Monitoring Hg2+ ions in food and environmental matrices using a novel ratiometric NIR fluorescent sensor via carbonothioate-deprotection reaction.

Mercury toxicity and its environmental impact are significant concerns for public health and environmental protection. Therefore, the development of effective, rapid, and reliable detection methods for trace levels of Hg2+ is crucial. Herein, a cyanine dye bearing a carbonothioate group is reported as a potential NIR fluorescent probe for Hg2+ detection. The spectral properties of the free probe have been characterized by the presence and absence of a series of analytes. The addition of Hg2+ leads to significant changes in the fluorescence signal with distinct red coloration compared to other competing analytes, indicating that the probe is highly selective for Hg2+. The fluorescence quantum yield increases from 0.073 to 0.315. The detection limit is 0.10 µM, indicating the high sensitivity of the probe to low Hg2+ levels. The most prominent sensing features of the probe include NIR fluorescence, low cytotoxicity, ratiometric fluorescence response, and fast response compared to most of the currently available fluorescent probes. In addition, the probe can detect Hg2+ in actual samples such as foodstuff, soil, water, and live cells. Bioimaging studies have demonstrated that the present probe is highly efficient in targeting mitochondria and possesses good imaging abilities for detecting Hg2+ in cells. Therefore, these results suggest that it can be proposed as a powerful NIR fluorescent probe for the highly sensitive detection of Hg2+.

Two red/blue-emitting fluorescent probes for quick, portable, and selective detection of thiophenol in food, soil and plant samples, and their applications in bioimaging.

Thiophenol (PhSH), which is widely used in many industries, poses significant health risks owing to its acute toxicity and irritating effects. Thus, the detection of PhSH is crucial for ensuring environmental and food safety. There is significant room for improvement in the sensing properties of the reported analytical methods, such as response time, detection limit, selectivity, and portable detection. Herein, we present two new red/blue fluorescence-emissive sensors (NS1 and NS2) for PhSH detection. After reacting with PhSH, NS1 exhibited a low detection limit (66.7 nM), red emission, fast response time of just 10 s, and large Stokes shift (240 nm). NS2 could detect PhSH with a low detection limit (75.8 nM), fast response time of 20 s, and blue emission. The noticeable color response and portability of the two probes made them suitable for on-site detection of PhSH in various samples, such as water, soil, plant, food samples, and living cells. Moreover, it has been shown that these probes could be used to determine PhSH content in smartphone applications, thin layer chromatography kits, and polysulfone capsule kits. Prepared probes have low cytotoxicity and show good permeability in tested living cells, which is important for early diagnosis, disease research, and emergency analysis. Compared with other studies, the proposed approach has remarkable advantages in terms of detection limit, portability, response time, and low cytotoxicity. Thus, it meets the crucial demand for ensuring health, environmental and food safety, and adherence to regulatory standards.

Novel mitochondrial and DNA damaging fluorescent Calix[4]arenes bearing isatin groups as aromatase inhibitors: Design, synthesis and anticancer activity.

Breast cancer causes a high rate of mortality all over the world. Therefore, the present study focuses on the anticancer activity of new lower rim-functionalized calix[4]arenes integrated with isatin and the p-position of calixarenes with 1,4-dimethylpyridinium iodine against various human cancer cells such as MCF-7 and MDA-MB-231 breast cancer cell lines, as well as the PNT1A healthy epithelial cell line. It was observed that compound 6c had the lowest values in MCF-7 (8.83 µM) and MDA-MB-231 (3.32 µM). Cell imaging and apoptotic activity studies were performed using confocal microscopy and flow cytometry, respectively. The confocal imaging studies with 6c showed that the compound easily entered the cell, and it was observed that 6c accumulated in the mitochondria. The Comet assay test was used to detect DNA damage of compounds in cells. It was found that treated cells had abnormal tail nuclei and damaged DNA structures compared with untreated cells. In vitro human aromatase enzyme inhibition profiles showed that compound 6c had a remarkable inhibitory effect on aromatase. Compound 6c displayed a significant inhibition capacity on aromatase enzyme with the IC50 value of 0.104 ± 0.004 µM. Thus, not only the anticancer activity of the new fluorescent derivatives, which are the subject of this study, but the aromatase inhibitory profiles have also been proven.

