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.
In the present work, 86 available high resolution X-ray structures of proteins that contain one or more guanidinium ions (Gdm
+
) are analyzed for the distribution and nature of noncovalent ...interactions between Gdm
+
and amino-acid residues. A total of 1044 hydrogen-bonding interactions were identified, of which 1039 are N-H O, and five are N-H N. Acidic amino acids are more likely to interact with Gdm
+
(46% of interactions, 26% Asp and 20% Glu), followed by Pro (19% of interactions). DFT calculations on the identified Gdm
+
-amino acid hydrogen-bonded pairs reveal that although Gdm
+
interacts primarily with the backbone amides of nonpolar amino acids, Gdm
+
does interact with the sidechains of polar and acidic amino acids. We classified the optimized Gdm
+
-amino acid pairs into parallel
p
, bifurcated
b
, single hydrogen bonded
s
and triple hydrogen bonded
t
types. The
p
and
t
type pairs possess higher average interaction strength that is stronger than that of
b
and
s
type pairs. Negatively charged aspartate and glutamate residues interact with Gdm
+
ion exceptionally tightly (−76 kcal mol
−1
) in
p
type complexes. This work provides statistical and energetics insights to better describe the observed destabilization or denaturation process of proteins by guanidinium salts.
Structural analysis of guanidinium-amino acid interaction pairs in protein crystal structures is coupled with an effective scheme for classifying the optimized pairs, to gain understanding of the guanidinium:protein hydrogen bonding modes.
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.
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•Cannabinoid research has greatly expanded•Structural biology and computational chemistry jointly provide mechanistic insight•Structural data are being generated at an exponentially increasing rate•Phytocannabinoid targeting of other GPCR receptors deserves investigation
Medical Substance; Supramolecular Chemistry; Molecular Biology; Structural Biology
The biosynthesis of the cannabinoids Tahir, M Nazir; Shahbazi, Fred; Rondeau-Gagné, Simon ...
Journal of cannabis research,
03/2021, Letnik:
3, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Cannabis has been integral to Eurasian civilization for millennia, but a century of prohibition has limited investigation. With spreading legalization, science is pivoting to study the pharmacopeia ...of the cannabinoids, and a thorough understanding of their biosynthesis is required to engineer strains with specific cannabinoid profiles. This review surveys the biosynthesis and biochemistry of cannabinoids. The pathways and the enzymes' mechanisms of action are discussed as is the non-enzymatic decarboxylation of the cannabinoic acids. There are still many gaps in our knowledge about the biosynthesis of the cannabinoids, especially for the minor components, and this review highlights the tools and approaches that will be applied to generate an improved understanding and consequent access to these potentially biomedically-relevant materials.
Calcium-ion batteries show promise as high-density, next-generation replacements for current lithium-ion batteries. The precise chemical structure of the carbonate electrolyte solvent has a large ...impact on calcium battery efficacy. In this computational study, we have investigated the solvation behavior of calcium tetrafluoroborate in both neat carbonates and carbonate mixtures using combined molecular dynamics simulations and quantum mechanical calculations. Our results indicate that both neat ethyl methyl carbonate and a mixture of ethylene carbonate and diethyl carbonate show the highest free energy of solvation for the Ca2+ ion, making them likely candidates for further focus. The cation’s interaction with the carbonyls of the coordinating solvents, rather than those with the tetrafluoroborate counterions, plays the primary role in delocalizing the charge on Ca2+. Detailed calculations indicate that the HOMO–LUMO energy gap (E g), electronic chemical potential (μ), and chemical hardness (η) of the calcium–carbonate complexes are directly proportional to the free energy of solvation of the complex. Comparison of these observed trends with our previous results from Li+, Na+, and Mg2+ ions shows that this correlation is also observed in solvated magnesium ions but not in lithium or sodium salts. This observation should assist in the rational design of next-generation battery materials in the rational selection of additives, counterions, or electrolyte solvents.
