Medicinal-Pharmaceutical Chemistry Commons^™

Effective Microwave-Assisted Approach To 1,2,3-Triazolobenzodiazepinones Via Tandem Ugi Reaction/Catalyst-Free Intramolecular Azide–Alkyne Cycloaddition, Maryna O. Mazur, Oleksii S. Zhelavskyi, Eugene M. Zviagin, Svitlana V. Shishkina, Vladimir I. Musatov, Maksim A. Kolosov, Elena H. Shvets, Anna Yu. Andryushchenko, Valentyn A. Chebanov

Department of Chemistry: Faculty Publications

A novel catalyst-free synthetic approach to 1,2,3-triazolobenzodiazepinones has been developed and optimized. The Ugi reaction of 2-azidobenzaldehyde, various amines, isocyanides, and acids followed by microwave-assisted intramolecular azide–alkyne cycloaddition (IAAC) gave a series of target heterocyclic compounds in moderate to excellent yields. Surprisingly, the normally required ruthenium-based catalysts were found to not affect the IAAC, only making isolation of the target compounds harder while the microwave-assisted catalyst-free conditions were effective for both terminal and non-terminal alkynes

Sulfur Anions: Comments Upon Structure, Charles A. Kingsbury

Department of Chemistry: Faculty Publications

This work emphasizes the need for solvent simulation as well as a counterion in calculations concerning anions, although optimization may be difficult. Solvent and counterion both play a large role in conformation of the ion. Part of the reason for the success of sulfur anions in chemical reactions may be the ability of sulfone oxygen(s) to coordinate with the counterion (usually lithium). The “solvent” partially dissociates lithium from the carbanion center.

Identifying Receptors For Neuropeptides And Peptide Hormones: Challenges And Recent Progress, Md Shadman Ridwan Abid, Somayeh Mousavi, James W. Checco

Department of Chemistry: Faculty Publications

Intercellular signaling events mediated by neuropeptides and peptide hormones represent important targets for both basic science and drug discovery. For many bioactive peptides, the protein receptors that transmit information across the receiving cell membrane are not known, severely limiting these signaling pathways as potential therapeutic targets. Identifying the receptor(s) for a given peptide of interest is complicated by several factors. Most notably, cell-cell signaling peptides are generated through dynamic biosynthetic pathways, can act on many different families of receptor proteins, and can participate in complex ligand-receptor interactions that extend beyond a simple one-to-one archetype. Here, we discuss recent methodological advances …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Structure Formation And Coupling Reactions Of Hexaphenylbenzene And Its Brominated Analog, Jacob D Teeter, Paulo S. Costa, Christoph Dobner, Mamun Sarker, Alexander Sinitskii, Axel Enders

Department of Chemistry: Faculty Publications

The on-surface coupling of the prototypical precursor molecule for graphene nanoribbon synthesis, 6,11-dibromo-1,2,3,4-tetraphenyltriphenylene (C₄₂Br₂H₂₆, TPTP), and its non-brominated analog hexaphenylbenzene (C₄₂H₃₀, HPB), was investigated on coinage metal substrates as a function of thermal treatment. For HPB, which forms non-covalent 2D monolayers at room temperature, a thermally induced transition of the monolayer’s structure could be achieved by moderate annealing, which is likely driven by π-bond formation. It is found that the dibrominated carbon positions of TPTP do not guide the coupling if the growth occurs on a substrate at temperatures that …

Peroxo Species Formed In The Bulk Of Silicate Cathodes, Zhenlian Chen, Bjoern Schwartz, Xianhui Zhang, Wenqiang Du, Lirong Zheng, Ailing Tian, Ying Zhang, Zhiyong Zhang, Xiao Cheng Zeng, Zhifeng Zhang, Liyuan Huai, Jinlei Wu, Helmut Ehrenberg, Deyu Wang, Jun Li

