Steven C. Zimmerman

Research

Research in our group focuses on the understanding, development, and application of molecular recognition processes. In particular, we design, synthesize, and study organic compounds that can: (1) act as synthetic antibodies to bind any target molecule, as well as signaling its presence, (2) bind to predefined sequences of DNA and RNA with very high affinity, (3) self-assemble into large, nanoscopic structures, and (4) act as supramolecular polymers. The applications of our work are in the areas of drug delivery, chemical sensors and medical diagnostics, anti-gene therapy, and novel materials.

Synthetic Antibodies by Molecular Imprinting: Nature is especially adept at producing molecules that can recognize other molecules. For example, the exquisitely selective molecular recognition shown by antibodies has long inspired chemists, who for decades have tried to synthesize analogous molecular receptors. We are working to create molecular receptors using a fully general approach in which one molecule imprints its structure within another, much like the way in which any object can cast its own shape in plaster of Paris. The overall process involves a molecular template forming an imprint of itself in a highly branched polymer called a dendrimer.

Molecular Recognition of DNA and RNA: My research group also has an interest in designing, synthesizing, and studying molecules that recognize specific sequences or structures of nucleic acids. A general DNA or RNA recognition scheme would provide a powerful strategy for gene regulation and, for example, allow the development of "genetic medicines". We are developing novel nucleobases and other small molecules that can complex certain DNA and RNA structures efficiently and selectively.

Nanoscopic Organic Structures by Self-Assembly: A largely unexplored area of organic chemistry involves molecules with "nanoscale" dimensions (1-10 nm). My group is attempting to synthesize nanoscale objects, such as hollow spheres and hollow nanotubes. A particularly powerful approach involves compounds that spontaneously assemble into larger structures. In the process we are learning the rules that guide this type of non-covalent organic synthesis.

Supramolecular Polymer Chemistry: What kinds of polymers can be made noncovalently? What are their properties? How can one modify existing polymers noncovalently? We are developing some simple recognition modules that allow these questions to be answered. One goal of this research is to modify cheap, commercially available polymers in a way that gives them more advanced materials properties.

Publications

Jonathan F. Arambula, Sreenivasa Rao Ramisetty, Anne M. Baranger, and Steven C. Zimmerman, "A Simple Ligand that Selectively Targets CUG Trinucleotide Repeats and Inhibits MBNL Protein Binding," Proc. Natl. Acad. Sci., accepted.

Ewelina Burakowska, Steven C. Zimmerman, and Rainer Haag, "Photoresponsive Cross-linked Hyperbranched Polyglycerols as Smart Nanocarriers for Guest Binding and Controlled Release," Small 2009, DOI: 10.1002/smll.200900465.

Jordan R. Quinn, Steven C. Zimmerman, Janet E. Del Bene, and Isaiah Shavitt, "Prebiotic Selection of the AU Base-Pair? A Physical Organic Approach to Understanding AT Base-Pair Stability Indicates Special Stability," in Chemical Evolution II: From Origins of Life to Modern Society", Lori Zaikowski and Jon M Friedrich, Editors, ACS Books, 2009.

Ewelina Burakowska, Jordan R. Quinn, Steven C. Zimmerman, Rainer Haag, "Cross-Linked Hyperbranched Polyglycerols as Hosts for Selective Binding of Guest Molecules," J. Am. Chem. Soc., 2009, 131, 10574-10580. (http://dx.doi.org/10.1021/ja902597h)

Andrew T. Zill and Steven C. Zimmerman, "A Route to Water-Soluble Molecularly Templated Nanoparticles Using Click Chemistry and Functional Polyglycerol Hyperbranched Polymers," Isr. J. Chem. 2009, 49, 71-78. (Isr. J. Chem. Link)

Eric M. Todd and Steven C. Zimmerman, "Modeling the Equilibria of Complex Supramolecular System," J. Chem. Ed. 2009, 86, 638-643. (J. Chem. Ed. Link)

Akihito Hashidzume and Steven C. Zimmerman, "Switching the Selectivity of a Polyglycerol Dendrimer Monomolecularly Imprinted with D-(—)-Fructose," Tetrahedron Lett. 2009, 50, 2204-2207.

