Spectroscopic and Computational Study of the Protonation Equilibria of Amino-Substituted benzo[b]thieno[2,3-b]pyrido[1,2-a]benzimidazoles as Novel pH-Sensing Materials

We present the synthesis and analytical, spectroscopic and computational characterization of three amino-substituted benzo[b]thieno[2,3-b]pyrido[1,2-a]benzimidazoles as novel pH probes with a potential application in pH-sensing materials. The designed systems differ in the number and position of the introduced isobutylamine groups on the pentacyclic aromatic core, which affects their photophysical and acid-base properties. The latter were investigated by UV-Vis absorption and fluorescence spectroscopies and interpreted by DFT calculations. An excellent agreement in experimentally measured and computationally determined pKa values and electronic excitations suggests that all systems are unionized at neutral pH, while their transition to monocationic forms occurs at pH values between 3 and 5, accompanied by substantial changes in spectroscopic responses that make them suitable for detecting acidic conditions in solutions. Computations identified imidazole imino nitrogen as the most favorable protonation site, further confirmed by analysis of perturbations in the chemical shifts of 1H and 13C NMR, and showed that the resulting basicity emerges as a compromise between the basicity-reducing effect of a nearby nitrile and a favorable contribution from the attached secondary amines. With this in mind, we designed a system with three amino substituents for which calculations predict pKa = 7.0 that we suggest as an excellent starting point for a potential pH sensor able to capture solution changes during the transition from neutral towards acidic media.

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Improved synthesis of SV2A targeting radiotracer [11C]UCB-J

EJNMMI Radiopharmacy and Chemistry ◽

10.1186/s41181-019-0080-5 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 2

Author(s):

Johanna Rokka ◽

Eva Schlein ◽

Jonas Eriksson

Keyword(s):

Methyl Iodide ◽

Water Solution ◽

Synthesis Method ◽

Radiochemical Yield ◽

Preparative Hplc ◽

Step Method ◽

Synaptic Density ◽

Excellent Starting Point ◽

Starting Point

Abstract Introduction [11C]UCB-J is a tracer developed for PET (positron emission tomography) that has high affinity towards synaptic vesicle glycoprotein 2A (SV2A), a protein believed to participate in the regulation of neurotransmitter release in neurons and endocrine cells. The localisation of SV2A in the synaptic terminals makes it a viable target for in vivo imaging of synaptic density in the brain. Several SV2A targeting compounds have been evaluated as PET tracers, including [11C]UCB-J, with the aim to facilitate studies of synaptic density in neurological diseases. The original two-step synthesis method failed in our hands to produce sufficient amounts of [11C]UCB-J, but served as an excellent starting point for further optimizations towards a high yielding and simplified one-step method. [11C]Methyl iodide was trapped in a clear THF-water solution containing the trifluoroborate substituted precursor, potassium carbonate and palladium complex. The resulting reaction mixture was heated at 70 °C for 4 min to produce [11C]UCB-J. Results After semi-preparative HPLC purification and reformulation in 10% ethanol/phosphate buffered saline, the product was obtained in 39 ± 5% radiochemical yield based on [11C]methyl iodide, corresponding to 1.8 ± 0.5 GBq at EOS. The radiochemical purity was > 99% and the molar activity was 390 ± 180 GBq/μmol at EOS. The product solution contained < 2 ppb palladium. Conclusions A robust and high yielding production method has been developed for [11C]UCB-J, suitable for both preclinical and clinical PET applications.

