Chemistry Commons^™

Rigorous Computational And Experimental Investigations On Mdm2/Mdmx-Targeted Linear And Macrocyclic Peptides, David J. Diller, Jon Swanson, Alexander S. Bayden, Chris J. Brown, Dawn Thean, David P. Lane, Anthony W. Patridge, Tomi K. Sawyer, Joseph Audie

Chemistry & Physics Faculty Publications

There is interest in peptide drug design, especially for targeting intracellular protein–protein interactions. Therefore, the experimental validation of a computational platform for enabling peptide drug design is of interest. Here, we describe our peptide drug design platform (CMDInventus) and demonstrate its use in modeling and predicting the structural and binding aspects of diverse peptides that interact with oncology targets MDM2/MDMX in comparison to both retrospective (pre-prediction) and prospective (post-prediction) data. In the retrospective study, CMDInventus modules (CMDpeptide, CMDboltzmann, CMDescore and CMDyscore) were used to accurately reproduce structural and binding data across multiple MDM2/MDMX data sets. In the prospective study, CMDescore, …

Molecular Determinants Of Substrate Specificity In Human Insulin-Degrading Enzyme, Lazaros Stefanidis, Nicholas D. Fusco, Samantha E. Cooper, Jilian E. Smith-Carpenter, Benjamin J. Alper

Chemistry & Physics Faculty Publications

Insulin-degrading enzyme (IDE) is a 110 kDa chambered zinc metalloendopeptidase that degrades insulin, amyloid beta, and other intermediate-sized aggregation prone peptides that adopt β-structures. Structural studies of IDE in complex with multiple physiological substrates have suggested a role for hydrophobic and aromatic residues of the IDE active site in substrate binding and catalysis. Here, we examine functional requirements for conserved hydrophobic and aromatic IDE active site residues that are positioned within 4.5 Angstroms of IDE bound insulin B chain and amyloid beta peptides in the reported crystal structures for the respective enzyme-substrate complexes. Charge, size, hydrophobicity, aromaticity, and other functional …

Functional Requirement For Human Pitrilysin Metallopeptidase 1 Arginine 183, Mutated In Amyloidogenic Neuropathy, Jilian E. Smith-Carpenter, Benjamin Alper

Chemistry & Physics Faculty Publications

Here we report the enzymologic characterization of recombinant human pitrilysin metallopeptidase 1 (Pitrm1) and derivative mutants including the arginine-to-glutamine substitution mutant Pitrm1 R183Q, which has been implicated in inherited amyloidogenic neuropathy. Recombinant Pitrm1 R183Q was readily expressed in and purified from E. coli, but was less active than the recombinant wild-type enzyme against recombinant amyloid beta peptide (Aβ 1-40). A novel fluorogenic substrate derived from the reported Aβ 1-40 core peptide cleavage sequence, Mca-KLVFFAEDK-(Dnp)-OH, was synthesized and applied to real-time kinetic study of Pitrm1 and derivative mutants including Pitrm1 R183Q. The Pitrm1 R183Q mutant exhibited significantly decreased rate of fluorogenic …

Application Of Factorial Design In The Analysis Of Factors Influencing Textile Dye Adsorption On Activated Carbon, Eid A. Alkhatib, Penny A. Snetsinger, Ahmad Alanazi, Sarah Aanonsen

Chemistry & Physics Faculty Publications

In this study, the use of factorial design software is applied to evaluate efficiently factors influencing the adsorption capacity of activated carbon in treating textile dyes. Activated carbon is usually used to treat wastewater effluents from textile industries in order to remove textile dyes before discharge into the environment. Most treatment facilities, particularly large industrial or wastewater treatment facilities use continuous flow reactors or packed columns to treat the dye. Due to the limited residence time in these types of reactors, adsorption equilibrium is not necessarily reached, and the absorption rate becomes an important factor in this treatment process. Other …

A Pes Study Of Factors Influencing Metal Partitioning In Aquatic Systems: “Design Of Experiment As, Cd, Co, Cr, Cu, Pb, Ni, And Zn”, Eid A. Alkhatib, John Rapaglia, Leon Theim

Chemistry & Physics Faculty Publications

Mobility and bioavailability of heavy metals are related to their partitioning amongst suspended sediment and water. A Particle Entrainment Simulator (PES) is used to simulate sediment resuspention in natural surface water systems. The simulations were carried out under various conditions of water/suspended solids conditions. Five factors, each at various levels, are tested collectively: the pH of water at two levels (4 and 8), shear stress on bottom sediment at three levels (0.1, 0.3, and 0.5 N/m2 ) salinity of water at two levels (0.01 and 14.0 ppt), organic matter in sediment at three levels (0.50, 1.93, and 3.80%) and temperature …

