A review and critique of academic lab safety research

Over the past ten years, there have been several high-profile accidents in academic laboratories around the world, resulting in significant injuries and fatalities. The aftermath of these incidents is often characterized by calls for reflection and re-examination of the academic discipline’s approach to safety research and policy. However, the study of academic lab safety is still underdeveloped and necessary data about changes in safety attitudes and behaviours has not been gathered. This Review article critically examines the state of academic chemical safety research from a multifactorial stance, including research on the occurrence of lab accidents, contributors to lab accidents, the state of safety training research and the cultural barriers to conducting safety research and implementing safer lab practices. The Review concludes by delineating research questions that must be addressed to minimize future serious academic laboratory incidents as well as stressing the need for committed leadership from our research institutions

L-tryptophan adsorption differentially changes the optical behaviour of pseudo-enantiomeric cysteine-functionalized quantum dots: Towards chiral fluorescent biosensors

Water-soluble chiral graphene quantum dots (GQDs) with a strong blue emission were synthesized by covalently immobilizing l-cysteine or d-cysteine onto the GQDs. Either the amine or the thiol group of cysteine was used to make the bond through amide coupling or thiol-ene click chemistry respectively. The functionalized chiral GQDs were the characterized by FT-IR and UV–vis. The enantiomeric pairs exhibit equal but opposite bands in circular dichroism spectra suggesting that there is no difference in the efficacy of conjugation. The fluorescent response of these chiral GQDs when exposed to l-tryptophan was then studied. The fluorescence of the amide-conjugated GQDs was quenched with the addition of l-Trp regardless of which enantiomer of cysteine was present on the surface. The thiol-linked d- Cys GQDs fluorescence was also quenched on exposure to l-Trp, but the fluorescence of the thiol-linked l-Cys GQDs was unaffected under the same conditions

Self-Destructing Polymers: Creating Thermally Sensitive End-Caps

Self-Destructing Polymers: Creating Thermally Sensitive End-Caps Trant Team – Rose Anne Fayoumi A broad and booming field of research and innovation, polymer science blends chemistry, physics and engineering and breeds countless modern materials and devices. Likewise, the degradation of these polymers is a field of interest due to the consideration of environmental, medical and economical factors. Nowadays, conventional biodegradable polymers degrade, but require an enzyme to cleave every single connection between monomers before complete disintegration. Numerous stimulus events are thus necessary, promoting inefficient and slow environmental degradation that can take weeks to years. To address this, the Trant Team is developing a new class of polymers that self-destruct “on-demand” using organic chemistry. Only one stimulus event, removing the end, destabilizes the polymer, which leads it to quickly disintegrate in only a few hours. These self-immolative polymers hence need ends with a functionality that can be triggered, as the “push” required to initiate the domino-like effect. In our case, this push is an elevated temperature that causes the end-cap to destabilize and degrade. Elevated temperatures can be induced via intersecting laser beams or magnetic fields to create heat in desired areas. In addition, the optimal temperature for the degradation of each end-cap will be determined through kinetic studies. Ultimately, specific reversible chemical reactions will be exploited to create such thermally-sensitive end-caps, allowing “on-demand” degradation of the polymer’s constituents by elevated temperatures. Accordingly, this innovation could potentially lead to endless possibilities and applications, including therapeutic, pharmaceutical, and biomedical applications. At this stage, however, it is too early to report findings as research and data collection are currently in progress. In spite of this, the presentation will review our preliminary results with this technology as well as shed light on its various potential applications

