Poster Presentations

Introducing students to research in general chemistry has the potential to reduce dropout rates and encourage retention in the major overall. This was implemented on the CSUS campus where second semester general chemistry students were introduced to a Metal Organic Framework (MOF) synthesis and utilization. The MOF project was then connected to the upper division chemical instrumentation course where students worked on term projects related to the MOF.

To further refine a portion of the MOF projects, we looked at the kinetics of degradation in water by analyzing the metal ion, copper, and the organic ligand, 1,3,5-benzenetricarboxylate (BTC). As the reaction proceeds, there should be an increase in the copper ions and BTC as the MOF decomposes. After synthesizing the MOF, it was placed in water, with aliquots removed at defined time intervals and filtered to separate solid from dissolved components. By removing the solids from the dissolved components, the reaction is effectively stopped. The copper in aliquots was measured by Atomic Absorption and showed a 3% degradation over 5.5 hours. The BTC was analyzed by HPLC and depicted an increase in concentration followed by a steady decline after 1.5 hours.

A multiclass materials science laboratory project has been developed and implemented in a second-semester introductory general chemistry laboratory course. This materials science project facilitates experimental synthesis, characterization, and application of a porous material, which connects to real-world problems. This project introduces students to cutting-edge solid-state analytical techniques, as well as the fields of materials science and environmental science.

Approximately 38.4 million people have been infected with HIV as of 2022. While there are treatment options to slow the progression of HIV to AIDS, there are very few preventative options. Truvada, Descovy and Apertude are currently the only FDA-approved medications for the prevention of HIV. However, these medications tend to be expensive and can give rise to severe side effects as well as viral resistance. The HIV virus infects host cells through binding to host cell receptors, which includes the ubiquitous heparan sulfate proteoglycans (HSPGs). This recognition event and early-stage viral binding and infection is observed for many other classes of virus, including SARS-CoV-2. The McReynolds research team seeks to address the lack of broad-spectrum antiviral drugs through designing novel carbohydrate mimics based on HSPG sugars. These mimics have the potential to inhibit viral binding and could be used as topical anti-viral agents targeting viral entry for HIV and SARS-CoV-2. In a minimal number of steps, sialic acid derivatives have been synthesized into glycodendrimers to mimic early-stage binding to host cells. Product formation was confirmed using NMR characterization. 

Human immunodeficiency virus, or HIV, affected over 38 million people worldwide as of 2021. There is no known cure once the virus has entered the host cell; however, there are multiple preventative medications available to be taken orally or by injection. Unfortunately, all three available preventatives share components with antiretroviral therapy, also known as ART, the only current treatment for HIV. There is concern that this may lead to drug resistant strains of HIV. It is the goal of the McReynolds lab to synthesize novel carbohydrate compounds that effectively prevent the binding of HIV to host cell. These compounds are most effective when there are many in close proximity to the binding site of the host cell. This can be accomplished by attaching the compounds to glycodendrimers. The focus of this project is the synthesis of novel glycodendrimers to which carbohydrate compounds with antiretroviral properties can ultimately be attached. 

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder commonly found among the elderly. In 2022 a total of 6.5 million in the U.S. were living with Alzheimer’s, representing 1 in 9 people over the age of 65. It is projected to affect nearly 13 million Americans by 2050. On a biochemical level, the disease is associated with decreased levels of the neurotransmitter acetylcholine (ACh) in the brain. Current pharmaceuticals have found reliable success in relieving onset symptoms of AD through reversible inhibitors of acetylcholinesterase (AChE). We have designed and prepared a library of novel AChE inhibitors that combine the isoflavone and carbamate functionalities within the same molecule. In addition to the isoflavone carbamate motifs, we are exploring the effectiveness of chalcones and coumarins converted to carbamates. We were successful in preparing several compounds within the chalcone, coumarin, and isoflavone libraries with varying but significant yields. These compounds were tested in Ellman’s assay which showed modest AChE inhibitory activity with IC50 values ranging from 5-90 μM. This was consistent with our findings from computational docking studies carried out using PyRx and Chimera. Our most recent focus has been on the conversion of coumarins to various carbamates. AChE inhibitor design, synthesis, computational docking, and preliminary inhibition data will all be presented. 

