Chemistry Commons^™

Scandium Triflate-Catalyzed Aromatic Aldehydic C-H Activation, Nicholas Griffin

Honors Projects

Herein described is a scandium triflate-catalyzed C-H activation of commercially available aromatic aldehydes achieved in low yields. The reaction occured in a one-pot synthesis over a two-hour duration and required minimal purification. Inclusion of a fluorine-tagged phenol allowed for reaction monitoring via ¹⁹FNMR.

Modeling Accuracy Matters: Aligning Molecular Dynamics With 2d Nmr Derived Noe Restraints, Milan Patel

Honors Scholar Theses

Among structural biology techniques, Nuclear Magnetic Resonance (NMR) provides a holistic view of structure that is close to protein structure in situ. Namely, NMR imaging allows for the solution state of the protein to be observed, derived from Nuclear Overhauser Effect restraints (NOEs). NOEs are a distance range in which hydrogen pairs are observed to stay within range of, and therefore experimental data which computational models can be compared against. To that end, we investigated the effects of adding the NOE restraints as distance restraints in Molecular Dynamics (MD) simulations on the 24 residue HP24stab derived villin headpiece subdomain to …

Extracellular Poly(Hydroxybutyrate) Bioplastic Production Using Surface Display Techniques, Kevin Beaver, Ashwini Dantanarayana, Willisa Liou, Markus Babst, Shelley D. Minteer

Chemistry Faculty Research & Creative Works

Poly(hydroxybutyrate) is a biocompatible, biodegradable polyester synthesized naturally in a variety of microbial species. A greener alternative to petroleum-based plastics and sought after for biomedical applications, poly(hydroxybutyrate) has failed to break through as a leading material in the plastic industry due to its high cost of production. Specifically, the extraction of this material from within bacterial cells requires lysis of cells, which takes time, uses harsh chemicals, and starts the process again with growing new living cells. Recently, surface display of enzymes on bacterial membranes has become an emerging technique for extracellular biocatalysis. In this work, a fusion protein lpp-ompA-phaC …

The Reversible Low-Temperature Instability Of Human Dj-1 Oxidative States, Tessa Andrews, Javier Seravallic, Robert Powers

Robert Powers Publications

DJ-1 is a homodimeric protein that is centrally involved in various human diseases including Parkinson disease (PD). DJ-1 protects against oxidative damage and mitochondrial dysfunction through a homeostatic control of reactive oxygen species (ROS). DJ-1 pathology results from a loss of function, where ROS readily oxidizes a highly conserved and functionally essential cysteine (C106). The over-oxidation of DJ-1 C106 leads to a dynamically destabilized and biologically inactivated protein. An analysis of the structural stability of DJ-1 as a function of oxidative state and temperature may provide further insights into the role the protein plays in PD progression. NMR spectroscopy, circular …

Tenvr: Matlab-Based Toolbox For Environmental Research, Aleksandar I. Goranov, Rachel L. Sleighter, Dobromir A. Yordanov, Patrick G. Hatcher

Chemistry & Biochemistry Faculty Publications

With the advancements in science and technology, datasets become larger and more multivariate, which warrants the need for programming tools for fast data processing and multivariate statistical analysis. Here, the MATLAB-based Toolbox for Environmental Research "TEnvR" (pronounced "ten-ver") is introduced. This novel toolbox includes 44 open-source codes for automated data analysis from a multitude of techniques, such as ultraviolet-visible, fluorescence, and nuclear magnetic resonance spectroscopies, as well as from ultrahigh resolution mass spectrometry. Provided are codes for processing data (e.g., spectral corrections, formula assignment), visualization of figures, calculation of metrics, multivariate statistics, and automated work-up of large datasets. TEnvR allows …