Department of Chemistry: Faculty Publications

Oxygen redox in Li-rich oxides may boost the energy density of lithium-ion batteries by incorporating oxygen chemistry in solid cathodes. However, oxygen redox in the bulk usually entangles with voltage hysteresis and oxygen release, resulting in a prolonged controversy in literature on oxygen transformation. Here, we report spectroscopic evidence of peroxo species formed and confined in silicate cathodes amid oxygen redox at high voltage, accompanied by Co2+/Co3+ redox dominant at low voltage. First-principles calculations reveal that localized electrons on dangling oxygen drive the OO dimerization. The covalence between the binding cation and the O-O dimer determines the degree of electron …

Dynamic Manipulation Of Droplets Using Mechanically Tunable Microtextured Chemical Gradients, Ali J. Mazaltarim, John J. Bowen, Jay M. Taylor, Stephen Morin

Department of Chemistry: Faculty Publications

Materials and strategies applicable to the dynamic transport of microdroplets are relevant to surface fluidics, self-cleaning materials, thermal management systems, and analytical devices. Techniques based on electrowetting, topographic micropatterns, and thermal/chemical gradients have advanced considerably, but dynamic microdroplet transport remains a challenge. This manuscript reports the fabrication of mechano-tunable, microtextured chemical gradients on elastomer films and their use in controlled microdroplet transport. Specifically, discreet mechanical deformations of these films enabled dynamic tuning of the microtextures and thus transport along surface-chemical gradients. The interplay between the driving force of the chemical gradient and the microtopography was characterized, facilitating accurate prediction of …

Coevolution, Dynamics And Allostery Conspire In Shaping Cooperative Binding And Signal Transmission Of The Sars-Cov-2 Spike Protein With Human Angiotensin-Converting Enzyme 2, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Binding to the host receptor is a critical initial step for the coronavirus SARS-CoV-2 spike protein to enter into target cells and trigger virus transmission. A detailed dynamic and energetic view of the binding mechanisms underlying virus entry is not fully understood and the consensus around the molecular origins behind binding preferences of SARS-CoV-2 for binding with the angiotensin-converting enzyme 2 (ACE2) host receptor is yet to be established. In this work, we performed a comprehensive computational investigation in which sequence analysis and modeling of coevolutionary networks are combined with atomistic molecular simulations and comparative binding free energy analysis of …

Design And Synthesis Of Core–Shell Microgels With One‐Step Clickable Crosslinked Cores And Ultralow Crosslinked Shells, Molla R. Islam, Chelsea Nguy, Sanika Pandit, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The present study is conducted to explore the engineering of core–shell microgels such that the core can be rapidly labeled with a variety of fluorophores, while the shell retains the softness needed in specific biomedical applications. Azide containing crosslinked core particles based on a crosslinked poly(N‐isopropylacrylamide) particle, using a one‐pot, multistep polymerization is synthesized. A core–shell microgel is then synthesized by growing a crosslinker‐free poly(N‐isopropylacrylamide)‐co‐acrylic acid (ULC10AAc) shell through a two‐step seed and feed polymerization. A simple “click” reaction between the azide present on the core and dibenzocyclooctyne containing fluorophores to make dyed core–shell …

Machine Learning Approaches For Improving Prediction Performance Of Structure-Activity Relationship Models, Gabriel Idakwo

Dissertations

In silico bioactivity prediction studies are designed to complement in vivo and in vitro efforts to assess the activity and properties of small molecules. In silico methods such as Quantitative Structure-Activity/Property Relationship (QSAR) are used to correlate the structure of a molecule to its biological property in drug design and toxicological studies. In this body of work, I started with two in-depth reviews into the application of machine learning based approaches and feature reduction methods to QSAR, and then investigated solutions to three common challenges faced in machine learning based QSAR studies.

