Chemicals and Drugs Commons^™

A Comparison Of Microcrystal Electron Diffraction And X-Ray Powder Diffraction For The Structural Analysis Of Metal-Organic Frameworks, Erik Biehler, Silvana Pagola, Daniel Stam, Johannes Merkelbach, Christian Jandl, Tarek M. Abdel-Fattah

Chemistry & Biochemistry Faculty Publications

This study successfully implemented microcrystal electron diffraction (microED) and X-ray powder diffraction (XRPD) for the crystal structure determination of a new phase, TAF-CNU-1, Ni(C₈H₄O₄)·3H₂O, solved by microED from single microcrystals in the powder and refined at the kinematic and dynamic electron diffraction theory levels. This nickel metal–organic framework (MOF), together with its cobalt and manganese analogues with formula M (C₈H₄O₄)·2H₂O with M = Mn ^II or Co^II, were synthesized in aqueous media as one-pot preparations from the corresponding hydrated metal chlorides and sodium terephthalate, as a promising `green' synthetic route to moisture-stable MOFs. The crystal structures of the …

Deciphering The Chemistry Of Condensed Aromatic "Black" Carbon And Nitrogen In Amazonian Anthrosols, João Vitor Dos Santos, Aleksandar I. Goranov, Laís G. Fregolente, Marcia C. Bisinoti, Zhenhuan Sun, Klaus Schmidt-Rohr, Patrick G. Hatcher

Chemistry & Biochemistry Faculty Publications

Amazonian anthrosols are renowned for their high fertility and dark color, properties primarily attributed to the abundance of condensed aromatic carbon (ConAC) in the soil organic matter. ConAC, commonly referred to as black carbon, play a key role in the stability and nutrient retention of these soils. However, the processes governing the formation of ConAC and its transformation into oxygenated derivatives remain poorly understood. In this study, we used multiple analytical platforms to investigate the chemistry of ConAC-rich humic acids (HA) extracted from Terra Mulata de Indio, a type of Amazonian anthrosol. The results reveal that ConAC are predominantly …

Corporate ‘Capture Strategies’ Impacting Human And Ecosystem Health, Alex T. Ford, Marlene Ågerstrand, Michael G. Bertram, Miriam L. Diamond, Rainer Lohmann, Andreas Schäffer, Martin Scheringer, Gabriel Sigmund, Anna Soehl, Maria Clara V.M. Starling, Noriyuki Suzuki, Marta Venier, Penny Vlahos

Graduate School of Oceanography Faculty Publications

The concept of regulatory capture has been extensively studied in academic literature, primarily within the social sciences. This phenomenon has been increasingly discussed in the environmental sciences as the impacts of regulatory capture on human and ecosystem health have become increasingly apparent. Regulatory capture is just one tactic employed by vested interests in the strategy of delaying, weakening, or abolishing policies designed to protect the public interest. Here, we define capture strategies as ‘the act of influencing individuals, organizations, or governments to prioritize corporate interests over those of human and ecosystem health’. Similar to the evolution of terms like whitewashing …

Asymmetric Synthesis Of The Hiv Protease Inhibitor Tmc-126 And An Anti-Malarial Agent Via A Titanium Tetrachloride Mediated Asymmetric Glycolate Aldol Addition Reaction. Redefining The Curtius Rearrangement Reaction Via Dehomologation Of Carboxylic Acids Bearing Alpha-Leaving Groups, Kweku Amaning Affram

Theses and Dissertations

Acquired Immune Deficiency Syndrome (AIDS) and malaria are two devastating infectious diseases caused by HIV and Plasmodium parasites. AIDS is caused by HIV-1 and HIV-2, transmitted through sexual contact, blood transfusions, needle sharing, and perinatal routes. Malaria, caused by plasmodium parasites through mosquito bites. Today, millions of people around the world have been infected with HIV and malaria and much research has been done to treat it. However, despite advancements in therapeutic options, these diseases remain a significant global health threat, particularly in developing countries due to the emergence of drug-resistant strains for both HIV and malaria complicating eradication efforts. …

Modified N-Heterocyclic Carbene Catalysts For Polyurethane Synthesis, Charise D. Young

Pomona Senior Theses

Polyurethanes are widely used polymers synthesized from diisocyanate and diol molecules. They are ubiquitous polymeric materials with important industrial applications. Their increasing market value prompts the need for selective and efficient production which can be achieved through N-Heterocyclic carbene (NHC) catalysis. N-heterocyclic carbenes are heterocyclic molecules containing a carbene atom and at least one nitrogen adjacent to the carbene center. The nitrogen substituents on the adjacent nitrogen play an important role in influencing their steric and electronic properties and resultant reactivity.^1,2 There is a lack of a comprehensive understanding of the steric and electronic properties of NHCs and how …