Multi-Regression Prediction Of Metal Partition Coefficients Under Various Physical/Chemical Conditions Design Of Experiments As, Cr, Cu, Ni And Zn, Eid A. Alkhatib, Danielle Grunzke, Trey Chabot

Chemistry & Physics Faculty Publications

The behavior of metals in surface water is complex and their partition coefficients can be impacted by many factors. Organic matter (OM) content in sediments, pH and salinity, are factors that may influence speciation and partitioning of metals. The difficulty in describing the impacts and relationships are that these processes are interconnected with no dominant associations among all. In this study, the partitioning of five metals (As, Cr, Cu, Ni and Zn) under different levels of salinity, pH, and OM content were investigated. A series of factorial design experiments are evaluated in which three levels of OM are tested each …

Prediction Of Metal Remobilization From Sediments Under Various Physical/ Chemical Conditions “Design Of Experiments Cd, Co And Pb”, Eid A. Alkhatib, Trey Chabot, Danielle Grunzke

Chemistry & Physics Faculty Publications

The metal partition coefficient Kd (L/kg) is the ratio of sorbed metal concentration on the solid phase m (mg/kg) to the dissolved metal concentration at equilibrium. The behavior of metals in surface water is complex and their partition coefficients can be impacted by many factors. Organic matter (OM) content in sediments, pH and salinity, are factors that may influence speciation and partitioning of metals. In this study, the partitioning coefficient of three metals (Cd, Co and Pb) under different levels of salinity, pH, and OM content were examined. A series of factorial experiments were evaluated in which three levels of …

Comprehensive Organic Synthesis Ii (Book Review), Jeffrey H. Glans

Chemistry & Physics Faculty Publications

Jeffrey Glans' review focuses on the online version available through ScienceDirect.

Knochel, Paul and Gary A. Molander, eds. Comprehensive Organic Synthesis II. 2nd ed. Amsterdam; Waltham, MA: Elsevier, 2014. Web.

http://www.sciencedirect.com/science/referenceworks/9780080977430

ISBN: 9780080977430 (e-book)

Peptide Drug Discovery: Innovative Technologies And Transformational Medicines, David J. Diller, Mark Jarosinski, Tomi K. Sawyer, Joseph Audie

Chemistry & Physics Faculty Publications

Interest in peptide drug discovery is surging. In the past several years,numerous pharmaceutical and biotech companies have committed considerable resources to peptide-based drug discovery. In part,this is being fueled by an increasing recognition that peptide drugs combine many of the virtues of small molecules and proteins, while minimizing several of their drawbacks, and that peptides can potentially expand the druggable space to include intracellular, extracellular and membrane associated protein–protein interactions. Moreover, powerful new in vitro and in silico technologies and breakthroughs in our understanding of natural peptides have emerged that provide peptide chemists with the toolsand insights they need to …

Drug Screening Target For Alzheimer's Disease And Method Of Screening Potential Drugs, Joseph Audie, Sergei Y. Ponomarev

Chemistry & Physics Faculty Publications

Drug screening targets and method of screening for potential drugs for treatment or amelioration of Alzheimer's Disease are provided.

Synthesis And Polymerization Of (E,E)-[6.2]-(2,5)Furanophane-1,5-Diene, Neil D. Doppler, Jeffrey H. Glans

Chemistry & Physics Faculty Publications

The goal of this research is to polymerize (E,E)-[6.2]-(2,5)furanophane to give a linear polymer. It will be synthesized by a 1,8-Hofmann Elimination using trimethyl-[(E)-3-(5-methyl-2-furyl)allyl] ammonium iodide. This diene will then be polymerized. The resulting polymeric [3.2] furanophane will then be oxidized to form a polymeric macrocycle tetra ketone. This compound will be tested for cation complexation.

Scifinder (Review), Jeffrey H. Glans

Chemistry & Physics Faculty Publications

Overview of SciFinder database, a Chemical Abstracts Service (www.cas.org), a division of the American Chemical Society.

Chemical Reactivity Worksheet, Noaa, Jeffrey H. Glans

Chemistry & Physics Faculty Publications

Website overview by Jeffrey H. Glans.

NOAA. Office of Response and Restoration. "Chemical Reactivity Worksheet, NOAA." http://response.restoration.noaa.gov/crw

Synthesis, Structure And Attempted Polymerization Of A Diepoxide Macrocycle, Paul Yarincik, Jeffrey H. Glans

Chemistry & Physics Faculty Publications

A novel diepoxide containing paracyclophane was synthesized by peracid oxidation of a known paracyclophane diene. The resulting diepoxide was characterized. It was investigated as a potential monomer for a cyclophane containing polyether by cationic ring opening polymerization. None of the standard catalyst systems for such a polymerization were successful in producing polymer.

