Chemistry Research Projects 2016

Brittney Beidelman
Dr. Sun
Temple University Chemistry Department

Synthesis of SiO2 Spherical Nanoparticles

Efficient energy conversion is important for increasing the performance of photovoltaic and photocatalyic devices for harvesting solar energy. The addition of metal plasmonic nanoparticles to a semiconductor, like SiO2, helps improve solar energy conversion by generating hot electrons, when in the presence of solar energy. SiO2 is a semiconductor with a large band gap that absorbs in the ultraviolet (UV) range. Since the major portion of the solar spectrum that reaches the surface of the earth is in the visible range, research is being done for new materials that have a high absorption in the visible range. SiO2 has a high electron-accepting capability, which is useful for the absorption of solar energy. Metal plasmonic nanoparticles, such as Cu, Al, Pd, At, and Au, can be added to SiO2 in order to shift the absorption spectrum from the UV into the visible spectrum. SiO2 is almost transparent in the visible region, so any change in absorption can be attributed to the addition of nanoparticles. We will use a modified Stöber process to synthesize the SiO2 particles, which utilizes hydrolysis and nucleation to create the spherical nanoparticles. The goal is to consistently obtain uniform nanoparticles of various sizes in the 200-350nm range and analyze their performance in photocatalysis.

Steffany Chou
Dr. Jason Schmink
Chemistry

Palladium Catalyzed Cross-Coupling of 1,3-Oxathiolanes and Aryl Bromides

Our lab explores palladium catalysis and the development of alternative nucleophiles. The focus of our research this summer will be to optimize the synthesis of aryl vinyl sulfides from the palladium catalyzed cross-coupling reaction of 1,3-oxathiolanes and aryl bromides. Such sulfide compounds are significant in organic chemistry syntheses, and have applications in both pharmaceuticals and materials sciences. We will be analyzing the data of reactions run under varying conditions to find the most efficient methods of synthesis, while striving to remain within the principles of green chemistry.

Alanna Goldberg
Advisor: Bill Malachowski
Department: Chemistry

Enantioselective Synthesis of Polycyclic Structures via Intramolecular Heck Reactions 

Many vital drugs, including steroids such as prednisone, are made up of polycyclic ring structures. Modern synthetic chemistry lacks the efficiency and specificity that is needed to research and develop polycyclic structures. This research will investigate efficient methods of enantioselectively synthesizing polycyclic molecules. The reactions are carried out using Birch reduction-alkylation reactions, and intramolecular Heck reactions; Birch reduction-alklyation will create an alkene-containing ring bonded linearly to an aromatic ring, the main components to be used in an intramolecular Heck reaction. Using the intramolecular Heck reaction, we will use a palladium catalyst with chiral ligands to enantioselectively generate a C-C bond between the aromatic ring and alkene ring, thereby creating polycyclic structures. This research will determine efficient synthetic procedures as well as effective palladium ligands for enantioselectivity. 

Sarah Lew
Dr. Jason Schmink
Chemistry

Palladium-catalyzed cross-coupling of aryl bromides with 2,2-diphenyl-1,3-oxathiolane

The palladium-catalyzed cross-coupling of aryl bromides with 2,2-diphenyl-1,3-oxathiolane creates vinyl sulfides. Palladium acts as a shuttle of electrons that allows for bonds to form and makes it possible to create leaving groups for there to be an E2 reaction. The methodology found from this research will allow pharmaceutical companies who need vinyl sulfides to create them. Currently the research has focused on finding the best method for making the starting material, 2,2-diphenyl-1,3-oxathiolane, as it cannot be bought. 

Alexandra Nagelski
Dr. Sharon J. N. Burgmayer
Chemistry Department

The Investigation of Pterin Reduction Dynamics in Synthetic Molybdenum Cofactor Models