Rwanda's Natural Remedies: A Fresh Look At The Fight Against Malaria, Leandre Nsabimana Ndisanze

Pomona Senior Theses

Malaria remains one of the most devastating parasitic diseases globally, disproportionately affecting sub-Saharan Africa, where Rwanda continues to face high transmission rates and rising resistance to conventional interventions. Despite decades of control efforts, the emergence of drug-resistant Plasmodium falciparum and insecticide-resistant Anopheles mosquitoes threatens to reverse recent gains. This research responds to the urgent need for sustainable and culturally relevant alternatives by exploring the therapeutic potential of Rwandan traditional medicinal plants. These indigenous remedies, long used by local healers, offer an underexplored reservoir of bioactive compounds that may provide the basis for novel antimalarial drugs.

The central hypothesis of this …

Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo

Graduate Theses/Dissertations

Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its …

Towards Developing Glut2 Specific Probes For Biochemical And Biomedical Applications, Abdelrahman Ismail

Dissertations, Master's Theses and Master's Reports

Facilitated Glucose transporters (GLUTs) are membrane proteins responsible for the uptake of simple sugars and other structurally similar metabolites in all mammalian cells. One of the hallmarks of cancer is dysfunctional sugar metabolism, known as the Warburg effect, and one of the manifestations of that effect is abnormal GLUT expression. There are 14 known GLUT proteins with different expression patterns in different tissues, and tumors tend to express certain GLUTs that are not present in surrounding healthy tissue. Therefore, selective targeting of GLUTs presents a potentially powerful tool for diagnostics and treatment of cancer and other diseases. This has been …

Optimization Of Serum And Salivary Cortisol Interpolation For Time-Dependent Modeling Frameworks In Healthy Adult Males, Nathaniel T. Berry, Travis Anderson, Christopher K. Rhea, Laurie Wideman

Rehabilitation Sciences Faculty Publications

Cortisol is an important marker of hypothalamic-pituitary-adrenal function and follows robust circadian and diurnal rhythms. However, biomarker sampling protocols can be labor-intensive and cost-prohibitive. Objectives: Explore analytical approaches that can handle differing biological sampling frequencies to maximize these data in more detailed and time-dependent analyses. Methods: Healthy adult males [N = 8; 26.1 (±3.1) years; 176.4 (±8.6) cm; 73.1 (±12.0) kg)] completed two 24 h admissions: one at rest and one including a high-intensity exercise session on the cycle ergometer. Serum and salivary cortisol were sampled every 60 and 120 min, respectively. Six alternative sampling profiles were defined by downsampling …

Phytochemical Analysis, Antioxidant, And Antibacterial Properties Of Partition Fractions Of Adansonia Digitata And Annona Muricata Extracts Using Chloroform, Ethyl Acetate, Ethanol, And Aqueous Solvent Systems, Fagbohun Oyenike Bushirat, Hassan Abdusalam Adewuyi, Sakariyau Adio Waheed, Maryam Nana Musa, Timothy God-Giveth Olusegun, Ayomide Babatunde Ishola, Agumage Idoko, Adeola Victor Kolawole, Adesanmi Adefunmilayo Oluwatuyi, Sarah Ngozi Agwasim

Chemistry & Biochemistry Faculty Publications

Adansonia digitata and Annona muricata are traditionally used medicinal plants with reported pharmacological properties. In this study, we aimed to elucidate the phytochemical composition, antioxidant activity, and antibacterial properties of partition fractions of Adansonia digitata and Annona muricata extracts obtained using chloroform, ethyl acetate, ethanol, and aqueous solvent systems. The plant extracts were successively partitioned using chloroform, ethyl acetate, ethanol, and aqueous solvent systems. Phytochemical analysis was performed using standard methods. Antioxidant activity was evaluated using FRAP and DPPH assays. Antibacterial activity was assessed using agar well diffusion and MIC determination. Phytochemical analysis revealed the presence of alkaloids (10.2-15.6%), flavonoids …

Automating The Amino Acid Identification In Elliptical Dichroism Spectrometer With Machine Learning, Ridhanya Sree Balamurugan, Yusuf Asad, Tommy Gao, Dharmakeerthi Nawarathna, Umamaheswara Rao Tida, Dali Sun