Organic Synthesis Based On Name Reaction: A Practical Guide To Over 700 Transformations (Book Review), Jeffrey H. Glans

Chemistry & Physics Faculty Publications

Book review by Jeffrey Glans:

Hassner, Alfred and I. Namboothiri. Organic Synthesis Based on Name Reaction: A Practical Guide to Over 700 Transformations. 3rd ed. Amsterdam; Boston: Elsevier, 2012.

ISBN 9780080966304

Dalton, David R.: Foundations Of Organic Chemistry: Unity And Diversity Of Structures, Pathways & Reactions (Book Review), Jeffrey H. Glans

Chemistry & Physics Faculty Publications

Book review by Jeffrey Glans.

Dalton, David R. Foundations of Organic Chemistry: Unity and Diversity of Structures, Pathways & Reactions. Hoboken, NJ: Wiley, 2011.

ISBN 9780470479087

Introduction To Molecular Motion In Polymers (Book Review), Jeffrey H. Glans

Chemistry & Physics Faculty Publications

A book review by Jeffrey H. Glans.

Pethrick, Richard A., T. Amornsakchai, and A. M. North. Introduction to Molecular Motion in Polymers. Dunbeath, Scotland: Whittles Pub.; Boca Raton, FL: Distributed in North America by CRC, 2011.

ISBN 9781849950084

Joule, John A. Heterocyclic Chemistry (Book Review), Jeffrey H. Glans

Chemistry & Physics Faculty Publications

Book review by Jeffrey H. Glans.

Joule, John A. and Keith Mills. "A Heterocyclic Chemistry. 5th ed. Wiley-Blackwell, 2010.

ISBN 9781405193658 (hardcover); 9781405133005 (pbk.)

Direct Immunosensor Design Based On The Electrochemical Reduction Of 4-((4-Nitrophenyl) Ethynyl) Benzenethiol Monolayers, Dwight A. Williams, Wraegen A. M. Williams, Melissa C. Rhoten, Charlene D. Crawley, Suzanne Ruder

Chemistry & Physics Faculty Publications

The synthesis and characterization of novel N-arylhydroxylamine-based molecular wires are described for use in the site-directed covalent immobilization of whole IgG antibodies onto gold electrode surfaces. The hydroxylamine, electrochemically generated in situ from reduction of the corresponding nitrobenzene, is stable under a wide range of solution conditions and reacts selectively with carbohydrate away from the antibody-binding site to allow the development of immunosensors with maximal activity. Cyclic voltammetric responses have shown a direct correlation between the structure and length of the molecular wire and its stability and concentration at the electrode surface.

Molecular Orbitals And Organic Chemical Reactions (Book Review), Jeffrey H. Glans

Chemistry & Physics Faculty Publications

Book review by Jeffrey Glans.

Fleming, Ian. Molecular Orbitals and Organic Chemical Reactions. Wiley-Blackwell, 2010, c2009.

ISBN: 9780470746608; 9780470746592 (pbk.)

Compendium Of Polymer Terminology And Nomenclature: Iupac Recommendations, 2008 (Book Review), Jeffrey H. Glans

Chemistry & Physics Faculty Publications

Book review by Jeffrey Glans.

Polymer Division, International Union of Pure and Applied Chemistry. Compendium of Polymer Terminology and Nomenclature: IUPAC Recommendations, 2008. Royal Society of Chemistry, 2009.

Continued Development Of An Empirical Function For Predicting And Rationalizing Protein–Protein Binding Affinities, Joseph Audie

Chemistry & Physics Faculty Publications

Here we summarize recent work on the continued development of our fast and simple empirical equation for predicting and structurally rationalizing protein–protein and protein–peptide binding affinities. Our empirical expression consists of six regression-weighted physical descriptors and derives from two key simplifying assumptions: (1) the assumption of rigid-body association and (2) the assumption that all contributions not explicitly considered in the equation make a net contribution to binding of ≈0 kcal. Within the strict framework of rigid-body association, we tested relative binding affinity predictions using our empirical equation against the corresponding experimental binding free energy data for 197 interface alanine mutants. …

Development And Validation Of An Empirical Free Energy Function For Calculating Protein–Protein Binding Free Energy Surfaces, Joseph Audie

Chemistry & Physics Faculty Publications

In a previous paper, we described a novel empirical free energy function that was used to accurately predict experimental binding free energies for a diverse test set of 31 protein–protein complexes to within ≈1.0 kcal. Here, we extend that work and show that an updated version of the function can be used to (1) accurately predict native binding free energies and (2) rank crystallographic, native-like and non-native binding modes in a physically realistic manner. The modified function includes terms designed to capture some of the unfavorable interactions that characterize non-native interfaces. The function was used to calculate one-dimensional binding free …

Arrow Pushing In Organic Chemistry: An Easy Approach To Understanding Reaction Mechanisms (Book Review), Jeffrey H. Glans

Chemistry & Physics Faculty Publications

A book review by Jeffrey Glans.