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Titanium Nitride Thin Film Based Low-Redox-Interference Potentiometric pH Sensing Electrodes

Sensors ◽

10.3390/s21010042 ◽

2020 ◽

Vol 21 (1) ◽

pp. 42

Author(s):

Shimrith Paul Shylendra ◽

Wade Lonsdale ◽

Magdalena Wajrak ◽

Mohammad Nur-E-Alam ◽

Kamal Alameh

Keyword(s):

Thin Film ◽

Titanium Nitride ◽

Orange Juice ◽

Ph Sensor ◽

Reference Electrode ◽

Cost Effective ◽

Ph Sensing ◽

Ph Sensors ◽

Potential Shift ◽

Double Junction

In this work, a solid-state potentiometric pH sensor is designed by incorporating a thin film of Radio Frequency Magnetron Sputtered (RFMS) Titanium Nitride (TiN) working electrode and a commercial Ag|AgCl|KCl double junction reference electrode. The sensor shows a linear pH slope of −59.1 mV/pH, R2 = 0.9997, a hysteresis as low as 1.2 mV, and drift below 3.9 mV/h. In addition, the redox interference performance of TiN electrodes is compared with that of Iridium Oxide (IrO2) counterparts. Experimental results show −32 mV potential shift (E0 value) in 1 mM ascorbic acid (reducing agent) for TiN electrodes, and this is significantly lower than the −114 mV potential shift of IrO2 electrodes with sub-Nernstian sensitivity. These results are most encouraging and pave the way towards the development of miniaturized, cost-effective, and robust pH sensors for difficult matrices, such as wine and fresh orange juice.

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Globalization Impact on Multinational Enterprises

World ◽

10.3390/world2020014 ◽

2021 ◽

Vol 2 (2) ◽

pp. 216-230

Author(s):

Justine Kyove ◽

Katerina Streltsova ◽

Ufuoma Odibo ◽

Giuseppe T. Cirella

Keyword(s):

Developing Country ◽

Multinational Enterprises ◽

Developed Countries ◽

Global Market ◽

Data Availability ◽

Negative Effects ◽

Developed Country ◽

Excellent Starting Point ◽

Starting Point ◽

The Impact

The impact of globalization on multinational enterprises was examined from the years 1980 to 2020. A scoping literature review was conducted for a total of 141 articles. Qualitative, quantitative, and mixed typologies were categorized and conclusions were drawn regarding the influence and performance (i.e., positive or negative effects) of globalization. Developed countries show more saturated markets than developing countries that favor developing country multinational enterprises to rely heavily on foreign sales for revenue growth. Developed country multinationals are likely to use more advanced factors of production to create revenue, whereas developing country multinationals are more likely to use less advanced forms. A number of common trends and issues showed corporate social responsibility, emerging markets, political issues, and economic matters as key to global market production. Recommendations signal a strong need for more research that addresses contributive effects in the different economies, starting with the emerging to the developed. Limitations of data availability and inconsistency posed a challenge for this review, yet the use of operationalization, techniques, and analyses from the business literature enabled this study to be an excellent starting point for additional work in the field.

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Analysis of saponins detoxification genes in Ilyonectria mors-panacis G3B inducing root rot of Panax notoginseng by RNA-Seq

Archives of Microbiology ◽

10.1007/s00203-021-02502-4 ◽

2021 ◽

Author(s):

Guohong Zeng ◽

Jin Li ◽

Yuxiu Ma ◽

Qian Pu ◽

Tian Xiao ◽

...

Keyword(s):

Root Rot ◽

Molecular Mechanisms ◽

Management Strategies ◽

Panax Notoginseng ◽

Glycoside Hydrolases ◽

Rna Seq ◽

Host Interaction ◽

Excellent Starting Point ◽

Starting Point ◽

Genes Encoding

AbstractSaponins are kinds of antifungal compounds produced by Panax notoginseng to resist invasion by pathogens. Ilyonectria mors-panacis G3B was the dominant pathogen inducing root rot of P. notoginseng, and the abilities to detoxify saponins were the key to infect P. notoginseng successfully. To research the molecular mechanisms of detoxifying saponins in I. mors-panacis G3B, we used high-throughput RNA-Seq to identify 557 and 1519 differential expression genes (DEGs) in I. mors-panacis G3B with saponins treatments for 4H (Hours) and 12H (Hours) compared with no saponins treatments, respectively. Among these DEGs, we found 93 genes which were simultaneously highly expressed in I. mors-panacis G3B with saponins treatments for 4H and 12H, they mainly belong to genes encoding transporters, glycoside hydrolases, oxidation–reduction enzymes, transcription factors and so on. In addition, there were 21 putative PHI (Pathogen–Host Interaction) genes out of those 93 up-regulated genes. In this report, we analyzed virulence-associated genes in I. mors-panacis G3B which may be related to detoxifying saponins to infect P. notoginseng successfully. They provided an excellent starting point for in-depth study on pathogenicity of I. mors-panacis G3B and developed appropriate root rot disease management strategies in the future.