Electrical & Computer Engineering Faculty Publications

Amino acid identification is crucial across various scientific disciplines, including biochemistry, pharmaceutical research, and medical diagnostics. However, traditional methods such as mass spectrometry require extensive sample preparation and are time-consuming, complex and costly. Therefore, this study presents a pioneering Machine Learning (ML) approach for automatic amino acid identification by utilizing the unique absorption profiles from an Elliptical Dichroism (ED) spectrometer. Advanced data preprocessing techniques and ML algorithms to learn patterns from the absorption profiles that distinguish different amino acids were investigated to prove the feasibility of this approach. The results show that ML can potentially revolutionize the amino acid analysis …

Interaction Of Cardiac Leiomodin With The Native Cardiac Thin Filament, Madison Little, Cristina M. Risi, Tania M. Larrinaga, Mason D. Summers, Tyler Nguyen, Garry E. Smith Jr., Jennifer Atherton, Carol C. Gregorio, Alla S. Kostyukova, Vitold E. Galkin

Department of Biomedical and Translational Sciences Faculty Publications

Every heartbeat depends on cyclical contraction-relaxation produced by the interactions between myosin-containing thick and actin-based thin filaments (TFs) arranged into a crystalline-like lattice in the cardiac sarcomere. Therefore, the maintenance of thin filament length is crucial for myocardium function. The thin filament is comprised of an actin backbone, the regulatory troponin complex and tropomyosin that controls interactions between thick and thin filaments. Thin filament length is controlled by the tropomodulin family of proteins; tropomodulin caps pointed ends of thin filaments, and leiomodin (Lmod) promotes elongation of thin filaments by a “leaky-cap” mechanism. The broader distribution of Lmod on the thin …

Structural Optimization And Stability Enhancement Of Uba(2) And Ntl9 Using The Computational Tool: Emcast, Bahar Ghazi Esfahani

Graduate Student Theses, Dissertations, & Professional Papers

This study enhances protein stability prediction by refining EmCAST (Empirical C-Alpha Stability Tool), a computational tool used to identify stabilizing mutations in protein domains. We applied EmCAST to two model proteins: the α-helical ubiquitin-associated domain 2 (UBA(2)) and the α/β N-terminal domain of ribosomal protein L9 (NTL9). Protein stability is critical for proper function, and mutations can lead to misfolding and disease. To validate EmCAST’s predictions, guanidine hydrochloride-induced denaturation was monitored using circular dichroism (CD) spectroscopy for both wild-type and mutant variants. Results guided refinements to EmCAST’s algorithm, incorporating new experimental datasets to improve accuracy. Additionally, we examined the assumption …

Insights Into Factors Influencing Radical Coupling Chemistry Of Monolignols During Lignification And Induced Changes In Plant Secondary Metabolism, Rachel Poornima Sutherland

Theses and Dissertations--Chemistry

Lignin is a complex aromatic biopolymer and an important constituent in plant cell walls. The process of lignin biosynthesis, known as lignification, is poorly understood and challenging to study but has important implications in a variety of fields including sustainable energy, bioengineering, and materials science and is therefore of interest to pursue. In the final stage of lignification, H-, G-, and S-monolignols are oxidized by laccase and peroxidase enzymes to generate radical species that couple to form dimers and further oligomeric species to ultimately produce the lignin polymer. Biomimetic lignin model systems utilize in vitro oxidative coupling reactions as an …

Redox Control In A Fused Electron Transfer Flavoprotein From A Thermophilic Archaeon And Expanded Significance Of A Hydrogen Bond From A Conserved Histidine Residue That Contributes To Flavin Redox Tuning And Activation For Covalent Modification, Debarati Das

Theses and Dissertations--Chemistry

In absence of O₂ as terminal electron acceptors in anaerobic bacteria and archaea, carbohydrate metabolism is 15 times less efficient compared to aerobic energy metabolism resulting in energy deficit conditions. Despite their meager resources these anaerobes were able to generate H₂ and a chemiosmotic potential able to drive energy demanding reactions such as CO₂ or N₂ fixation. These observations raised concerns as production of high energy reductants (H₂) from mediocre fuels (NADH) defied the laws of thermodynamics.