Levy, Daniel E. Arrow Pushing in Organic Chemistry: An Easy Approach to Understanding Reaction Mechanisms. New York: Wiley, 2008.

ISBN 9780470171103

Wet Weather Impact On Trihalomethane Formation Potential In Tributaries To Drinking Water Reservoirs, Eid A. Alkhatib, R. Peters

Chemistry & Physics Faculty Publications

During rain storm events, land surface runoff and resuspension of bottom sediments cause an increase in Trihalomethane (THM) precursors in rivers. These precursors, when chlorinated at water treatment facilities will lead to the formation of THMs and hence impact drinking water resources. In order to evaluate the wet weather impact on the potential formation of THMs, river samples were collected before, during and after three rain storms ranging from 15.2 to 24.9 mm precipitation. The samples were tested for THM formation potential and other indicators including UV254 absorbance, turbidity and volatile suspended solid (VSS). Average levels of THMs increased from …

Simulation Of Arsenic Partitioning In Tributaries To Drinking Water Reservoirs, Eid A. Alkhatib

Chemistry & Physics Faculty Publications

Arsenic released by bottom sediments was determined by experiments in which the sediments were artificially re-suspended using a particle entrapment simulator (PES) to simulate river conditions. Sediment cores were collected from various tributaries to drinking water reservoirs in Connecticut spiked with arsenic, and run in the PES at simulated bed-flow shear stresses from 0.0 to 0.6 N/m2. Under equilibrium conditions, the dissolved fraction of arsenic was found to range from 8.3 to 22.1 ug/1, which in most cases exceeded EPA Maximum Contaminant Level (MCL) of 10 ug/1. Experimental results from these simulations have shown that bed-flow shear stress causes an …

A Novel Empirical Free Energy Function That Explains And Predicts Protein–Protein Binding Affinities, Joseph Audie, Suzanne Scarlata

Chemistry & Physics Faculty Publications

A free energy function can be defined as a mathematical expression that relates macroscopic free energy changes to microscopic or molecular properties. Free energy functions can be used to explain and predict the affinity of a ligand for a protein and to score and discriminate between native and non-native binding modes. However, there is a natural tension between developing a function fast enough to solve the scoring problem but rigorous enough to explain and predict binding affinities. Here, we present a novel, physics-based free energy function that is computationally inexpensive, yet explanatory and predictive. The function results from a derivation …

Parameters Affecting Partitioning Of 6 Pcb Congeners In Natural Sediments, Eid A. Alkhatib, Carl Weigand

Chemistry & Physics Faculty Publications

Polychlorinated biphenyls (PCBs) released by bottom sediments were determined by experiments in which the sediments were artificially resuspended using sediment contaminated with PCBs in a particle entrainment simulator (PES). Sediment cores, spiked with PCBs, were collected from the Housatonic River in Connecticut and run in the PES at simulated shear stresses from 0 to 0.6 N m(-2). Experimental results from these simulations have shown that mean concentration of PCBs in the solid phase for sites with high volatile organic carbon (VOC) were significantly greater than samples with low VOC; the reverse was true for the water phase. In addition, on …

Thermodynamics Of Water Superheated In The Microwave Oven, Ben H. Erné, Penny A. Snetsinger

Chemistry & Physics Faculty Publications

A simple visual demonstration is proposed that provokes thinking about the elementary thermodynamics of heating and boiling. Water is conveniently heated above its normal boiling point in a microwave oven in a glass microwave oven teapot. Water stops boiling soon after heating is interrupted, but subsequently added rough particles can still act as nucleation centers for a brief, spectacular burst of steam bubbles. The heat to make those steam bubbles obviously comes from the water itself, so that one can conclude that the boiling water was superheated, which is confirmed with a thermometer. Besides illustrating chemical thermodynamics, the demonstration also …

Parameters Influencing Sediments Resuspension And The Link To Sorption Of Inorganic Compounds, Eid A. Alkhatib, Keith Castor

Chemistry & Physics Faculty Publications

In the aquatic environment, the accumulation of chemicalcontaminants by sediments poses a potential threat to endemiclife forms and drinking water resources. Trace metals such asCd, Cu, Cr, Ni, Pb, and toxic organic compounds, are among awide variety of contaminants having an affinity for sediments.In this study, experiments were performed simulating sedimentresuspension in the lower Housatonic River, Connecticut, using aParticle Entrainment Simulator. Analyses of grain sizedistributions, porosities and total organic contents of thesediments suggested that these parameters influence theredistribution and entrainment of settleable solids in the watercolumn. These findings were established by evaluating the impactof one parameter on sediment resuspension as …