Research Interests

Priorities
• Develop chemical syntheses that are important to address global needs
• Train graduate and undergraduate students
• Matched trainees with projects according to experience and interest
• Promote student development via co-authorship and student presentation
• A collaborative and safe environment for training and scientific development

We are engaged in three main areas of research.

1. Environmentally friendlier organic transformations
Background: The need to supplant conventional synthetic methods with environmentally sustainable approaches requires environmentally friendly (green) synthetic organic chemistry. The goal of this project is to develop greener methods of asymmetric synthesis employing economical and safe analogs to transfer chirality in hydroxylic environments. We reported the outlines of such a system in 2002, which is depicted in the scheme below. My group is continuing to investigate various aspects of this system: counter ion (Y+), steering group (R), solvent, use of other amino acids and dienophile units, cyclocondensation mechanism, and applications to other asymmetric transformations.

Current research interest includes solid state nanoporous metal-organic frameworks and nanoparticles, self-assembled by coordination of suitable metal ions/clusters with organic building blocks. Such porous materials are of great interest for their potential applications in gas storage, separations, sensors, catalysis and electronics. The current challenge for the synthesis of such materials is to functionalize their nano-sized cavities; so that they can be well suited for specific host-guest interactions and practical applications. Our goals here are to develop synthetic approaches to address the challenge by the emerging crystal design and pre-constructed building blocks strategies. The synthesized materials will be structurally characterized, examined and rationalized for above mentioned functional properties.

2. Medicinal chemistry
2.1 Novel amino acid-based lipids and their applications in nanosphere delivery vehicles. The goal of these studies is to enhance the competence of nanocapsules (liposomes) in medicinal agent delivery applications using novel fatty amino acids developed in our laboratory (see example below). Asparagine-derived lipids enhance the acid stability of DSPC liposomes (in preparation). We also performed preliminary experiments demonstrating the chemical feasibility of attaching ligands to the asparagine-based lipids. In ongoing studies we are: (1) verifying that the ligand-modified lipopeptide (see construct below) inserts into preformed nanocapsules, (2) examining the binding of a ligand-modified lipopeptide to its receptor target, and (3) developing chemical mechanisms to enhance the release of nanocapsule contents once they have reached the target tissue.

3. Compounds for photo-harvesting applications
We are developing synthetic routes to new compounds with potential application as components in photocells to harvest solar energy. We have already prepared perylene photo-promoted electron donors (see below in green) and are developing syntheses of quinazolinium electron acceptors (in blue). Preliminary chemical studies indicate that the perylene analog is an excellent electron donor, as predicted.

4. Novel synthetic molecules as vaccines, anti-microbials, and cancer therapeutics. We are preparing novel synthetic vaccine constructs and experimental therapeutics in collaboration with colleagues at UTSA and at the UTHSCSA. Biological aspects of this project will be conducted at the laboratories of collaborators.

Selected Publications

“Tandem Friedel-Crafts Annulation to Novel Perylene Analogs”
Mark A. Penick, Mathew P.D. Mahindaratne, Robert D. Gutierrez, Terrill D. Smith, Edward R.T. Tiekink, and George R. Negrete
J. Org. Chem. 2008, 73, 6378–6381.

“One-pot Reductive Cyclization to Antitumor Quinazoline Precursors”
Sandip K. Kundu, Mathew P.D. Mahindaratne, Maritza V. Quintero, Ande Bao, and George R. Negrete
ARKIVOC 2008 (ii), 33–42.

“Salt, Concentration, and Temperature Effects on an Asparagine-Based, Aqueous Diels-Alder Cycloaddition”
Mathew P.D. Mahindaratne, Brian A. Quiñones, Antonio Recio III, Eric A. Rodriguez, Frederick J. Lakner, and George R. Negrete
Tetrahedron 2005, 61, 9495–9501.

“A Fully-Telescoped Auxiliary-Mediated Asymmetric Diels-Alder Cycloaddition”
Mathew P.D. Mahindaratne, Brian A. Quiñones, Antonio Recio III, Erik A. Rodriguez, Frederick J. Lakner, and George R. Negrete
ARKIVOC 2005 (vi), 321-328.

"Direct ^99mTc Labeling of Pegylated Liposomal Doxorubicin (DoxilÆ) for Pharmacokinetic and Non-invasive Imaging Studies, J. Pharma. Exptl. Therap.
Ande Bao, Beth Goins, Robert Klipper, George Negrete, and William T. Phillips
2004, 308, 419-425.

"¹⁸⁶Re-Liposome Labeling Using ¹⁸⁶Re-SNS/S Complexes: In Vitro Stability, Imaging, and Biodistribution in Rats"
Ande Bao, Beth Goins, Robert Klipper, George Negrete, William T. Phillips
J. Nucl. Med. 2003, 44, 1992–1999.

“A Novel Liposome Radiolabeling Method Using ^99mTc-"SNS/S" Complexes: In Vitro and In Vivo Evaluation”
Ande Bao, Beth Goins, Robert Klipper, George Negrete, Mathew Mahindaratne, and William T. Phillips
J. Pharma. Sci. 2003, 92, 1893–1904.

“Syntheses of cis- and trans-7-Chloro-7,8,9,10-tetrahydrobenzo[α]pyren-8-ol: A Remarkable Solvent Effect on Epoxide Hydrochlorination Diastereoselectivity”
Mathew P.D. Mahindaratne, Hesham T.Y. Fahmy, Jesus A. Garcia, and George R. Negrete
Synth. Commun. 2003, 33, 1391–1398.

“⁹⁹Tc/¹⁸⁶Re/¹⁸⁸Re - Liposome Radiolabeling for Nuclear Imaging and Targeted Radionuclide Therapy”
In Technetium, Rhenium, and Other Metals in Chemistry and Nuclear Medicine Vol. 6; M. Nicolini and U. Mazzi, Eds.; SGE Editoriali: Padova, Italy, 2002,
Ande Bao, William T. Phillips, George R. Negrete, Robert Klipper, and Beth A. Goins
pp 381–386.

“A New and Convenient Chiral Auxiliary for Asymmetric Diels-Alder Cycloadditions in Environmentally Benign Solvents”
Frederick J. Lakner and George R. Negrete
Synlett 2002, 643–645.