John Frederick Trant

University of Windsor · Department of Chemistry and Biochemistry

Arginine (Arg) forks are noncovalent recognition motifs wherein an Arg interacts with the phosphates and guanine nucleobases of RNA, providing extraordinary specific RNA:protein recognition. In this work, we carried out an in-depth DFT based quantum mechanical investigation on all known classes of Arg forks to estimate their intrinsic structural st...

Selectively inducing apoptosis in cancer cells is an effective therapeutic strategy, but the reality of success of existing chemotherapeutics is compromised by emergent tumor cell resistance and systemic off-target effects. Therefore, the discovery of new classes of pro-apoptotic compounds with minimal systemic side-effects remains an urgent need....

Several recent articles by Cui and coworkers claim syntheses of γ-graphyne, a novel sp2/sp1 allotrope of carbon, directly from calcium carbide. Here, we describe the replication of the key experiments from this series of articles. We did not observe the formation of γ-graphyne under the reported conditions. The characterization data from our replic...

The emergence of drug-resistance-inducing mutations in Hepatitis C virus (HCV) coupled with genotypic heterogeneity has made targeting NS3/4A serine protease difficult. In this work, we investigated the mutagenic variations in the binding pocket of Genotype 3 (G3) HCV NS3/4A and evaluated ligands for efficacious inhibition. We report mutations at 1...

The emergence of drug resistance inducing mutations in Hepatitis C virus (HCV) coupled with genotypic heterogeneity has made targeting NS3/4A serine protease difficult. In this work, we investigated the mutagenic variations in the binding pocket of Genotype 3 (G3) HCV NS3/4A and evaluated ligands for efficacious inhibition. We report mutations at 1...

Background: Invadopodia facilitate cancer cell extravasation, but the molecular mechanism whereby invadopodia-specific proteases such as MT1-MMP are called to invadopodia is unclear. Methods: Mass spectrometry and immunoprecipitation were used to identify interactors of MT1-MMP in metastatic breast cancer cells. After identification, siRNA and s...

Cyclodipeptide synthases (CDPSs) are enzymes that synthesize cyclodipeptides using two aminoacyl-tRNAs as substrates, but their mechanism remains unclear. This study aims to elucidate the mechanism of AlbC, a CDPS that produces cyclo(L-Phe-L-Phe). We employed small-model quantum mechanics (QM) calculations to propose an intrinsic pathway and molecu...

CB1, a member of the G protein-coupled receptor class, is the putative protein target of THC, the psychoactive component of cannabis. To better identify new synthetic cannabinoids with increased activity, all cannabinoids with reported experimental binding to the CB1 receptor were modelled in silico to build a predictive model for CB1 affinity of s...

Currently, it has been reported a high incidence of aflatoxin M1 (AFM1) in milk. This poses a risk to human health, because AFM1 is considered a class 1 carcinogen. Among the various strategies that have been studied to reduce AFM1 contamination in milk, the use of lactic acid bacteria has attracted considerable attention. This approach takes advan...

The recent global pandemic created an unprecedented demand for alcohol-based hand sanitizers. This stimulated the entry of many new producers into the market, both to provide an alternative income stream during the initial lockdowns, and to meet the needs of a society suddenly using far more sanitizer than was available due to production and transp...

Semiconducting polymers, driving the leading edge of organic electronics and emerging soft technologies, feature a range of key attributes including broad solubility for large-scale solution deposition and charge transport properties comparable to amorphous silicon. The optoelectronic and thermomechanical properties of these π-conjugated materials...

CB1, a member of the G protein-coupled receptor class, is the putative protein target of THC, the psychoactive component of cannabis. To better identify new synthetic cannabinoids with increased activity, all cannabinoids with reported experimental binding to the CB1 receptor were modelled in silico to build a predictive model for CB1 affinity of s...

The aluminum ion battery (AIB) is a promising technology, but there is a lack of understanding of the desired nature of the batteries’ electrolytes. The ionic charge carriers in these batteries are not simply Al3+ ions but the anionic AlCl4− and Al2Cl7−, which form in the electrolyte. Using computational analysis, this study illustrates the effect...

