Novel An Efficient Fluorescent Probe Based on Calix[4]triazacrown-5 With Naphthalimide Group for Co2+, Cd2+ and Dopamine Detection.

A novel naphthalimide-substituted calix[4]triazacrown-5 (Nap-Calix) at cone conformation was designed and synthesized to employ as a fluorescent probe, which enables the simultaneously detection of Co2+ and Cd2+ metal ions as well as dopamine (DA). 1H-NMR, 13C-NMR, ESI-MS and elemental analysis techniques were carried out to characterize its structure. Cation binding property of Nap-Calix against various metal ions such as Ba2+, Co2+, Ni2+, Pb2+, Zn2+, and Cd2+ exhibited that the sensor selectively binds to Co2+ and Cd2+ metal ions with a remarkable affinity. Introduction of Co2+ and Cd2+ metal ions to a solution of Nap-Calix in DMF/water (1:1, v/v) resulted with a new emission band at 370 nm when excited at 283 nm. In addition, the fluorescence sensing affinity of the probe Nap-Calix against a catecholamine neurotransmitter (dopamine) was investigated in a wide range of concentration of DA (0-0.1 mmol L-1) in 50% DMF/PBS (pH = 5.0). The fluorescence intensity of Nap-Calix, with excitation/emission peaks at 283/327 nm, is highly enhanced by DA. It was also observed that Nap-Calix exhibits excellent fluorescence behavior towards DA with a very low detection limit as 0.21 µmol L-1.

A highly selective and sensitive fluorescence probe for dopamine determination based on a bisquinoline-substituted calix[4]arene carboxylic acid derivative.

Dopamine (DA) at normal levels in the human body exhibits a high potential for maintaining a proper neuron network. However, their abnormalities in humans can bring out aggressive disorders such as Schizophrenia, hypertension, Tourette's syndrome, Alzheimer's disease, bipolar depression, Parkinson's disease, drug addiction and attention-deficit hyperactivity diseases. Hence, in this study, a bis-quinoline-substituted calix[4] arene carboxylic acid derivative (Quin-Calix-CO2H) at cone conformation was developed as an effective fluorescent sensor for the detection of a catecholamine neurotransmitter (dopamine). The structure of Quin-Calix-CO2H was confirmed using 1H-NMR, 13C-NMR, ESI-MS and elemental analysis techniques. The calixarene-based fluorescent sensor (Quin-Calix-CO2H) has shown fluorescence emission at 404 nm under the excitation of 270 nm. Further, biomolecules binding property of Quin-Calix-CO2H against various biomolecules such as L-cysteine (L-Cys), α-D-glucose (D-Glu), (+)-sodium-L-ascorbate (SAA), urea (UR), L-alanine (L-Ala) and dopamine (DA) exhibited that the fluorescent sensor enables selectively and sensitively detection for DA with a remarkable affinity. The probe Quin-Calix-CO2H has shown fluorescence quenching towards DA concentration ranging from 0 to 4.0 µM with a very low limit of detection (LOD) of 88.5 nmol L-1. In addition, the binding constant and stoichiometry as well as the mechanism of quenching have been also determined from the fluorescence data.Communicated by Ramaswamy H. Sarma.

Electronic structure and photophysical properties of some promising organic molecules for organic solar cells.

CONTEXT: Three novel organic semiconductors (Fig. 1), which are molecule (a) and molecule (c) have the same wing unit molecules (b) and (c) have the same core unit were reported. Thus, the influence of wing units on solar cell device performance parameters such us the opto-electronics properties, non-linear optics (NLO), electronic properties, and natural bond orbitals (NBO) were calculated in order to evincing molecular structure-property relations. The all studied molecules would be promising materials for photovoltaic applications, but molecule (c) could be an excellent candidate for high efficiency organic solar cells with a small energy gap, a lowest ΔGreg, highest Voc, and LHE values. According to all these results, it is seen that the wing units of the molecules affect both the opto-electronic properties and NLO properties more than the core units. These theoretical calculations is expected to obtain new strategies to synthesize efficient materials for organic solar cell devices. METHOD: Density functional (DFT) and time-dependent density functional (TDDFT) theory simulations for the solar cell device performance parameters, non-linear optics, and natural bond analysis were performed using the Gaussian 09w software. The ground state properties of molecules have been studied with hybrid functional of Beckethree-Lee-Yang-Parr (B3LYP), and excited state properties have been calculated CAMB3LYP and our DFT calculations were performed using 6-31++G(d,p) basis set on fully optimized geometries.