Engineering a "turn-on" NIR fluorescent sensor-based hydroxyphenyl benzothiazole with a cinnamoyl unit for hydrazine and its environmental and in-vitro applications.

Hydrazine (N2H4), a chemical compound widely used in various industrial applications, causes significant environmental and biological hazards. Therefore, it is crucial to develop methodologies for the visualization and real time tracking of N2H4. In this regard, we have constructed a novel near-infrared fluorescent probe (HBT-Cy) that can effectively detect N2H4 in various samples. HBT-Cy contains 2-(2'-hydroxyphenyl)benzothiazole (HBT), cinnamoyl (Cy), and pyridinium (Py) moieties. Importantly, HBT-Cy exhibits a rapid, selective, and highly sensitive response to N2H4. This response results in the release of HBT-Py and the generation of considerable colorimetric changes along with a significant NIR (near infrared) fluorescence signal, peaking at 685 nm. Advantages of this system include turn on NIR fluorescence with large Stokes shift, (approximately 171 nm), low limit of detection (LOD = 0.11 µM) and quantum yield (0.211). The probe with low cytotoxic behavior demonstrates strong NIR fluorescence imaging capabilities to visualize endogenous and exogenous N2H4 in live cells. This mitochondria-targetable probe shows effective subcellular localization. These results suggest that HBT-Cy is a valuable probe for tracking and investigating the behavior of N2H4 in biological systems and environmental samples.

Cu2+-assisted sensing of fungicide Thiram in food, soil, and plant samples and the ratiometric detection of Hg2+ in living cells by a low cytotoxic and red emissive fluorescent sensor.

Metal ions and pesticides are extensively used in many industries and agriculture. However, they cause significant environmental pollution and various adverse health effects. Therefore, the development of sensitive and selective techniques to detect them is necessary for human health and the ecosystem. In this paper, we report a novel red-emitting fluorescence probe with a large Stokes shift (∼220 nm) based on rhodamine and isophorone units. The probe shows a ratiometric fluorescence response toward Hg2+ ions; however, Cu2+ ions quench the red fluorescence signal. The decomposition of the probe-Cu2+ complex allows detection of Thiram followed by recovery of the red fluorescence signal of the probe. In addition, the probe shows a good linear response to Hg2+, Cu2+, and Thiram, with detection limits of 122.0 nM, 29.0 nM, and 72.0 nM, respectively. The practical applicability of the probe has been successfully tested in real samples. Moreover, smartphone detection and light-responsive capsule fabrication have been established, for easy and quick detection. The probe possesses very low cytotoxicity and allows visualization of Hg2+ and Cu2+ ions in HeLa cells. Therefore, the present probe is expected to be an effective tool assisting in easy, quick, and reliable detection of Thiram, Hg2+, and Cu2+ ions.

Lighting up trace carbon monoxide and residual palladium species by a low cytotoxic mitochondria targetable red fluorescent probe: Its large scaled applications.

High levels of residual palladium can lead to serious negative health effects. Carbon monoxide (CO) is a significant gasotransmitter in transporting intermolecular and intramolecular signals to balance several physiological processes. Therefore, there is a need for rapid detection of CO and palladium residue. To address these issues, we have designed a novel light-up fluorescent probe for the detection of Pd and CO. It can not only detect Pd and CO selectively with a remarkable chromogenic and red fluorescent response over other metal ions allowing detection with naked eyes but also discriminate Pd0 and Pd2+/Pd4+ species. The detection reaction is confirmed by HPLC analysis. The probe demonstrates biocompatibility and mitochondrial target ability for potential biological applications. The practical applications based on drug residue and soil analysis, and smartphone have been successfully performed. Bioimaging of the concentration change of Pd and CO in HeLa cells using the probe is successfully applied. Therefore, the present approach can provide early diagnosis of Pd and CO with low detection limit, low cytotoxicity, high selectivity, and sensitivity.