Nematodes are one of the most adverse pests of the agricultural industry. With over $80 million worth of damages annually, there were no safe and effective methods of pesticides available for commercial use. The present methods pose serious hazards to organic life and the environment. With this motivation, Dr. Alejandro Calderon-Urrea and his team conducted background research at CSU Fresno and concluded two classes of nematodes were most affected by nematicides containing a chalcone scaffold. Of the hundred of chalcones screened, three were found to be especially potent. Importantly, the mode of action by which the chalcones kill the nematodes has been difficult to elucidate. We were then tasked with synthesizing the nematicidal chalcones with a fluorescent moiety to facilitate analysis via in vivo fluorescence microscopy. After extensive synthetic investigations with fluorescein and fluoresceinamine, we recently were successful in coupling the potent chalcones to pyrene in good yields ranging from 50 to 60%. We then scaled up our syntheses and have produced hundreds of milligrams of these fluorescent chalcones and the Calderon-Urrea group will soon assess their efficacy and begin experiments to elucidate the nematicides’ mode of action. Compound design, all synthetic work, and spectral analysis will be presented. 

In our upper division integrated laboratory sequence, we have introduced experiments that require chemistry majors to investigate the versatility and limitations of modern spectroscopic techniques such as IR, 1H NMR, UV and computational analyses. Such an experiment is the determination of the conformational preference of the conformationally mobile 2-bromo-3,3,5,5-tetramethylcyclohexanone in solvents of varying polarity. Exo- and endo-2-bromobicyclo[3.2.1]octan-3-one is a model system that is conformationally static allowing for quantitative assessment of the conformational preferences in the mobile bromoketone. The classical synthesis of the bicycloketone precursor involves a relatively poor three step conversion (carbene addition, allylic halide removal, and acidic hydrolysis if a vinyl halide). Herein, we have developed a higher yielding synthetic sequence utilizing a [4 + 3] cycloaddition. Included in this project is a computational study of this cycloaddition process. 

Using commercially available Ellman’s auxiliary (R, S, and racemic 2-methyl-propanesulfinamide) we have developed a robust and scalable syntheses to precursors of chiral alkynyl functionalized beta amino acids. Beta-amino acids have been shown to possess enhanced stability to proteolysis, biological activity, as beta peptides, and as valuable moieties in drug design. An example of a drug utilizing a betaamino acid is Sitagliptin for therapeutic treatment of type 2 diabetes mellitus. Initial studies developed are conversion of 1,3-propanediol to a monosilyl protected product which is then oxidized to a monosilyl aldehyde. This aldehyde is then converted to a chiral sulfinimine using Elmann’s chiral auxillary. A substituted acetylide anion is added to the sulfinimine forming a chiral sulfinamide. We have synthesized substituted arylacetylenes by Buchwald-Hartwig couplings for use in forming various forms of the above sulfinamides. 

The electrochemical cyclization of cyclohexane-1,2-diacetic acid diethyl ester was performed through a two-step process involving the reaction of cyclohexane-1,2-diol via the Wittig Olefination reaction and reduction through organic electrochemistry. The reaction was modified to run at varying temperatures, from 5℃ to 25℃ using a water jacketed bulk electrolysis cell. The cyclized products were analyzed via GC/MS and NMR spectroscopy to determine the cis-trans ratios of the isomers.

Quinoxalinones and their derivatives exhibit significant biological activity, appearing in antiparasitic, antibacterial, antiviral, and anticancer drugs to name a few. Furthermore, the quinoxalinone structure can be used in the synthesis of industrial compounds which act as corrosion inhibitors or electroluminescent materials. A new method for the preparation of quinoxalinones was formulated by the Kellen-Yuen research group through the introduction of a Microwave Assisted Organic Synthesis (MAOS) approach. This project explores an array of modifications to the original procedure to optimize yields and further expand on this environmentally friendly synthetic approach. Variations in solvent and substituent studies will be discussed in this presentation. 