Enhancing The Conformational Stability Of The Cl-Par-4 Tumor Suppressor Via Site-Directed Mutagenesis, Samjhana Pandey, Krishna K. Raut, Andrea M. Clark, Antoine Baudin, Lamya Djemri, David S. Libich, Komala Ponniah, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Intrinsically disordered proteins play important roles in cell signaling, and dysregulation of these proteins is associated with several diseases. Prostate apoptosis response-4 (Par-4), an approximately 40 kilodalton proapoptotic tumor suppressor, is a predominantly intrinsically disordered protein whose downregulation has been observed in various cancers. The caspase-cleaved fragment of Par-4 (cl-Par-4) is active and plays a role in tumor suppression by inhibiting cell survival pathways. Here, we employed site-directed mutagenesis to create a cl-Par-4 point mutant (D313K). The expressed and purified D313K protein was characterized using biophysical techniques, and the results were compared to that of the wild-type (WT). We have …

Meta-Analysis Reveals Both The Promises And The Challenges Of Clinical Metabolomics, Heidi E. Roth, Robert Powers

Chemistry Department: Faculty Publications

Clinical metabolomics is a rapidly expanding field focused on identifying molecular biomarkers to aid in the efficient diagnosis and treatment of human diseases. Variations in study design, metabolomics methodologies, and investigator protocols raise serious concerns about the accuracy and reproducibility of these potential biomarkers. The explosive growth of the field has led to the recent availability of numerous replicate clinical studies, which permits an evaluation of the consistency of biomarkers identified across multiple metabolomics projects. Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related death and has the lowest five-year survival rate primarily due to the lack of an …

The Synthesis Of Deuterated Isohumulones For Use As Internal Standards In Lc-Ms Stable Isotope Dilution Assays, Patrick Gleason, Bruce Hamper Dr.

Undergraduate Research Symposium

Humulones are compounds that are prevalent in the hops flowers (Humulus Lupulus) used in beer brewing. These compounds undergo isomerization during the brewing process, and the resulting isohumulones are considered to be the primary contributors to the bitter flavors present in beer. As such, quantifying their presence, and the relative presence of their homologs(n-, co-, ad-), is of great importance in the characterization of beer. In this effort, one of the homologs of humulone (co) was isolated before being subsequently isomerized and deuterated for the purpose of analyzing beer by stable isotope dilution assay mass spectrometry(SIDA-MS). The addition of this …

Chemical Shift Assignments Of The N-Terminal Domain Of Psd95 (Psd95-Nt), Yonghong Zhang, Johannes W. Hell, James B. Ames

Chemistry Faculty Publications and Presentations

Postsynaptic density protein-95 (PSD95) contributes to the postsynaptic architecture of neuronal synapses and plays an important role in controlling synaptic plasticity. The N-terminal domain of PSD95 (residues 1–71, called PSD95-NT) interacts with target proteins (calmodulin, α-actinin-1 and CDKL5), which regulate the Ca2+-dependent degradation of glutamate receptors. We report complete backbone NMR chemical shift assignments of PSD95-NT (BMRB No. 50752).

Comparison Of Bifurcated Halogen With Hydrogen Bonds, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

Bifurcated halogen bonds are constructed with FBr and FI as Lewis acids, paired with NH₃ and NCH bases. The first type considered places two bases together with a single acid, while the reverse case of two acids sharing a single base constitutes the second type. These bifurcated systems are compared with the analogous H-bonds wherein FH serves as the acid. In most cases, a bifurcated system is energetically inferior to a single linear bond. There is a larger energetic cost to forcing the single σ-hole of an acid to interact with a pair of bases, than the other way …

Synthetic Pathways For Potential Platinum 1,10-Phenanthroline Compounds, Jacob Young

Mahurin Honors College Capstone Experience/Thesis Projects

There are extremely important uses for platinum when it comes to the treatment of cancers and dementias. One potential therapeutic combines platinum with a structure known as phenanthroline. This platinum phenanthroline structure is normally extremely water-insoluble, rendering it difficult to study and use in biological systems. The Williams’ Biochemistry Laboratory endeavored to find a simpler synthetic pathway for a water-soluble phenanthroline product. While unsuccessful in identifying a product as of yet, many synthetic pathways have been ruled out, and more hypothetical pathways are being formulated for testing.

