1. Lipid Metal Complexes. The development of metal complexes with amphiphilic properties and rich coordination chemistry has been the focus of our research. Metal complexes of this type occur in Nature and are part of the metal-transport mechanism of some bacteria and fungi (Martinez, J. S. et al. Science, 2000, 287, 1245). However, we took Nature's design, which procures coordinatively saturated species, and modified it to allow for coordinatively active structures. In the course of one year, we developed seventeen amphiphilic ligands (1-17), some of which are bidentate and tridentate amine-containing ligands, 2,2'-bipyridyl derivatives, and trialkyl phosphine ligands; Figure 1.

Figure 1. Lipid ligand systems (1-17).

The lipid ligands 1-17 allowed us to investigate, for the first time, the intrinsic chemical and physical properties of their corresponding metal complexes. Although these ligand donors have been well studied in the past with various transition metals, when the lipid groups become part of the molecular structure, they introduce self-assembly properties that organize the metal centers into supramolecular structures of nanoscopic dimensions in water. We explored the resulting chemical and physical properties of these nanostructured materials. In this report, we highlight three of the most interesting results that we have obtained in the past year.

1a. Lipid Cu(II) complexes with bio-functional properties. The Cu(II) bis-complex of ligands 7 and 10 formed metallo-liposomes of 400 nm in diameter. TEM imaging revealed their bilayer structure, and EXAFS studies confirmed the conservation of the Cu(II) coordination structure while  in water.  Using fluorescent optical microscopy, the critical micelle concentration (cmc) of these lipid complexes was measured. Given the cationic nature of the metallo-liposomes, we investigated their ability to condense DNA strands. We found that these lipid complexes exhibit the ability to deliver long DNA strands containing genes encoding for reporting proteins, such as the GFP (Green Fluorescent Protein), into the nucleus of mammalian cells with an efficiency that matches existing commercial products with undisclosed formulae (40%, Lipofectamine, Bio-Rad Inc.). This work was recently reported in the journal of Chemical Communications (Campa-Cruz, I. et al. Chem.Comm., 2007; 2944), and a full article reporting evidence for the use of a new mechanistic pathway for DNA delivery into eukaryotic cells using analogous lipid Zinc(II) complexes of ligands 5-10  is under preparation.

1b. Lipid Zn(II) complexes with catalytic properties in water. We prepared coordinatively unsaturated Cu(II) and Zinc(II) complexes of ligands 3,4,7, and 15 and prepared their corresponding metallo-liposomes in water. These asymmetric lipid complexes catalyze the hydrolysis of carboxylic esters and phosphate esters at mild conditions (pH 7.1 and 22 ^oC). The model substrates p-nitrophenylacetate and p-nitrophenylphosphate were used for these studies. We are currently investigating the relationship between molecular and supramolecular structure with respect to the rate of hydrolysis, Figure 2. Potential applications of this research are in the area of green processes for the recycling of polyester products and the environmental remediation of pollutants. A full article reporting this work is under preparation.

Figure 2. Catalytic hydrolysis of p-nitrophenylacetate by lipid complexes A and B in water (pH 7, 22 ^oC).

1c. Novel Pt(II) lipid metal complexes. The cis-alkylphosphine Pt(II) chloride complexes of ligands 13 and 14 were prepared and characterized with multinuclear NMR spectroscopy, EXAFS, elemental analysis, and Mass Spectrometry. The supramolecular structures generated were characterized with AFM, TEM, and Cryo-EM . These cis-alkylphosphine Pt(II) complexes form multi-nuclear discrete complexes with multi-pyridyl-donor ligands, and in aqueous media, they undergo a further level of self-organization that produces novel supramolecular structures. Currently, we are evaluating the use of Pd(II) complexes of these lipids ligands in green carbon-carbon coupling reactions in aqueous media.  

2. Academic Development of Participants. This research was conducted with the assistance of undergraduate and graduate students from UTEP. Students trained in advanced techniques of organic and inorganic chemistry; in particular, air-sensitive synthetic techniques. For example, uncoordinated alkyl amines readily react with carbon dioxide from air and alkyl phosphines react with dioxygen, therefore, Schlenk techniques and the glove box were routinely used during the project. Additionally, students were exposed to cross-disciplinary techniques that involved advanced physical measurements such as EXAFS, TEM, AFM, DLS, and UV-vis as well as biochemical techniques that included handling DNA, Gel-electrophoresis, and cell cultivations and gene transfection protocols.

As an Assistant Professor in Chemistry, the ACS PRF grant gave me the financial support to pursue the ideas that I most cherished at a critical point in my career. It allowed me to support undergraduate students during two summers and during the entire school year. Thanks to the ACS PRF funds, we believe that we have developed the initial work of an unprecedented area of research that will pave the way to possibly three important areas in functional materials.