Lorneic acids are natural products whose structures can be described as tri-alkyl

substituted aromatic polyketides. These molecules exhibit significant inhibitory activity as phosphodiesterase 5 inhibitors. PDE5 inhibitors contain the ability to prevent the

inactivation of secondary messengers and thus ensure that several physiological processes can continue efficiently. The synthesis of lorneic acids are of high interest due to their possible applications within the pharmaceutical industry to treat several

neurodegenerative and cardiovascular diseases. Our research lab has reported the total synthesis of lorneic acids A and J in 7 steps in 23% yield under Results in Chemistry. The objective of this project is to complete the first total synthesis of lorneic acid F in an efficient fashion and in high yield. Starting from a commercially available reagent, 2-iodo-5-methyl-1-benzaldehyde, a Grignard addition with propyl magnesium bromide forms a secondary alcohol product that is then subjected to an acid catalyzed elimination reaction to convert the alcohol to the trans olefin. A Pd-catalyzed Suzuki cross-coupling reaction between the aryl iodide and an alkene boronic ester introduces the 6-carbon side chain with trans selectivity. Hydrolysis of the ester to the carboxylic acid under basic conditions forms the desired natural product, lorneic acid F.

The main objective of this project is to evaluate the most efficient method to carry out bromination addition reactions in a student laboratory and introduce students to green chemistry principles and practices. Bromine was generated in situ from sodium bromide and sodium perborate (SPB), two inexpensive and stable compounds. The results of bromination using this new methodology were compared with previously established bromination methods. Application of green chemistry metrics showed evidence that the new methodology is significantly greener and safer, and it is less expensive to carry out in a teaching laboratory. After the thorough evaluation and optimization of SPB/NaBr bromination addition reaction, it was determined that this reaction fulfills an increase in safety, sustainability, and accessibility. 

The anions 2-aminobenzoate, hydrogen phthalate and 2-oH Benzoate were explored with the Gemini surfactant N, N’- bis(dimethyl dodecyl)-1,2-pentane-diammonium dibromide (12-5-12) in 1:1 stoichiometric mixtures. The surfactant preparation involved a comparison of multiple methods of the 12-5-12 Gemini surfactant but was not the primary concentration. The critical micelle concentrations (CMC) were determined by three methods: conductivity, fluorescence, and nuclear magnetic resonance (NMR). Methods of experimentation for producing the 12-5-12 Gemini surfactant included microwave and reflux. The microwave and reflux experimentations of 12-5-12 were accomplished and the average reflux percent yields were 89%, and 79.295%, respectively. The microwave experimentation, while more time efficient, the average percent yields were 70.11%, 82%, and 62.54%, respectively. Overall the reflux, while less time efficient, provided a better yield on average between the three anions. These reaction conditions were not optimized since the research focus was on the anions and the formation of micelles. The CMC of these surfactants with the three benzoates have values paralleling the hydrophobicity values of the respective benzoic acids. The 12-5-12 surfactant with sodium salicylate yielded the smallest CMC values with 0.30, 0.20, 0.30 mM for the respective methods of conductivity, fluorescence, and NMR. The 12-5-12 surfactant with sodium ortho-aminobenzoate CMC values were 0.34, 0.20, 0.38 mM for the three respective methods, and the 12-5-12 surfactant with hydrogen phthalate yielded the highest respective CMC values of 0.515, 0.55, 0.56 mM. The general decrease in the CMC is in agreement with literature of the influence of benzoate anions in comparison to the inorganic bromide anion. The lower CMC value from fluorescence is common among the other surfactants, likely due to the intensity level of the fluorescence used or the calculated concentration ratio of surfactant, in comparison to NMR and conductivity CMC values. 

The cationic Gemini surfactant N, N′-bis(dimethyl dodecyl)-1,2-pentane-diammonium dibromide (12-5-12) was explored with sodium 2,6-difluoro benzoate and sodium 2-fluoro benzoate. Critical micelle concentrations (CMC) were determined via conductivity, fluorescence, and nuclear magnetic resonance (NMR). These benzoate anions were added in a 1:1 stoichiometric ratio to the surfactant. They were synthesized as a diquat dibromide salt, with an added stock solution of 12-5-12 sodium 2,6-difluoro benzoate and sodium 2-fluoro benzoate. The average CMC for 12-5-12 2,6-difluoro benzoate using conductivity was 0.67 mM and the fluorescence and NMR CMC values were 0.49 mM. The 2-fluoro benzoate conductivity and NMR studies indicated an average CMC of 0.4 mM while the fluorescence results indicated a lower CMC of 0.3 mM. The lower CMC value from fluorescence is common among other surfactants and is likely due to the fluorescein seeding micelle formation. The 2,6-difluoro benzoate and ortho-fluoro benzoate anions reduce the cmc values reflecting their hydrophobicity values in comparison to the surfactant with the bromide alone. The 12-5-12 surfactant was prepared by two methods: microwave synthesis and reflux method. The syntheses via rapid microwave and reflux were compared for the production of 12-5-12 Gemini surfactant. The microwave resulted in an average percent yield of 72.3%. In comparison, the reflux yielded an average percent yield of 84.2%. To be more energy efficient, prevent waste, and reduce wait time, the rapid microwave should be used to produce 12-5-12 Gemini surfactant. 

