Oxidative stress in the brain is a known contributor to the development of neurodegenerative diseases, including Alzheimer’s. The focus of this project is to target the amyloid-β plaque formations and reactive oxygen species (ROS) derived from mis-regulated metal-ions that lead to disease-causing oxidative stress. The present investigation measures both the antioxidant reactivity and metal chelating ability of 1,4,11,13-tetra-aza-bis(2,6-pyridinophane)-8,17-ol (L4).  L4 contains two radical scavenging pyridol groups along with a metal-binding nitrogen rich ligand system.  It was hypothesized that increasing the number of pyridol groups on the ligands in our small molecule library would increase the radical scavenging activity, which in turn may provide cells protection from oxidative stress.  The radical scavenging ability of L4 was quantified using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay. This was compared to other radical scavenging small molecules to evaluate the effect of the additional radical scavenging group on the antioxidant activity.  The interaction of L4 with redox active metal-ions such as copper(II) was also evaluated using the coumarin-3-carboxylic acid (CCA) assay to show the molecule’s ability to target mis-regulated metal-ions in diseased tissues. With the end goal being to develop a potential biological therapeutic agent, metabolic stability studies were also performed.

Non-conventional solvents, such as room-temperature ionic liquids and deep-eutectic solvents, have attracted a lot of attention in recent years due their diverse applications in various areas of sciences, medicine and engineering. The ability to control physical properties of these solvents by simply adjusting their structure and/or the ratio of the components favorably distinguishes ionic and eutectic solvents from traditionally used molecular solvents as it allows to custom design specific types of media for given applications.

This presentation will highlight our efforts on various aspects of the synthesis of ionic liquids and deep-eutectic solvents as well as it will describe our investigations on the physical properties and nanostructural organization of these liquids using environmental probes, such as those that feature BODIPY and aza-BODIPY motifs. In addition, our initial studies on the design of multiphase systems that utilize ionic, eutectic and molecular solvents will be presented.

This project is aimed to modify a leucyl-tRNA synthetase (LeuRS) to incorporate fluorescent amino acids into proteins to produce fluorescent proteins in living cells. Fluorescent proteins are useful because they are easily analyzed and tracked in living organisms. In a small scale, we successfully prepared the library of LeuRS variants in which five amino acids are randomized in the leucine-binding site of a functional LeuRS without its editing domain. Currently, we are working on a large scale production of viable bacterial cells that cover the whole diversity of library (at least 34 million different LeuRS molecules). Initially, we attempted two-step process in which an N-terminal library fragment (for two randomized amino acids) is generated first and a C-terminal fragment (for three randomized amino acids) is added later. However, this two-step cloning process did not produce enough viable cells to cover all the possible variants. In a new approach, a complete library of LeuRS will be produced by overlapping extension PCR and introduced to E. coli in a single step to ensure highest possible transformation efficiency. Consequently, the library of LeuRS variants will be subject to a genetic selection experiment to obtain LeuRS variants that incorporate only fluorescent amino acids into proteins.

Abacavir or Ziagen, is an antiretroviral medicine that is used in conjunction with other
medicines to treat HIV. Although it is not a cure, it has been clinically proven to be
effective in diminishing the rate of HIV replication. The synthetic process of creating
Abacavir is both timely and costly, so therefore a new synthetic process has been
created to generate a chemical analog (specifically a triazine derivative) that is cheaper
to produce that can be if not potentially more chemically effective than Abacavir. Once
the analog is produced, a series of analytical tests will be done on a micro organismic
level to determine if the analog is both effective and safe enough to be used in human
clinical studies further down the road.

The pyrrolophenanthridone alkaloid pratosine is a natural product related to hippadine, which is known to be a powerful but reversible inhibitor of spermatogenesis in rats. Hippadine has also shown cardiovascular as well as anticancer activity. Given the structural similarities between the two molecules, it is expected that pratosine and hippadine will demonstrate similar biological effects. Our work toward a laboratory synthesis of pratosine will facilitate large-scale production thus affording sufficient quantities of the material for a complete pharmacological study of its properties. Although we have a synthetic plan for preparing pratosine, several reactions have failed due to solubility problems. This research focuses on solving these problems by using an alternate starting material. The commercially available compound vanillin, which is extracted from vanilla beans, is a simple and inexpensive aldehyde with an appropriate structure for attaching other groups that should improve the solubility properties of several of the synthetic intermediates. Our goal is to find a specific substituent that will provide the required characteristics but which can also be removed later to generate the final product.