Chemistry and Biochemistry

Douglas B. Grotjahn

Professor
Organic, organometallic, catalysis, bio-organometallic

Graduate Admissions, University Copyright and Patent Committee, University Conflict of Interest Committee, General Member of the Moores UCSD Cancer Center

Office: CSL 205
Office Phone: 619-594-0231
e-mail: grotjahn_at_chemistry.sdsu.edu

Research Interests

Organic, organometallic, catalysis, bio-organometallic

We are contributing to innovation and understanding in catalysis, clean energy production, nanotechnology, and medicine.

The importance of catalysis is highlighted by a recent report, which states that catalysis-based chemical syntheses are involved in 60% of today's chemical products and 90% of current chemical processes. In the U.S., the chemical industry makes the largest trade surplus of any non-defense-related sector ($20.4 billion in 1995), represents 10% of all manufacturing, and employs more than 1 million people.

We create catalysts which operate in new ways, transforming organic molecules more quickly, in higher yield, with fewer by-products and less waste, contributing to sustainability and green chemistry. Moreover, we are applying what we have learned to new ways to make hydrogen from renewable resources. In separate research projects, we are using organic synthesis to make contributions to nanotechnology and health care.  Specific research areas are:

1. bifunctional organometallic catalysts for the enhanced reaction of non-polar organics with polar reactants such as water (funding: NSF and San Diego Foundation)
2. synthesis of MRI contrast agents for diagnosis of cancer and evaluation of nanodevices (funding: NIH)
3. catalysts to produce hydrogen directly from water, and use hydrogen in fuel cells
4. metal complexes of ketenes and carbenes (past funding: NSF, Petroleum Research Foundation)
5. gas-phase organometallic chemistry (past funding: NSF)
6. metal complexes of proteins, peptides, amino acids and other biomolecules

In the first area (catalysis), we are probing the combined effects of a metal and ligands capable of donating or accepting protons or hydrogen bonds. As an example of the power of bifunctional catalysis, we have been able to make catalysts for anti-Markovnikov hydration of alkynes which are more than 1000 times faster than others reported in the literature, accomplishing within minutes a reaction that would take more than a million years to complete without catalyst! A paper from our group was featured in Chemical and Engineering News (October 4, 2004 issue, page 31). This work has led to a patented catalyst which is sold for research purposes by Strem Chemicals. In ongoing work, we are trying to understand fully the reasons for the high activity, productivity, and selectivity of the new catalyst.

A second example of the power of bifunctional catalysis is shown in eq. 2, where we find that the catalyst shown can move alkene double bonds up to 30 positions down a chain of carbon atoms, yet shows useful selectivity in other alkene isomerization reactions. Control experiments showed that the heterocycle accelerates reactions by factors of up to 10,000. This paper was recently featured in Chemical and Engineering News (July 23, 2007 issue, page 29). This and other reactions are the subjects of exciting investigations in the Grotjahn lab.

In the second area (contrast agents for medical imaging), we are making molecules which bind gadolinium tightly, while also conferring certain properties for maximum detection sensitivity in MRI (magnetic resonance imaging). This work involves total synthesis of compounds with several chiral centers. In collaboration with researchers at University of Pittsburgh Medical Center, these molecules are being used to create new nanodevices for the detection of various forms of cancer. In addition, we are trying to answer fundamental questions about the ways in which nanoparticles are metabolized by the body.

Students in my group are exposed to a wide variety of techniques: Organic synthesis is used to make new ligands, inorganic and organometallic chemistry are used to make new metal complexes, and NMR spectroscopy is used extensively to study reactants and products. In fact, we run many reactions inside NMR tubes because we can easily detect some sensitive reaction intermediates. Many complexes are air-sensitive, so students in my group learn how to handle compounds in inert-atmosphere glove boxes or in Schlenk apparatus. In addition, we are now using combinatorial methods to screen ever-larger numbers of catalysts.

Students graduating from my group enjoy a thorough preparation in fields such as organic synthesis, catalysis, spectroscopy, organometallics, coordination chemistry, and computational chemistry. Students with different interests and preferences can emphasize any or all of these areas in their work. In the area of organic synthesis, we work with a wide variety of heterocycles and other nitrogen-containing compounds, organolithiums and other polar organometallics, phosphines, and chiral compounds, to name a few compound classes. Our group strives to publish in high-profile, internationally respected journals such as J. Am. Chem. Soc., Angewandte Chemie, etc. My graduate students have gone on to postdoctoral positions and permanent jobs in the pharmaceutical industry, national labs, or universities. Undergraduates from my group have gone on to either jobs using their organic and organometallic skills, or to graduate programs at institutions such as Harvard, Scripps Research Institute, and UC Irvine.

Selected Publications (full list here)