Our research group is particularly interested in core crosslinked star polymers because this structure - with a crosslinked core and arms that extend out from that core - allows for isolation of specific reactive species from the surrounding chemical environment. One of the overarching goals of our group’s research is to use structured polymers as scaffolds to achieve tandem catalysis through confinement and site-isolation. Thus, the isolating core of the star polymer is well-suited to supporting and confining a transition metal-based catalytic center. We have synthesized star polymers from a range of monomers including: styrene, tert-butylstyrene, tert-butylacrylate, and N-isopropylacrylamide. These monomers vary in steric bulk and polarity which allows us to compare the impact of these factors on the catalytic ability of the supported catalysts. The present work focuses on advancements in the synthesis of well-defined poly(tert-butylstyrene) and poly(tert-butylacrylate) star polymers through an arm-first method using reversible addition fragmentation chain transfer (RAFT) polymerization. 

The decarbonylation of carbonyl-containing compounds is an important C–C bond-cleaving reaction that has been applied to target-driven synthesis. Haller and Bauer discovered base-mediated protodebenzoylation of aromatic ketones in the early 1900’s. Aldehydes are considered unsuitable for Haller–Bauer decarbonylation since they typically disproportionate into carboxylic acid and tertiary alcohol under basic conditions. In pursuit of a more atom-economical, transition metal-free, and ambient temperature decarbonylation, we have developed a Haller–Bauer protodeformylation of α-quaternary homobenzaldehydes that affords isopropyl arenes. Mechanistic insight from isotopic labeling and spectroscopic studies is provided.

Quantum dots (QDs) are fluorescent semiconducting nanoparticles that have been used in LEDs and sensors. We recently developed a concise three-step synthetic route to enable the preparation of small libraries of liquid crystal-like ('mesogenic') primary amine-bearing ligands. These ligands have been used to prepare ligand-modified QDs and direct their self-assembly into microstructures. Here we describe an investigation of the efficiency of the exchange of our mesogenic amine ligands with the alkylamine ligands supplied on commercial quantum dots using various characterization techniques, including 1H NMR. Understanding the relationship between ligand structure and exchange efficiency will help inform ongoing QD self-assembly studies conducted by our collaborators.

Ovarian cancer is one of the leading causes of cancer related deaths in women, and chances of survival dramatically increase with early diagnosis. But there are no simple and reliable diagnostics available for screening. In hopes of helping to solve this problem, we are working to develop bioaffinity probes to target specific disease biomarkers. The biomarker we have been focusing on is a type of post-translational modification (PTM), glycosylation. Previous studies have shown aberrant glycosylation to be correlated with early stages of developing cancers, potentially through its significance in cellular communication. With the diversity and complexity of glycan structures, they provide a challenging target for analytical characterization. This project focuses on the development of oligonucleotide probes, termed aptamers, with increased selectivity and sensitivity for their specific target. We have been concentrating on isolating aptamers for cancer-associated glycoforms of thrombospondin-1 (TSP-1). TSP-1 exhibits tumor-specific glycosylation when isolated from patients with endometrioid ovarian cancer compared to TSP-1 isolated from non-cancerous patients. Our goal is to use capillary electrophoresis (CE) selection techniques to identify aptamers with increased affinity and specificity to cancerous glycoforms of TSP-1 over the non-cancerous protein. Previous efforts in our lab have already successfully used CE to yield aptamers with increased specificity for a glycosylated VEGF peptide versus the non-glycosylated variant.

Paper-based microfluidics offer a method for point-of-care diagnostics as paper is a cheap, lightweight, and thin material, capable of effective separation of analytes which can be integrated with various detection methods. Using a standard inkjet printer, hydrophobic toner ink can be deposited onto the surface of filter paper, and when heated at the fusion temperature of ink, it permeates into the paper, forming hydrophobic barriers. Through the use of computer-aided design software, paper-based analytical devices (PADs) are dimensioned and scaled for printing, providing a means for cheap and accurate channel customization for the manipulation of fluid flow on the surface of paper. Current efforts in the lab are focused on optimizing reagent volumes, heating conditions, and channel dimensions of a nickel(II)-dimethylglyoxime assay to achieve a more linear response on the PAD. With the experience gained exploring this well studied assay, the Suljak lab intends to create novel, paper-based assays integrating aptamers, ssDNA or RNA affinity ligands, to screen for early-stage endometrioid ovarian cancer. 

