Chemistry at Illinois University of Illinois at Urbana-Champaign

Steven C. Zimmerman

Roger Adams Professor of Chemistry
Professor, Materials Research Lab

 

Professor Steven C. Zimmerman attended the University of Wisconsin as an undergraduate. After obtaining his B.S. in 1979, he moved to New York City where in 1983 he obtained his Ph.D. from Columbia University. He held an NSF-NATO Postdoctoral Fellowship at the University of Cambridge in England and joined the Illinois faculty in 1985. Professor Zimmerman's research interests are in bioorganic, synthetic organic, and physical organic chemistry.

Research

Research in the Zimmerman group focuses on the application of “smart molecules” and “smart polymers” to problems that lie at the interface of chemistry and biology or chemistry and materials. Thus, these efforts generally involve the design, synthesis, and study of novel small molecules and polymers and work in the subfields of biomedicine, chemical biology, or materials chemistry. More specifically, our research in molecular design is to develop compounds that can: (1) serve as DNA or RNA-targeted therapeutic agents, (2) function as stable and biocompatible imaging agents, (3) act as encapsulants to carry active agents and deliver them in a stimuli-responsive manner, and (4) deliver drugs or cells specifically to diseased tissue. Students in our group can learn a range of skills from organic synthesis and chemical biology to computer modeling and advanced materials development and characterization.

DNA or RNA-Targeted Therapeutic Agents: There are a number of diseases that originate in aberrant DNA or RNA, in particular the triplet-repeat diseases (TREDs) which involve expansion of sequences within our genomes. One current effort is to develop small molecules that target CTG repeats in DNA or their CUG repeat RNA transcripts, both of which cause myotonic dystrophy type 1, the most common form of muscular dystrophy. These smart molecules are designed to enter the cell nucleus, bind the target DNA or RNA specifically and operate to reverse the deleterious effects of the expanded repeats.


Bioimaging Agents: There is a critical need for fluorescent probes and MRI contrast agents that are nontoxic, long-lived, and extremely bright (fluorophores) or that provide exceptional contrast (MRI). Another challenge is developing "monovalent” agents, probes that can be linked to a single targeting agent (e.g., antibody, ligand, oligonucleotide, etc.). We are developing small molecules, polymers, and nanoparticles that fulfill these criteria and applying them in both in vitro and in vivo settings.


Degradable Polymers and Novel Delivery Systems: Polymeric materials that can degrade rapidly and completely in response to specific stimuli such as light, heat, pressure, and pH are being developed as novel encapsulating materials. The goal is to create thin, spherical shells that hold and protect their contents indefinitely, yet instantly release their cargo upon the appropriate stimulation.


Drug and Cell Delivery Systems: This effort focuses on the targeted delivery of stem cells or drugs to diseased tissues. The approach we are taking uses smart self-assembling materials, for example polymers that can coat the surfaces of stem cells and display peptides that target inflammation, or self-assembled particles that can be tracked in vivo as they travel to the target site and then release their cargo of drugs.