First, to improve the prediction accuracy of learning …

Investigating Chitosan Modified With Triethylammonium Butanamide And Triethylphosphonium Butanamide As Non-Viral Gene Delivery Vectors By Examining Cytotoxicity And Transfection Efficiency, Deborah C. Ehie

Graduate Theses/Dissertations

Gene therapy is a very challenging field, especially with new emerging genetic disorders. Chitosan (CS), due to chitosan’s flexibility, biocompatibility, and biodegradability, has been of interest in the world of gene therapy especially as researchers are gravitating towards non-viral vectors due to the problems caused by viral vectors. Nevertheless, there are still issues regarding solubility, cellular uptake of cargos being transported in vitro or in vivo, increased cytotoxicity levels, as well as many other things that prevent chitosan from being an efficient gene delivery agent. Here I present five derivatives of chitosan, which were all modified with either triethylphosphonium …

Isolation, Identification, And Investigation Of A Novel Bioactive Furanocoumarin From Leaves Of Amyris Elemifera, Amy K. Bracken

Honors Theses

Plants produce biologically active compounds that humans have utilized for many agricultural applications. Amyris elemifera was investigated due to the known bioactivity of its family, Rutaceae, and its use in medicines in tribes of the Bahamas. Biotage® and TLC guided fractionation of the EtOAc, hexane, and MeOH extracts of the leaves of Amyris elemifera yielded bioactive compounds. Most significantly, a novel furanocoumarin, 8-(3-methylbut-2-enyloxy)-marmesin acetate (1), and its analog 8-(3-methylbut-2-enyloxy)-marmesin (2), were isolated. The structures were identified via NMR and X-ray crystallography techniques; the X-ray crystal structure for 1 was reported for the first time, and the …

Resolving The Puzzle Of Single-Atom Silver Dispersion On Nanosized Γ-Al2o3 Surface For High Catalytic Performance, Fei Wang, Jinzhu Ma, Shaohui Xin, Qiang Wang, Jun Xu, Changbin Zhang, Hong He, Xiao Cheng Zeng

Department of Chemistry: Faculty Publications

Ag/γ-Al2O3 is widely used for catalyzing various reactions, and its performance depends on the valence state, morphology and dispersion of Ag species. However, detailed anchoring mechanism of Ag species on γ-Al2O3 remains largely unknown. Herein, we reveal that the terminal hydroxyls on γ-Al2O3 are responsible for anchoring Ag species. The abundant terminal hydroxyls existed on nanosized γ-Al2O3 can lead to single-atom silver dispersion, thereby resulting in markedly enhanced performance than the Ag cluster on microsized γ-Al2O3. Density-functional-theory calculations confirm that Ag atom is mainly anchored by the terminal hydroxyls on (100) surface, forming a staple-like local structure with each Ag …

Methods Of Making And Using Lignin Derivatives, Mark Alan Helle, Chin Li Cheung

Department of Chemistry: Faculty Publications

Materials and methods for preparing reactive lignin and for preparing a bio-based adhesive are described herein.

This disclosure generally relates to methods of making and using reactive lignin. This disclosure also generally relates to methods of making and using bio-based adhesives. Lignin is the second most abundant natural polymer behind cellulose, yet lignin has very little commercial value despite years of research. Lignin is one of the major components of the cell wall in wood and other plant based materials such as hemp or crop wastes. It is produced in enormous quantities each year, primarily as a by-product in the …

Nanotoxicity Of Zrs3 Probed In A Bioluminescence Test On E. Coli Bacteria: The Effect Of Evolving H2s, Olga Zakharova, Alexander Gusev, Jehad Abourahma, Nataliia S. Vorobeva, Dmitry V. Sokolov, Dmitry S. Muratov, Denis V. Kuznetsov, Alexander Sinitskii

Department of Chemistry: Faculty Publications

Materials from a large family of transition metal trichalcogenides (TMTCs) attract considerable attention because of their potential applications in electronics, optoelectronics and energy storage, but information on their toxicity is lacking. In this study, we investigated the toxicity of ZrS3, a prominent TMTC material, toward photoluminescent E. coli bacteria in a bioluminescence test. We found that freshly prepared ZrS3 suspensions in physiological saline solution with concentrations as high as 1 g/L did not exhibit any toxic effects on the bacteria. However, ZrS3 suspensions that were stored for 24 h prior to the bioluminescence tests were very toxic to the bacteria …