Among the strategies analyzed are varying solvent, reagents, apparatus, methodology, and temperature in …

Direct Determination Of Absolute Stereochemistry Of Α-Methylselenocysteine Using The Mosher Method, Robert J. Wehrle, Douglas R. Powell, Douglas S. Masterson

Faculty Publications

Mosher amides of α-methylselenocysteine were synthesized to determine the absolute stereochemistry of the sterically hindered α-carbon utilizing ¹H, ¹³C, ¹⁹F, and ⁷⁷Se NMR spectroscopies. After analysis of these spectra using the established Mosher method, the stereochemistry of the α-carbon was determined to be (R), which was subsequently confirmed using x-ray crystallography.

Phosphorus Nmr And Its Application To Metabolomics, Paula Evans, Fatema Bhinderwala, Robert Powers, Martha Morton, Thomas Smith

UCARE Research Products

Stable isotopes are routinely employed by NMR metabolomics to highlight specific metabolic processes and to monitor pathway flux. 13C-carbon and 15N-nitrogen labeled nutrients are convenient sources of isotope tracers and are commonly added as supplements to a variety of biological systems ranging from cell cultures to animal models. Unlike 13C and 15N, 31P-phosphourous is a naturally abundant and NMR active isotope that doesn’t require an external supplemental source. To date, 31P NMR has seen limited usage in metabolomics because of a lack of reference spectra, difficulties in sample preparation, and an absence of two-dimensional (2D) NMR experiments. But, 31P NMR …

Ribbon Α-Conotoxin Ktm Exhibits Potent Inhibition Of Nicotinic Acetylcholine Receptors, Leanna A. Marquart, Matthew W. Turner, Lisa R. Warner, Matthew D. King, James R. Groome, Owen M. Mcdougal

Chemistry and Biochemistry Faculty Publications and Presentations

KTM is a 16 amino acid peptide with the sequence WCCSYPGCYWSSSKWC. Here, we present the nuclear magnetic resonance (NMR) structure and bioactivity of this rationally designed α-conotoxin (α-CTx) that demonstrates potent inhibition of rat α3β2-nicotinic acetylcholine receptors (rα3β2-nAChRs). Two bioassays were used to test the efficacy of KTM. First, a qualitative PC12 cell-based assay confirmed that KTM acts as a nAChR antagonist. Second, bioactivity evaluation by two-electrode voltage clamp electrophysiology was used to measure the inhibition of rα3β2-nAChRs by KTM (IC₅₀ = 0.19 ± 0.02 nM), and inhibition of the same nAChR isoform by α-CTx MII (IC₅₀ = …

Synthesis Of Novel Reiii And Rev Metallointercalator Complexes For Use As Dna Damage Probes, Eli Schwartz

Honors Program Theses and Projects

Cancer is a disease that affects millions around the globe. Treatments such as radiation and chemotherapy are often used to treat cancerous tumors, but are not 100% effective in curing the patient. Alternatively, some research groups have proposed the use of metallointercalators, metal complexes consisting of a rhodium, ruthenium, or iridium metal center with bidentate supporting ligands such as bipyridine and phenanthroline, or tridentate ligands such as terpyridine. The complexes also contain a bidentate intercalating group such as dipyridophenazine. These complexes possess the ability to directly bind to DNA through intercalation between the stacks of DNA base pairs, giving them …

The Characterization Of A New Metabolite From A Trichodesmium Bloom, Kelly M. Mcmanus