Publications

  1. Clickable Polyglycerol Hyperbranched Polymers and Their Application to Acid Labile Nanocarriers and Gold Nanoparticles
    Andrew Zill, Alexandra Rutz, Richie E. Kohman, Alaaldin Alkilany, Catherine J. Murphy, Hyunjoon Kong, Steven C. Zimmerman, Chem. Commun. 2011, 47, 1279-1281.
  2. Selective Inhibition of MBNL1-CCUG Interaction by Small Molecules for Myotonic Dystrophy Type 2 (DM2)
    Chun-Ho Wong, Sreenivasa Rao Ramisetty, Yuan Fu, Anne M. Baranger, Steven C. Zimmerman, Nuc. Acids. Res. 2011, 39, 8881-8890.
  3. Monovalent and Clickable, Uncharged Water-Soluble Perylenediimide-Cored Dendrimers for Target-Specific, Fluorescent Biolabeling
    Si Kyung Yang, Xinghua Shi, Seongjin Park, Sultan Doganay, Taekjip Ha, and Steven C. Zimmerman, J. Am. Chem. Soc. 2011, 131, 9964–9967.
  4. Synthesis of a Redox-Responsive Quadruple Hydrogen-Bonding Unit for Applications in Supramolecular Chemistry
    Ying Li, Taiho Park, J. Kwansima Quansah, and Steven C. Zimmerman, J. Am. Chem. Soc. 2011, 133, 17118–17121.
  5. Top-Down Synthesis of Versatile Polyaspartamide Linkers for Single-Step Protein Conjugation to Materials
    Chaenyung Cha, Jae Hyun Jeong, Xin Tang, Andrew T. Zill, Y. S. Prakash, Steven C. Zimmerman, Taher A. Saif, Hyun-Joon Kong, Bioconjug. Chem. 2011, 22, 2377-2382.
  6. Synthesis and Properties of Fluorescent Dyes Conjugated to Hyperbranched Polyglycerols
    Andrew T. Zill, Kai Licha, Rainer Haag, Steven C. Zimmerman, New J. Chem. 2012, 36, 419-427.
  7. Calix[8]arene Functionalized Polyglycerol Nanogels for Encapsulation and Stabilization of Fluorescent Dyes
    Dirk Steinhilber, Florian Paulus, Andrew T. Zill, Steven C. Zimmerman and Rainer Haag, MRS Proceedings, 2012, 1403, 185-193.
  8. Polyglycerol-Dendronized Perylenediimides as Stable, Water-soluble Fluorophores
    Si Kyung Yang and Steven C. Zimmerman, Adv. Funct. Mater., 2012, 22, 3023-3028.
  9. Azobenzene Dye Coupled Quadruple Hydrogen Bonding Modules as Colorimetric Indicators for Supramolecular Interactions
    Yagang Zhang and Steven C. Zimmerman, Beilstein J. Org. Chem., 2012, 8, 486–495.
  10. Investigating the Binding Mode of an Inhibitor of the MBNL1-RNA Complex in Myotonic Dystrophy Type 1 (DM1) Leads to the Unexpected Discovery of a DNA-Selective Binder
    Chun-Ho Wong, Stacie L. Richardson, Yen-Jun Ho, Alex M. H. Lucas, Tiziano Tuccinardi, Anne M. Baranger, and Steven C. Zimmerman, ChemBioChem 2012, 13, 2505-2509.
  11. Orthogonality in Organic, Polymer, and Supramolecular Chemistry: from Merrifield to Click Chemistry
    Chun-Ho Wong and Steven C. Zimmerman, Chem. Commun. 2013, 49, 1679-1695. DOI:. Cover Article.
  12. A Novel CUGexp·MBNL1 Inhibitor with Therapeutic Potential for Myotonic Dystrophy Type 1
    Amin Haghighat Jahromi, Lien Nguyen, Yuan Fu, Kali Miller, Anne M. Baranger, and Steven C.
    Zimmerman, ACS Chem. Biol. 2013, 8, 1037-1043. Cover Article.
  13. High-Affinity DNA Base Analogs as Supramolecular, Nanoscale Promoters of Macroscopic Adhesion
    Cyrus A. Anderson, Amanda R. Jones, Ellen M. Briggs, Eric J. Novitsky, Darrell W. Kuykendall, Nancy R. Sottos, and Steven C. Zimmerman, J. Am. Chem. Soc. 2013, 135, 7288–7295.
  14. Leukocyte-Mimicking Stem Cell Delivery via In situ Coating of Cells with a Bioactive Polyglycerol
    John J. Schmidt, Jae Hyun Jeong, Richie Kohman, Andrew Zill, Ross DeVolder, Steven C. Zimmerman, and Hyunjoon Kong, J. Am. Chem. Soc. 2013, 135, 8770-8773. Cover Article.
  15. Single molecule study of the CUG Repeat-MBNL1 Interaction and its Inhibition by Small Molecule
    Amin Haghighat Jahromi, Masayoshi Honda, Steven C. Zimmerman, and Maria Spies, Nucl. Acids Res. 2013, 41 (13), 6687-6697. Cover Article.
  16. Ring-fused BODIPY as a Single- Molecule Optical Probe with Suppressed Blinking and Long Lifetime
    Si Kyung Yang, Xinghua Shi, Taekjip Ha, and Steven C. Zimmerman, Nature Chem. 2013, 5, 692-697.
  17. Quadruply Hydrogen Bonding Modules as Highly Selective Nanoscale Adhesive Agents
    Yagang Zhang, Cyrus A. Anderson, and Steven C. Zimmerman, Org. Lett. 2013, 15 (14), 3506–3509.
  18. Supramolecular Chemistry for Biology, Materials and Medicine
    Alanna Schepartz and Steven C. Zimmerman, Isr. J. Chem. 2013, 53, 495-496.
  19. Hydrogen Bonding Modules for Use in Supramolecular Polymers
    Si Kyung Yang and Steven C. Zimmerman, Isr. J. Chem. 2013, 53, 511-520. Cover Article.
  20. A Polymeric Fastener to Localize Gadolinium on a Liposome Surface for Enhanced Magnetic Resonance Imaging
    Cartney E. Smith , Artem Shkumatov , Sarah G. Withers , James F. Glockner , Sanjay Misra , Edward J. Roy , Chun-Ho Wong , Steven C. Zimmerman , and Hyunjoon Kong, ACS Nano 2013, 7, 9599-9610.
  21. Developing Bivalent Ligands to Target CUG Triplet Repeats as the Causative Agent of Myotonic Dystrophy Type 1
    Amin Haghighat Jahromi, Yuan Fu, Lien Nguyen, Kali A. Miller, Anne M. Baranger, and Steven C. Zimmerman, J. Med. Chem. 2013, 56(23), 9471–9481.
  22. Proton Switch for Modulating Oxygen Reduction by a Copper Electrocatalyst Embedded in a Hybrid Bilayer Membrane
    Christopher J. Barile, Edmund C. M. Tse, Ying Li, Thomas B. Sobyra, Steven C. Zimmerman, Ali Hosseini, and Andrew A. Gewirth, Nature Mater. 2014, 13, 619–623.
  23. Isaiah Shavitt: Computational Chemistry Pioneer
    Steven C. Zimmerman and Russell M. Pitzer, Theor. Chem. Acct. 2014, 113, (1488), 1-7.
  24. Targeting Toxic RNAs that Cause Myotonic Dystrophy Type 1 (DM1) with a Bisamidinium Inhibitor
    Chun-Ho Wong, Lien Nguyen, Jessie Peh, Long M. Luu, Jeannette S. Sanchez, Stacie L. Richardson, Tiziano Tuccinardi, Tsoi Ho, Edwin H. Y. Chan, Wood-Yee Chan, Anne M. Baranger, Paul J. Hergenrother, and Steven C. Zimmerman, J. Am. Chem. Soc. 2014, 136, 6355–6361.
  25. Practical Synthesis of Water-Soluble Organic Nanoparticles with a Single Reactive Group and a Functional Carrier Scaffold
    Yugang Bai, Hang Xing, N. Gabriel Lemcoff, Yi Lu, and Steven C. Zimmerman, Chem. Sci. 2014, 5, 2862-2868.
  26. Small Molecules that Target the Toxic RNA in Myotonic Dystrophy Type 2
    Lien Nguyen, JuYeon Lee, and Steven C. Zimmerman, ChemMedChem 2014, in press

