Chemistry, Department of

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Enabling a High-Throughput Characterization of Microscale Interfaces within Coated Cathode Particles

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-09-10
Abstract: 

Lithium ion batteries represent an emerging field. The development of battery materials could benefit from quick techniques that enable atomic-level diagnostics. High performance cathodes, such as high-voltage spinel, often require coatings to protect against the destructive electrochemical environments at the particle-to-electrolyte interface. The preparations of these coating are still in the early phases of development, and their analytical inspection by high resolution scanning and transmission electron microscopy (HR-S/TEM) techniques presents a significant challenge due to the microscale dimensions of cathode particles. In this work, a high throughput ultramicrotome technique was assessed for the characterization of the particle to coating interface. The ultramicrotome technique enabled the rapid preparation of cross-sections with a thickness of 126 ± 66 nm as determined by electron energy loss spectroscopy (EELS) measurements. Cathode particles composed of high-voltage spinel, LiNi0.5Mn1.5O4 (LNMO), coated with lithium niobate (LiNbO3) were synthesized and cross-sections were inspected using HR-S/TEM techniques. These ultra-thin cross-sections enabled the ability to obtain nanoscale information regarding the composition and crystallinity of the particle-to-coating interface over lateral areas of >1 µm. Accessible correlations between the electrochemical performance of the LiNbO3 coated LNMO particles and the HR-S/TEM results were enabled by the high-throughput method. Discharge capacity measurements were acquired over a series of 100 electrochemical cycles for both the LiNbO3 coated and the as-prepared LNMO particles. The limitations of the ultramicrotome technique are also discussed herein with respect to the coating morphology and the procedure for guidance toward technique optimization. The rapid preparation of ultra-thin cross-sections can assist the advancement of protective coatings on the surfaces of cathode particles for an efficient characterization of bulk-to-surface interfaces.

Document type: 
Article

Contact Transfer of Engineered Nanomaterials in the Workplace

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-08-18
Abstract: 

This study investigates the potential spread of cadmium selenide quantum dots in laboratory environments through contact of gloves with simulated dry spills on laboratory countertops. Secondary transfer of quantum dots from the contaminated gloves to other substrates was initiated by contact of the gloves with different materials found in the laboratory. Transfer of quantum dots to these substrates was qualitatively evaluated by inspection under ultraviolet illumination. This secondary contact resulted in the delivery of quantum dots to all the evaluated substrates. The amount of quantum dots transferred was quantified by elemental analysis. The residue containing quantum dots picked up by the glove was transferred to at least seven additional sections of the pristine substrate through a series of sequential contacts. These results demonstrate the potential for contact transfer as a pathway for spreading nanomaterials throughout the workplace, and that 7-day-old dried spills are susceptible to the propagation of nanomaterials by contact transfer. As research and commercialization of engineered nanomaterials increase worldwide, it is necessary to establish safe practices to protect workers from the potential for chronic exposure to potentially hazardous materials. Similar experimental procedures to those described herein can be adopted by industries or regulatory agencies to guide the development of their nanomaterial safety programmes.

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Article
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Tuning the Surface Chemistry of Second-Harmonic-Active Lithium Niobate Nanoprobes Using a Silanol–Alcohol Condensation Reaction

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-06-15
Abstract: 

The surface functionalization of nanoparticles (NPs) is of a great interest for improving the use of NPs in, for example, therapeutic and diagnostic applications. The conjugation of specific molecules with NPs through the formation of covalent linkages is often sought to provide a high degree of colloidal stability and biocompatibility, as well as to provide functional groups for further bioconjugation. Nanoparticles of lithium niobate (LiNbO3) have been explored for use in second harmonic generation (SHG) based bioimaging, expanding the applications of SHG based microscopy techniques. The efficient use of SHG active LiNbO3 NPs as probes will, however, require the functionalization of their surfaces with molecular reagents such as polyethylene glycol and fluorescent molecules to enhance their colloidal and chemical stability, and to enable a correlative imaging platform. Herein, we demonstrate the surface functionalization of LiNbO3 NPs through the covalent attachment of alcohol-based reagents through a silanol-alcohol condensation reaction. Alcohol-based reagents are widely available and can have a range of terminal functional groups such as carboxylic acids, amines, and aldehydes. Attaching these molecules to NPs through the silanol-alcohol condensation reaction could diversify the reagents available to modify NPs, but this reaction pathway must first be established as a viable route to modifying NPs. This study focuses on the attachment of a linear alcohol functionalized with carboxylic acid and its use as a reactive group to further tune the surface chemistry of LiNbO3 NPs. These carboxylic acid groups were reacted to covalently attach other molecules to the NPs using copper-free click chemistry. This derivatization of the NPs provided a means to covalently attach polyethylene glycols and fluorescent probes to the NPs, reducing NP aggregation and enabling multimodal tracking of SHG nanoprobes, respectively. This extension of the silanol-alcohol condensation reaction to functionalizing the surfaces of LiNbO3 NPs can be extended to other types of nanoprobes for use in bioimaging, biosensing, and photodynamic therapies.