Functional Assay for Measuring Bacterial Degradation of Gemcitabine Chemotherapy.

Drug biotransformation by the host microbiome can impact the therapeutic success of treatment. In the context of cancer, drug degradation can take place within the microenvironment of the targeted tumor by intratumor bacteria. In pancreatic cancer, increased chemo-resistance against the frontline chemotherapy gemcitabine is thought to arise from drug degradation by the tumor microbiome. This bacterial-drug interaction highlights the need for developing rapid assays for monitoring bacterial gemcitabine breakdown. While chemical approaches such as high-performance liquid chromatography are suitable for this task, they require specialized equipment and expertise and are limited in throughput. Functional cell-based assays represent an alternate approach for performing this task. We developed a functional assay to monitor the rate of bacterial gemcitabine breakdown using a highly sensitive bacterial reporter strain. Our method relies on standard laboratory equipment and can be implemented at high throughput to monitor drug breakdown by hundreds of strains simultaneously. This functional assay can be readily adapted to monitor degradation of other drugs. Key features Quantification of gemcitabine breakdown by incubating bacteria that degrades the drug and subsequently testing the growth of a reporter strain on filtered supernatant. Use of an optimized reporter strain that was genetically engineered to be a non-degrader strain and highly sensitive to gemcitabine. A high-throughput assay performed in microplates that can be adjusted for identifying bacteria with a fast or slow gemcitabine degradation rate. The assay results can be compared to results from a standard curve with known drug concentrations to quantify degradation rate.

Evolved bacterial resistance to the chemotherapy gemcitabine modulates its efficacy in co-cultured cancer cells.

Drug metabolism by the microbiome can influence anticancer treatment success. We previously suggested that chemotherapies with antimicrobial activity can select for adaptations in bacterial drug metabolism that can inadvertently influence the host's chemoresistance. We demonstrated that evolved resistance against fluoropyrimidine chemotherapy lowered its efficacy in worms feeding on drug-evolved bacteria (Rosener et al., 2020). Here, we examine a model system that captures local interactions that can occur in the tumor microenvironment. Gammaproteobacteria-colonizing pancreatic tumors can degrade the nucleoside-analog chemotherapy gemcitabine and, in doing so, can increase the tumor's chemoresistance. Using a genetic screen in Escherichia coli, we mapped all loss-of-function mutations conferring gemcitabine resistance. Surprisingly, we infer that one third of top resistance mutations increase or decrease bacterial drug breakdown and therefore can either lower or raise the gemcitabine load in the local environment. Experiments in three E. coli strains revealed that evolved adaptation converged to inactivation of the nucleoside permease NupC, an adaptation that increased the drug burden on co-cultured cancer cells. The two studies provide complementary insights on the potential impact of microbiome adaptation to chemotherapy by showing that bacteria-drug interactions can have local and systemic influence on drug activity.

Assembling stable syntrophic Escherichia coli communities by comprehensively identifying beneficiaries of secreted goods.

Metabolic cross-feeding frequently underlies mutualistic relationships in natural microbial communities and is often exploited to assemble synthetic microbial consortia. We systematically identified all single-gene knockouts suitable for imposing cross-feeding in Escherichia coli and used this information to assemble syntrophic communities. Most strains benefiting from shared goods were dysfunctional in biosynthesis of amino acids, nucleotides, and vitamins or mutants in central carbon metabolism. We tested cross-feeding potency in 1,444 strain pairs and mapped the interaction network between all functional groups of mutants. This network revealed that auxotrophs for vitamins are optimal cooperators. Lastly, we monitored how assemblies composed of dozens of auxotrophs change over time and observed that they rapidly and repeatedly coalesced to seven strain consortia composed primarily from vitamin auxotrophs. The composition of emerging consortia suggests that they were stabilized by multiple cross-feeding interactions. We conclude that vitamins are ideal shared goods since they optimize consortium growth while still imposing member co-dependence.

