Lyle Isaacs

Professor

Education

  • 1987 – 1991 B.S. Chemistry, University of Chicago.
  • 1991 – 1992 M.S. Chemistry, University of California, Los Angeles (UCLA).
  • 1992 – 1995 Ph.D. Organic Chemistry, Swiss Federal Institute of Technology (ETH Zurich) Research with Prof. François Diederich.
  • 1995 – 1998 Postdoc Supramolecular Chemistry, Harvard University, NIH postdoctoral fellow with Prof. George M. Whitesides.

Professional Experience

1998 – present University of Maryland, College Park. Currently Professor of Chemistry.

Research Interests
The Isaacs group is interested in supramolecular and synthetic chemistry with an emphasis on molecular container molecules known as cucurbit[n]urils (CB[n]). Molecular containers – most commonly cyclodextrins – have enormous everyday applications including scent release and odor control (e.g. Febreeze) in consumer products and foodstuffs. We believe that CB[n] containers will supplant the cyclodextrins in a variety of practical and academic applications with all the attendant societal impact.

 Professional Societies

American Chemical Society; American Association for the Advancement of Science.

Major Recognitions and Honors

  • 2003 – 2004 Visiting Professor at the Center for Supramolecular Chemistry, Universität Duisberg-Essen and Central China Normal University
  • 2001 Junior Faculty Award, College of Life Sciences, University of Maryland
  • 2001 Cottrell Scholar, Research Corporation
  • 1996 – 1998 National Institutes of Health Postdoctoral Fellow
  • 1996 Silver Medallion Dissertation Award (ETH Zürich)
  • 1991 – 1992 U.S. Department of Defense Graduate Fellow (Awarded 1991 – 1994)

Significant Professional Service and Activities
Co-organizer of the 2013 International Symposium on Macrocyclic and Supramolecular Chemistry; Co-organizer of the 1st NSF-sponsored International “Workshop on CB[n] Molecular Containers” Local Organizing Committee for “Calixarene 2007″ and “Reaction Mechanisms” conferences; Ad hoc reviewer for NIH study section panels. Director of the NSF-MRSEC Research Experience for Undergraduates program (2006); Editorial Board of the Journal of Systems Chemistry.

Students Mentored
The Isaacs group has mentored high school (1), undergraduate (23), graduate (19), and postdoctoral (7) students including a number (7) from groups under-represented in science. Most have pursued scientific careers in academics, industry, or government.

CUCURBIT[N]URIL MOLECULAR CONTAINERS

Introduction. Molecular containers compounds bind to, sequester, and thereby modify the properties of compounds bound within their interiors. Currently, the most well-known and widely used class of molecular container compounds is the cyclodextrins (Figure 1). Cyclodextrins are cyclic oligosaccharides that come in three useful sizes (α-, β-, and γ-cyclodextrin; volumes = 174, 262, 427 Å3). Cyclodextrins function as molecular containers that bind to hydrophobic substances in aqueous solution. Cyclodextrins are used in a wide range of practical applications including the formulation of hydrophobic drug species in water, as an immobilized component of chiral chromatographic stationary phases, as an additive to mask unpleasant odors in foods, and even as the active ingredient in the household product Febreze where it releases perfume and sequesters malodorant molecules. The use of cyclodextrins for these applications are particularly noteworthy given their modest binding constants (Ka up to 104 M-1), rapid guest release rates (on the order of seconds), and difficulties in performing their selective functionalization. Despite these limitations, cyclodextrins, cyclodextrin derivatives, and value added cyclodextrin products currently constitute a > $1 billion / year industry.

We, and others, have been investigating a relatively new class of molecular container compounds known as cucurbit[n]urils (Figure 1).2 Cucurbit[n]urils (CB[n], n = 5, 6, 7, 8, 10) are macrocyclic methylene bridged glycoluril oligomers comprising n glycoluril rings. These currently known CB[n] compounds have cavity volumes (82, 164, 279, 479, and 870 Å3) that span and exceed those available with the cyclodextrins. In addition to the range of sizes available, CB[n] complexes are typically quite strong (Ka up to 1012 M-1), show very high selectivities based on small structural changes, and some exhibit dissociation kinetics that are remarkably slow (koff ≈ 10-9 s-1).3,4 CB[n]•guest pairs are also very highly responsive to environmental stimuli (e.g. pH, photochemical, electrochemical, or chemical) which makes them extraordinarily well suited for the preparation of molecular machines. In these regards, CB[n]•guest complexes behave more like protein-ligand pairs than typical synthetic host-guest systems.
Known Applications of CB[n] Compounds. Because of their outstanding recognition properties, CB[n] molecular containers have been used in a variety of applications including: drug delivery, waste water purification, fluorophore stabilization, scent release and odor control, transmembrane ion- and molecular transport, and gene transfection.

Isaacs Group Applications of CB[n] Compounds.
 Our research group has expertise in the synthesis of new CB[n] compounds and pursues new applications of the obtained molecular containers. For example, within CB[10] – a container with a 1000 Å3 cavity and no parallel in the cyclodextrins – we have created molecular switches that respond to small organic molecules, entrapped catalysts for oxidation of alkanes, and created fluorescent sensors for certain organic bases. We are using multi-cavity nor-seco-CB[n] to develop methods for “non-covalent dimerization” in water, in the preparation of stimuli responsive polymers, and for chiral recognition of drug molecules. Other applications of interest include affinity column purification, non-covalent immobilization on solid supports, and as a component of enzyme assays.

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