Senior Honors Projects

Our laboratory has been investigating blooms of Trichodesmium, a genus of ecologically important, nitrogen-fixing cyanobacteria, collected from Padre Island in the Gulf of Mexico. Trichodesmium species are an underexplored biological source of cyanobacteria – a taxa that has been shown to produce chemically diverse secondary metabolites. With our focus on the isolation and structure characterization of new bioactive marine natural products, our research group has discovered over 25 new-to-science compounds over the past three years from these blooms. UV and mass spectrometry-guided isolation of Trichodesmium chromatography fractions were utilized to isolate a new metabolite. Isolation of this metabolite was …

Nmr Metabolomics Protocols For Drug Discovery, Fatema Bhinderwala, Robert Powers

Chemistry Department: Faculty Publications

Drug discovery is an extremely difficult and challenging endeavor with a very high failure rate. The task of identifying a drug that is safe, selective and effective is a daunting proposition because disease biology is complex and highly variable across patients. Metabolomics enables the discovery of disease biomarkers, which provides insights into the molecular and metabolic basis of disease and may be used to assess treatment prognosis and outcome. In this regard, metabolomics has evolved to become an important component of the drug discovery process to resolve efficacy and toxicity issues, and as a tool for precision medicine. A detailed …

Palladium Complexes Bearing Κ²-N,N And Κ³-N,N,O Pendant Amine Bis(Phenolate) Ligands, Brendan J. Graziano, Eric M. Collins, Nathaniel C. Mccutcheon, Claire L. Griffith, Nicole M. Braunscheidel, Trilisa M. Perrine, Bradley M. Wile

Chemistry and Biochemistry Faculty Scholarship

The synthesis and characterization of ten new palladium(II) amine bis(phenolate) complexes is reported. Solution and single-crystal X-ray diffraction studies reveal the presence of both κ²-N,N and κ³-N,N,O binding modes in these square planar complexes. For complexes with sterically less demanding phenolate donors, addition of external acidic or basic reagents allows for the selective masking of a coordination site at Pd. Complexes bearing bulky cumyl substituents on phenolate donors exhibited unusual ¹H NMR spectroscopic features that are consistent with an anagostic interaction with the palladium center. Computational analysis …

Structural Basis Of 7sk Rna 5′ Γ-Phosphate Methylation And Retention By Mepce, Yuan Yang, Catherine D. Eichhorn, Yaqiang Wang, Duilio Cascio, Juli Feigon

Chemistry Department: Faculty Publications

Among RNA 5′-cap structures, γ-phosphate monomethylation is unique to a small subset of noncoding RNAs, 7SK and U6 in humans. 7SK is capped by methylphosphate capping enzyme (MePCE), which has a second non-enzymatic role as a core component of the 7SK RNP that is an essential regulator of RNA transcription. We report 2.0 and 2.1 Å X-ray crystal structures of human MePCE methyltransferase domain bound to S-adenosylhomocysteine (SAH) and uncapped or capped 7SK substrates, respectively. 7SK recognition is achieved by protein contacts to a 5′ hairpin-single-stranded RNA region, explaining MePCE specificity for 7SK and U6. The structures reveal SAH and …

Conformational Flexibility In The Enterovirus Rna Replication Platform, Meghan S. Warden, Kai Cai, Gabriel Cornilescu, Jordan E. Burke, Komala Ponniah, Samuel E. Butcher, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

A presumed RNA cloverleaf (5′CL), located at the 5′-most end of the noncoding region of the enterovirus genome, is the primary established site for initiation of genomic replication. Stem–loop B (SLB) and stem–loop D (SLD), the two largest stem–loops within the 5′CL, serve as recognition sites for protein interactions that are essential for replication. Here we present the solution structure of rhinovirus serotype 14 5′CL using a combination of nuclear magnetic resonance spectroscopy and small-angle X-ray scattering. In the absence of magnesium, the structure adopts an open, somewhat extended conformation. In the presence of magnesium, the structure compacts, bringing SLB …

1h And 13c Nmr Assignments For (N-Methyl)-(−)-(Α)-Isosparteinium Iodide And (N-Methyl)-(−)-Sparteinium Iodide, Kavoos Kolahdouzan, O. Maduka Ogba, Daniel J. O'Leary