Synthesis of new anthracene-substituted calix[4]triazacrown-5 as highly sensitive fluorescent chemosensor and extractant against hazardous dichromate anion.

A new fluorogenic anthracene functionalized calix[4]triazacrown-5 (Ant-AzClx) was successfully synthesized using a simple Schiff's base reaction. The 1 H-NMR, 13 C-NMR, ESI-MS, and elemental analysis techniques were performed to characterize its structure. Excited at 370 nm, Ant-AzClx reveals excimer emission at 418 nm. Therefore, its anion binding properties were investigated against F- , HCO3 - , H2 PO4 - , NO3 - , Cr2 O7 2- , and SO4 2- ions. When hazardous dichromate anion was introduced into medium, the fluorescence intensity of Ant-AzClx was markedly quenched. The binding constant, stoichiometry, the detection limits and Stern-Volmer equation for the complex formed between Ant-AzClx and Cr2 O7 2- ion were determined. Furthermore, the 1 H-NMR technique was also performed to assess the mechanism of the complex (Ant-AzClx@Cr2 O7 2- ). Apart from its excellent fluorescent chemosensor properties for selective and sensitive recognition of Cr2 O7 2- ion, Ant-AzClx was used as an efficient extractant towards dichromate anion. The extraction results indicated that Ant-AzClx exhibited high extraction capability, leading to it being a promising extractant for the removal of dichromate anions from water.

Synthesis of New Quinoline-Conjugated Calixarene as a Fluorescent Sensor for Selective Determination of Cu2+ Ion.

A novel quinoline-functionalized calix [4] arene derivative (Quin-Calix) has been successfully synthesized at partial cone conformation and duly characterized by using FTIR, 1H-NMR, 13C-NMR, ESI-MS and elemental analysis techniques. Moreover, the cation-binding property of the calix [4] arene derivative (Quin-Calix) has been investigated towards Cu2+, Ba2+, Cd2+, Co2+, Ni2+, Zn2+ and Fe3+ ions, and the recognition event monitored by UV-Vis absorption and fluorescence studies. The results indicated that Quin-Calix displays a remarkable affinity and selectivity only for Cu2+ ion. The binding constant and stoichiometry of the complex formed between Quin-Calix and Cu2+ ion have been also calculated from the fluorescence data. In addition, Stern-Vohmer equation has been used to elucidate the mechanism of quenching.

Evolved bacterial resistance against fluoropyrimidines can lower chemotherapy impact in the Caenorhabditis elegans host.

Metabolism of host-targeted drugs by the microbiome can substantially impact host treatment success. However, since many host-targeted drugs inadvertently hamper microbiome growth, repeated drug administration can lead to microbiome evolutionary adaptation. We tested if evolved bacterial resistance against host-targeted drugs alters their drug metabolism and impacts host treatment success. We used a model system of Caenorhabditis elegans, its bacterial diet, and two fluoropyrimidine chemotherapies. Genetic screens revealed that most of loss-of-function resistance mutations in Escherichia coli also reduced drug toxicity in the host. We found that resistance rapidly emerged in E. coli under natural selection and converged to a handful of resistance mechanisms. Surprisingly, we discovered that nutrient availability during bacterial evolution dictated the dietary effect on the host - only bacteria evolving in nutrient-poor media reduced host drug toxicity. Our work suggests that bacteria can rapidly adapt to host-targeted drugs and by doing so may also impact the host.

Harnessing robotic automation and web-based technologies to modernize scientific outreach.

