- Bioorganic and bioinorganic chemistry
- Metal ion catalysts, nucleic acid structure
and recognition
- B. S., University of California, Santa Barbara
- Ph.D., University of North Carolina - Chapel Hill
- NSF Postdoctoral Fellow, University of Bordeaux
- Postdoctoral Fellow, University of California, San Diego
- Alfred P. Sloan Fellow (1994-96)
- NSF Visiting Professor, University of Rochester (1996-97)
- NSF Special Creativity Award (2007)
Synthesis of compounds for the recognition and cleavage of RNA, lanthanide luminescence spectroscopy of metal ion binding sites in proteins and nucleic acids, catalysts and materials, magnetic resonance imaging contrast agents
Work in the Morrow laboratory focuses on the bioinorganic and medicinal chemistry. Projects include the synthesis of small molecules that bind selectively to nucleic acids and catalyze the hydrolytic cleavage of an RNA strand. Students on this project are generally involved in several different aspects of this project including the synthesis of hybrid organic/inorganic RNA recognition agents, synthesis of ligands for metal ion catalysts and mechanistic analysis of the kinetics of cleavage. A second project entails the development of magnetic resonance imaging (MRI) contrast agents that function by chemical exchange saturation transfer. In addition, we are interested in the application of lanthanide ion luminescence to study the solution chemistry of lanthanides as catalysts and as probes for metal ion binding sites in proteins and in nucleic acids. This work utilizes a laser system built expressly to study the direct excitation-luminescence of lanthanide ions.
Synthesis of small molecules for the inactivation of therapeutic RNA targets.
A growing appreciation of the diverse biochemical roles of RNA in organisms has lead to efforts to design small molecule drugs to inactivate RNA. RNA folds into complex three-dimensional structures, making it an interesting target for molecular recognition. Proteins are frequently associated with RNA and mediate interactions of the RNA with other biomolecules in the cell. Blocking specific protein-RNA interactions is one strategy for interfering with biological function. For example, a drug might modulate the biological activity of RNA by preventing binding of its protein partner. Antibiotics such as tetracycline and streptomycin are well-recognized examples of drugs that interfere with RNA function by inhibiting protein synthesis in prokaryotic ribosomal RNA.
It is a tremendous challenge to design molecules that bind specifically to different RNA structural motifs. Our efforts in this area are toward the recognition and cleavage of the phosphodiester backbone of RNA. In the recognition arena we are exploiting metal ion-RNA interactions by incorporating metal ion binding sites into the design of our compounds as an important element of RNA recognition. Dinuclear metal ion complexes are under development as catalysts for the hydrolytic cleavage of RNA. In this work we strive to elucidate the mechanism of RNA cleavage by using different RNA analogs as substrates. Other work is directed toward the goal of combining recognition and cleaving agents to bring the catalyst in close proximity to the desired cleavage site.
Luminescent lanthanide probes for biomacromolecules, catalysis and materials.
As spectroscopic probes, lanthanide ions (Ln(III)) are among the premier probes of metal ion binding sites in chemistry and biology. However, electronic transitions between states with a 4fn configuration are electric dipole forbidden; as a result, Ln(III) ion fluorescence is weak and an intense source is needed for excitation. In collaboration with Professor Frank Bright, we have built a laser system for the study of direct excitation-luminescence of several of the lanthanide elements. The new system is based on a high energy Nd:YAG pump laser (Spectra-Physics Quanta-Ray-270-10) feeding an optical parametric oscillator crystal (MOPO-SL) with frequency doubler (MOPO-FDO-970) for high energy (up to 80 mJ/pulse), narrow band (<0.2 cm-1) excitation in the UV, visible and near-IR (220-1800 nm), full spectral scanning over this region, emission wavelength scanning with ~1 nm resolution, and time-resolved measurements. The laser system is currently available to researchers for collaborative work. Our interests are in the application of laser-induced luminescence to study metal ion binding sites in RNA, nucleic acid materials, proteins and lanthanide(III) macrocyclic catalysts and contrast agents.
Magnetic resonance imaging contrast agents
Paramagnetic complexes are widely used in clinical medicine as contrast agents for MRI. Work in our laboratory centers on the development of paramagnetic lanthanide complexes that act as chemical exchange saturation transfer agents (CEST). In the CEST experiment, the NMR resonance of a group on the contrast agent that is in slow exchange with bulk water is irradiated with a presaturation pulse prior to collection of imaging data, leading to a reduction in the total water signal. In order to increase the sensitivity of these agents and to incorporate selective binding functionality, we study lanthanide macrocyclic complexes with alcohol groups, dinuclear lanthanide complexes with unusual recognition properties and supramolecular complexes.
Selected Recent Publications