Monoterpene synthases convert geranyl diphosphate to a variety of ten-carbon isomers in the presence of a divalent metal cation. These proteins serve as models for understanding how enzymes catalyze reaction sequences involving carbocation intermediates. Pinene synthase from Abies grandis catalyzes the conversion of geranyl diphosphate to (-)-alpha-pinene and (-)-beta-pinene. Unlike most terpene synthases that use either Mg2+ or Mn2+ to support catalysis, pinene synthase has an exclusive requirement for Mn2+ and an additional requirement for a monovalent cation such as K+. Analysis of the X-ray crystal structure of pinene synthase would provide insight into how this unique class of monoterpene synthase catalyzes the cyclization of geranyl diphosphate. To generate sufficient protein to support crystallization studies, pinene synthase containing a 6X-his tag was expressed in Escherichia coli then purified using metal ion affinity chromatography followed by size-exclusion chromatography. Expressed pinene synthase was shown to be catalytically active, and SDS-PAGE analysis showed that it was sufficiently pure for crystallization trials. The purified protein was submitted for crystallization screens in the laboratory of Dr. Dave Wilson at University of California, Davis. 

Terpenes represent the largest group of secondary metabolites which play key roles in defense and signaling. Pinene synthase catalyzes the conversion of geranyl diphosphate to generate the monoterpenes (-)-α-pinene and (-)-β-pinene. The importance of pinene synthase lies in its value as a model in studying electrophilic reaction cascades and its use as a potential biosynthetic catalyst. A pinene synthase of particular interest is that found in Abies grandis, the grand fir tree. Unlike typical terpene synthases, the Abies grandis pinene synthase requires a monovalent metal cation to function and cannot use Mg2+ as a divalent metal cation cofactor (Mn2+ is preferred). However, it is unclear whether Mg2+ may be able to partially support catalysis in the presence of sub-optimal levels of Mn2+ or whether it actively inhibits Mn2+-supported catalysis. This study evaluates the effect of varying concentrations of Mg2+ on overall levels of catalytic activity and product distribution of Abies grandis pinene synthase incubated with Mn2+. 

ATP-binding cassette (ABC) transporters utilize ATP energy to move substrates across membranes against concentration gradients, playing a crucial role in several essential cellular functions. Mutations in human ABC transporters have been linked to various conditions, such as cystic fibrosis, liver disease, and diabetes. However, the mechanism of ABC transporters is still poorly understood. Our research aims to examine the mechanisms of substrate specificity and transport using a model system found in bacteria, specifically the E. coli methionine import system, which consists of a membrane-embedded transporter, MetNI, and a cognate binding protein, MetQ. In this study, we have characterized the substrate binding affinities of several MetQ variants using isothermal titration calorimetry (ITC). Our data have shown that single amino acid mutations in the substrate binding site reduce the affinity for L-methionine by approximately 100-fold. Interestingly, our preliminary results have shown that wild-type MetQ can bind to either L-methionine or D-methionine, while a glutamate to glutamine mutation loses the ability to bind to D-methionine but retains the ability to bind the L-isomer. Future investigations of this single amino acid mutation will be conducted to understand this phenomenon. With these binding affinities in hand, we will conduct further experiments using both MetNI and MetQ to dissect the mechanisms of ABC transport. 

As the San Francisco Bay Area is expected to undergo further industrialization and urbanization, it is more important than ever to monitor trace metal pollution in coastal wetlands surrounding the San Francisco Bay Estuary. Trace metal pollution threatens an ecosystem’s ability to provide high-quality ecological goods and services to human communities. The main goal of this study is to assess trace metal concentrations in surface sediments from two small, coastal, urban wetlands. Five sediment cores were previously obtained from two local estuarine sites: Martinez Regional Shoreline and Bay Point Regional Shoreline. Sediment samples were analyzed by MP-AES to measure the concentrations of four trace metals in each core: chromium, copper, nickel, and lead. A field-portable XRF instrument was also utilized to quantify trace metal concentrations in sediments as a means of comparison. Our results were compared to the EPA’s Sediment Quality Guidelines to determine pollution level. In conclusion, no significant levels of trace metal pollution were present in any of the surface sediments of each core. 

