Chemistry Commons^™

Catalytic Synthesis Of Protoberberine Alkaloids And Their Evaluation As Selective Dopamine Receptor Ligands, Ashok Reddy Gudipally

Dissertations, Theses, and Capstone Projects

Dopamine regulates motor control, cognition, reward, motivation, and neuroendocrine signaling. Disruption of dopaminergic neurotransmission is closely linked to central nervous system disorders, including Parkinson’s disease, schizophrenia, addiction, and related neuropsychiatric conditions. Because these functions are mediated by multiple dopamine receptor subtypes with distinct roles in physiology and disease, the discovery of subtype-selective ligands remains an important goal in neuropharmacology. Within this context, protoberberine alkaloids, particularly tetrahydroprotoberberines (THPBs), are attractive molecular frameworks because they combine structural complexity with broad biological relevance, including measurable activity in CNS-related diseases. Prior work from our laboratory and others established (–)-stepholidine (1.60) as an important lead …

Multicomponent Reaction-Initiated Synthesis Of Polyheterocyclic Compounds, Ashutosh Nath

Graduate Doctoral Dissertations

Efficient synthesis of novel heterocycles with biological interest remains a challenge in modern organic chemistry. This dissertation presents the development of efficient synthetic strategies that combine multicomponent reactions (MCRs) with sequential reactions for rapid access a diverse array of polyheterocyclic compounds. The projects are: 1) Groebke-Blackburn-Bienaymé (GBB) reaction followed by N-acylation and Friedel-Crafts (FC) cyclization for the construction of imidazopyridine- and indole-fused azepinones involving an unusual ring-expansion process. 2) Modified GBB condensation products for intramolecular Diels-Alder (IMDA) cycloaddition and dehydrative re-aromatization to access imidazopyridine-fused isoquinolinones. 3) Integration of the Ugi-three component reaction (Ugi-3CR) and Pictet-Spengler (PS) reaction followed by …

Norman H. Cromwell, Unl Chemistry; Nu System Dean; Eppley Cancer Center Director, Norman H. Cromwell, Pete Boughn, Mark A. Griep

UNL ORCA Interview Series

This 1980 interview of Normal Cromwell was done by Pete Boughn at the University of Nebraska Medical Center in Omaha. He asked about Cromwell’s history but mostly about his time as director of the Eppley Cancer Center. The interview is reproduced with permission from the UNMC McGoogan Library.

Cromwell was born in 1913 in Terre Haute, Indiana. In 1935, he earned a bachelor’s degree in chemical engineering from the Rose-Hulman Institute of Technology in his hometown. In 1939, three things happened: he earned a doctorate in organic chemistry from the University of Minnesota, he got married, and he was hired …

Isolation Of Lavender Compounds Via Steam Distillation, Emma Norris, Gwendolyn Flippin

Discovery Day - Daytona Beach

Steam distillation was used to extract (R)- Linalool, Linalyl acetate, and Camphor from lavender during the steam distillation experiment. The compounds were extracted via a steam distillation apparatus. A 250 mL two-neck round-bottom flask, a thermometer adapter, 25 mL a thermometer, a condenser, a distillation head, a vacuum adapter, lab jacks, and clamps made up the apparatus. Then the lavender was massed out and added to a beaker with 100 mL of water. Over time, the distillate is collected in a vial to be analyzed. (R)- Linalool is a nonaromatic alcohol containing two alkenes with the chemical formula C_10 H_18 …

Chemical Profiling Of Star Anise (Illicium Verum) Via Gc–Ms: Identifying Compounds With Pharmaceutical Potential, Legacy Wilson, Yegor Bushnev

Discovery Day - Daytona Beach

Title: Chemical Profiling of Star Anise (Illicium verum) via GC–MS: Identifying Compounds with Pharmaceutical Potential   Abstract: Star anise (Illicium verum) has been used for both medicinal and culinary applications due to its diverse bioactive compounds. It is a primary natural source of shikimic acid (𝐶7𝐻10𝑂5), a key precursor in the synthesis of the antiviral drug oseltamivir (Tamiflu), used to treat influenza. Additionally, star anise has been used to treat respiratory and digestive conditions and is widely used for flavoring due to its licorice-like aroma, mainly from trans-anethole (𝐶10𝐻12𝑂) , its major component. Previous studies have also demonstrated mild central nervous …