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

(‒)-Sparteine (1) and (–)-(α)-isosparteine (2) are members of the lupine alkaloid family.^[1-2] Sparteine has found extensive use in asymmetric organic transformations, including lithiations^[3] and Pd-catalyzed oxidations.^[4-7] (α)-Isosparteine, which can be made from sparteine, has been utilized as a chiral ligand for a limited number of stereoselective reactions.^[8-9] The two compounds differ in that 1 displays an exo-endo arrangement of the bridgehead hydrogens at C-11 and C-6, respectively, while 2 retains an exo-exo arrangement of these atoms (Figure 1). This study is focused on assigning 1H chemical shifts and coupling constants and 13C chemical shifts for N-methyl …

Corrigendum: Composition Of Dissolved Organic Matter In Pore Waters Of Anoxic Marine Sediments Analyzed By 1h Nuclear Magnetic Resonance Spectroscopy, Christina A. Fox, Hussain A. Abdulla, David J. Burdige, James P. Lewicki, Tomoko Komada

OES Faculty Publications

No abstract provided.

Bioinformatic And Biophysical Analyses Of Proteins, Jonathan Catazaro

Department of Chemistry: Dissertations, Theses, and Student Research

The prevailing dogma in structural genomics is the existence of a strong correlation between protein sequence, structure, and biological function. Proteins with high sequence similarity typically have a similar, if not the same, structure and function. In many cases this logic can fail due to distantly related proteins having very low sequence similarity, a lack of a representative structure, structural novelty, or the absence of a characterized function. Further, the paradigm fails to account for dynamics, which have a significant effect on structural stability and enzymatic efficacy.

Nuclear magnetic resonance (NMR) spectroscopy is uniquely capable of solving the structure, assisting …

The Effects Of Carrier Ligands On Cisplatin Binding To Cysteine And Methionine, Adam C.R Smith

Masters Theses & Specialist Projects

We have reacted several derivatives of the anticancer drug cisplatin with N-acetyl-Lcysteine (N-AcCys) and N-acetyl-L-methionine (N-AcMet), which are two of the primary amino acid targets of platinum. NMR spectroscopy was used to monitor the reactions and determine the effect the different ligands would have on the platinum reactivity. Several of the platinum compounds were tested at pH of 4 and 7, and with platinum:amino acid ratios of 1:1, 2:1 and 1:2. Competition reactions between cysteine and methionine were done to confirm which would react with the platinum compound first. [Pt(dien)(NO3)]+ reacts faster with methionine than with cysteine at both pH …

Reactivity Of Ketyl And Acetyl Radicals From Direct Solar Actinic Photolysis Of Aqueous Pyruvic Acid, Alexis J. Eugene, Marcelo I. Guzman

Chemistry Faculty Publications

The variable composition of secondary organic aerosols (SOA) contributes to the large uncertainty for predicting radiative forcing. A better understanding of the reaction mechanisms leading to aerosol formation such as for the photochemical reaction of aqueous pyruvic acid (PA) at λ ≥ 305 nm can contribute to constrain these uncertainties. Herein, the photochemistry of aqueous PA (5-300 mM) continuously sparged with air is re-examined in the laboratory under comparable irradiance at 38° N at noon on a summer day. Several analytical methods are employed to monitor the time series of the reaction, including (1) the derivatization of carbonyl (C═O) functional …

Metabolic Investigations Of The Molecular Mechanisms Associated With Parkinson’S Disease, Robert Powers, Shulei Lei, Annadurai Anandhan, Darrell D. Marshall, Bradley Worley, Ronald Cerny, Eric D. Dodds, Yuting Huang, Mihalis I. Panayiotidis, Aglaia Pappa, Rodrigo Franco