Quantitative Nmr-Based Biomedical Metabolomics: Current Status And Applications, Alexandra A. Crook, Robert Powers

Department of Chemistry: Faculty Publications

Nuclear Magnetic Resonance (NMR) spectroscopy is a quantitative analytical tool commonly utilized for metabolomics analysis. Quantitative NMR (qNMR) is a field of NMR spectroscopy dedicated to the measurement of analytes through signal intensity and its linear relationship with analyte concentration. Metabolomics-based NMR exploits this quantitative relationship to identify and measure biomarkers within complex biological samples such as serum, plasma, and urine. In this review of quantitative NMR-based metabolomics, the advancements and limitations of current techniques for metabolite quantification will be evaluated as well as the applications of qNMR in biomedical metabolomics. While qNMR is limited by sensitivity and dynamic range, …

Methods Ofmaking And Using Lignin Derivatives, Mark Alan Helle, Chin Li Cheung

Department of Chemistry: Faculty Publications

Materials and methods for preparing reactive lignin and for preparing a bio-based adhesive are described herein.

Polarization-Independent Metasurface Lens Based On Binary Phase Fresnel Zone Plate, Jonathan Baine, Jing Tang, Xing Li

Department of Chemistry: Faculty Publications

Based on the binary phase Fresnel zone plate (FZP), a polarization-independent metasurface lens that is able to focus incident light with any polarization state, including circular, linear, and elliptical polarizations, has been proposed and investigated. We demonstrate that the metasurface lens consisting of metal subwavelength slits can operate in a wide bandwidth in the visible range, and has a higher focusing efficiency than that of an amplitude FZP lens without phase modulation. A multi-focus FZP metasurface lens has also been designed and investigated. The proposed lens can provide potential applications in integrated nanophotonic devices without polarization limitations.

Metabolic Changes Associated With Adaptive Resistance To Daptomycin In Streptococcus Mitis-Oralis, Allison Parrett, Joseph M. Reed, Stewart G. Gardner, Nagendra N. Mishra, Arnold S. Bayer, Robert Powers, Greg A. Somerville

Department of Chemistry: Faculty Publications

Background: Viridans group streptococci of the Streptococcus mitis-oralis subgroup are important endovascular pathogens. They can rapidly develop high-level and durable non-susceptibility to daptomycin both in vitro and in vivo upon exposure to daptomycin. Two consistent genetic adaptations associated with this phenotype (i.e., mutations in cdsA and pgsA) lead to the depletion of the phospholipids, phosphatidylglycerol and cardiolipin, from the bacterial membrane. Such alterations in phospholipid biosynthesis will modify carbon flow and change the bacterial metabolic status. To determine the metabolic differences between daptomycin-susceptible and non- susceptible bacteria, the physiology and metabolomes of S. mitis-oralis strains 351 (daptomycin-susceptible) and 351-D10 (daptomycin …

Carbon Oxidation State In Microbial Polar Lipids Suggests Adaptation To Hot Spring Temperature And Redox Gradients, Grayson M. Boyer, Florence Schubotz, Roger E. Summons, Jade Woods, Everett L. Shock

Department of Chemistry: Faculty Publications

The influence of oxidation-reduction (redox) potential on the expression of biomolecules is a topic of ongoing exploration in geobiology. In this study, we investigate the novel possibility that structures and compositions of lipids produced by microbial communities are sensitive to environmental redox conditions. We extracted lipids from microbial biomass collected along the thermal and redox gradients of four alkaline hot springs in Yellowstone National Park (YNP) and investigated patterns in the average oxidation state of carbon (Z_C), a metric calculated from the chemical formulae of lipid structures. Carbon in intact polar lipids (IPLs) and their alkyl chains becomes …

Surface Modification Of Silicon Nanowire Based Field Effect Transistors With Stimuli Responsive Polymer Brushes For Biosensing Applications, Stephanie Klinghammer, Sebastian Rauch, Sebastian Pregl, Petra Uhlmann, Larysa Baraban, Gianaurelio Cuniberti