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4-Phenethyl-1-Propargylpiperidine-Derived Dual Inhibitors of Butyrylcholinesterase and Monoamine Oxidase B

Molecules ◽

10.3390/molecules26144118 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4118

Author(s):

Tjaša Mazej ◽

Damijan Knez ◽

Anže Meden ◽

Stanislav Gobec ◽

Matej Sova

Keyword(s):

Monoamine Oxidase ◽

Docking Studies ◽

Monoamine Oxidase B ◽

Mao B ◽

Initial Expectation ◽

Excellent Starting Point ◽

Starting Point ◽

Dependent Inhibition ◽

Dual Inhibitors ◽

Time Dependent Inhibition

The multi-target-directed ligands (MTDLs) strategy is encouraged for the development of novel modulators targeting multiple pathways in the neurodegenerative cascade typical for Alzheimer’s disease (AD). Based on the structure of an in-house irreversible monoamine oxidase B (MAO-B) inhibitor, we aimed to introduce a carbamate moiety on the aromatic ring to impart cholinesterase (ChE) inhibition, and to furnish multifunctional ligands targeting two enzymes that are intricately involved in AD pathobiology. In this study, we synthesized three dual hMAO-B/hBChE inhibitors 13–15, with compound 15 exhibiting balanced, low micromolar inhibition of hMAO-B (IC50 of 4.3 µM) and hBChE (IC50 of 8.5 µM). The docking studies and time-dependent inhibition of hBChE confirmed the initial expectation that the introduced carbamate moiety is responsible for covalent inhibition. Therefore, dual-acting compound 15 represents an excellent starting point for further optimization of balanced MTDLs.

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Revisiting the CompCars Dataset for Hierarchical Car Classification: New Annotations, Experiments, and Results

Sensors ◽

10.3390/s21020596 ◽

2021 ◽

Vol 21 (2) ◽

pp. 596

Author(s):

Marco Buzzelli ◽

Luca Segantin

Keyword(s):

Real World ◽

High Performance ◽

Ad Hoc ◽

Future Research ◽

Levels Of Detail ◽

Excellent Starting Point ◽

Starting Point ◽

Hierarchical Nature ◽

Multiple Levels ◽

Entire Dataset

We address the task of classifying car images at multiple levels of detail, ranging from the top-level car type, down to the specific car make, model, and year. We analyze existing datasets for car classification, and identify the CompCars as an excellent starting point for our task. We show that convolutional neural networks achieve an accuracy above 90% on the finest-level classification task. This high performance, however, is scarcely representative of real-world situations, as it is evaluated on a biased training/test split. In this work, we revisit the CompCars dataset by first defining a new training/test split, which better represents real-world scenarios by setting a more realistic baseline at 61% accuracy on the new test set. We also propagate the existing (but limited) type-level annotation to the entire dataset, and we finally provide a car-tight bounding box for each image, automatically defined through an ad hoc car detector. To evaluate this revisited dataset, we design and implement three different approaches to car classification, two of which exploit the hierarchical nature of car annotations. Our experiments show that higher-level classification in terms of car type positively impacts classification at a finer grain, now reaching 70% accuracy. The achieved performance constitutes a baseline benchmark for future research, and our enriched set of annotations is made available for public download.