Development Of Minimalist Trifunctional Building Blocks For Chemical Biology Probe Synthesis, Luke E. Bohrer

Electronic Theses and Dissertations

The completion of the Human Genome Project in 2003 generated expectations that genomic information would accelerate the discovery of new protein drug targets and FDA-approved therapies. However, many small-molecule drug candidates continue to fail in clinical trials, and much of the human proteome remains undercharacterized in terms of structure, function, and disease relevance. Chemical tools are therefore essential for defining protein function, mapping protein interactions, and identifying disease-associated molecular mechanisms. Among these tools, small-molecule chemical probes provide a powerful strategy for connecting biological activity with target identification, functional analysis, and the development of effective therapies.

This dissertation describes the development …

Enhanced Transdermal Immunization Via Solid-In-Oil Nanodispersions Incorporating Dendritic Cell-Targeting Peptide, Md Samiul Islam, Md. Shahin Ekka Sarker, Yoshirou Kawaguchi, Rie Wakabayashi, Noriho Kamiya, Muhammad Moniruzzaman, Masahiro Goto

Publications and Research

Transdermal immunization represents a promising needle-free alternative to conventional vaccination. However, efficient antigen delivery and robust immune activation remain major challenges. In this study, a solid-in-oil (S/O) nanodispersion system comprising a dendritic cell-targeting peptide (HR8), ovalbumin (OVA), and an adjuvant was developed for transdermal immunization. The HR8 peptide along with OVA was successfully incorporated into an S/O nanodispersion with an optimal hydrodynamic diameter of particles (< 200 nm) and exhibited stable physical properties for up to 90 days. In vitro and in vivo studies demonstrated enhanced antigen delivery with insignificant skin irritation in C57BL/6N mice. Moreover, in vivo transdermal immunization studies demonstrated that the addition of the HR8 peptide enhanced OVA-specific IgG responses (~1.5-fold). Notably, the HR8 peptide also promoted an approximately 2.5-fold increase in IgG2c levels, suggesting a shift toward a more T helper type 1-biased immune response, as reflected by an increased IgG2c/IgG1 ratio. Overall, these findings demonstrate that the incorporation of HR8 peptide into an S/O nanodispersion enables efficient transdermal antigen delivery and improved immunogenicity, highlighting its potential as a simple, non-invasive, and patient-friendly immunization strategy.

Solvent-Free Ball-Milling Synthesis Of 1,2-Disubstituted Benzimidazoles, Zachary A. Jaffery, Katherine E. Christopher, Kyle A. Grice

DePaul Discoveries

The search for sustainability in chemistry has led to the development of the field of Green Chemistry, comprised by 12 guiding principles. Existing syntheses of benzimidazoles, a heterocycle widely used in medicinal chemistry, utilize methods with much room for improved sustainability. This work presents a solventless mechanochemical synthesis of 1,2-disubsituted substituted benzimidazoles from the condensation of phenylenediamines and aryl aldehydes. The effect of milling aid on yield and selectivity was investigated and montmorillonite K10 was determined to be the best milling aid. The purification protocol was optimized as well, with a heptane:EtOAc extraction and subsequent recrystallization from EtOH found to …

Laminarin-Loaded Solid-In-Oil Nanodispersion For Enhanced Non-Invasive Transdermal Immunization, Md. Shahin Ekka Sarker, Yoshirou Kawaguchi, Rie C. Wakabayashi, Noriho J. Kamiya, Muhammad Moniruzzaman, Masahiro Goto

