Chemistry and Biochemistry

George Gokel

 

barton1Professor 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 and also serves as the Director of the Center for Nanoscience.

gokelg@umsl.edu
Office:B428
Phone: (314) 516-5321
Fax: (314) 516-5342

Professor Gokel's Research Home Page

Research Interests

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". . These compounds not only function as ion channels in membranes, they enhance the efficacy of FDA-approved antibiotics such as rifampicin, a first line drug used against TB, by up to 16-fold. .

Anion, particularly chloride, permeability is essential for volume, pH, and membrane potential regulation in all cells. We have developed a chloride-selective channel (shown). We are currently studying some very simple tris-arene molecules that have proved to be effective transformation and transfection agents. These non-toxic compounds enhance the transport of DNA across the cellular boundaries of bacteria, yeast, plants, and mammalian cells. Two lab members have founded a company called Genetix Fusion LLC that is developing this technology. 

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 pyrogallol[4]arene 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.  The individual elements that form the nanotube also foster ion transport in natural membranes.

Selected Recent Publications

"Ion transport through bilayer membranes mediated by pyrogallol[4]arenes ," S. Negin, R. Li, O. V. Kulikov, M. M. Daschbach and G. W. Gokel, Inorg. Chim. Acta 2014, (in press).

"Morphologies of branched-chain pyrogallol[4]arenes in the solid state," O. V. Kulikov, S. Negin, N. P. Rath and G. W. Gokel, Supramolecular  Chem. 2014, (in press).

 "Synthetic ion channels: From pores to biological applications," G. W. Gokel and S. Negin, Acc. Chem. Res., 2013, 46, 2024.

"Properties of Long Alkyl-chained Resorcin[4]arenes 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. 2013, 37, 105.

 "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.

"Pyrogallo[4]arenes 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 Pyrogallol[4]arenes", N. Saeedeh; M. M. Daschbach, O. V. Kulikov, N. P. Rath, G. W. Gokel, J. Am. Chem. Soc. 2011, 133, 3234.