Fatty acid binding protein 1 (FABP1) is a lipid transporter primarily expressed in the liver where it helps move fatty acids between lipid membranes. Inhibition of FABP1 has potential therapeutic implications for nonalcoholic fatty liver disease, metabolic syndrome & obesity, diabetes, and inflammatory & cardiovascular diseases. Curiously, FABP1 is...

Cyclin-dependent kinases (CDKs) play a key role in activating essential cell biology processes including cellular proliferation. Inappropriate regulation of CDKs has been implicated in driving several different forms of cancer. One of the regulatory factors is the need to bind to Cyclin-partners before they can be activated and advance the cell cyc...

Ionic liquid (IL) based composite materials have shown great promise as antimicrobial coatings, owing to their inherent germicidal properties, as well as their ability to stabilize metal nanoparticles (NPs) which...

Nucleobase-specific noncovalent interactions (i.e., inter-RNA base pairing and stacking) play a crucial role in the RNA-driven biochemical process of translation. Although the structural details of translation are well studied, especially base-pairing, the role of nucleobase-specific inter-RNA stacking interactions is still not fully appreciated. H...

Background: This article highlights the formulation of a solid Δ9-tetrahydrocannabinol (THC)-loaded ingestible prepared from pure THC distillate. Methods: A THC-containing ethanol-assisted cannabinoid nanoemulsion (EACNE) was created using a solvent displacement technique. Subsequently, the EACNE was converted to a solid powdery material while stil...

Post-transcriptionally modified bases play vital roles in many biochemical processes involving RNA. Analysis of the non-covalent interactions associated with these bases in RNA is crucial for providing a more complete understanding of the RNA structure and function; however, the characterization of these interactions remains understudied. To addres...

Ionic liquid (IL) based composite materials have shown great promise as antimicrobial coatings, owing to their inherent germicidal properties, as well as their ability to stabilize metal nanoparticles (NPs), which may serve as a secondary antimicrobial reservoir. Here, we show that tetraalkylphosphonium ILs (TAPILs) on their own can annihilate path...

h i g h l i g h t s Boron nitride nanotubes (BNNT) are functionalizable with Mg adatoms. BNNTs adsorb more H 2 than carbon nanotubes due to inherent polarity. Mg-doped BNNTs could adsorb up to 9.6% of their mass in H 2 , well above DOE targets. Each Mg atom can favorably interact with seven H 2 molecules; eight is not possible within the first coor...

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...

We previously demonstrated that 50% of children with obesity from consanguineous families from Pakistan carried pathogenic variants in known monogenic obesity genes. Here, we have discovered a novel monogenetic recessive form of severe childhood obesity, using an inhouse computational staged approach. This included analysis of whole-exome sequencin...

The limited diversity in targets of available antibiotic therapies has put tremendous pressure on the treatment of bacterial pathogens, where numerous resistance mechanisms that counteract their function are becoming increasingly prevalent. Here, we utilize an unconventional anti-virulence screen of host-guest interacting macrocycles, and identify...

Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low toxicity. Although noncanonical residues can always be used, employing only the natural 20 residues restricts the chemical space to a finite dimension allowing for comprehensive in silico screening. Towards this goal, t...

Background: This paper highlights the formulation of a solid THC-loaded ingestible prepared from pure THC distillate. A THC ethanol-assisted cannabinoid nanoemulsion (EACNE) was created without the need for specialized emulsification equipment such as a high-pressure homogenizer or a microfluidizer. Stress-testing was performed on the EACNE to eval...

The limited diversity in targets of available antibiotic therapies has put tremendous pressure on the treatment of bacterial pathogens, where numerous resistance mechanisms that counteract their function are becoming increasingly prevalent. Here, we utilize an unconventional anti-virulence screen of host-guest interacting macrocycles, and identify...

Weak intermolecular forces are typically very difficult to observe in highly competitive polar protic solvents as they are overwhelmed by the quantity of competing solvent. This is even more challenging for three‐component ternary assemblies of pure organic compounds. In this work, we overcome these complications by leveraging the binding of fused...