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Saudi anti-human cancer plants database (SACPD): A collection of plants with anti-human cancer activities

Oncology Reviews ◽

10.4081/oncol.2018.349 ◽

2018 ◽

Cited By ~ 1

Author(s):

Ateeq Ahmed Al-Zahrani

Keyword(s):

Saudi Arabia ◽

Cell Lines ◽

Anticancer Drugs ◽

Plant Species ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Anticancer Activities ◽

Excellent Starting Point ◽

Starting Point

Several anticancer drugs have been developed from natural products such as plants. Successful experiments in inhibiting the growth of human cancer cell lines using Saudi plants were published over the last three decades. Up to date, there is no Saudi anticancer plants database as a comprehensive source for the interesting data generated from these experiments. Therefore, there was a need for creating a database to collect, organize, search and retrieve such data. As a result, the current paper describes the generation of the Saudi anti-human cancer plants database (SACPD). The database contains most of the reported information about the naturally growing Saudi anticancer plants. SACPD comprises the scientific and local names of 91 plant species that grow naturally in Saudi Arabia. These species belong to 38 different taxonomic families. In Addition, 18 species that represent16 family of medicinal plants and are intensively sold in the local markets in Saudi Arabia were added to the database. The website provides interesting details, including plant part containing the anticancer bioactive compounds, plants locations and cancer/cell type against which they exhibit their anticancer activity. Our survey revealed that breast, liver and leukemia were the most studied cancer cell lines in Saudi Arabia with percentages of 27%, 19% and 15%, respectively. The current SACPD represents a nucleus around which more development efforts can expand to accommodate all future submissions about new Saudi plant species with anticancer activities. SACPD will provide an excellent starting point for researchers and pharmaceutical companies who are interested in developing new anticancer drugs. SACPD is available online at https://teeqrani1.wixsite.com/sapd

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Ruthenium Oxide pH Sensing for Organs-On-Chip Studies

Proceedings ◽

10.3390/proceedings2130709 ◽

2018 ◽

Vol 2 (13) ◽

pp. 709 ◽

Cited By ~ 2

Author(s):

Esther Tanumihardja ◽

Wouter Olthuis ◽

Albert van den Berg

Keyword(s):

Ph Sensor ◽

Ruthenium Oxide ◽

Open Circuit ◽

Biological Medium ◽

Similar Response ◽

Ph Sensing ◽

Ph Sensors ◽

Cross Sensitivity ◽

On Chip

A ruthenium oxide (RuOx) electrode is being developed as potentiometric pH sensor for organs-on-chip applications. Open-circuit potential (OCP) of the RuOx electrode showed a response of −58.05 mV/pH, with no cross-sensitivity to potentially interfering/complexing ions (tested were lithium, sulfate, chloride, and calcium ions). Similar response was observed in complex biological medium. The electrode stored in liquid had a long-term drift of −0.8 mV/hour (corresponding to ΔpH of 0.013/hour) and response time in complex biological medium was 3.7 s. Minimum cross-sensitivity to oxygen was observed as the OCP shifted ~3 mV going from deoxygenated to oxygenated solution. This response is one magnitude lower than previously reported for metal- oxide pH sensors. Overall, the RuOx pH sensor has proven to be a suitable pH sensor for organs- on-chip applications.

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Are the amide bonds in N-acyl imidazoles twisted? A combined solid-state 17O NMR, crystallographic, and computational study

Canadian Journal of Chemistry ◽

10.1139/cjc-2014-0397 ◽

2015 ◽

Vol 93 (4) ◽

pp. 451-458 ◽

Cited By ~ 7

Author(s):

Xianqi Kong ◽

Aaron Tang ◽

Ruiyao Wang ◽

Eric Ye ◽

Victor Terskikh ◽

...

