Ph.D., University of London, Imperial College of Science and Technmology, 1976
Phone: 718-951-5000 x2827
Grant Support: NIH SCORE, $733,000; PRF: $100,000
Nature of Research:
PROJECT 1
METAL-BASED DRUGS AGAINST MALARIA AND CANCER
Because of the high incidence of malaria and cancer and the emergence of drug resistance, effective and safe new chemotherapies are urgently needed. Our long-term goal is to discover new leads for metal-based anti-malarial and anti-tumor agents and to elucidate their mechanisms of action. The primary focus of the project is the synthesis and characterization of new metal complexes containing biologically active ligands and the evaluation of their therapeutic potential and mechanisms of action against malaria or cancer, through the study or their physicochemical characteristics and their ability to interact with e.g. heme and DNA. The specific aims are:
1. The synthesis of Ru complexes containing biologically active N-donor ligands, with molecular structures specifically designed to provide multi-functional capabilities required for anti-malarial and anti-tumor activity.
2. Studies of heme aggregation inhibition by in vitro assays, as an indicator of anti-malarial potential of the new compounds and as a test for our mechanistic hypothesis.
3. Spectroscopic studies of the hydrolysis of Ru complexes as a function of pH, and of their interaction with heme, DNA, and proteins, to provide additional indications of anti-malarial or anti-cancer activity.
Rotational Proposal:
- Synthesis and characterization of an organometallic complex (use of vacuum lines and glove box, techniques for handling air-sensitive materials; FT-IR and NMR spectroscopy)
- Interaction of metal complex with a biologically important molecule, e.g. hemin or DNA (spectrophotometric and fluorimetric titrations, heme aggregation inhibition, DNA melting, CD spectroscopy)
References
- A. Martinez, Ch. Rajapakse, B. Naoulou, Y. Kopkalli, R. A. Sánchez-Delgado, “On the Mechanism of Antimalarial Action of Ruthenium Chloroquine Complexes” J. Biol. Inorg. Chem. 2008. DOI 10.1007/s000775-008-0356-9 (available on line)
- M. Strasberg-Rieber, A. Anzellotti, R. A. Sánchez-Delgado and M. Rieber, “Apoptosis induced by Ruthenium(II) ketoconazole irrespective of p53 status is enhanced in non-susceptible carcinoma by monoclonal antibody to EGF receptor.” Int. J. Cancer,2004, 112, 376-384
Project 2
NANOSTRUCTURED CATALYSTS FOR HYDROGEN ACTIVATION
The goal of this project is to develop novel nanocomposite materials specifically designed to promote the heterolytic splitting of molecular hydrogen and ionic hydrogenation mechanisms, by use of ruthenium nanoparticles immobilized on polymers containing a basic functionality like poly(vinylpyridine); to study and optimize their catalytic properties in reactions of relevance to the manufacture of petroleum-derived fuels and biofuels; to understand the origin of the catalytic behavior as a function of catalyst structure; and to establish the principal reaction mechanisms through reactor studies, in parallel with the synthesis and reactions of model molecular Ru complexes.
The specific aims are:
1. The synthesis of Ru particles immobilized on functional polymers, expected to provide nano-structures capable of promoting the heterolytic hydrogen splitting and the ionic hydrogen transfer to unsaturated organic molecules.
2. Their evaluation and optimization as catalysts for hydrogenation reactions of organic compounds of relevance to the manufacture of conventional fuels and biofuels.
3. The synthesis and reactions of soluble molecular complexes as mechanistic models for the nano-structured solid materials.
Typical activities in a rotation and skills to be developed:
- Synthesis and characterization of metallic nano-particles on polymers or of an organometallic complex (use of vacuum lines and glove box, techniques for handling air-sensitive materials; FT-IR, NMR spectroscopy, electron microscopy)
- Evaluation of catalytic properties (use of pressure reactors, GC and GC-MS analysis)
References
R. A. Sanchez-Delgado, N. Machalaba and N. Ng-a-qui Catal. Commun. 2007, 8, 2115-2118.
R. A. Sánchez-Delgado. “Hydrodesulfurization and Hydrodenitrogenation”. in Comprehensive Organometallic Chemistry III, R. H. Crabtree and D. M. P. Mingos, Eds. Elsevier: Oxford (2006). ISBN: 008044590X. Vol. 1, Ch. 1.27, pp. 759-800.