Technological breakthroughs in the past two decades have ushered in a new era of biomedical research, turning it into an information-rich and technology-driven science. This scientific revolution, though evident to the research community, remains opaque to nonacademic audiences. Such knowledge gaps are likely to persist without revised strategies for science education and public outreach. To address this challenge, we developed a unique outreach program to actively engage over 100 high-school students in the investigation of multidrug-resistant bacteria. Our program uses robotic automation and interactive web-based tools to bridge geographical distances, scale up the number of participants, and reduce overall cost. Students and teachers demonstrated high engagement and interest throughout the project and valued its unique approach. This educational model can be leveraged to advance the massive open online courses movement that is already transforming science education.

Fabrication and Application of a New Modified Electrochemical Sensor Using Newly Synthesized Calixarene-Grafted Mwcnts for Simultaneous Determination of Cu(II) and Pb(II).

A rapid, simple, selective and highly sensitive simultaneous determination of Cu(II) and Pb(II) via newly fashioned 5,11,17,23-tetra-tert-butyl-25,27-dihydrazinamidecarbonylmethoxy-26,28-dihydroxycalix[4]arene-grafted multi-walled carbon nanotubes-modified carbon paste electrode (CNT-Calix/CPE) by differential pulse anodic stripping voltammetry (DPASV) has been introduced. It was observed that CNT-Calix/CPE exhibits higher selectivity and stability for Cu(II) and Pb(II). Different operational parameters such as pH, deposition potential/time, pulse amplitude (5, -1.0 V vs. Ag/AgCl, 300 s, 2 s, 0.05 V) were also optimized for calculation and statistical evaluation of linear range, detection limit and limit of quantification. Interference study shows that the electrode is highly selective for the simultaneous determination of Cu(II) and Pb(II). Standard addition method was used to apply CNT-Calix/CPE in waste water, plant leaves and soft drinks and it was found that the concentration of Cu(II) and Pb(II) were corresponding to standardized values.

Electrical characterization of two analogous Schottky contacts produced from N-substituted 1,8-naphthalimide.

The aim of this study was to analyze the interface states (Nss) in pure Al//p-Si/Al, Al/N-F Nft/p-Si/Al and Al/N-T Nft/p-Si/Al Schottky barrier diodes (SBDs). N-Substituted 1,8-naphthalimide thin films were deposited on a p-Si substrate by spin coating and annealed at ∼200 °C for 60 s under an air atmosphere. Al contacts were obtained via reactive magnetron sputtering. The current voltage (I-V) characteristics of the SBDs were measured at room temperature. From the I-V characteristics, the SBDs ideality factor (n) and zero-bias barrier height values (Φb) of 1.27, 1.00, and 1.05 and 0.66 eV, 0.70 eV, and 0.64 eV were observed for the Al//p-Si/Al, Al/N-F Nft/p-Si/Al and Al/N-T Nft/p-Si/Al Schottky barrier diodes, respectively. The interface state density distribution profile (Nss) as a function of (Ess-Ev) was extracted from the forward-bias I-V measurements by considering the effective barrier height and (Φe) and series resistance (Rs) of the Schottky diode. The obtained Nss plot tendency showed that the existence of interface states has no significant effect on the rectifying and capacitance characteristics. The Nss values with the 1,8-naphthalimide layer were lower than that without it. This shows that naphthalimide exhibits a strong contribution by blocking the unwanted states and some traps in the conduction mechanism, which may cause possible cracks or deep paths for carriers to travel along the junction.

Gold Electrodes Modified with Calix[4]arene for Electrochemical Determination of Dopamine in the Presence of Selected Neurotransmitters.

Here, we present an electrochemical sensor based on gold electrodes modified with calix[4]arene functionalized with carboxypiperidino groups at the upper rim. It has been demonstrated that these groups are involved in a complex formation with dopamine (DA) on the surface of gold electrodes. The supramolecular complex calix[4]arene-DA created on the gold electrode surface has been characterized electrochemically and the measuring conditions have been optimized. The presented sensor displayed a detection limit in the pM range. The DA determination was performed successfully in the presence of ascorbic acid, uric acid and selected neurotransmitters.

Calixarene assembly with enhanced photocurrents using P(SNS-NH2)/CdS nanoparticle structure modified Au electrode systems.