Document type: 
Article

Tandem Bioorthogonal Labeling Uncovers Endogenous Cotranslationally O-GlcNAc Modified Nascent Proteins

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2020-09-01
Abstract: 

Hundreds of nuclear, cytoplasmic, and mitochondrial proteins within multicellular eukaryotes have hydroxyl groups of specific serine and threonine residues modified by the monosaccharide N-acetylglucosamine (GlcNAc). This modification, known as O-GlcNAc, has emerged as a central regulator of both cell physiology and human health. A key emerging function of O-GlcNAc appears to be to regulate cellular protein homeostasis. We previously showed, using overexpressed model proteins, that O-GlcNAc modification can occur cotranslationally and that this process prevents premature degradation of such nascent polypeptide chains. Here, we use tandem metabolic engineering strategies to label endogenously occurring nascent polypeptide chains within cells using O-propargyl-puromycin (OPP) and target the specific subset of nascent chains that are cotranslationally glycosylated with O-GlcNAc by metabolic saccharide engineering using tetra-O-acetyl-2-N-azidoacetyl-2-deoxy-d-galactopyranose (Ac4GalNAz). Using various combinations of sequential chemoselective ligation strategies, we go on to tag these analytes with a series of labels, allowing us to define conditions that enable their robust labeling. Two-step enrichment of these glycosylated nascent chains, combined with shotgun proteomics, allows us to identify a set of endogenous cotranslationally O-GlcNAc modified proteins. Using alternative targeted methods, we examine three of these identified proteins and further validate their cotranslational O-GlcNAcylation. These findings detail strategies to enable isolation and identification of extremely low abundance endogenous analytes present within complex protein mixtures. Moreover, this work opens the way to studies directed at understanding the roles of O-GlcNAc and other cotranslational protein modifications and should stimulate an improved understanding of the role of O-GlcNAc in cytoplasmic protein quality control and proteostasis.

Document type: 
Article
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4-Phenylnaphtho[2,3-c]furan-1(3H)-one, 9-Phenylnaphtho[2,3-c]furan-1(3H)-one and 3a,4-Dihydro-9-phenylnaphtho[2,3-c]furan-1(3H)-one Crystal Structures

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-07-23
Abstract: 

The crystal structures are reported for two unsubstituted arylnaphthalene lactones, 4-phenylnaphtho[2,3-c]furan-1(3H)-one (2), 9-phenylnaphtho[2,3-c]furan-1(3H)-one (3) and a non-aromatic dihydro arylnaphthene lactone, 3a,4-dihydro-9-phenylnaphtho[2,3-c]furan-1(3H)-one (5). There are only minor differences in the geometrical parameters of these structures. However, in certain cases, both isomers of arylnaphthalene lactones (termed Type I and Type II) were found in the same asymmetric unit cell.

Document type: 
Article
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Metabolism of Vertebrate Amino Sugars with N-Glycolyl Groups: INTRACELLULAR β-O-LINKED N-GLYCOLYLGLUCOSAMINE (GlcNGc), UDP-GlcNGc, AND THE BIOCHEMICAL AND STRUCTURAL RATIONALE FOR THE SUBSTRATE TOLERANCE OF β-O-LINKED β-N-ACETYLGLUCOSAMINIDASE

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2012-08-17
Abstract: 