Department of Chemistry: Faculty Publications

We demonstrate the functionalization of silicon nanowire based field effect transistors (SiNW FETs) FETs with stimuli-responsive polymer brushes of poly(N-isopropylacrylamide) (PNIPAAM) and poly(acrylic acid) (PAA). Surface functionalization was confirmed by atomic force microscopy, contact angle measurements, and verified electrically using a silicon nanowire based field effect transistor sensor device. For thermo-responsive PNIPAAM, the physicochemical properties (i.e., a reversible phase transition, wettability) were induced by crossing the lower critical solution temperature (LCST) of about 32 ◦C. Taking advantage of this property, osteosarcomic SaoS-2 cells were cultured on PNIPAAM-modified sensors at temperatures above the LCST, and completely detached by simply cooling. Next, …

Rapid And Accurate Determination Of Atomistic Rna Dynamic Ensemble Models Using Nmr And Structure Prediction, Honglue Shi, Atul Rangadurai, Hala Abou Assi, Rohit Roy, David A. Case, Daniel Herschlag, Joseph D. Yesselman, Hashim M. Al-Hashimi

Department of Chemistry: Faculty Publications

Biomolecules form dynamic ensembles of many inter-converting conformations which are key for understanding how they fold and function. However, determining ensembles is challenging because the information required to specify atomic structures for thousands of conformations far exceeds that of experimental measurements. We addressed this data gap and dramatically simplified and accelerated RNA ensemble determination by using structure prediction tools that leverage the growing database of RNA structures to generate a con- formation library. Refinement of this library with NMR residual dipolar couplings provided an atomistic ensemble model for HIV-1 TAR, and the model accuracy was independently sup- ported by comparisons …

A Luminescence-Based System For Identification Of Genetically Encodable Inhibitors Of Protein Aggregation, Travis J. Nelson, Shuo Liang, Cliff I. Stains

Department of Chemistry: Faculty Publications

Molecules that disrupt protein aggregation represent potential tool compounds for the investigation of numerous human disease states. However, the identification of small molecules capable of disrupting protein aggregation has proven challenging. Larger biomolecules such as antibodies and proteins are promising alternatives due to their increased size. Despite the promise of protein-based inhibitors, generalizable assays are needed to more readily identify proteins capable of inhibiting aggregation. Herein, we utilize our previously reported self- assembling NanoLuc luciferase fragments to engineer a platform in which both detection reagents are expressed from the same plasmid, enabling facile co-transformation with a genetically encodable inhibitor. This …

Constructing Stable And Potentially High-Performance Hybrid Organic-Inorganic Perovskites With “Unstable” Cations, Qing Yang, Menghao Wu, Xiao Cheng Zeng

Department of Chemistry: Faculty Publications

A new family of functional hybrid organic-inorganic perovskites (HOIPs) is theoretically designed based on the following chemical+ insights: when a proton is adhered to molecules like water or ethanol, the newly formed larger-sized cations (e.g., H5O2 ,++ C2H5OH2 , and CH3SH ) entail low electron affinities mimicking superalkalis; they are conjugated acids of weak bases that cannot survive in solution, while their chemistry behavior in the HOIP frameworks, however, may be markedly different due to greatly enhanced cohesive energies of the proton, which facilitate the formation of new HOIPs. First-principles computations show that the putative formation reactions for these newly …

Domain Wall Conduction In Calcium-Modified Lead Titanate For Polarization Tunable Photovoltaic Devices, Chong-Xin Qian, Hong-Jian Hong-Jian, Qiang Zhang, Jiawei He, Zi-Xuan Chen, Ming-Zi Wang, Xiao Cheng Zeng

Department of Chemistry: Faculty Publications

Ferroelectric domain wall (DW) conduction, confirmed in recent experiments, has attracted intense attention due to its promising applications in optoelec- tronic devices. Herein, we provide theoretical evidence of electric conduction in Pb0.8Ca0.2TiO3 (PCT) DWs. The separation of charge accumulation in DWs, corresponding to the electronic conduction-band minimum (CBM) and valence-band maximum (VBM), weakens the tendency for the electron-hole recombination, thereby providing more efficient channels for charge transfer. We fabricate PCT-based functional photovoltaic devices with polarization tunable charge transfer to exploit the combined conduction and ferroelectric properties of the DW. The photovoltaic performance of the devices can be regu- lated by …