1. "Bifunctional catalysts and related complexes: structures and properties,” invited Perspectives article for Dalton Trans. 2008, 6497-6508.
2. "Imidazol-2-yl Complexes of Cp*Ir as Bifunctional Ambident Reactants,” with Valentin Miranda-Soto, Antonio G. DiPasquale and Arnold L. Rheingold, J. Am. Chem. Soc. 2008, 130, 13200-13201 (communication).
3. "Finding the Proton in a Key Intermediate of anti-Markovnikov Alkyne Hydration by a Bifunctional Catalyst,” with Elijah J. Kragulj, Constantinos D. Zeinalipour-Yazdi, Valentin Miranda-Soto, Daniel A. Lev, and Andrew L. Cooksy, J. Am. Chem. Soc. 2008, 130, 10860-10861.
4. "Hydrogen Bond Acceptance of Bifunctional Ligands in an Alkyne-Metal π Complex,” with Valentin Miranda-Soto, Elijah J. Kragulj, Daniel A. Lev, Gulin Erdogan, Xi Zeng, and Andrew L. Cooksy J. Am. Chem. Soc. 2008, 130, 20-21.
5. "Extensive Isomerization of Alkenes using a Bifunctional Catalyst: An Alkene Zipper,” with Casey R. Larsen, Jeffery L. Gustafson, Reji Nair, and Abhinandini Sharma, J. Am. Chem. Soc. 2007, 129, 9592-9593.
6. "Experimental and Computational Study of the Transformation of Terminal Alkynes to Vinylidene Ligands on trans-(Chloro)bis(phosphine)Rh Fragments and Effects of Phosphine Substituents,” with Xi Zeng, Andrew L. Cooksy, W. Scott Kassel, Antonio G. DiPasquale, Lev. N. Zakharov, and Arnold L. Rheingold, Organometallics 2007, 26, 3385-3402.
7. "Bifunctional Imidazolylphosphine Ligands as Hydrogen Bond Donors Promote N-H and O-H Activation on Platinum,” with Yi Gong, Antonio G. DiPasquale, Lev N. Zakharov, and Arnold L.Rheingold, Organometallics 2006, 25, 5693-5695. [one of the 20 most-accessed articles in Organometallics published between September and December, 2006]
8. "Alkyne-to-vinylidene Transformation on trans-(Cl)Rh(phosphine)₂: Acceleration by a Heterocyclic Ligand and Absence of Bimolecular Mechanism," with Xi Zeng and Andrew L. Cooksy, J. Am. Chem. Soc. 2006, 128, 2798-2799.
9. "Changes in Coordination of Sterically Demanding Hybrid Imidazolylphosphine Ligands on Pd(0) and Pd(II)," with Yi Gong, Lev Zakharov, James A. Golen, and Arnold L. Rheingold, J. Am. Chem. Soc. 2006, 128, 438-453.
10. "Bifunctional Organometallic Catalysts involving Proton Transfer or Hydrogen Bonding," a Concepts article in Chemistry – a European Journal, 2005, 11, 7147-7153.
11. "A general bifunctional catalyst for the anti-Markovnikov hydration of terminal alkynes to aldehydes gives enzyme-like rate and selectivity enhancements," with Daniel A. Lev, J. Am. Chem. Soc. 2004, 126, 12232-12233. [see also “Organometallic catalysts are enzyme-like,” Science and Technology Concentrates section of Chemical and Engineering News, 4 October 2004 issue, page 31.]
12. "Gas-Phase Synthesis, Submillimeter Spectra, and Precise Structure of Monomeric, Solvent-Free CuCH₃," with DeWayne T. Halfen, Lucy M. Ziurys, and Andrew L.Cooksy, J. Am. Chem. Soc. 2004, 126, 12621-12627.
13. "Double C-H activation during functionalization of phenyl(methyl)ketene on iridium(I) using alkynes. A synthesis of 1,4-dien-3-ones," with Justin M. Hoerter and John L. Hubbard, J. Am. Chem. Soc. 2004, 126, 8866-8867.
14. "Controlled, Reversible Conversion of a Ketene Ligand to Carbene and CO Ligands on a Single Metal Center," with Galina A. Bikzhanova, Laura S. B. Collins, Thomas Concolino, Kin-Chung Lam, and Arnold L.Rheingold, J. Am. Chem. Soc. 2000, 122, 5222-5223. [see also “Ketene ligand cleaved to carbene and CO ligands reversibly,” Science and Technology Concentrates section of Chemical and Engineering News, 29 May 2000 issue, page 52. “Of Ketenes and Carbenes,” Highlights of the Recent Literature, Editor’s Choice, Science, 2 June 2000 issue, vol. 288, page 154. “Metal-Assisted Cleavage of a C-C Double Bond: Simple and Reversible,” by H. Werner and E. Bluel, Highlights section of Angewandte Chemie, Int. Ed. Engl. 2001, 40, 145-146.]
15. "Synthesis of CH₃K in the Gas Phase: Structural and Mechanistic Trends for Monomeric, Unsolvated CH₃M and HCCM (M = Li, Na, K)," with T. C. Pesch, M. A. Brewster, and L. M. Ziurys, J. Am. Chem. Soc. 2000, 122, 4735-4741.
16. "High Arenophilicity and Water Tolerance in Direct Derivatization of Peptides and Proteins by Metal p-Coordination," with Camil Joubran, David Combs, and Daniel C. Brune, J. Am. Chem. Soc. 1998, 120, 11814-11815.

Recently graduated students and postdocs and where they went after SDSU

1. Yi Gong, Ph.D. – Solvay, Los Angeles, CA
2. Allan Mallari, B.S. – Materia, Pasadena, CA
3. Tiffany Hoerter, M.S. – AstraZeneca, Wilmington, DE
4. Justin Hoerter, postdoc - DuPont, Wilmington, DE
5. Dan Lev, Ph.D.– Ropes and Gray, Boston; J.D., Northwestern University Law School
6. Robin Hurt, B.S. – Ph.D. program, UC Irvine
7. Shirley Leung, M.S. – Novartis, Boston, MA
8. Xi Zeng, M.S. – Diazyme Laboratories / General Atomics, San Diego, CA
9. Jeff Gustafson, B.S. – Ph.D. program, Yale
10. Christie Schulte, B.S. – GlaxoSmithKline, North Carolina