Aerosols present in the upper troposphere and lower stratosphere (UT/LS) are composed of sulfuric acid (40-80 wt.%) and water; therefore, climate models treat them as highly scattering to sunlight, resulting in an overall cooling effect. However, airborne measurements have shown that many UT/LS aerosols also contain a significant fraction of organic compounds potentially altering their climate-forcing properties. We have previously shown that reactions of propanal in sulfuric acid produce highly colored surface films which are composed of complex mixtures of aldol condensation products, acetals, and propanal itself. The typical aerosol lifetime in the UT/LS  can range from months to years. During this time reactions of organic compounds in the aerosols can continue to occur, potentially altering the chemical composition of the surface films and changing their climate-forcing properties. To analyze the effects of aging, the surface films formed on these mixtures were chemically analyzed over a 3-week period via proton nuclear magnetic resonance (NMR) spectroscopy. The preliminary results indicate that the chemical composition of organic films formed on the surface of aerosols can change with time, and potentially impact their optical, chemical, and/or cloud-forming properties. 

Glyoxal and methylglyoxal species are common in atmospheric aerosols and their speciation may be altered during cloud formation as water activity and pH change drastically, which may drive hydration, hydrolysis, and/or polymerization reactions. Water uptake during cloud formation was simulated by approximately 100-fold dilution of 40 wt. % glyoxal or methylglyoxal. Chemical speciation changes were monitored via high-resolution quadrupole mass spectrometry. Results indicate that glyoxal and methylglyoxal polymers persist after dilution. Multiple polymer masses were observed for each organic due to hydration either of the monomer precursors or of the polymers themselves. The largest peaks in the mass spectra corresponded to dimers and trimers while polymers up to the hexamer for glyoxal and up to the octamer for methylglyoxal were also observed. Overall polymer kinetic behavior was consistent with sequential decomposition from large polymers to smaller ones and eventually to monomers. 

The interconversion of benzene-oxide and oxepin has relevance to biosynthetic pathways, as benzene oxides are common metabolic intermediates, and numerous natural products contain oxepin subunits. To fully understand the kinetics of these interconversions in biochemical systems, we report computational results aimed at assessing the contribution of heavy-atom tunneling to the rates. Using DFT and CCSD(T) methods, the conversion of benzene-oxide to oxepin is computed to have a ca. 6 kcal/mol barrier and to be approximately energetic (within 2 kcal/mol).Rate constants computed with and without multidimensional tunneling contributions yield a tunneling-inclusive rate constant of 4.6x10-5 and a >99% contribution of tunneling at 60 K, suggesting that tunneling dominate the equilibrium. 

Six-electron electrocyclic reactions usually require relatively high temperatures; however recent research has shown that such reactions can occur at significantly lower temperatures in biosynthetic and biomimetic pathways. Sometimes, these reactions can proceed at least partly via tunneling, a quantum mechanical phenomenon where particles can tunnel through energy barriers rather than pass over them, provided that the atoms do not have to move very far. While tunneling by hydrogen is well established in enzymatic reactions, very little is known about the contribution of heavy-atom tunneling in biochemistry. Our group has embarked on an effort to provide a more complete picture about biochemical kinetics by using computation to explore the possible contributions of heavy-atom tunneling (e.g. by carbon) to biosynthetic pathways and biomimetic syntheses. Pathways utilizing bicyclo[4.2.0]octa-2,4-diene motifs arise from thermally allowed electrocyclic reactions as seen in the synthesis of sclerocitrin and elysiapyrone A and B. For these motifs with and without substituents, tunneling contributions were moderate at around 32% to 17% at biologically relevant temperatures of 240 K to 340 K. These values suggest that these types of thermally allowed electrocyclic reactions are not dominated by tunneling. 