TheO-GlcNAcmodificationinvolvestheattachmentofsingle-O-linkedN-acetylglucosamine residues to serine and threo-nine residues of nucleocytoplasmic proteins. Interestingly, pre-vious biochemical and structural studies have shown thatO-GlcNAcase (OGA), the enzyme that removesO-GlcNAc fromproteins, has an active site pocket that tolerates variousN-acylgroups in addition to theN-acetyl group of GlcNAc. Theremarkable sequence and structural conservation of residuescomprising this pocket suggest functional importance. Wehypothesized this pocket enables processing of metabolic vari-ants ofO-GlcNAc that could be formed due to inaccuracy withinthe metabolic machinery of the hexosamine biosynthetic path-way. In the accompanying paper (Bergfeld, A. K., Pearce, O. M.,Diaz, S. L.,Pham, T., and Varki, A. (2012)J. Biol. Chem.287,28865–28881),N-glycolylglucosamine (GlcNGc) wasshown to be acatabolite of NeuNGc. Here, we show that the hexosamine sal-vage pathway can convert GlcNGc to UDP-GlcNGc, which isthen used to modify proteins withO-GlcNGc. The kinetics of incorporation and removal ofO-GlcNGc in cells occur in adynamic manner on a time frame similar to that ofO-GlcNAc.Enzymatic activity ofO-GlcNAcase (OGA) toward a GlcNGcglycoside reveals OGA can process glycolyl-containing sub-strates fairly efficiently. A bacterial homolog (BtGH84) of OGA,from a human gut symbiont, also processesO-GlcNGc sub-strates, and the structure of this enzyme bound to a GlcNGc-derived species reveals the molecular basis for tolerance andbinding of GlcNGc. Together, these results demonstrate thatanalogs of GlcNAc, such as GlcNGc, are metabolically viablespecies and that the conserved active site pocket of OGA likelyevolved to enable processing of mis-incorporated analogs ofO-GlcNAc and thereby prevent their accumulation. Such plas-ticity in carbohydrate processing enzymes may be a generalfeature arising from inaccuracy in hexosamine metabolicpathways.

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Article
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Insights into O-Linked N-Acetylglucosamine ([0-9]O-GlcNAc) Processing and Dynamics through Kinetic Analysis of O-GlcNAc Transferase and O-GlcNAcase Activity on Protein Substrates*

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2012-05-01
Abstract: 

Cellular O-linked N-acetylglucosamine (O-GlcNAc) levels are modulated by two enzymes: uridine diphosphate-N-acetyl-D-glucosamine:polypeptidyltransferase (OGT) and O-GlcNAcase (OGA). To quantitatively address the activity of these enzymes on protein substrates, we generated five structurally diverse proteins in both unmodified and O-GlcNAc-modified states. We found a remarkably invariant upper limit for k(cat)/K(m) values for human OGA (hOGA)-catalyzed processing of these modified proteins, which suggests that hOGA processing is driven by the GlcNAc moiety and is independent of the protein. Human OGT (hOGT) activity ranged more widely, by up to 15-fold, suggesting that hOGT is the senior partner in fine tuning protein O-GlcNAc levels. This was supported by the observation that K(m,app) values for UDP-GlcNAc varied considerably (from 1 μM to over 20 μM), depending on the protein substrate, suggesting that some OGT substrates will be nutrient-responsive, whereas others are constitutively modified. The ratios of k(cat)/K(m) values obtained from hOGT and hOGA kinetic studies enable a prediction of the dynamic equilibrium position of O-GlcNAc levels that can be recapitulated in vitro and suggest the relative O-GlcNAc stoichiometries of target proteins in the absence of other factors. We show that changes in the specific activities of hOGT and hOGA measured in vitro on calcium/calmodulin-dependent kinase IV (CaMKIV) and its pseudophosphorylated form can account for previously reported changes in CaMKIV O-GlcNAc levels observed in cells. These studies provide kinetic evidence for the interplay between O-GlcNAc and phosphorylation on proteins and indicate that these effects can be mediated by changes in hOGT and hOGA kinetic activity.