Keyword(s):

Solid State ◽

Chemical Shift ◽

Crystal Structures ◽

Computational Study ◽

Chemical Shifts ◽

Amide Bond ◽

Chemical Shift Tensors ◽

Amide Bonds ◽

Bond Rotation ◽

Quadrupole Coupling

We report synthesis of 17O-labeling and solid-state 17O NMR measurements of three N-acyl imidazoles of the type R-C(17O)-Im: R = p-methoxycinnamoyl (MCA-Im), R = 4-(dimethylamino)benzoyl (DAB-Im), and R = 2,4,6-trimethylbenzoyl (TMB-Im). Solid-state 17O NMR experiments allowed us to determine for the first time the 17O quadrupole coupling and chemical shift tensors in this class of organic compounds. We also determined the crystal structures of these compounds using single-crystal X-ray diffraction. The crystal structures show that, while the C(O)–N amide bond in DAB-Im exhibits a small twist, those in MCA-Im and TMB-Im are essentially planar. We found that, in these N-acyl imidazoles, the 17O quadrupole coupling and chemical shift tensors depend critically on the torsion angle between the conjugated acyl group and the C(O)–N amide plane. The computational results from a plane-wave DFT approach, which takes into consideration the entire crystal lattice, are in excellent agreement with the experimental solid-state 17O NMR results. Quantum chemical computations also show that the dependence of 17O NMR parameters on the Ar–C(O) bond rotation is very similar to that previously observed for the C(O)–N bond rotation in twisted amides. We conclude that one should be cautious in linking the observed NMR chemical shifts only to the twist of the C(O)–N amide bond.

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Tryptophan 207 is crucial to the unique properties of the human voltage-gated proton channel, hHV1

The Journal of General Physiology ◽

10.1085/jgp.201511456 ◽

2015 ◽

Vol 146 (5) ◽

pp. 343-356 ◽

Cited By ~ 27

Author(s):

Vladimir V. Cherny ◽

Deri Morgan ◽

Boris Musset ◽

Gustavo Chaves ◽

Susan M.E. Smith ◽

...

Keyword(s):

Transmembrane Helix ◽

Ph Sensor ◽

Proton Channel ◽

Tryptophan Residue ◽

Ph Sensing ◽

Ph Sensors ◽

Voltage Gated ◽

Karlodinium Veneficum ◽

Channel Opening ◽

External Ph

Part of the “signature sequence” that defines the voltage-gated proton channel (HV1) is a tryptophan residue adjacent to the second Arg in the S4 transmembrane helix: RxWRxxR, which is perfectly conserved in all high confidence HV1 genes. Replacing Trp207 in human HV1 (hHV1) with Ala, Ser, or Phe facilitated gating, accelerating channel opening by 100-fold, and closing by 30-fold. Mutant channels opened at more negative voltages than wild-type (WT) channels, indicating that in WT channels, Trp favors a closed state. The Arrhenius activation energy, Ea, for channel opening decreased to 22 kcal/mol from 30–38 kcal/mol for WT, confirming that Trp207 establishes the major energy barrier between closed and open hHV1. Cation–π interaction between Trp207 and Arg211 evidently latches the channel closed. Trp207 mutants lost proton selectivity at pHo >8.0. Finally, gating that depends on the transmembrane pH gradient (ΔpH-dependent gating), a universal feature of HV1 that is essential to its biological functions, was compromised. In the WT hHV1, ΔpH-dependent gating is shown to saturate above pHi or pHo 8, consistent with a single pH sensor with alternating access to internal and external solutions. However, saturation occurred independently of ΔpH, indicating the existence of distinct internal and external pH sensors. In Trp207 mutants, ΔpH-dependent gating saturated at lower pHo but not at lower pHi. That Trp207 mutation selectively alters pHo sensing further supports the existence of distinct internal and external pH sensors. Analogous mutations in HV1 from the unicellular species Karlodinium veneficum and Emiliania huxleyi produced generally similar consequences. Saturation of ΔpH-dependent gating occurred at the same pHo and pHi in HV1 of all three species, suggesting that the same or similar group(s) is involved in pH sensing. Therefore, Trp enables four characteristic properties: slow channel opening, highly temperature-dependent gating kinetics, proton selectivity, and ΔpH-dependent gating.

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