Mechanistic Insights Into The Acetate-Accelerated Synthesis Of Crystalline Ceria Nanoparticles, Tamra J Fisher, Deepa Choudhry, Kaitlynn Derr, Soodabeh Azadehranjbar, Dan Stasko, Chin Li Cheung

Department of Chemistry: Faculty Publications

Recent increasing uses of ceria in research and industrial applications have fostered continuing developments of efficient routes to synthesize the material. Here we report our investigation of the effects and the mechanistic roles of lithium acetate to accelerate the growth of crystalline ceria nanoparticles in ozone-mediated synthesis. By increasing the mole ratio of the acetate to cerium nitrate in the reactions, the reaction yields of ceria nanoparticles were observed to increase from ca. 10% to up to over 90% by cerium content in 30 min reactions. Microscopy images and Raman spectra of the assynthesized nanoparticles revealed that increasing the acetate …

A Click-Based Modular Approach To Introduction Of Peroxides Onto Molecules And Nanostructures, Alissa Horn, Patrick H. Dussault

Department of Chemistry: Faculty Publications

Copper-promoted azide/alkyne cycloadditions (CuAAC) are explored as a tool for modular introduction of peroxides onto molecules and nanomaterials. Dialkyl peroxide-substituted alkynes undergo Cu(I)- promoted reaction with azides in either organic or biphasic media to furnish peroxide-substituted 1,2,3- triazoles. Heterolytic fragmentation of the peroxide to an aldehyde, a side reaction that appears to be related to the formation of the triazole, can be suppressed by use of excess alkyne, the presence of triethylsilane, or by use of iodoalkyne substrates. Complementary reactions of simple alkynes with azidosubstituted peroxides are much less efficient. Click reactions of alkynyl peroxyacetals are also reported; reductive fragmentation …

Agbis2 As A Low-Cost And Eco-Friendly All-Inorganic Photovoltaic Material: Nanoscale Morphology– Property Relationship†, Ming-Gang Ju, Jun Dai, Liang Ma, Yuanyuan Zhou, Xiao Cheng Zeng

Department of Chemistry: Faculty Publications

Solar cells made of low-cost solution-processed all-inorganic materials are a promising alternative to conventional solar cells made of high-temperature processed inorganic materials, especially because many high-temperature processed inorganic materials contain toxic element(s) such as lead or cadmium (e.g., CsPbI₃ perovskite, PbS, CdTe and CdS(Se)). AgBiS₂ nanocrystals, consisting of earth-abundant elements but without lead and cadmium, have already emerged as a promising candidate in highperformance solar cells. However, the nanoscale morphology–optoelectronic property relationship for AgBiS₂ nanocrystals is still largely unknown. Herein, we investigate the electronic properties of various AgBiS₂ nanocrystals by using first-principles computation. We show that …

“Treat Me Covalently” – New Tools To Improve Covalent Drug Design For Advancement Of Cancer Treatments, Yuliya Mazo

Student Theses and Dissertations

The goal of this project was to investigate the complex mechanism of covalent bonding among different molecules and their targets in a modeling software ICM-Pro. Specifically, it included the identification of fundamental aspects of a covalent bonding mechanism of the Michael addition reaction. Michael addition reaction of electrophilic α, β-unsaturated carbonyl compounds with a nucleophilic cysteine residue in thymidylate synthase, papain, and EGFR tyrosine kinase were examined. Thymidylate synthase and EGFR were chosen because they are important targets in the treatment of various types of cancer. In order to find the most optimal parameters, identification and assessment of the effect …

Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry Iii, Cj Deleon, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro-inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zolendronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zolendronate on the concentrations of tumor necrosis factor alpha-type (TNFɑ) in 32 ovariectomized Wistar rats. Throughout a five …