George R. Negrete

Research in the Negrete Laboratory

Projects that are available for graduate and undergraduate students are excellent training experiences for developing scientists. Students are matched with projects according to experience and interest. Small groups of laboratory researches approach problems in teams. All students including graduates and undergraduates who make good progress on these projects will be included as co-authors and are expected present data at scientific meetings. We provide a collaborative environment for training and scientific development.

1.0 Environmentally friendlier organic transformations

Background: The need to supplant conventional synthetic methods with environmentally sustainable approaches requires environmentally friendly (green) synthetic organic chemistry.

1.1 Aqueous, auxiliary-mediated methodologies based on asparagine. The goal of this project is to develop greener methods of asymmetric synthesis employing economical and safe analogs to transfer chirality in hydoxylic environments. We reported in 2002 the outlines of such a system, which is depicted in the scheme below. In summary, cyclocondensation of asparagine with aryl or alkyl aldehyde followed by acylation with acryloyl chloride (R’ = H) yields a chiral acrylamide. This substrate can utilized directly in a subsequent asymmetric cycloaddition step to generate the Diels-Alder adduct, which can be easily cleaved from the heterocycle to give chiral 2-norbornene carboxylic acid.

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.

1.2 Catalytic asymmetric transformations. We are testing the use of amino acid-based heterocycles as organocatalysts for asymmetric transformation. Aspects of structure, solvent, and metal influence learned from the auxiliary studies described above are guiding the development of this project.

2.0 Medicinal chemistry

2.1 Novel amino acid-based lipids and their applications in nanosphere delivery vehicles. The goal of these studies is enhance the competence of nanocapsules (liposomes) in medicinal agent delivery applications using a novel of fatty amino acids developed in our laboratory (see example below). We prepared new amphiphilic amino acid analogs by combining asparagine-, cysteine-, and serine fatty aldehydes and fatty acid chlorides (or fatty formyl chlorides) in a heterocycle synthesis similar to those described above. To date, we prepared a series of analogs with dissymmetric fatty chains. We are examining preliminary indications that a lipo-asparagine (generated from dodecyl aldehyde and stearoyl chloride) can be used in liposome preparations and that the resulting nanocapsules exhibit enhanced stability in acidic media. Further studies will examine the synthesis and characterization of a series of lipopeptide analogs, their formation in liposomal preparations, and the impact on nanocapsule properties.

We also performed preliminary experiments demonstrating the chemical feasibility of attaching ligands to the asparagine-based lipopeptide using conventional peptide coupling agents: one sample was coupled to an omega-amino acid and subsequently bonded to benzylamine. 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, (3) developing chemical mechanisms to enhance the release of nanocapsule contents once they have reached the target tissue.

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

3.0 Compounds for photo-harvesting applications

We are developing synthetic routes to new compounds with potential application as components in photocells for 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.

Double-click on the animation below to view photo-harvesting cartoon

Our (happy!) laboratory participants

Bottom row, left to right: George Negrete, Mark Penick, Matt Mahindaratne, and Adelphe Mfuh Middle Row, left to right: Terrill Smith, Maritza Quintero, Crystal Zuñiga, and Yael Garner Top row, left to right: Robert Boone, Robert Gutierrez, and Mahesh Krishnan.

Missing (but not forgotten): Mark Penick

Don’t hesitate to communicate with me (george.negrete@utsa.edu) or with Matt (mathewmahindaratne@yahoo.com) if you have any questions or comments.

Selected Publications