Publications and Research

Simple and non-invasive transdermal vaccination is an attractive alternative to conventional injection-based immunization. However, the effectiveness of transdermal vaccines is often constrained by the stratum corneum barrier. Although the use of solid-in-oil (S/O) nanodispersion technology has successfully facilitated skin permeation to induce an immunological response, the antibody titers remain suboptimal. Herein, a dectin-1 selective ligand, laminarin, was used as an immunostimulatory adjuvant to enhance the immune response. S/O nanodispersions loaded with laminarin and ovalbumin (OVA) were systematically developed and characterized in terms of particle size, in vitro OVA release behavior, and skin permeation performance using excised mouse skin. In vivo …

Supramolecular Assembly In Short Peptide Systems For Selective Metabolite Recognition And Drug Nanoencapsulation, Maithreyi Ramakrishnan

Dissertations, Theses, and Capstone Projects

Short peptides can form adaptive supramolecular assemblies, and understanding how minimal sequences organize around neurometabolites or hydrophobic cancer drugs enables the rational design of functional materials. This thesis combines molecular dynamics with experimental validation to establish design rules linking peptide sequence to emergent structure and function. Chapter 1 outlines the molecular determinants governing peptide assembly. Chapter 2 reviews computational workflows that reveal sequence-dependent conformations and supramolecular organization. Chapter 3 applies these principles to Dynamic Peptide Libraries which identify tetrapeptides that selectively interact with neurometabolites. Chapter 4 extends the same interaction-driven framework to design tryptophan-rich pentapeptides that co-assemble with kinase inhibitors …

Computer-Aided Development Of Novel Antioxidants, Rita Bernadett Vlocsko

Graduate Doctoral Dissertations

Physiological redox homeostasis is a fine balance between prooxidants and antioxidants that are integrated elements of several reduction-oxidation mechanisms at molecular, organellar, cellular and tissue levels. When this equilibrium is disrupted and prooxidants become dominant, the body relies on endogenous and exogenous antioxidants to counterbalance the dysregulation and ultimately prevent the progression of oxidative stress. Reactive species (reactive oxygen species, reactive nitrogen species, or reactive sulfur species) are significant contributors to prooxidant activity. Over the years, substantial knowledge has been accumulated regarding their origin and roles in disease development, leading to the discovery and development of antioxidants that effectively target …

Small Molecule Antioxidants As Potential Therapeutics For Preeclampsia, Maxim Mastyugin

Graduate Doctoral Dissertations

The major goal of this work was to develop a therapeutic intervention against preeclampsia (PE). Preeclampsia affects up to 5-7% of all pregnancies and has no causative treatments. It is associated with oxidative stress caused by a prolonged ischemic state and increase in reactive oxygen species (ROS) in the placenta. The cardinal symptoms include high blood pressure, kidney dysfunction, and in severe cases, eclampsia. With no treatment for the underlying causes available, we offer small molecule antioxidants which may scavenge ROS in the placenta arising from the initiating event of PE, the oxidative stress. By reducing placental ROS, these antioxidants …

Predicting And Decoding Allosteric Binding Sites Using Protein Language Models And Structure-Based Machine Learning: An Energy Landscape-Guided Explainable Ai Framework, Kamila Riedlová, Vít Skrhák, William G. Gatlin, Max Ludwick, Lucas Turano, Marian Novotný, David Hoksza, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Computational prediction of allosteric binding sites in protein structures remains a persistent challenge, as these regulatory pockets evade detection by both sequence-based and structure-based algorithms. Both computational and physical origins of this predictive asymmetry remain insufficiently understood. In this study, we systematically examine the determinants of binding site predictability using a dual framework that integrates a fine-tuned protein language model and the structure-based method P2Rank as complementary tools probing a diverse data set of 453 human kinases, together with a physics-based interpretability layer derived from energy landscape frustration analysis. Both predictors exhibit a sharp and reproducible dichotomy on protein kinases, …

Reversible, Light-Controlled Inhibition Of Stim1-Mediated Calcium Signaling Using Photoswitchable Ml-9 Derivatives In Jurkat-Lucia Nfat Reporter T Cells, José L. Matute Gálvez

