Ph.D., Public University of Navarra, Spain, 1996
Phone: 718-951-5000 x2833
Nature of Research
Our Group research’s focuses on the area of inorganic chemistry and, more specifically, in the chemistry of coordination and organometallic compounds of gold in different oxidation states. We thus have two main projects in the areas of homogenous catalysis and green chemistry and in the area of medicinal chemistry:
1) Greener Homogeneous Gold Catalysts
We are developing gold homogeneous catalysts (coordination and organometallic compounds) to be used in different reactions with potential industrial and pharmaceutical applications. The reactions we study are mainly: a) addition of nucleophiles to multiple bonds; b) oxidation reactions and, c) hydrogenation reactions (with a special emphasis in the use of water and alcohols as solvents).
Our main goal is to study reaction mechanism by in situ spectroscopic techniques (mainly multinuclear NMR) in order to identify reaction intermediates and the possible catalytically active species. This molecular insight will help us to optimize and design more efficient, selective and greener gold catalysts.
Scheme 1. Liquid-liquid biphase gold-catalyzed oxidation reactions.
Our second goal is the design of water- and fluorous-soluble gold compounds to be used as recoverable and recyclable catalysts in some of the reactions described above. We use liquid-liquid bi-phase approaches1,2 to recover these gold catalysts. E.g. in scheme 1.
[1]. Cornils, B.; Herrmann, W.A. ‘Aqueous-phase catalysis’. In Multiphase Homogeneous Catalysis. Cornils, B.; Herrmann, W.A.; Horváth, I.T.; Leitner, W.; Mecking, S.; Olivier-Bourbigou, H.; Vogt, D. Eds. 2005, 1, 25-305 (Wiley-VCH) and refs. therein.
[2]. Horváth, I.T.; ‘Fluorous Catalysis’. In Multiphase Homogeneous Catalysis. Cornils, B.; Herrmann, W.A.; Horváth, I.T.; Leitner, W.; Mecking, S.; Olivier-Bourbigou, H.; Vogt, D. Eds. 2005, 2, 339-403 (Wiley-VCH) and refs. therein.
This research line involves synthesis (Organic, Inorganic, Organometallic Chemistry) at air and under inert atmosphere (schlenk techniques and dry-box), structural characterization techniques (IR, NMR, x-ray, Mass Spectrometry), and the use of GC-Chromatographs and High Pressure Reactors.
2. Application of gold compounds as anticancer agents
The long term goals of this research line are: a) the design of gold-anticancer pharmaceuticals that overcome some of the existing clinical problems associated with the use of platinum drugs in cancer chemotherapy and b) to understand the mechanism of action of gold derived anticancer pharmaceuticals, identify their final target and the corresponding molecular lesion.
Some gold complexes may prove to be effective antitumor agents acting through different mechanisms than those of cisplatin. An increasing number of reports on the biological activity of gold(I) and gold(III) complexes have brought to light their capacity to act against solid cancer tumors. Interestingly, some of the compounds have displayed a high cytotoxicity against cisplatin-resistant cell lines. Plausible reaction mechanisms for some of these compounds have been proposed quite recently but the data obtained to date is limited. It appears that most of the gold compounds have a biological mechanism different than those described for cisplatin (primarily noted to bind and damage DNA). Some of the effects of gold compounds in vitro appear to be a consequence of direct interference with redox-dependent mitochondrial functions (inhibition of mitochondrial enzymes).3-5 It also appears that gold(I) and gold(III) complexes behave differently. It is not clear if this is due to the coordinating ligands used, thiolates and phosphines for gold(I) and nitrogen-based ligands for gold(III), or from the oxidation state of the gold center. Therefore, there is a need to have enough structurally related gold complexes in order to systematically probe different mechanisms of biological action. We work on the design of those (cytotoxicity studies) and the study of their interactions with a) DNA and b) mitochondrial proteins.
Rotation Projects
Involves synthesis (Organic, Inorganic, Organometallic Chemistry), structural characterization techniques (IR, NMR, x-ray, Mass Spectrometry), study of possible interactions of the compounds with DNA (and other molecular targets such as mitochondrial proteins). The techniques for the latter experiments are a) spectrophotometric titration and DNA melting point determination, b) ITC (isothermal titration calorimetry), c) gel electrophoresis, and d) circular dichroism measurements (which is the appropriate technique to monitor the conformational variations of DNA). Studies of gold compounds with a few model proteins (serum albumin, cytochrome c, ubiquitin) or enzymes (such as thioredoxin reductase) can be monitored by spectroscopic methods as well.
References
Project 1
[1]. Cornils, B.; Herrmann, W.A. ‘Aqueous-phase catalysis’. In Multiphase Homogeneous Catalysis. Cornils, B.; Herrmann, W.A.; Horváth, I.T.; Leitner, W.; Mecking, S.; Olivier-Bourbigou, H.; Vogt, D. Eds. 2005, 1, 25-305 (Wiley-VCH) and refs. therein.
[2]. Horváth, I.T.; ‘Fluorous Catalysis’. In Multiphase Homogeneous Catalysis. Cornils, B.; Herrmann, W.A.; Horváth, I.T.; Leitner, W.; Mecking, S.; Olivier-Bourbigou, H.; Vogt, D. Eds. 2005, 2, 339-403 (Wiley-VCH) and refs. therein.
[3]. Rigobello, M.P.; Scutari, G.; Boscolo, R.; Bindoli, A. ‘Induction of mitochondrial permeability transition by auranofin, a gold(I)-phosphine derivative’. British J. Pharmacol. 2002, 136, 1162.
[4]. Rigobello, M.P.; Scutari, G.; Folda, A.; Bindoli, A. ‘Mitochondrial thioredoxin reductase inhibition by gold(I) compounds and concurrent stimulation of permeability transition and release of cytochrome c’. Biochem. Pharmacol. 2004, 67, 689.
[5]. Barnard, P.J.; Baker, M.V.; Berners-Price, S.J.; Day, D.A. ‘Mitocondrial permeability transition induced by dinuclear gold(I)-carbene complexes: potential new antimitochondrial antitumour agents’. J. Inorg. Biochem. 2004, 98, 1642.