusual amphiphilic properties. The figure below shows a section of nanotube along with the adjacent tubes interlocked with it.
Selected Recent Publications
"Properties of Long Alkyl-chained Resorcinarenes in Bilayers and on the Langmuir Trough," P. Ogirala, S. Negin, C. Agena, C. Schäfer, T. Geisler, J. Mattay, and G. W. Gokel, New J. Chem. 2012, In press
"Anion Complexation and Transport by Isophthalamide and Dipicolinamide Derivatives: DNA Plasmid Transformation in E. coli," J. L. Atkins, M. B. Patel, M. M. Daschbach, J. W. Meisel, and G. W. Gokel, J. Am. Chem. Soc., 2012, 134, 13546
"Aggregation and Supramolecular Membrane Interactions that Influence Anion Transport in Tryptophan-Containing Synthetic Peptides.," M. M. Daschbach, S. Negin, L. You, M. Walsh and G. W. Gokel, Chem. A Eur. J. 2012, 18, 7608.
"Rapid acyl migration between pyrogallyl 1,2- and 1,3-dipivaloates," Y. Shan, J. Liu, N. P. Rath and G. W. Gokel, Nat. Prod. Commun. 2012, 7, 333.
"Synthetic amphiphilic peptides that self assemble to memberane active anion transporters," G. W. Gokel and M. M. Daschbach, Anion Coord. Chem. 2012, pp. 465-519, (Ed: K. Bowman-James, A. Bianchi and E. Garcia-Espana).
"Synthetic memberane active amphiphiles," G. W. Gokel and S. Negin, Adv. Drug Delivery Rev. 2012, 64, 784.
"Pyrogalloarenes show highly Variable Amphiphilic Behavior at the Air-Water Interface Dependent Upon side Chain Length and Branching", M. M Daschbach, O. V. Kulikov, E. F. Long and G. W. Gokel, Chem. A Eur. J. 2011, 17, 8913
"In vivo cell death mediated by synthetic ion channels", B. A Smith, M. M.; Daschbach, S. T Gammon, S. Xiao, S. E Chapman, C. Hudson, M. Suckow, D. Piwnica-Worms, G. W Gokel and W. M. Leevy, Chem. Commun. 2011, 79779.
"Pore formation in phospholipid bilayers by amphiphilic cavitands", I. Elidrisi, S. Negin, P. V. Bhatt, T. Govender, H. G. Kruger, G. W. Gokel and G. E. M. Maguire, Org. & Biomolec. Chem. 2011, 9, 4498
"UV resonance Raman study of cation-p interactions in an indole crown ether", D. E. Schlamadinger, M. M. Daschbach, G. W. Gokel and J. E. Kim, J. Raman Spectrosc. 2011, 42, 633.
"In Vivo Optical Imaging of Acute Cell Death Using a Near-Infrared Fluorescent Zinc-Dipicolylamine Probe", B. A. Smith, S. T. Gammon, S. Xiao, W. Wang, S. Chapman, R. McDermott, M. A.; Suckow, J. R. Johnson, D. Piwnica-Worms, G. W Gokel,. B. D. Smith and W. M. Leevy, Molecular Pharmaceutics, 2011, 8, 583.
"Pore Formation in Phospholipid Bilayers by Branched-Chain Pyrogallolarenes", N. Saeedeh; M. M. Daschbach, O. V. Kulikov, N. P. Rath, G. W. Gokel, J. Am. Chem. Soc. 2011, 133, 3234.
"Dianilides of dipicolinic acid function as synthetic chloride channels", C. R. Yamnitz, S. Negin, I. A. Carasel, R. E. K. Winter and G. W. Gokel, Chem. Commun. 2010, 2838.
"Alkali metal and ammonium cation-arene interactions with tetraphenylborate anion", R. Li, R. E. K. Winter, J. Kramer and G. W. Gokel, Supramolec. Chem. 2010, 221-2, 73
"Synthetic, biologically active amphiphilic peptides" C. R. Yamnitz and G. W. Gokel, Peptibiotics. 2009, 657.