Heavy-atom tunneling occurs when an atom larger than hydrogen, such as carbon, does not have sufficient energy to go over a barrier, so it tunnels through it instead. This phenomenon is reported to be prevalent in certain reactions in which atoms have to move only short distances. Whereas numerous hydrogen transfer processes in biochemistry are dominated by hydrogen tunneling, there are not yet any reported observations of heavy-atom tunneling in biochemical reactions. However, heavy-atom tunneling was recently predicted to make a modest contribution to the rates of pericyclic reactions in the biosynthesis of tetrahydrocannabinol. Motivated by the common occurrence of pericyclic reactions in biochemistry, we used computational chemistry to study various model reactions relevant to biosynthetic pathways, such as the electrocyclization of hexatriene. This work focuses on the 6-electron electrocyclization step in the biosynthesis of occidentalol. M06-2X/6-31G* results of multidimensional tunneling calculations suggest that tunneling by carbon is predicted to dominate the rate (>50%) at temperatures of 220K or lower. The prediction of significant tunneling in such processes potentially broadens the scope of heavy-atom tunneling into biochemistry, and allows us to identify structural features that enhance such tunneling in biochemical reactions. 

Gram-positive bacteria like Staphylococcus aureus are responsible for causing a variety of illnesses in humans, ranging from minor infections to pneumonia. S. aureus, particularly a methicillin resistant strain called MRSA, is the leading cause of hospital-associated infections worldwide as antibiotic resistance increases in S. aureus. As a result of this, new treatment methods are required to combat the virulence of MRSA. A novel approach being investigated is that of covalent inhibitor molecules that inhibit the virulence of MRSA without killing the bacteria. Jaudzems et al. reported a covalent inhibitor of Sortase A, an enzyme that anchors surface proteins of Gram-positive bacteria to the cell wall peptidoglycan of a target cell by catalyzing a covalent attachment. This reaction is catalyzed by the active site cysteine of Sortase A, which the Jaudzems inhibitor binds to inhibit this action while making few other noncovalent interactions with its kojic acid core. This work aims to modify the kojic acid core at the C2 position by adding aromatic substituents to take advantage of a nearby hydrophobic pocket. This type of work is understudied, and towards this end, we aim to explore a decarboxylative crosscoupling approach. In this work, various trial reactions of the crosscoupling were explored in order to optimize for the desired result. To optimize the reaction, modifications of reaction time, temperature, stoichiometric equivalence, and catalyst were varied. The best reaction conditions have yielded a 22% yield of the desired product with proto-decarboxylation and an undesired cross-coupling occurring at the C6 position producing a major byproduct in 46% yield. Future directions for this work include further varying metal catalysts, varying protecting groups on the C5 hydroxyl group, and varying solvents.

Current chemotherapeutic drugs that are available and used in clinical settings, while effective, are limited by their low selectivity and high toxicity. These drugs are cytotoxic molecules that cause damage in cells in order to trigger apoptosis, specifically, by reacting with DNA bases. Our goal is to synthesize a DNA alkylating chemotherapeutic prodrug that would remain active in cancer cells, but undergo an intramolecular cyclization elsewhere in the body to become inert, taking advantage of carboxylesterase downregulation in certain cancer types to achieve selectivity. Thus far, the Curtius Rearrangement, which is the first step in this six step synthesis, has been completed at the 100 mg scale and 300 mg scale. Denaturing gel electrophoresis was used to visualize the degree of DNA damage caused by the compound, and the efficacy of the enzyme in rendering the compound inert. In order to prepare for this assay, linearized pRSETa_eGFP was generated by replicating the pRSETa_eGFP plasmid, and linearizing the product via restriction enzyme digestion—followed by a purification after each step. The future foci of this project include testing various electrophilic warheads for DNA damage and various R groups for improved solubility, and studying how the specificity, rate of cyclization, and degree of alkylation can be improved upon.

Many current anticancer treatments do not have adequate selectivity between cancer cells and healthy cells, causing negative side effects that the patient has to endure. As a result, there is a need for drugs that can differentiate cancer cells from healthy cells. DNA intercalators are flat, planar molecules that bind noncovalently to DNA, altering its conformation and resulting in altered gene expression, inhibition of DNA replication, and can cause cell death. DNA intercalators that can transform from planar to nonplanar when interacting with normal cells while maintaining planarity in cancer cells can increase the selectivity for this specific subset of anticancer drugs. A model intercalator was synthesized via 5 steps with low percent yield using a Heck reaction, Hydrogenation, and Curtius Rearrangement as key synthetic transformations. For future experiments, a Suzuki-Miyaura and a palladium-catalyzed Heck reaction of aryl chlorides will be investigated to yield a DNA intercalator that is able to switch from planar to nonplanar during biological assays.