Self-immolative polymers, which degrade by an end-to-end depolymerization mechanism in response to the cleavage of a stabilizing end-cap from the polymer terminus, are of increasing interest for a ...wide variety of applications ranging from sensors to controlled release. However, the preparation of these materials often requires expensive, multistep monomer syntheses, and the degradation products such as quinone methides or phthalaldehydes are potentially toxic to humans and the environment. We demonstrate here that polyglyxoylates can serve as a new and versatile class of self-immolative polymers. Polymerization of the commercially available monomer ethyl glyoxylate, followed by end-capping with a 6-nitroveratryl carbonate, provides a poly(ethyl glyoxylate) that depolymerizes selectively upon irradiation with UV light, ultimately generating ethanol and the metabolic intermediate glyoxylic acid hydrate. To access polyglyoxylates with different properties, the polymerization and end-capping approach can also be extended to other glyoxylate monomers including methyl glyoxylate, n-butyl glyoxylate, and benzyl glyoxylate, which can be easily prepared from their corresponding fumaric or maleic acid derivatives. Random copolymers of these monomers with ethyl glyoxylate can also be prepared. Furthermore, using a multifunctional end-cap that is UV-responsive and also enables the conjugation of another polymer block via an azide–alkyne “click” cycloaddition, amphiphilic self-immolative block copolymers are also prepared. These block copolymers self-assemble into micelles in aqueous solution, and their poly(ethyl glyoxylate) blocks rapidly depolymerize upon UV irradiation. Overall, these strategies are expected to greatly expand the utility of self-immolative polymers by providing access for the first time to self-immolative polymers with tunable properties that can be readily obtained from simple monomers and can be designed to depolymerize into nontoxic products.
Polymers that undergo end-to-end depolymerization in response to the cleavage of a stimuli-responsive end-cap are promising for diverse applications from drug delivery to responsive coatings and ...plastics. It is critical that the end-cap is designed to respond to an appropriate stimulus for the application. In the current work, end-caps for triggering the depolymerization of poly(ethyl glyoxylate) (PEtG) were explored. First, a phenylboronate, a disulfide, and an azobenzene were utilized to impart redox-responsive properties to PEtG. Then, methoxy-substituted trityl groups were used to provide sensitivity to mild acid. A multiresponsive platform was also introduced, allowing PEtG to respond to multiple stimuli, either simultaneously or independently. Incorporation of a cross-linkable trialkene end-cap enabled the preparation of networks that could subsequently be depolymerized. Finally, high molar mass PEtG could be depolymerized by mechanical stimulation independent of the end-cap. It is anticipated that the versatility in end-capping strategies and potential depolymerization stimuli will not only expand PEtG’s utility for different applications but also be useful for other classes of end-to-end depolymerizable polymers.
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two "major cannabinoids". However, their incorporation into clinical and nutraceutical preparations is challenging, owing to their limited ...bioavailability, low water solubility, and variable pharmacokinetic profiles. Understanding the organic chemistry of the major cannabinoids provides us with potential avenues to overcome these issues through derivatization. The resulting labile pro-drugs offer ready cannabinoid release
in vivo
, have augmented bioavailability, or demonstrate interesting pharmacological properties in their own right. This review identifies and discusses a subset of these advanced derivatization strategies for the major cannabinoids, where the starting material is the pure phytocannabinoid itself, and the final product either a cannabinoid pro-drug, or a novel pharmacoactive material.
The derivatization of THC and CBD for improved bioactivity is reviewed, demonstrating the pharmacophoric versatility, and the limitations of chemical modification, of the cannabinoids. Regulatory and scientific challenges are highlighted.
A thermo-responsive end-cap based on a retro-Diels-Alder and subsequent furan elimination reaction was developed. It was used to cap poly(ethyl glyoxylate), allowing end-to-end depolymerization upon ...thermal triggering. Using block copolymers, thermo-responsive micelles and vesicles were prepared and shown to disassemble upon heating. Thermal degradation could also be triggered indirectly by magnetic field hyperthermia after incorporation of iron oxide nanoparticles into the assemblies.
Understanding the frequency and structural context of discrete noncovalent interactions between nucleotides is of pivotal significance in establishing the rules that govern RNA structure and ...dynamics. Although T-shaped contacts (i.e., perpendicular stacking contacts) between aromatic amino acids and nucleobases at the nucleic acid-protein interface have recently garnered attention, the analogous contacts within the nucleic acid structures have not been discussed. In this work, we have developed an automated method for identifying and unambiguously classifying T-shaped interactions between nucleobases. Using this method, we identified a total of 3261 instances of T-shaped (perpendicular stacking) contacts between two nucleobases in an array of RNA structures from an up-to-date data set of ≤3.5 Å resolution crystal structures deposited in the Protein Data Bank.
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