Honors Scholar Theses

Store-operated calcium entry (SOCE) through calcium release-activated

calcium (CRAC) channels is the dominant pathway for sustained Ca2+ influx in

non-excitable cells and is essential for T cell activation, driving downstream

signaling through the calcineurin-NFAT transcriptional axis. Dysregulation of

SOCE produces multi-systemic disease phenotypes, establishing that precise,

spatiotemporally controlled modulation of this pathway is a fundamental

therapeutic requirement. ML-9 is one of the only characterized small molecules

capable of targeting SOCE upstream at the level of STIM1 localization, but lacks

the selectivity, pharmacokinetic properties, and spatiotemporal control necessary

for therapeutic development.

This work describes the design, synthesis, and biological evaluation of …

Membrane Organization Of Rheb And Rhoa: Roles In Function And Allosteric Druggability, Chase M. Hutchins

Dissertations and Theses (Open Access)

Small GTPases of the Ras superfamily are membrane-bound molecular switches that regulate nearly all major cellular processes, and their dysregulation drives cancers, neurological disorders, and metabolic diseases. While anchored to cellular membranes, the catalytic domains of small GTPases undergo orientation dynamics, adopting distinct configurations that can occlude or expose effector-binding surfaces and modulate signaling output. These dynamics have been characterized in the Ras oncoproteins, but whether they extend across the superfamily and influence allosteric druggability has remained unknown.

In this dissertation, I address these questions through Rheb and RhoA, two small GTPases with complementary differences in subfamily lineage, membrane localization, …

Synthesis, Structural Elucidation, In Vitro Antibacterial Activity Of Mononuclear Ag(I) Complex Derived From (E)-N-(4-Fluorophenyl)-1-(Pyridin-2-Yl) Methanimine And Triphenylphosphine Ancillary Ligand., Olufemi Stephen Odulaja, Saliu Alao Amolegbe, Muritala Adeniyi Olusola

Tanzania Journal of Science

Chemo-therapeutic application of metal complexes to remediation and subjugation of emerging infectious diseases with a view to improving potency and efficacy of a variety of drugs is gaining more momentum, especially in the 21st century. This research work designed a new biologically active complex [AgL(PPh3)2]NO3,C, obtained from the reaction of Ag(I) nitrate with bidentate pyridinyl Schiff base ligand (E)-N-(4-fluorophenyl)-1-(pyridin-2-yl) methanimine L, with triphenylphosphine (PPh3) as co-ligand. Characterisation was done by FT-IR, UV-Vis, NMR, (TGA/DTA), X-ray crystallography, and elemental analysis. The combined effects of pyridinyl Schiff base ligand and PPh3 on the antibacterial activities against Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, …

Synthesis And Characterization Of Thiazole Derivatives As Potential Antitumor Agents, Kaylee Leddy

Create@State

Melanoma is the 5th most common cancer in both men and women in the USA. It originates in melanocytes, which make the melanin pigment that gives skin its color. While treatable in early stages, melanoma becomes nearly incurable once metastasized. Thiazole derivatives have been recognized in many pharmaceutical classes including anticancer, antimicrobial, antimalarial, anti-tuberculosis, and diuretics. They have long been researched for their natural pharmacological properties and have shown potential to inhibit melanoma cell growth. In this study, catechol-substituted thiazole derivatives were synthesized using the Hantzsch-Thiazole synthesis. A total of 13 novel compounds were made using 2-chlorodihydroxyacetophenone with various catechol-substituted …

Desialylation And Sialidase Secretion From Monocytes And Macrophages Upon Lps Activation, Yu Zhao, Majdi Aljohani, Morgan Pychowycz, Xue-Long Sun

Chemistry Faculty Publications

Introduction The cell surface expresses a dense layer of glycans often terminated with sialic acids (Sias), known as sialylation, which represents different cellular statuses. Meanwhile, the removal of Sias from the glycans catalyzed by sialidase (desialylation) is also involved in many biological processes, such as inflammatory responses. Previous studies demonstrated that desialylation is involved in LPS/TLR4 signaling pathway and pro-inflammatory cytokine production. In this report, we systematically profiled desialylation and sialidase activity, expression and secretion from monocytes and macrophages upon LPS activation.Methods THP-1 monocytes and THP-1 macrophages were activated by LPS (100 ng/mL) for 24 hours. The cellular Sia changes …