In 2008, a known mechanism “electron bifurcation” but with flavins as redox mediators instead of quinones was …

Advancing Continuous Manufacturing: The Role Of Process Analytical Technology In Process Development, Samuel R. Henson

Electronic Theses and Dissertations

The pharmaceutical industry is actively pursuing technologies which improve manufacturing processes with the goal of producing high-quality pharmaceutical products for patients, manifesting in an industry-wide investment in continuous manufacturing (CM). Process analytical technology (PAT) has been recognized for its successful monitoring of critical quality attributes during routine production and is often cited alongside CM due to its ability to make timely, in-line measurements of intermediate materials. Various PAT tools are valuable in process development, particularly as continuous wet granulation processes are developed for use within pharmaceutical manufacturing. This work applied PAT and chemometric modeling during CM process development to enhance …

Assembly Of Ppsu-Oligomers, Mariam Nesterov

Student Theses and Dissertations

The development of nanostructures for delivering multiple proteins to targeted antibodies has become a promising avenue in biotechnology, driven by advancements in synthetic polymers like poly(propylene sulfone), PPSU. However, the PPSU polymer faces a major limitation - its high insolubility. To address this challenge, this study investigates whether PPSU oligomers can enhance both the solubility and stability of lysozyme, a model protein that is cost-effective and widely accessible. Using dimer, trimer, tetramer, and hexamer configurations, we analyzed the interactions between PPSU oligomer and lysozyme under varying conditions. Our results show that the dimer and trimer are water soluble (no aggregate …

Comparing Multivalent Cross-Linked Sodium Alginate/ Montmorillonite Beads Containing Curcumin Or Cayenne Pepper As Drug Carriers And Their Antimicrobial Resistance, Shionainn Traynor, Shubham Sharma

SURE Journal: Science Undergraduate Research Experience Journal

The aim of the following work was to investigate and compare curcumin and cayenne pepper in microbeads composed of sodium alginate (SA) crosslinked with montmorillonite (MMT) to act as drug carriers and their antimicrobial resistance. The microbeads were prepared through ion-exchange in multivalent solutions of CaCl₂, MgCl₂ and AlCl₃. The microbeads were characterized by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray analysis (EDX) and the time required for intercalation of curcumin and cayenne pepper with MMT. Simulated intestinal fluid (pH 7.3) and gastric fluid (pH 1.2) at 37°C were used for comparison in swelling studies. …

Editorial - Sure Journal Vol 6, Anne M. Friel, Eva Campion, Sinead Loughran

SURE Journal: Science Undergraduate Research Experience Journal

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Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

Alphafold2-Based Characterization Of Apo And Holo Protein Structures And Conformational Ensembles Using Randomized Alanine Sequence Scanning Adaptation: Capturing Shared Signature Dynamics And Ligand-Induced Conformational Changes, Nishank Raisinghani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Proteins often exist in multiple conformational states, influenced by the binding of ligands or substrates. The study of these states, particularly the apo (unbound) and holo (ligand-bound) forms, is crucial for understanding protein function, dynamics, and interactions. In the current study, we use AlphaFold2, which combines randomized alanine sequence masking with shallow multiple sequence alignment subsampling to expand the conformational diversity of the predicted structural ensembles and capture conformational changes between apo and holo protein forms. Using several well-established datasets of structurally diverse apo-holo protein pairs, the proposed approach enables robust predictions of apo and holo structures and conformational ensembles, …

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

Subterranean Medicinal Bottles Are Treasures That Reveal The Growth Of Lincoln's Early Drug Stores, Mark Griep, June Weber, Erik Schulz, Effie Athanassopoulos

Department of Anthropology: Faculty Publications

Archeologists unearthed medicine bottles embossed with the names of nine early Lincoln (Nebraska) drug stores, giving insight into the rapid growth of pharmacies and health care from the 1880s up to the Pure Food and Drug Act of 1906.

Quinoxaline 1,4-Di-N-Oxide Derivatives As New Antinocardial Agents, Isidro Palos, Alonzo Gonzalez-Gonzalez, Alma D. Paz-Gonzalez, José C. Espinoza-Hicks, Debasish Bandyopadhyay, Norma Paniagua-Castro, Marlene S. Galeana-Salazar, Jorge Ismael Castañeda-Sánchez, Julieta Luna-Herrera, Gildardo Rivera-Sanchez

School of Integrative Biological & Chemical Sciences Faculty Publications

Mycetoma is currently considered as a neglected tropical disease. The incidence of mycetoma is unknown but most of the worldwide cases are present in the “mycetoma belt” including countries like Mexico, India, Senegal, and others. The treatment of mycetoma depends on the etiological agent responsible for the case. Treatment success reaches 60 to 90%; however, common treatment has been reported to be ineffective in some cases, due in part to resistance to the prescribed antibiotics. Therefore, it is necessary to develop new therapeutic options. In the past two decades, quinoxaline derivatives have shown relevance as antibacterial agents. Therefore, in this …