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

Sikyung Yang’s Nature Chem. paper (2013, 5, 692–697 DOI:10.1038/nchem.1706.) was
highlighted in a piece entitled “Branches reduce blinking” in Nature Materials. Sikyung’s
review in Isr. J. Chem. 2013, 53, 511-520. DOI: 10.1002/ijch.201300045 was selected
for the cover (click here). See also Steve’s invited editorial with Alanna Schepartz:
“Supramolecular Chemistry for Biology, Materials and Medicine,” Isr. J. Chem. 2013, 53,
495-496. DOI: 10.1002/ijch.201310007.

Cyrus Anderson’s JACS paper on nanoscale adhesion promoters (J. Am. Chem. Soc.
2013, 135, 7288–7295. DOI: 10.1021/ja4005283 was highlighted in RSC Chemistry
World
in a piece entitled “Coming unstuck with DNA.” The author, Cara Sutton
describes our results with a “DNA-based glue.”

Chun-Ho Wong’s review on orthogonality, “Orthogonality in Organic, Polymer, and
Supramolecular Chemistry: from Merrifield to Click Chemistry,” Chem. Commun. 2013,
49, 1679-1695. DOI: 10.1039/c2cc37316e received the cover of that issue (click here).

Andy and Richie’s JACS paper (together with Joon Kong’s group) “Leukocyte-Mimicking
Stem Cell Delivery via In situ Coating of Cells with a Bioactive Polyglycerol,” J. Am.
Chem. Soc.
2013, 135, 8770-8773. DOI: 10.1021/ja4005283 highlighted with the cover
(click here) and was selected for a JACS Spotlight entitled “Stem cells masquerade as
immune cells for therapy
.”

Amin Jahromi and Lien Nguyen’s paper “A Novel CUGexp·MBNL1 Inhibitor with
Therapeutic Potential for Myotonic Dystrophy Type 1,” ACS Chem. Biol. 2013, 8,
1037-1043. DOI: 10.1021/cb400046u was highlighted with the cover (click here) and by
the UIUC News Bureau. Both Amin and Lien were highlighted in meet the authors
pieces (click their names).

Jonathan Arambula's early Myotonic Dystrophy Type 1 (DM1) targeting ligand was highlighted by the UIUC News Bureau, C&E News, Science Daily, e!Science News, and United Press International.

 

Patents

Photo of Steven C. Zimmerman