Self-Destructing Polymers: Creating Thermally Sensitive End-Caps

Self-Destructing Polymers: Creating Thermally Sensitive End-Caps Trant Team – Rose Anne Fayoumi A broad and booming field of research and innovation, polymer science blends chemistry, physics and engineering and breeds countless modern materials and devices. Likewise, the degradation of these polymers is a field of interest due to the consideration of environmental, medical and economical factors. Nowadays, conventional biodegradable polymers degrade, but require an enzyme to cleave every single connection between monomers before complete disintegration. Numerous stimulus events are thus necessary, promoting inefficient and slow environmental degradation that can take weeks to years. To address this, the Trant Team is developing a new class of polymers that self-destruct “on-demand” using organic chemistry. Only one stimulus event, removing the end, destabilizes the polymer, which leads it to quickly disintegrate in only a few hours. These self-immolative polymers hence need ends with a functionality that can be triggered, as the “push” required to initiate the domino-like effect. In our case, this push is an elevated temperature that causes the end-cap to destabilize and degrade. Elevated temperatures can be induced via intersecting laser beams or magnetic fields to create heat in desired areas. In addition, the optimal temperature for the degradation of each end-cap will be determined through kinetic studies. Ultimately, specific reversible chemical reactions will be exploited to create such thermally-sensitive end-caps, allowing “on-demand” degradation of the polymer’s constituents by elevated temperatures. Accordingly, this innovation could potentially lead to endless possibilities and applications, including therapeutic, pharmaceutical, and biomedical applications. At this stage, however, it is too early to report findings as research and data collection are currently in progress. In spite of this, the presentation will review our preliminary results with this technology as well as shed light on its various potential applications

Which colour do you want for your cells, pink or blue? -Improving the synthesis of cyanine dyes

Cyanine dyes are fluorescent compounds commonly used in biosensors because of their great compatibility in vivo and high extinction coefficient, which has made it the perfect choice for our previous studies investigations into prostate cancer. Although cyanine dyes are commercially available, they are very expensive with only few suppliers and problematic synthesis. To facilitate our cancer research projects, we have sought to develop improved synthetic routes to these useful compounds. In this presentation I will describe our work towards the improved synthesis of some of the cyanine dyes, Cy3 and Cy5. The difficulties (and successes) of the synthesis will be analysed and extension of these methods to other members of the family will be discussed

Unnatural Amino Acids Improve Affinity and Modulate Immunogenicity: Developing Peptides to Treat MHC Type II Autoimmune Disorders

Many autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), and celiac disease (CD), arise from improper immune system recognition of self or benign peptides as threats. No autoimmune disease currently has a cure. Many treatments suppress the entire immune system to decrease symptom severity. The core molecular interaction underlying these diseases involves specific alleles of the human leukocyte antigen (HLA) receptor hosting the immunodominant peptides associated with the disease (i.e. myelin basic protein, Type II collagen, or α-gliadin) in their binding groove. Once bound, circulating T-cells can recognize the HLA-antigen complex and initiate the complex cascade that forms an adaptive immune response. This initial HLA-antigen interaction is a promising target for therapeutic intervention. Two general strategies have been pursued: altered peptide ligands (APLs) that attempt to recruit a different class of T-cell to induce an anti-inflammatory response to balance the pro-inflammatory response associated with the antigen; and HLA blockers (HLABs), peptides that, due to a much higher affinity for the HLA receptor, quantitatively displace the antigen, inhibiting the immune response. Both approaches would benefit from improved HLA-drug binding, but as the HLA receptors are highly promiscuous, the binding sites are not specific for any natural amino acid. Unnatural amino acids, either designed or screened through high-throughput assays, may provide a solution. This review summarizes the nascent field of using non-canonical residues to treat MS, RA and CD, focusing on the importance of specific molecular interactions, and provides some examples of the synthesis of these unnatural residues

Synthesis, characterization and stress-testing of a robust quillaja saponin stabilized oil-in-water phytocannabinoid nanoemulsion