Metal-salens have been the focus of many studies due to their unique properties and potential applications in various fields, including catalysis and materials science. As potential photosensitizers, they have shown promising photophysical properties. Investigating these properties requires a thorough examination of their UV-vis spectra, which reveal their ability to absorb and emit light. This study aims to calculate the UV-vis spectra for metal-salens with aliphatic and aromatic backbones with four different metals (NiII, ZnII, CoII, and CuII) and 12 different substituents (ranging from electron-withdrawing to electron-donating) to examine correlations between the substituent Hammett σp parameters and the longest wavelength absorptions and most intense absorptions in the UV-vis spectra of the metal-salens. Time-dependent density functional theory (TD-DFT) was used to compute the UV-Vis spectra for the different combinations of metal-salens, metal centers, and substituents. The ωB97-XD functional was chosen for its accuracy in modeling charge transfer transitions. Hammett plots are generated for the UV-vis absorptions for each type of metal-salen (aliphatic or aromatic) with each metal center versus their substituent Hammett σp parameters. The electronic transitions are also assigned for the observed absorptions in the UV-vis spectra. 

Quinoxalenediynes are heterocyclic compounds containing a ring complex made up of a benzene ring and a pyrazine ring which supports an enediyne functional group. Introducing nitrogen heterocycles can improve delivery to biological targets and DNA intercalation for biological applications. The cyclization of enediyne functional groups creates reactive diradicals that cleave DNA double helices by stripping hydrogen atoms from the sugar phosphate backbone, leading to cell death. As such, enediyne functional groups have been used in anticancer therapies. The standard thermal cyclization of quinoxalenediynes is not sensitive to substituents on the enediynes; however, radical anion cyclization demonstrates increased sensitivity to remote substituents due to the crossing of out-of-plane and in-plane π molecular orbitals near the transition state. This study employed density functional theory (DFT) calculations to investigate the radical anion cyclization of quinoxalenediynes with various electron-withdrawing and electron-donating enediyne substituents. The energetics of C1-C5 and C1-C6 radical anion cyclization reactions with the substituted quinoxalenediynes was determined. The activation enthalpies and reaction enthalpies for both cyclization pathways were correlated with the Hammett σp parameters for the substituents to understand the effects of substituents on the radical anion cyclizations. 

Our lab has developed a droplet microfluidic technique dubbed Sorting by Interfacial Tension (SIFT) that allows for the sorting of droplets based on their interfacial tension, which changes as a function of droplet pH. The technique has been used for the label-free sorting of cells with different levels of glycolysis. The current design has three sections that run inline within a single microfluidic chip: cell encapsulation, droplet incubation, and cell sorting.

The inline nature of the system results in significant efficiency and functionality complications. Each section requires specific conditions to function efficiently, and in order to reach these conditions, flow rates (controlled by a syringe pump) are altered. In reaching one section's conditions, another section is often compromised, resulting in a lengthy and inconsistent process before we can reach optimal conditions to run our sorting experiment effectively.

I seek to solve these problems by partitioning our chip. This would allow for more effective and efficient control over the conditions each section requires for optimal function by removing the concern of altering another section's functionality. The main challenge with partitioning is maintaining the overall system's effectiveness, as each junction requires a transition that does not compromise cell viability or droplet integrity, all while keeping with the ideal of a streamlined sorting chip.

Tunneling by hydrogen is known to be common in enzymatic reactions, but little is known about the extent of tunneling by heavy atoms (e.g. carbon) in biochemistry. Some electrocyclic reactions— dominated by heavy atom motions— have been found or predicted to involve a significant contribution of tunneling to the rate. Many biosynthetic pathways involve electrocyclic reactions, making these pathways reasonable candidates to begin exploring the prevalence of tunneling in biosynthesis. This computational study examines key steps in the oxa-6π electrocyclic cascade in model systems of thiaplidiaquinone A, an apoptosis-inducing marine metabolite. The ability of this compound to transport electrons is biologically significant and makes it a good candidate to study tunneling in the biochemical context. The electrocyclic ring opening of 2H-pyran and electrocyclic ring closing of ortho-quinone methides were used as model systems for the analogous reaction. It was found that heavy-atom tunneling contributes modestly to the reactions at biochemically relevant temperatures, with contributions ranging from 14-20% at 310 K.