Synthesis And Characterization Of Metal Complexes Of Oxindole-Based Β-Lactams, Kenya Rosas, Erick Morales Orrante, Carlos Sifuentes, Alexsei Nazarov

Posters - 2026

• β-lactams are essential structural components of many antibiotics and widely studied due to their biological importance and synthetic versatility.
• The Ugi reaction is a multicomponent reaction, involving a primary amine, carboxylic acid, isocyanide, and an aldehyde or a ketone, that rapidly generates α-acetamido carboxamide derivatives (Ugi adducts).
• The synthesis and characterization of four oxindole-based β-lactam derivatives:
  • 1-Benzyl-N-(tert-butyl)-2-oxo-3-(2-oxoazetidin-1-yl)indoline-3-carboxamide (4a).
  • N-(tert-butyl)-2-oxo-3-(2-oxoazetidin-1-yl)-1-phenylindol-3-carboxamide (4ab).
  • N-(tert-Butyl)-2-oxo-3-(2-oxoazetidin-1-yl)indoline-3-carboxamide (4d).
  • N-(tert-butyl)-1-methyl-2-oxo-3-(2-oxoazetidin-1-yl)indol-3-carboxamide (4e).
• The coordination of the four Ugi adducts with Cu (II) and Ni (II) at different pH points to enhance their stability and improve biological activity.

Design, Synthesis, And Bioevaluation Of Moxifloxacin Hydrazide Metal Complexes: Integrated Spectroscopic, Computational, Antimicrobial, And Anticancer Investigations, Abbas Mamdoh Abbas, Sara Reda Fisal, Ibrahim A.I. Ali, W. Christropher Boyd, Haitham F. Kalil, Adel Sayed Orabi

Chemistry Faculty Publications

This study reports the synthesis, spectroscopic characterization, and biological evaluation of a novel moxifloxacin hydrazide derivative (MOX-H) and its metal complexes with Co(II), Ni(II), Cu(II), VO(IV), and Gd(III). The ligand was synthesized by hydrazinolysis of moxifloxacin hydrochloride, and the resulting hydrazide was subsequently complexed with the respective metal salts. The interaction between MOX-H and the metal ions yielded the corresponding complexes, formulated as [Co(H2O)Cl(MOX-H)2]Cl & centerdot;2.5H2O, [Ni(H2O)Cl(MOX-H)2]Cl.4.5H2O, [VO(MOX-H)2]SO4.3.5H2O, [Gd (H2O)(MOX-H)2(NO3)2]NO3.2H2O, and [Cu(MOX-H)2(H2O)Cl]Cl & centerdot;xH2O (where x = 2, 2.5, 0.5, for products synthesized via template, microwave-assisted, and hydrothermal methods, respectively). The synthesized analogues were characterized by elemental analysis (CHN), FT-IR, …

From Latent Manifolds To Targeted Molecular Probes: An Interpretable, Kinome-Scale Generative Machine Learning Framework For Family-Based Kinase Ligand Design, Gennady M. Verkhivker, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

Scaffold-aware artificial intelligence (AI) models enable systematic exploration of chemical space conditioned on protein-interacting ligands, yet the representational principles governing their behavior remain poorly understood. The computational representation of structurally complex kinase small molecules remains a formidable challenge due to the high conservation of ATP active site architecture across the kinome and the topological complexity of structural scaffolds in current generative AI frameworks. In this study, we present a diagnostic, modular and chemistry-first generative framework for design of targeted SRC kinase ligands by integrating ChemVAE-based latent space modeling, a chemically interpretable structural similarity metric (Kinase Likelihood Score), Bayesian optimization, and …

Investigating The Role Of Humic Acid In The Adsorption Mechanics Of Acetaminophen On Potassium Persulfate-Aged Polyethylene Terephthalate (Pet), Andrew Littleton, Maria Danielle Garrett, Phd

SPARK Symposium Presentations

Pharmaceutical contaminants such as acetaminophen (APAP) are showing a rising presence in aquatic environments, where their interactions with microplastics (MPs) can potentially modulate natural degradation mechanisms. Concurrent presence of the two substances has been shown to potentiate increase their individual harmful effects. This study investigates whether oxidative aging and humic-acid surface modification of PET microplastics influence APAP adsorption.