Background This study describes the design, optimization, and stress-testing of a novel phytocannabinoid nanoemulsion generated using high-pressure homogenization.QNaturale® role= presentation \u3eQNaturale®, a plant-derived commercial emulsifier containing quillaja saponin, was used to stabilize the lipid phase droplets in water. Stress-testing was performed on this nanoemulsion in order to evaluate its chemical and colloidal stability under the influence of different environmental factors, encompassing both physical and chemical stressors. Methods Extensive optimization studies were conducted to arrive at an ideal nanoemulsion formulation. A coarse emulsion containing 16.6 wt% CBD-enriched cannabis distillate and 83.4 wt% carrier (soybean) oil dispersed in 10 wt%QNaturale® role= presentation \u3eQNaturale® (1.5 wt% quillaja saponin) solution after 10 homogenization cycles at a pressure of 30,000 psi produced a stable nanoemulsion. This nanoemulsion was then subjected to the stress studies. Results The optimized nanoemulsion had an average droplet diameter of ca. 120 nm and average droplet surface ζ potentials of ca. -30 mV. It was imaged and characterized by a variety of protocols. It proved to be stable to droplet agglomeration and phase separation upon storage under ambient conditions for 6 weeks, as well as under a variety of physical stressors such as heat, cold, dilution, and carbonation. pH values ≤2 and moderately high salt concentrations (\u3e 100 mM), however, destabilized the nanoemulsion, eventually leading to phase separation. Cannabis potency, determined by HPLC, was detrimentally affected by any changes in the nanoemulsion phase stability. Conclusions Quillaja saponin stabilized cannabidiol(CBD)-enriched nanoemulsions are stable, robust systems even at low emulsifier concentrations, and are therefore significant from both a scientific as well as a commercial perspective

Recent advances in the application of carbohydrates as renewable feedstocks for the synthesis of nitrogen-containing compounds

Carbohydrates, in the form of chitin, chitosan and cellulose, are one of the most available, renewable, and sustainable chemical feedstocks. Their conversion to biofuels, fine chemicals, and industrially-relevant monomers is becoming increasingly viable and promising as innovation decreases the price of this technology, and climate change and the price of fossil fuels increases the social and economic costs of using traditional feedstocks. In recent years, carbohydrates have been increasingly used as sources for nitrogen-containing fine chemicals. This chapter, with 86 references, provides a brief overview of the conversion of carbohydrate biomass to the standard hydrocarbon and oxygen-containing derivatives, and then provides a survey of recent progress in converting the biopolymers, and the derived mono and di-saccharides, into nitrogen-containing molecules with a special focus on N-heterocycle synthesis for medicinal applications

Adsorption of bovine serum albumin (BSA) by bare magnetite nanoparticles with surface oxidative impurities that prevent aggregation

Bare, uncoated magnetite nanoparticles, synthesized using an electrochemical surfactant-free synthesis, have highly oxidized surfaces that prevent aggregation. These particles have demonstrated highly intriguing biological activity showing extremely potent antibiotic activity against both gram-positive and gram-negative bacteria with little toxicity to rats. This difference in activity could be ascribed to the nature of the protein corona. In this study the kinetics and thermodynamics of the binding of bovine serum albumin, used as a model serum protein, to these magnetite nanoparticles was analyzed. There is no significant change in particle diameter by dynamic light scattering following adsorption indicating corona formation does not induce aggregation. The maximum adsorption capacity of the particles was determined to be 300 mg of BSA/g of magnetite. The particles are able to adsorb 90% of the BSA at protein concentrations as high as 500 mg/L. The adsorption is best described using a pseudo-second-order model and a Langmuir Type III isotherm model. Thermodynamic analysis showed that the process is entropically driven and is spontaneous at all tested temperatures and conditions. However, it appears to be a weak to moderate physical adsorption. This moderate binding affinity could indicate the differential biological activity of these particles towards bacteria and mammalian cells and further support the contention that these are potentially useful new tools for targeting antibiotic-resistant bacteria

Cannabinoids and Cannabinoid Receptors: The Story so Far

Like most modern molecular biology and natural product chemistry, understanding cannabinoid pharmacology centers around molecular interactions, in this case, between the cannabinoids and their putative targets, the G-protein coupled receptors (GPCRs) cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). Understanding the complex structure and interplay between the partners in this molecular dance is required to understand the mechanism of action of synthetic, endogenous, and phytochemical cannabinoids. This review, with 91 references, surveys our understanding of the structural biology of the cannabinoids and their target receptors including both a critical comparison of the extant crystal structures and the computationally derived homology models, as well as an in-depth discussion about the binding modes of the major cannabinoids. The aim is to assist in situating structural biochemists, synthetic chemists, and molecular biologists who are new to the field of cannabis research