Richie E. Kohman and Steven C. Zimmerman, "Degradable Dendrimers Divergently Synthesized via Click Chemistry," Chem. Commun. 2009, 794-796. (Chem. Commun. Link)

Hugo C. Ong, Jonathan F. Arambula, Sreenivasa R. Ramisetty, Anne M. Baranger, and Steven C. Zimmerman, "Molecular Recognition of a Thymine Bulge by a High Affinity, Deazaguanine-based (D-A-D) Hydrogen Bonding Ligand," Chem. Commun. 2009, 668-670. (Chem. Commun. Link)

Darrell W. Kuykendall, Cyrus A. Anderson, and Steven C. Zimmerman, "The Hydrogen Bonded Heterocomplex DeUG•DAN. Structure and Stability and a Scalable Synthesis of DeUG with Clickable Functionality," Org. Lett. 2009, 11, 61-64. (Org. Lett. Link)

Amy M. Balija, Richie E. Kohman, "Substituted 1,3,5-Triazaadamantanes: Biocompatible and Degradable Building Blocks," Angew. Chem. Int. Ed. 2008, 47, 8072-8074. (Angew. Chem. Int. Ed. Link)

Eric M. Todd and Steven C. Zimmerman, "Bis-Ureidodeazapterin (Bis-DeAP) as a General Route to Supramolecular Star Polymers," Tetrahedron (Symposium in Print) 2008, 64, 8558-8570.

Stephanie L. Elmer, Sonny Man and Steven C. Zimmerman, "Synthesis of Polyglycerol, Porphyrin-Cored Dendrimers Using Click Chemistry," Eur. J. Org. Chem. 2008, 3845-3851. (Eur. J. Org. Chem. Link)

Eric M. Todd and Steven C. Zimmerman, " Supramolecular Star Polymers. Increased Molecular Weight with Decreased Polydispersity Through Self-Assembly," J. Am. Chem. Soc. 2007, 129, 14534-14535. (J. Am. Chem. Soc. Link)

Steven C. Zimmerman, Jordan R. Quinn, Ewelina Burakowska, and Rainer Haag, "Cross-linked Glycerol Dendrimers and Hyperbranched Polymers as Ionophoric, Organic Nanoparticles Soluble in Water and Organic Solvents," Angew. Chem. Int. Ed. 2007, 46, 8164-8167. (Angew. Chem. Int. Ed. Link)

Stephanie L. Elmer, N. Gabriel Lemcoff, "Exploring the Reversibility of the Ring-Closing Metathesis Mediated Cross-linking of Dendrimers," Macromolecules 2007, 40, 8114-8118. (Macromolecules Link)

Darrell Kuykendall and Steven C. Zimmerman, "A Very Versatile Nanocapsule," Nature Nanotechnol. 2007, 2, 201-202.

Taiho Park, Steven C. Zimmerman, Hugo C. Ong, Eric M. Todd, Darrell W. Kuykendall, Kwansima Quansah, "Supramolecular polymers formed by intermolecular interaction of hydrogen bonding," PMSE Preprints 2007, 96, 138-139.

Jordan R. Quinn, Steven C. Zimmerman, Janet E. Del Bene, and Isaiah Shavitt , "Does the A•T or G•C Base-Pair Possess Enhanced Stability? Quantifying the Effects of CH•••O Interactions and Secondary Interactions on Base-Pair Stability Using a Phenomenological Analysis and Ab Initio Calculations", J. Am. Chem. Soc. 2007, 128, 934 - 941. (J. Am. Chem. Soc. Link)

Awards

• Fellow, American Chemical Society
• Fellow, American Association for the Advancement of Science
• Arthur C. Cope Scholar Award, American Chemical Society
• Buck-Whitney Award, Eastern New York Section of American Chemical Society
• Presidential Young Investigator Award, National Science Foundation
• Alfred P. Sloan Fellowship
• Camille and Henry Dreyfus Teacher-Scholar Award
• Cyanamid Academic Award
• Eli Lilly Grantee
• American Cancer Society Junior Faculty Award
• School of Chemical Sciences Teaching Awards (3 total)

Highlights

The Zimmerman Group has been highlighted in C&E News for their work on targetting RNA. Read the C&E News article here.

Dr. Zimmerman and Dr. Anne Baranger have designed a small molecule that blocks an aberrant pathway associated with myotonic dystrophy type 1, the most common form of muscular dystrophy. Their research has been highlighted by the UIUC News Bureau, Science Daily, e!Science News, United Press International, and many more.

Work in the Zimmerman group has featured in numerous magazines and newspapers. Examples of these featured items include:

• Our work on imprinted dendrimers has been published in 2002 Nature magazine and was featured in Nature's News and Views, Nature Biotechnology, Science News, C&EN, and in the news periodicals such as Technology Review and The News Gazette, to name a few.
• Our earliest self-assembling dendrimer appeared on the cover of Science magazine (February 1996). This work was also featured in November 1, 1999 and June 3, 1996 C&EN articles about dendrimers. A picture of one of our dendrimers was on the cover of June 3, 1996 issue, as well.