Molybdoenzymes catalyze oxygen atom transfer reactions and exist in nearly all organisms. In their catalytic site, molybdoenzymes contain the molybdenum cofactor (Moco). Moco is not stable outside of the protein matrix, therefore the use of small molecule analogues provides an alternate way to study Moco. This research focuses on the molybdopterin (MPT), which describes one or two conserved pyranopterin dithiolene ligands on Moco and its role in the catalytic function of Moco. Although there is little known about the relationship between MPT and the catalytic function of Moco, without MPT, Moco loses its catalytic efficiency. MPT is the most redox active ligand in all of biology, which suggests that the oxidation state may play a role in catalysis. The Burgmayer lab has created the model systems [TEA][Tp*Mo(O)(S2C2(pterin)(C(CH3)2R)], where TEA is tetraethylammonium, Tp* is tris(3,5-dimethylpyrazolyl)hydroborate, Mo exists in the Mo(IV) or Mo(V) oxidation state, and R can be a hydroxyl (1) or methyl (2). In (1), the complex experiences reversible intramolecular cyclization that is dependent upon the dielectric constant of the solvent, producing a pyran ring, as shown in Figure 1. The related complex (2), where the hydroxyl group (depicted in red in Figure 1) is isosterically replaced with a methyl group, prevents this intramolecular cyclization, thereby creating a standard to compare the behavior of (1).

The tetrahydropyranopterin form of (1), which has already been synthesized in our lab, closely resembles the Moco pyranopterin structure observed in molybdoenzymes crystal structures. We hope to achieve the reduced dihydro form and the fully reduced uncyclized tetrahydro form of (1) and (2). From reducing the oxidized pterin in these model complexes, we can learn more about the changes on the catalytic efficiency and the electronics that it may exhibit.

Alexandra Nagelski chemistry graphic

Figure 1: [TEA][Tp*Mo(O)S2BMOPP], where BMOPP is 6-(3-butynyl-2-methyl-2-ol)-2-pivaloyl pterin.

Nam Nguyen
Dr. Sharon J. N. Burgmayer
Department of Chemistry

The pathway to Molybdenum pyranopterin dithiolene complex

The transition metal Molybdenum plays an important role in living organisms because of the ubiquitous molybdenum-containing enzymes. Despite its relevance in biological lives, there is still little understanding about the molybdopterin chemistry. The first goal is to create ligands 2-pivaloyl-6-chloropterin and BMOPP to further develop the molybdenum complex that our research group has already successfully modeled [TEA][Tp*Mo(X)pterin-C(CH3)2R-dithiolene], where TEA stands for tetraethylammonium and Tp* is tris(3,5-dimethylpyrazolyl)hydroborate, X is either oxygen or sulfur atom and investigate the molybdenum pterin dithiolene chemistry. The quality of the compounds will be evaluated through the characterization techniques including NMR, IR, GC-MS, etc. Apart from focusing on reproducing results to examine the complex, my summer research also seeks to optimize our current procedures and raise the standards of our materials. 

Ami Okazaki
Mentor: Jason Schmink
Chemistry Department

Palladium-catalyzed synthesis using 2,2-diphenyl-1,3-oxathiolanes

The characteristics of palladium-catalyzed chemistry is widely studied in the field of organometallics. As a transition metal, palladium’s multiple oxidation states help to facilitate the transfer of electrons and create bonds between two separate organic molecules that otherwise would not interact. In previous years, 2,2-dimethyl-1,3-oxathiolane was predicted to function as a nucleophile in palladium-catalyzed cross-coupling reactions with aryl halides, but due to the absence of electron-withdrawing groups, it unfortunately did not function as such nucleophile. This summer, we will focus on using 2,2-diphenyl-1,3-oxathiolanes instead, because this molecule contains electron-withdrawing groups and has the potential to undergo palladium-catalyzed cross-coupling with aryl bromides to create aryl vinyl sulfides, a synthetic compound in the field of organic chemistry not widely understood. In determining the optimal reagents and conditions needed for the efficient synthesis of our desired product, fundamental characteristics of individual atoms and electron-withdrawing groups will be considered in addition to varying the reaction time, temperature, and amount of catalyst used. By applying past understandings of thiolanes, oxathiolanes, and electron-withdrawing groups to our current project, we hope to gain a better understanding of the capabilities of palladium-catalyzed cross-coupling reactions.

Zauraiz Syeda
Mentor: Susan White
Chemistry Department, Bryn Mawr College

Stability of the L30e WT and Mutant Proteins

The Saccharomyces cerevisiae (yeast) ribosomal protein L30e can regulate its own gene splicing and translation by binding to pre-mRNA.  A kink turn motif in the structure of the RNA is needed in order for the protein to bind.  At the binding site, the protein has specific amino acids that interact with the RNA. Changing these amino acids to create mutated proteins can significantly impact the thermal stability of the protein as well as its ability to form an RNA complex. Mutants will be used in this experiment to make sure that the overall structure of the protein is not affected.