In this study, UV-aging was reproduced using an iron (II)-activated potassium persulfate (Fe(II)-KPS) oxidation system. Aqueous dissolved organic matter (DOM) is simulated using multi-hour exposure to humic acid. The MPs are then removed from the solution to examine adsorption mechanisms. While most …

Exploring The Limitations Of Substrate Scope In Dimethylallyltryptophan Synthases, Evan T. Miller

Theses and Dissertations--Pharmacy

Natural products (NPs), are the largest source of bioactive compounds in Nature, and are essential to the treatment of human disease. Nearly 50% of drugs approved for use from 1981 to 2019 owe some aspect of their development to NPs, either in terms of their structure, pharmacophore, or mechanism of action. However, NPs are difficult to structurally optimize. Chemoenzymatic methods for NP derivatization have been increasingly seen as practical alternatives to traditional synthetic methods. Prenyltransferases (PTs) are involved in the primary and secondary metabolism of plants, bacteria, and fungi, and they are key enzymes in the biosynthesis of many clinically …

Investigating The In Vitro Antimicrobial Potential And Comprehensive Computational Studies Of New Schiff Base Derivatives, Abrar Hussain, Shahzaib Akhter, Hammad Nasir, Khurram Shahzad, Muhammad Arfan, Sand Hyun Park

Chemistry & Biochemistry Faculty Publications

Antimicrobial resistance (AMR) is a growing global health threat driven by multidrug-resistant bacteria (Staphylococcus aureus, Pseudomonas aeruginosa), and fungi (Candida albicans, and C. parapsilosis). This study evaluated six novel Schiff base derivatives (HSB-1 to HSB-6) through integrated in vitro antimicrobial activity and comprehensive computational studies. In vitro disk diffusion assay demonstrated the largest zones of inhibition against S. aureus for HSB-6 and HSB-1 (15–17 mm), activity against P. aeruginosa for HSB-5 and HSB-6 (12 mm), and moderate antifungal activity for HSB-4 (8–11 mm). Molecular docking results correlated with the in vitro findings with the binding energy ΔG = −12.3 kcal/mol …

Physicochemical, Pharmacognostic Standardisation And Phytochemical Analyses Of The Homoeopathic Drug Justicia Adhatoda, Bibaswan Biswas, Satish Patel, Digvijay Verma, Satyajit Maity, Shilpi Singh, Paulami Majumdar, Narasimha Kumar Gv

Indian Journal of Research in Homoeopathy

Background: Justicia adhatoda (J. adhatoda), also well known as Vasaka in India is a medicinal plant chiefly used to treat respiratory ailments in traditional and alternative medical systems. Objective: This study aimed to establish the physicochemical, pharmacognostic, and phytochemical standardisation parameters of the drug. The study involved the measurement of physicochemical parameters and chemical profiling of the raw drug. The chemical characteristics of the in-house mother tincture (prepared from in-house raw drug) and commercial mother tinctures available in India were also evaluated to assess the quality of commercially available mother tinctures. Materials and Methods: The present study …

Selenium Nanoparticles As Versatile Delivery Tools, Amir Nasrolahi Shirazi, Rajesh Vadlapatla, Ajoy Koomer, Kyle Yep, Keykavous Parang