Two novel calix[n]arene-adorned gold electrodes producing high photocurrent intensities were successfully constructed by embedding gold electrode surfaces with both P(4-(2,5-di(thiophen-2-yl)-1H-pyrrol-1-yl)benzenamine) conducting polymer and 4-mercaptoboronic acid-functionalized semiconductor CdS nanoparticles to facilitate the binding of calix[n]arene sulfonic acids with nanoparticles. This structure enabled an electron transfer cascade that both induced effective charge separation and efficiently generated photocurrent. The prepared electrodes were used to generate photocurrent by relying on the host-guest interactions of guests Br3(-) and I3(-), which if positioned well in the system was able to fill electron-hole pairs of CdS nanoparticles. As a result, host calixarene derivatives crucially held Br3(-) and I3(-) ions at a substantial distance from CdS nanoparticles. Furthermore, the effects of various calixarenes on the photocurrent obtained indicate that the generation of photocurrent intensities by the system depends on the cavity sizes of calixarene derivatives, which provide an essential center for Br3(-) and I3(-) ions.

Downregulation of the Host Gene jigr1 by miR-92 Is Essential for Neuroblast Self-Renewal in Drosophila.

Intragenic microRNAs (miRNAs), located mostly in the introns of protein-coding genes, are often co-expressed with their host mRNAs. However, their functional interaction in development is largely unknown. Here we show that in Drosophila, miR-92a and miR-92b are embedded in the intron and 3'UTR of jigr1, respectively, and co-expressed with some jigr1 isoforms. miR-92a and miR-92b are highly expressed in neuroblasts of larval brain where Jigr1 expression is low. Genetic deletion of both miR-92a and miR-92b demonstrates an essential cell-autonomous role for these miRNAs in maintaining neuroblast self-renewal through inhibiting premature differentiation. We also show that miR-92a and miR-92b directly target jigr1 in vivo and that some phenotypes due to the absence of these miRNAs are partially rescued by reducing the level of jigr1. These results reveal a novel function of the miR-92 family in Drosophila neuroblasts and provide another example that local negative feedback regulation of host genes by intragenic miRNAs is essential for animal development.

Improvement of catalytic activity of lipase in the presence of calix[4]arene valeric acid or hydrazine derivative.

Sol-gel encapsulation is a simple but powerful method to enhance the enantioselectivity of lipase-catalyzed transformations in an isooctane/aqueous buffer solution. Candida rugosa lipase was encapsulated according to a sol-gel procedure in the presence and absence of calix[4]arene hydrazine or carboxylic acid derivatives with Fe3O4 magnetic nanoparticles as an additive. The activity of the encapsulated lipases was evaluated for the enantioselective hydrolysis of racemic Naproxen methyl ester and the hydrolysis of p-Nitrophenylpalmitate. The results indicate that the encapsulated lipase without calix[4]arene derivative has lower conversion and enantioselectivity compared to the encapsulated lipase with calix[4]arene derivative. It was found that the calix[4]arene hydrazine and carboxylic acid-based encapsulated lipases have excellent activity and enantioselectivity (E >300) compared to encapsulated lipase without the calix[4]arene derivatives.

Development of a pH sensing membrane electrode based on a new calix[4]arene derivative.

A new pH sensing poly(vinyl chloride) (PVC) membrane electrode was developed by using recently synthesized 5,17-bis(4-benzylpiperidine-1-yl)methyl-25,26,27,28-tetrahydroxy calix[4]arene as an ionophore. The effects of membrane composition, inner filling solution and conditioning solution on the potential response of the proposed pH sensing membrane electrode were investigated. An optimum membrane composition of 3% ionophore, 67% o-nitrophenyl octyl ether (o-NPOE) as plasticizer, 30% PVC was found. The electrode exhibited a near-Nernstian slope of 58.7±1.1 mV pH(-1) in the pH range 1.9-12.7 at 20±1 °C. It showed good selectivity for H(+) ions in the presence of some cations and anions and a longer lifetime of at least 12 months when compared with the other PVC membrane pH electrodes reported in the literature. Having a wide working pH range, it was not only applied as a potentiometric indicator electrode in various acid-base titrations, but also successfully employed in different real samples. It has good reproducibility and repeatability with a response time of 6-7s. Compared to traditional glass pH electrode, it exhibited excellent potentiometric response after being used in fluoride-containing media.