Hydrogen is one of the cleanest ways to store energy in a post-fossil fuel economy. However, it can be dangerous as bulk gas and additional methods for hydrogen storage are needed. Physisorption on graphene sheets and nanotubes has been proposed as an effective approach due to their exceedingly high surface area and storage capacity similar to, or...

CB1, a member of the G protein-coupled receptor class, is the putative protein target of THC, the psychoactive component of cannabis. To better identify new synthetic cannabinoids with increased activity, all cannabinoids with reported experimental binding to the CB1 receptor were modelled in silico to build a predictive model for CB1 affinity of s...

Nucleobase π-π stacking is one of the crucial organizing interactions within three-dimensional (3D) RNA architectures. Characterizing the structural variability of these contacts in RNA crystal structures will help delineate their subtleties and their role in determining function. This analysis of different stacking geometries found in RNA X-ray cr...

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 wi...

Peptide-based therapeutics are increasingly coming to the forefront of biomedicine with their promise of high specificity and low toxicity. Although noncanonical residues can always be used, employing only the natural 20 residues restricts the chemical space to a finite dimension allowing for comprehensive in silico screening. Towards this goal, th...

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...

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. Aci...

Mono- and (bis)benzimidazoliums were evaluated both experimentally and computationally for their potential as pseudopolyrotaxane axle building blocks. Their aggregation and photophysical behavior, along with their potential to form a [2]pseudorotaxane with dibenzyl-24-crown-8, was studied through the synergistic application of 1D/2D and diffusion-o...

A vital component in the fight against climate change is the development of highly efficient energy storage for renewable resources. The aluminum ion battery (AIB) is a promising technology, but there is a lack of understanding of the desired nature of the batteries’ electrolytes. These properties cannot simply be extrapolated from other metal ion...

Cancer chemotherapy is often accompanied by severe off-target effects that both damage quality of life and can decrease therapeutic compliance. This could be minimized through selective delivery of cytotoxic agents directly to the cancer cells. This would decrease the drug dose, consequently minimizing side effects and cost. With this goal in mind,...

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 interfa...

A series of readily regenerable thioimidazolium‐based ionic liquids, which can transfer alkyl groups to nucleophiles, are immobilized on crosslinked polystyrene beads. Different alkyl groups can be loaded onto the resin, highlighting the tunability of the material. The efficiency of these materials is demonstrated by their screening against a serie...

Invariant natural killer (iNK) T cells, Type I iNKTs, are responsible for the production of pro‐inflammatory cytokines which induce a systemic immune response. They are distinctive in possessing an semi‐invariant T‐cell receptor that recognizes glycolipid antigens presented by CD1d, a protein closely related to the class I major histocompatibility...

Doubly and triply deprotonated 2-bromo-C-alkylresorcinarene anions form host–guest complexes with both tetramethylammonium cations and bis-protonated dimethyl piperazine cations. The trianion forms a fully closed dimeric capsule with one endo- and two exo-cavity bis-protonated dimethyl piperazine cations. Interestingly, the dianion crystallized fro...

In this study, the interaction of four deep eutectic solvents (DESs): [Choline chloride][Urea] ([ChCl][U]), [Choline chloride][Ethylene glycol] ([ChCl][EG]), [Choline chloride][Glycerol] ([ChCl][Gly]) and [Choline chloride][Benzoic acid] ([ChCl][BA]), with pristine carbon nanotube (CNT) and its defects: double-vacancy and Stone–Wales structures (CN...

Mono and (bis)benzimidazoliums were evaluated both experimentally and computationally for their potential as pseudopolyrotaxane axle building blocks. Their aggregation and photophysical behavior, along with their potential to form a [2]pseudorotaxane with dibenzyl-24-crown-8, was studied through the synergistic application of 1D/2D and diffusion or...

Kynurenic acid is a by-product of tryptophan metabolism in humans, with abnormal levels indicative of disease. There is a need for water-soluble receptors that selectively bind kynurenic acid, allowing for detection and quantification. We report here the high-affinity binding of kynurenic acid in aqueous media to a resorcinarene salt receptor decor...