Pharmacy Faculty Articles and Research

Selenium nanoparticles (SeNPs) have emerged as promising metal-based nanoparticles for drug delivery due to their unique physicochemical properties, intrinsic bioactivity, and biocompatibility. SeNPs offer a lower toxicity, higher bioavailability, and flexibility to be customized for surface chemistry compared to traditional selenium compounds. Advances in synthetic strategies, including chemical reduction, green biosynthesis, and surface functionalization with polymers, peptides, or ligands, have improved their stability, targeting capability, and circulation time. SeNP-based systems have demonstrated unique anticancer, antimicrobial, and anti-inflammatory activities, as they can function as drug carriers and active therapeutic agents. The surface of SeNPs has been functionalized with ligands such as …

Computational Molecular Docking Of Fluorinated Morphine Derivatives For Improved Pain Management, Mirabella Romano, Emily Chen

Student Scholar Symposium Abstracts and Posters

The opioid epidemic impacts 60 million people worldwide every year. Morphine, a commonly prescribed opioid, binds to the μ-opioid receptor (MOR) in the body via protonation of its tertiary amino group and the MOR. An unfortunate side effect of this binding process is its non-selectivity in both peripheral and central tissues. While activation within inflamed peripheral tissues results in pain relief, activation within central tissues results in the unwanted and addictive side effects of opioids. Because there is a discrepancy in pH between healthy (central) and inflamed (peripheral) tissue, selective binding within the inflamed tissues could provide pain relief without …

Synthesis And Study Of Stable Organic Radicals For Mri Contrast Agents And New Materials, Sabina Dhakal

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

The first part of this dissertation focuses on the design, synthesis, and characterization of a thermally robust S =1/2 phototetrazolinyl monoradical and the development of synthetic methodologies for a high-spin (S = 1) phototetrazolinyl diradical. Electrochemical studies of the phototetrazolium cation (precursor to the monoradical) revealed a remarkably narrow electrochemical band gap (Ecell ≈ 0.82 V), suggesting promising electrical conductivity. Thermal analysis of the monoradical demonstrated excellent stability, with the onset of decomposition at 232 °C. Building on the excellent thermal stability and promising properties for electrical conductivity of the monoradical, we developed two condensation-based synthetic routes that provide viable …

Allosteric Control Overcomes Steric Limitations For Neutralizing Antibodies Targeting Conserved Binding Epitopes Of The Sars-Cov-2 Spike Protein: Exploring The Intersection Of Binding, Allostery, And Immune Escape With A Multimodal Computational Approach, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Understanding the atomistic basis of multi-layer mechanisms employed by broadly reactive neutralizing antibodies of the SARS-CoV-2 spike protein without directly blocking receptor engagement remains an important challenge in coronavirus immunology. Class 4 antibodies represent an intriguing case: they target a deeply conserved, cryptic epitope on the receptor-binding domain yet exhibit variable neutralization potency across subgroups F1 (CR3022, EY6A, COVA1-16), F2 (DH1047), and F3 (S2X259). The molecular basis for this variability is not fully understood. Here, we employed a multi-modal computational approach integrating atomistic and coarse-grained molecular dynamics simulations, binding free energy calculations, mutational scanning, and dynamic network analysis to elucidate …

Dynamic Mutational Profiling Of Binding Interactions And Allosteric Networks In Conformational Ensembles Of The Sars-Cov-2 Spike Protein Complexes With Classes Of Antibodies Targeting Cryptic Binding Sites: Confluence Of Binding And Allostery Determines Molecular Mechanisms And Hotspots Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The ongoing evolution of SARS-CoV-2 variants has underscored the need to understand not only the structural basis of antibody recognition but also the dynamic and allosteric mechanisms that could underlie complexity of broad and escape-resistant neutralization. In this study, we employed a multi-scale approach integrating structural analysis, hierarchical molecular simulations, mutational scanning and network-based allosteric modeling to dissect how Class 4 antibodies (represented by S2X35, 25F9, and SA55) and Class 5 antibodies (represented by S2H97, WRAIR-2063 and WRAIR-2134) can modulate conformational behavior, binding energetics, allosteric interactions and immune escape patterns of the SARS-CoV-2 spike protein. Using hierarchical simulations of the …