Alphafold2 Modeling And Molecular Dynamics Simulations Of The Conformational Ensembles For The Sars-Cov-2 Spike Omicron Jn.1, Kp.2 And Kp.3 Variants: Mutational Profiling Of Binding Energetics Reveals Epistatic Drivers Of The Ace2 Affinity And Escape Hotspots Of Antibody Resistance, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

AlphaFold2-based atomistic predictions of structures and conformational ensembles of the SARS-CoV-2 spike complexes with the host receptor ACE2 for the most dominant Omicron variants JN.1, KP.1, KP.2 and KP.3 to examine the mechanisms underlying the role of convergent evolution hotspots in balancing ACE2 binding and antibody evasion. Using the ensemble-based mutational scanning of the spike protein residues and computations of binding affinities, we identified binding energy hotspots and characterized the molecular basis underlying epistatic couplings between convergent mutational hotspots. The results suggested the existence of epistatic interactions between convergent mutational sites at L455, F456, Q493 positions that protect and restore …

Improving Ligand Pharmacokinetics Via Bioisosteric Substitution Of Amides With 1, 2, 3-Triazoles While Maintaining Dopamine D4 Receptor Selectivity And Potency, Mohammad Alkhatib

Theses and Dissertations

Several neurophysiological functions, such as attention, cognition, and emotional regulation, are regulated by the binding of dopamine on G-Protein coupled receptors. D4Rs are mainly located in the prefrontal cortex and the hippocampus and are known to have a key role in decision-making, memory formation, cognition, and attention. Administration of D4Rs- selective ligands during the preclinical studies enhance the outcomes and the results in animal models suffering from neuropsychiatric disorders, including ADHD, substance use disorders (SUD), and Alzheimer's disease. Recently, we reported a group of D4R-selective ligands with different efficacies depending on their phenylpiperazine ring scaffold to illustrate D4R function during …

Incorporating Solvation Thermodynamic Mapping In Computer-Aided Drug Design, Yeonji Ji

Dissertations, Theses, and Capstone Projects

Advancements in computational techniques have revolutionized structure-based drug design, substantially improving the efficiency and effectiveness of the drug discovery process by reducing time, costs, and labor requirements. These advancements include various methods, such as investigating small molecule ligands binding to proteins, exploring alternative protein conformations, and solvation mapping on the protein surfaces. Among these methods, understanding the correlation between protein-ligand binding and the role of solvation is important.

A fundamental concept in protein-ligand binding is shape and electrostatic complementarity, which is complicated by the inherent flexibility of proteins. In the absence of small molecule ligands, proteins are complementary to surface …

Occurrence, Inputs, And Ecological Significance Of Antibiotics And Pharmaceuticals In Western Nebraska Streams, Katelyn F. Glause

School of Natural Resources: Dissertations, Theses, and Student Research

Few emerging environmental contaminants are as concerning as antibiotics. Human and animal health benefits greatly from the prudent use of antibiotics, yet we give little thought to environmental release of these biologically active compounds. Environmental occurrence of these and other pharmaceutical compounds must be measured in different environmental compartments such as municipal wastewater and in the vicinity of large animal feeding operations to understand potential effects. This study reports the results of a monitoring study in western Nebraska, with a large population of livestock and smaller but more concentrated population of humans, comparing the relative environmental concentrations and loading from …

Innovation Path At Institute For Protein Design Of Washington University And Its Enlightenment For Construction Of New Life Sciences R&D Institutions, Runzhou Zhao, Ming Ni, Yunzhi Fa, Xiaochen Bo, Jian Jiao

Bulletin of Chinese Academy of Sciences (Chinese Version)

The Institute for Protein Design (IPD) at the University of Washington is a pioneering local and state-supported non-profit scientific research institution. Since its establishment in 2012, IPD has seized the opportunity of AI for Science and open science, and continuously enhanced its capabilities of fundamental innovations, breakthrough technologies, and industrial impact. We summarized five factors contributing to IPD’s development, including focusing on the cutting-edge issues of basic scientific research to gain a first-mover advantage and then further expand, integrating AI-enhanced digital tools and solid experimental validations, facilitating the integrated development of innovation and industrial chains, giving full play to the …

A Model Of Oocyte Population Dynamics For Fish Oogenesis, Louis Fostier, Frédérique Clément, Romain Yvinec, Violette Thermes

Biology and Medicine Through Mathematics Conference

No abstract provided.