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.

Urea is a low-cost, water-soluble fertilizer that is used as the major source of nitrogen in agricultural production. However, the problem with leaching, in which urea in soil is rapidly washed away through rain and irrigation, results in inefficiency in nutrient absorption, low crop yield, poor harvest, and economic failure for farmers (Broadbent 1958), as well as the environmental pollution of groundwater by the release of excessive amounts of nitrate, which adversely affects this non-rechargeable water source. Therefore, recent research attempts to design a suitable system to prolong the release of urea from water in soil to improve soil fertility, agricultural economy, and ground water protection. A prospective approach is to integrate urea into a stable matrix that releases the desired material with an optimal time window.

Porous Silicon (pSi) has been studied as the material of diverse interest, due to its surface chemistry and porous morphology that has promoted many nanotechnology advances, in conjunction with its biocompatibility and biodegradability (Canham 2014). Since pSi degrades slowly in aqueous media and does not react with the soil component, it is selected to be a possible matrix for sustaining urea release. pSi is believed to interact with urea via hydrogen bonds (via surface silanol species), and thus its porous structure is the key to trap urea particles for relatively long periods in water, while exposing the fertilizer to plants. This bioactive pSi material is produced from the eco-friendly Tabasheer-derived silica, during which pSi porosity is maintained (Kalluri et al. 2016). Loading of urea into pSi is carried out using ethanol as a solvent, with theoretical loadings ranging from 27-33% of the composite mass. Release kinetics of urea from water is currently being investigated using highly sensitive colorimetric assay that applies Jung’s method (Jung et al. 1975).

The urea-loaded pSi prepared in these experiments were characterized using several different techniques. X-ray diffraction (XRD) evaluates the crystallinity of pSi after fabrication, with the presence of three peaks consistent with a cubic unit cell structure [Si (111), (220), and (311)]. Thermal gravimetric analysis (TGA) gives the mass loss percentage between melting (132oC) and boiling (203oC) points of urea, which represents the practical loading of urea in a given sample. The results deviate 1-2% from the theoretical loading percentage. TGA also shows the stability of the composite over two months at room temperature, with the recent loading measurement analyses consistent with the previous ones. Differential scanning calorimetry (DSC) analysis confirms that the urea is incorporated in the pSi matrix. Loading and characterization studies were conducted in triplicate to ensure reproducibility of results.

A library of novel tetra-aza macrocyclic molecules, specifically 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene derivatives, capable of chelating metal ions in vivo have been synthesized. Applications of these complexes are currently being pursued as a 1) therapeutic focusing on radical scavenging and metal chelation and 2) diagnostic tool such as magnetic resonance imaging (MRI) contrast agents when complexed with specific metal ions. However, a full study of the electronic effects imparted by substitution to the pyridyl moiety (position 13) and the subsequent impact on the metal center have not been explored. The objective of the present study is to characterize metal complexes of four tetra-aza macrocyclic metal chelating molecules. The pyridyl functional groups studied include: A) unmodified pyridyl, B) p-hydroxyl, C) p-nitrile, and D) m-hydroxyl modified pyridyls on a pyclen base structure (position 13). Notable progress has been made in developing an optimal procedure for obtaining copper (II) complexes and will be presented. Analysis of the resulting copper (II) complex of the p-nitrile tetra-aza macrocycle indicate a six-coordinate metal center based on X-ray diffraction. UV-Visible spectroscopy and electrochemistry help to confirm donor strength among the ligand series as well as a comparison to other tetra-aza macrocycles. Ultimately, this project is focused on understanding the electronic contribution of these functional groups on the pyridine ring and the influence of the ligand and complexed systems as therapeutic and diagnostic agents.

Molecules previously developed by the Green Research Group (L2 and L3) have been shown to reduce reactive oxygen species (ROS) through multiple pathways of activity. Although unclear if ROS is the only source, Alzheimer’s disease and other neurodegenerative disorders are known to be initiated from the formation of these ROS. For these molecules to appropriately execute their antioxidant and radical scavenging ability, they must enter into the brain where the damaging ROS are located. The blood brain barrier (BBB) is a natural obstacle that prevents toxins and infections from reaching the brain. The L2 and L3 ligands must penetrate this barrier to be in the desired site of action to reduce the number of ROS. Addition of a glucose moiety to other therapeutic molecules has been shown to increase permeability across the BBB. The target of this project is to enhance these synthetic pathways of glycosylation and increase product yield. Initially, direct addition of the glucose moiety to the L2 and L3 molecules was achieved. However, challenges with purification techniques suggested a different route to purification or design should be considered and one new route is presented here. With L2 and L3 being inherently hydrophilic, addition of an aliphatic chain to the hydroxyl group of L2 or L3 should increase the hydrophobicity of the molecule allowing for different purification techniques, which can ultimately be glycosylated to give purified desired compounds.