Document type: 
Article
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Supervisor(s): 
Canadian Institutes of Health Research (CIHR)
Natural Sciences and Engineering Research Council of Canada (NSERC)

Limits on Performance and Survival of Juvenile Sockeye Salmon (Oncorhynchus Nerka) During Food Deprivation: A Laboratory-Based Study

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-03-24
Abstract: 

Long-distance migrations can be energetically demanding and can represent phases of high mortality. Understanding relationships between body condition and migratory performance can help illuminate the challenges and vulnerabilities of migratory species. Juvenile anadromous sockeye salmon (Oncorhynchus nerka) may migrate over 1000 km from their freshwater nursery habitats to estuary and ocean feeding grounds. During the period corresponding to the seaward migration of sockeye salmon, we held smolts in the laboratory to ask the following: (i) Does non-feeding migration duration influence prolonged swim performance and survival? (ii) What are the relationships between individual body condition and swim performance and survival? Wild sockeye salmon were intercepted during their migration and held without food for up to 61 days to represent the non-feeding freshwater migration and the extremes of poor estuary habitat. We conducted 40 sets of prolonged swim trials on 319 fish from 3 treatment groups that represented entrance to the marine environment on (i) an average,(ii) a delayed and (iii) a severely delayed migration schedule. Experimentally controlled freshwater migration duration did not impact swim performance or survival. Swim performance decreased concomitant with condition factor, where smolts with a Fulton’s condition factor of <0.69 were less likely (<50% probability) to complete the swim test (90 min swim test, at ~0.50 m/s). Survival of salmon smolts in the laboratory was less likely at energy densities of less than 3.47 MJ/kg. Swim performance decreased much sooner than survival, suggesting that swim performance, and therefore condition factor, may be a good indicator of survival of migratory smolts, as fish with reduced swim performance will likely be predated. These two relationships, one more ecologically relevant and one more clinical, help reveal the limits of long-distance migration for juvenile salmon and can be used to determine population-specific starvation risk associated with various freshwater and marine habitat conditions.

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Article
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Design, Synthesis, Pharmacokinetics, and Biodistribution of a Series of Bone-Targeting EP4 Receptor Agonist Prodrugs for Treatment of Osteoporosis and Other Bone Conditions

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-03-10
Abstract: 

A series of bone-targeting EP4 receptor agonist conjugate pro-drugs were prepared wherein a potent EP4 receptor agonist was bound to a biologically inactive, bisphosphonate-based bone-targeting moiety. Single and double radiolabeled conjugates were synthesized and were shown to be stable in blood, to be rapidly eliminated from the bloodstream and to be effectively taken up into bone in vivo after intravenous dosing. From these preliminary studies a preferred conjugate 4 (also known as C3 and Mes-1007) was selected for follow up bio-distribution and elimination studies. Double radiolabeled conjugate 4 was found to partition largely to liver and bones and both labels were eliminated from liver at the same rate indicating the conjugate was eliminated intact. Quantification of the labels in bones indicated that free EP4 agonist (EP4a)(2a) was released from the bone-bound 4 with a half-time of about 7 days. When dosed orally, the radiolabeled 4 was not absorbed and passed through the gastrointestinal tract essentially unchanged and only traces of radiolabel were found in liver, blood or bones. 4 was found to bind rapidly and completely to powdered bone mineral or to various forms of calcium phosphate to form a stable matrix suitable for implant and that could made into powders or solid forms and be sterilized without decomposition or release of 4. Basic hydrolysis released free EP4 agonist 2a quantitatively from the material.

Document type: 
Article

Functional and Versatile Superhydrophobic Coatings via Stoichiometric Silanization

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-02-12
Abstract: 

Superhydrophobic coatings have tremendous potential for applications in different fields and have been achieved commonly by increasing nanoscale roughness and lowering surface tension. Limited by the availability of either ideal nano-structural templates or simple fabrication procedures, the search of superhydrophobic coatings that are easy to manufacture and are robust in real-life applications remains challenging for both academia and industry. Herein, we report an unconventional protocol based on a single-step, stoichiometrically controlled reaction of long-chain organosilanes with water, which creates micro- to nano-scale hierarchical siloxane aggregates dispersible in industrial solvents (as the coating mixture). Excellent superhydrophobicity (ultrahigh water contact angle >170° and ultralow sliding angle <1°) has been attained on solid materials of various compositions and dimensions, by simply dipping into or spraying with the coating mixture. It has been demonstrated that these complete waterproof coatings hold excellent properties in terms of cost, scalability, robustness, and particularly the capability of encapsulating other functional materials (e.g. luminescent dyes).

Document type: 
Article
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