Differential scanning fluorimetry (DSF) will be used to measure the thermal stability of the mutated proteins (K28A, F85A, and F85W), which will be compared to the stability of the wild type L30e protein. Similar thermal stabilities will confirm that each mutation does not significantly change the rest of the protein structure.  Since these amino acids are involved in binding to the RNA, they are on the outside of the L30e protein, suggesting that there will be little structural adjustment. A thermal cycler instrument will use temperature to denature the protein, and, as it unfolds, a hydrophobic fluorescent dye will be able to bind to it. The increasing intensity of fluorescence will show the unfolding of the protein. This thermal denaturation experiment will determine the stability of each mutant.    

Nazifa Tabassum
Advisor: Sharon Burgmayer
Department: Chemistry

Synthesis of Molybdopterins

Molybdenum-containing enzymatic cofactors (Moco) are found in most living organisms except for in saccharomyces cerevisiae (baker’s yeast) and catalyze vital reactions in their bodies. They are also a part of the carbon, sulfur and nitrogen cycles in the environment, and act primarily as redox cofactors. Despite being ubiquitous in nature, molybdenum cofactors have been studied very little. Hence it is of importance to investigate their character and activity.

Moco have several active parts in addition to the metal (molybdenum) which include dithiolene and pterin. Molybdopterin is one of the most redox active ligands of Moco. In order to study molybdopterins, they must be synthesized. This synthesis is a lengthy, multistep process. First, 6-chloropterin is synthesized from starting material in a four-step process. It is then pivolated to produce 2-pivaloyl-6-chloropterin, which is then used to make BMOPP. BMOPP is the specific pterin precursor that is then used in the model molybdopterin dithiolene to be studied. Although it is difficult to characterize and determine the purity of the pterin solids synthesized due to their insolubility in water, NMR and IR spectroscopy are used for characterization purposes.

Name: Jingyi (Alice) Tang
Advisor: William P. Malachowski
Department: Chemistry

IDO inhibitor

Inhibitors of indoleamine 2,3-dioxygenase (IDO) are designed to be potential drugs for the treatment of cancer. IDO is involved in controlling the host immune response to cancer. Cancer cells express IDO to limit the body’s immune response and thereby allow the cancer cells to grow. By creating inhibitors of IDO, we can limit the ability of cancer cells to evade detection.

Over the summer, I will be conducting synthetic organic chemistry to make newly designed inhibitors of IDO. These inhibitors are proposed to have a unique mechanism of inhibition: covalent or irreversible inhibition. That is, they are going to react with IDO and covalently link to the enzyme thereby killing it. My particular focus will be on irreversible inhibitors with a benzofuran core. The research activities in the lab on the IDO project include designing target compounds, ordering and gathering necessary chemicals and equipment to conduct the experiment, carrying out the experiment, monitoring the reaction, isolating target compounds using appropriate purification techniques, confirming purity and structure of the compound using NMR, GC/MS, LC/MS and IR techniques, and submitting the compounds to biological testing by the collaborator at Albert Einstein College of Medicine. 

Zidu Zeng
Department of Chemistry
Advisor: Dr. Bill Malachowski

Indoleamine 2,3-dioxygenase inhibitor design and synthesis

My research project is currently targeting the synthesis of a new structural class of IDO enzyme inhibitors for the treatment of cancer. Due to the fact that tumors are capable of escaping immune control during their development, and IDO enzyme was found to enable these immune escape events, the study and synthesis of IDO enzyme inhibitors is critical to help the body reverse the immune system suppression that enables cancer’s growth.

To date, the Malachowski group has synthesized three IDO enzyme inhibitor structural classes that can be used as potential drugs for cancer treatment. During this summer, the Malachowski group is focusing on the synthesis of a new IDO inhibitor that will hopefully react with IDO via covalent or irreversible inhibition.The new inhibitor uses knowledge about the enzyme mechanism and, in particular, the radicals formed during the IDO catalyzed reaction to undermine the normal process.  To accomplish this, the synthesis of an indole derivative that contains a cyclopropane ring will be undertaken. A series of chemical reactions, including a tosylation reaction, a Wittig reaction, a cyclopropanation reaction, and a saponification reaction will be done. The effectiveness of these inhibitors in reducing IDO’s catalytic activity will be tested by our collaborators at Albert Einstein College of Medicine.