Enhanced catalysis and enantioselective resolution of racemic naproxen methyl ester by lipase encapsulated within iron oxide nanoparticles coated with calix[8]arene valeric acid complexes.

In this study, two types of nanoparticles have been used as additives for the encapsulation of Candida rugosa lipase via the sol-gel method. In one case, the nanoparticles were covalently linked with a new synthesized calix[8]arene octa valeric acid derivative (C[8]-C4-COOH) to produce new calix[8]arene-adorned magnetite nanoparticles (NP-C[8]-C4-COOH), and then NP-C[8]-C4-COOH was used as an additive in the sol-gel encapsulation process. In the other case, iron oxide nanoparticles were directly added into the sol-gel encapsulation process in order to interact electrostatically with both C[8]-C4-COOH and Candida rugosa lipase. The catalytic activities and enantioselectivities of two novel encapsulated lipases (Enc-NP-C[8]-C4-COOH and Enc-C[8]-C4-COOH@Fe3O4) in the hydrolysis reaction of racemic naproxen methyl ester were evaluated. The results showed that the activity and enantioselectivity of the lipase were improved when the lipase was encapsulated in the presence of calixarene-based additives. Indeed, the encapsulated lipases have an excellent rate of enantioselectivity, with E = 371 and 265, respectively, as compared to the free enzyme (E = 137). The lipases encapsulated with C[8]-C4-COOH and iron oxide nanoparticles (Enc-C[8]-C4-COOH@Fe3O4) retained more than 86% of their initial activities after 5 repeated uses and 92% with NP-C[8]-C4-COOH.

Improving catalytic hydrolysis reaction efficiency of sol-gel-encapsulated Candida rugosa lipase with magnetic ß-cyclodextrin nanoparticles.

A silica-based ß-cyclodextrin was immobilized on magnetic nanoparticles to obtain a macrocyclic compound with magnetic property. Then, the ß-cyclodextrin-grafted magnetic nanoparticles were encapsulated with Candida rugosa lipase in sol-gel matrices using alkoxysilane precursors. The catalytic activity of the encapsulated lipases was evaluated with model reactions, i.e., the hydrolysis of p-nitro-phenylpalmitate (p-NPP) and the enantioselective hydrolysis of rasemic Naproxen methyl ester that was studied in an aqueous buffer solution/isooctane reaction system. The results indicate that the cyclodextrin-based, encapsulated lipase particularly exhibited high conversion and enantioselectivity behavior compared to the sol-gel free lipase. It was also observed that excellent enantioselectivity (E=399) was obtained for the encapsulated lipase with magnetic ß-cyclodextrin that has an ee value of S-Naproxen acid of about 98%.

Preparation of new Calix[4]arene-immobilized biopolymers for enhancing catalytic properties of Candida rugosa lipase by sol-gel encapsulation.

The article describes preparation of new calixarene biopolymers consisting of the immobilization of convenience calixarene derivative onto cellulose and chitosan biopolymers, and the encapsulation of these calixarene biopolymers with Candida rugosa lipase within a chemical inert sol-gel supported by polycondensation with tetraethoxysilane and octyltriethoxysilane. The catalytic properties of immobilized lipase were evaluated into model reactions employing the hydrolysis of p-nitrophenylpalmitate and the enantioselective hydrolysis of naproxen methyl esters from racemic prodrugs in aqueous buffer solution/isooctane reaction system. The resolution studies using sol-gel support have observed more improvement in the enantioselectivity of naproxen E = 300 with Cel-Calix-E than with encapsulated lipase without calixarene-based materials. Furthermore, the encapsulated lipase (Cel-Calix-E) was still retained about 39 % of their conversion ratios after the fifth reuse in the enantioselective reaction.