6-alkoxy-2-aminopurine derivatives are potent inhibitors of Cyclin Dependent Kinases (CDKs), with some selectivity towards CDK2 and thus have potential as cancer therapeutics. Development of these inhibitors for targeting CDK2-cyclin A/E complexes has previously involved a thorough investigation of structure activity relationships of the C 2 amine...

With expanding recent outbreaks and a lack of treatment options, the Zika virus (ZIKV) poses a severe health concern. The availability of ZIKV NS2B-NS3 co-crystallized structures paved the way for rational drug discovery. A computer-aided structure-based approach was used to screen a diverse library of compounds against ZIKV NS2B-NS3 protease. The...

Preparative thin layer chromatography (prepTLC) is a commonly used method of purification suitable for small scale reactions. However, descriptions of the preferred methodology to load, run, and recover samples from prepTLC are non-standard and varied, making it part of the “hidden curriculum” of laboratory technique. In this article we report on t...

Significance Glutamate-ureido-lysine (GUL) probes are specific for prostate-specific membrane antigen (PSMA), overexpressed by most prostate cancers. This antigen can be lost as the cancer progresses. Recent reports have indicated that GUL probes can still identify these PSMA-negative tumors, indicating that the expression of alternative PSMA-like...

The global pandemic has created an unprecedented demand for alcohol-based hand sanitizers. This stimulated the entry of many new producers of hand sanitizers, both to provide a new business during the general shutdowns, and to meet the needs of society. Similarly, this created a need for alcohol sources well beyond what had been produced for the co...

N-Alkyl ammonium resorcinarene chloride receptors, NARX4, have been shown to act as high-sensitivity detectors of pyrophosphate (PPi), a biomarker of disease, in aqueous media through the chloride-to-PPi exchange [NAR(Cl)4 to...

6-alkoxy-2-aminopurine derivatives are potent inhibitors of Cyclin Dependent Kinases (CDKs), with some selectivity towards CDK2 and thus have potential as cancer therapeutics. Development of these inhibitors for targeting CDK2-cyclin A/E...

Fluorescent-small molecules offer an excellent source of chemosensors when optimized for detection of anions with sensitivity and selectivity, low-cost and robust synthesis. In the present study we synthesized new quinoline-based...

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...

Background This study describes the design, optimization, and stress-testing of a novel phytocannabinoid nanoemulsion generated using high-pressure homogenization. $\text {QNaturale}^{\circledR }$ QNaturale Ⓡ , a plant-derived commercial emulsifier containing quillaja saponin, was used to stabilize the lipid phase droplets in water. Stress-testing...

Preparative thin layer chromatography (prepTLC) is a commonly used method of purification suitable for small scale reactions. However, descriptions of the preferred methodology to load, run, and recover samples from prepTLC are non-standard and varied, making it part of the “hidden curriculum” of laboratory technique. In this article we report on t...

Hexagonal boron nitride is a promising material for a variety of electronic, optical, and material science applications. Both the synthesis of the material through exfoliation, and its various applications almost inevitably require its solvation. Deep eutectic solvents (DES) are extremely useful solvents for these types of applications due to their...

Invariant natural killer T cells (iNKT) are responsible for the production of pro-inflammatory cytokines which induce a systemic immune response. They are distinctive in possessing an invariant T-cell receptor that recognizes glycolipid antigens presented by the class I major histocompatibility complex-related protein CD1d, conserved across multipl...

Invariant natural killer T cells (iNKT) are responsible for the production of pro-inflammatory cytokines which induce a systemic immune response. They are distinctive in possessing an invariant T-cell receptor that recognizes glycolipid antigens presented by the class I major histocompatibility complex-related protein CD1d, conserved across multipl...

The total synthesis of the Thomsen-nouveau (Tn) antigen, a tumour-associated O-linked mucin glycopeptide, was achieved through a concise route. The key glycosylation step proved challenging to reproduce from the literature...

Flexible pressure sensors with self-healing abilities for wearable electronics are being developed, but generally either lack autonomous self-healing properties or require sophisticated material processing methods. To address this challenge, we developed flexible, low-cost and autonomously self-healing capacitive sensors using a crosslinked poly(di...