Robert Powers Publications

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by fibrillar cytoplasmic aggregates of α-synuclein (i.e., Lewy bodies) and the associated loss of dopaminergic cells in the substantia nigra. Mutations in genes such as α -synuclein (SNCA) account for only 10% of PD occurrences. Exposure to environmental toxicants including pesticides and metals (e.g., paraquat (PQ) and manganese (Mn)) is also recognized as an important PD risk factor. Thus, aging, genetic alterations, and environmental factors all contribute to the etiology of PD. In fact, both genetic and environmental factors are thought to interact in the promotion of idiopathic PD, but the mechanisms …

Rapid Screening And Quantification Of Synthetic Cannabinoids In Dart-Ms And Nmr Spectroscopy, Michael A. Marino Ed.D., Robert B. Cody, A. John Dane, Ling Huang

Faculty Works: Biology, Chemistry, and Environmental Studies

The usage of herbal incenses intentionally doped with synthetic cannabinoids has caused an increase in medical incidents and has triggered legislation to ban these products throughout the world. Law enforcement agencies are experiencing sample backlogs due to the variety of the products and the addition of new and still-legal compounds. In our study, proton Nuclear Magnetic Resonance spectroscopy (NMR) was employed to promptly identify the synthetic cannabinoids after their rapid, direct detection on the herbs and in the powders by Direct Analysis in Real Time-Mass Spectrometry (DART-MS). Compared to conventional lengthy pre-NMR sample clean-up and purification, a simple sample preparation …

Rapid Identification Of Synthetic Cannabinoids In Herbal Incenses With Dart-Ms And Nmr, Michael A. Marino Ed.D., Robert Cody, Brandy Voyer, Mercurio Veltri, Ling Huang, A. John Dane

Faculty Works: Biology, Chemistry, and Environmental Studies

The usage of herbal incenses containing synthetic cannabinoids has caused an increase in medical incidents and triggered legislations to ban these products throughout the world. Law enforcement agencies are experiencing sample backlogs due to the variety of the products and the addition of new and still-legal compounds. In our study, proton nuclear magnetic resonance (NMR) spectroscopy was employed to promptly screen the synthetic cannabinoids after their rapid, direct detection on the herbs and in the powders by direct analysis in real time mass spectrometry (DART-MS). A simple sample preparation protocol was employed on 50 mg of herbal sample matrices for …

Detailed Source-Specific Molecular Composition Of Ambient Aerosol Organic Matter Using Ultrahigh Resolution Mass Spectrometry And H Nmr, Amanda S. Willoughby, Andrew S. Wozniak, Patrick G. Hatcher

Chemistry & Biochemistry Faculty Publications

Organic aerosols (OA) are universally regarded as an important component of the atmosphere that have far-ranging impacts on climate forcing and human health. Many of these impacts are related to OA molecular characteristics. Despite the acknowledged importance, current uncertainties related to the source apportionment of molecular properties and environmental impacts make it difficult to confidently predict the net impacts of OA. Here we evaluate the specific molecular compounds as well as bulk structural properties of total suspended particulates in ambient OA collected from key emission sources (marine, biomass burning, and urban) using ultrahigh resolution mass spectrometry (UHR-MS) and proton nuclear …

Comparison Of Ch∙∙O, Sh∙∙O, Chalcogen, And Tetrel Bonds Formed By Neutral And Cationic Sulfur-Containing Compounds, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

The ability of neutral and charged S-compounds to form different sorts of noncovalent bonds is examined by ab initio calculations. Neutrals are represented by CH3SH and fluoro substituted FSCH3; cations are (CH3)3S+, CH3SH2+, and FHSCH3+. Each is paired with N-methylacetamide (NMA) whose O atom serves as common electron donor. Charged species engage in much stronger noncovalent bonds than do the neutral molecules, by as much as an order of magnitude. The strongest noncovalent bond for any system is a O∙∙SF chalcogen bond wherein the O lies directly opposite a S-F covalent bond, amounting to as much as 39 kcal/mol. Second …