Keith J. Stine, Chair
Undergraduate Program Advising
Undergraduate Scholarships and Awards
Research for Undergraduates
Graduate Program Overview
Application to Graduate Program
Graduate Program Contact Information
Faculty Contact Information
Graduate Student Seminars
Robert W. Murray Lecture
Distinguished Alumni Lecture
Visiting Speaker Seminars
|Professor Gokel attended Tulane and USC for BS and PhD degrees, respectively, and UCLA, where he was a postdoc with D.J. Cram. He was a faculty member at Penn State, Maryland, Miami and Washington University prior to joining UMSL as Distinguished Professor in 2006.||
Research InterestsSynthetic cation and anion channels
During the past decade, our lab has developed and elaborated classes of structurally different synthetic ion transporters. 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 important FDA-approved antibiotics by up to 16-fold
Two types of anion transporters are illustrated in the adjacent figure. The left panel shows a hydraphile cation transporter embedded in a phospholipid membrane. The right panel shows a cutaway of a heptapeptide chloride anion transporter that functions as a dimer. Only one of the dimeric pair is shown.
Mechanisms of Channel Formation and Biological Activity.The compounds that have been designed, synthesized, and studied in the Gokel Lab are amphiphiles. These are compounds that have an affinity both for aqueous and for hydrocarbon environments. Lariat ethers, hydraphiles, and bis-tryptophans all fit this category and all of them form ion-conducting channels. Details of these and other synthetic ion channels are described in an article that may be found in Wikipedia. https://en.wikipedia.org/wiki/Synthetic_ion_channels.
These synthetic ion channels enter membranes and conduct ions. They also increase membrane permeability in bacterial membranes and disrupt the function of efflux pumps. This allows them to function as antimicrobial agents and to enhance the potency of other antibiotics. Certain of the hydraphiles and bis-tryptophans are especially active (low nanomolar activity) against Gram negative, Gram positive, and even mycobacteria. We are currently exploring activity against hospital acquired pneumonia, a disease that has a high mortality rate in the US.
Selected Recent Publications
″Crown ethers having side arms: a diverse and versatile supramolecular chemistry,″ M. R. Gokel, M. McKeever, J. W. Meisel, S. Negin, M. H. Patel, S. Yin and G. W. Gokel, J. Coord. Chem. 2021, Ahead of Print
“Supramolecular pore formation as an antimicrobial strategy,“ H. Gill, M. R. Gokel, M. McKeever, S. Negin, M. H. Patel, S. Yin, and G. W. Gokel, Coord. Chem. Rev. 2020, 412, 213264
“Composition and Methods for Synthetic Ampiphile-induced Changes in Plant Root Morphology,“ G. W. Gokel and M. B. Patel, US Patent No. 10,548,318, issued Feb 4, 2020.
″Synthetic ionophores as non-resistant antibiotic adjuvants,″ M. H. Patel, E. Garrad, J. W. Meisel, S. Negin, M. R. Gokel and G. W. Gokel, RSC Advances, 2019, 9, 2217.
″Molecules that inhibit efflux pumps in multi-drug resistant bacteria and uses thereof,″ G. W. Gokel, M. R. Gokel, S. Negin and M. B. Patel, U.S. Pat. No. 10,463,044. issued Nov. 5, 2019.
″Selective alteration of the root morphology of Arabidopsis thaliana by synthetic anion transporters (SATs)″, M. B. Patel, E. C. Garrad, S. Korb, S. Negin, M. R. Gokel, S. Sedinkin, S. Yin and G. W. Gokel, Chem. Sci. Int. J., 2019, 27, 1.
“Bis-Amino acid based compound and use thereof,” G. W. Gokel, j. W. Meisel and M. B. Patel, United States published Patent Application, US 2019/0201379 A1, issued July 4, 2019.
″Supramolecular cationtransporters alter root morphology in the Arabidopsis thaliana plant, ″ M. B. Patel, S. Negin, A. Stavri and G. W. Gokel, Inorg. Chim. Acta, 2017 468, 183.
″Condensation of plasmid DNA by benzyl hydraphiles and lariat ethers: dependence on pH and chain length,″ J. W. Meisel, M. H. Patel and G. W. Gokel Supramolecular Chem. 2017, A29, 167.
″Comprehensive Supramolecular Chemistry II″, Ed: J. L. Atwood, G. W. Gokel and l. J. Barbour, Elsevier, Amsterdam, 2nd edn. 2017, 4568pp
″The varied supramolecular chemistry of pyrogallolarenes,″ S. Negin and G. W. Gokel, Organic Nanoreactors, 2016, 235.
″Antibiotic Potency against E. coli Is Enhanced by Channel-Forming Alkyl Lariat Ethers,″ S. Negin, M. H. Patel, M. R. Gokel, J. W. Meisel and G. W. Gokel, ChemBioChem, 2016, 17, 2153.
″Reversal of Tetracycline Resistance in Escherichia coli by Noncytotoxic bis(Tryptophan)s,″ J. W. Meisel, M. H. Patel, E. Garrad, R. A. Stanton and G. W. Gokel, J. Am. Chem. Soc. 2016, 38, 10571.
″A Simplified Direct Lipid Mixing Lipoplex Preparation: Comparison of Liposomal-, Dimethylsulfoxide-, and Ethanol-Based Methods,″ J. W. Meisel and G. W. Gokel, Sci. Reports, 2016, 6, 27662.
″Synthetic Receptors for Alkali Metal Cations,″ G. W. Gokel and J. W. Meisel. Monographs in Supramolecular Chem. 2015, 14, 86.