Visual and quantitative monitoring of thiophenol by a novel deep-red emitting fluorescent probe in environmental and biological systems.

Detection of highly toxic thiophenols in biological or environmental systems is of great importance. Therefore, fast, reliable, and sensitive probes are needed to detect thiophenols. Herein, a novel triphenylamine conjugated dicyanoisophorone-based near infrared fluorescence probe is reported to determine trace thiophenol (PhSH) levels. The probe demonstrates a distinct "turn-on" fluorescence response to thiophenol among the tested analytes and its quantum yield (Φ) increases from 0.011 to 0.142. It has low cytotoxicity with cell viability of 90-100% up to 10.0 µM of the probe, a strong anti-interference capability, a large Stokes shift (150 nm), and a fast response time (<1 min). In addition, the probe exhibits a good linear response to PhSH over the range from 0 to 15.0 µM with a detection limit of 32.3 nM (R2 = 0.9978). The detection process is also confirmed through HPLC. The practical applicability of the probe is proved by a smartphone platform, TLC kit, plant tissue imaging, soil assay, tap, and lake water analysis with good recovery values (92.3-117%), and concentration-dependent live cell bioimaging PhSH from 5.0 to 15.0 µM. Therefore, the present probe is a robust candidate for monitoring PhSH levels in biological and environmental systems.

A fully water-soluble Calix[4]arene probe for fluorometric and colorimetric detection of toxic hydrosulfide and cyanide ions: Practicability in living cells and food samples.

Although hydrosulfide and cyanide anions play important roles in daily life that they are available in a lot of foods. However, their excess amounts contaminate water, land, and food and cause serious problems to human health. Herein, we introduce a water-soluble macrocyclic sensor based-on Calix[4]arene (MPI-Calix[4]) with dual response sites for fluorescence recognizing cyanide (CN-) and hydrogen sulfide (HS-) under longwave light. MPI-Calix[4] exhibits a high selectivity and sensitivity in the detection of CN- and HS-, where the limits of detection were as low as 0.115 and 8.12 µmol/L, respectively. The cell imaging studies shows that this probe can be easily used in the detection of CN- and HS- on living cells. Full understanding of these results paved a fruitful system to improve an applicable analytical process for food safety and quality.

Discrimination of Pd-species by an ultra-fast, long wavelength and biocompatible fluorescent sensor: Its on-site kit assay, drug, and cancer/epithelial cell studies.

Extensive use of palladium in many catalysts and catalytic converters causes a high degree of pollution of water and soil resources. Therefore, there is an urgent need to develop rapid and sensitive palladium probes. Herein, a novel "turn-on" near-infrared (NIR) fluorescence and colorimetric probe for Pd has been designed on the basis of the deallylation of the probe, followed by the release of NIR emissive fluorophore through the Tsuji-Trost reaction. The probe can selectively discriminate between the oxidation states of Pd0 and Pd2+. Sensing results demonstrates that the probe has excellent selectivity, sensitivity, fast response time, NIR fluorescence, high biocompatibility, and low detection limit for the Pd detection over a series metal ion. The probe has been successfully applied in visualization of residual Pd content from water, soil, drug and living cell samples by fluorescence observation with the naked eye.

An effective benzothiazole-indandione D-π-A fluorescent sensor for "ratiometric" detection of hydrazine: Its solvatochromism properties and applications in environmental samples and living cells.

Hydrazine (N2H4) has high toxic impact and is widely used as raw material. As a result, it poses serious health risks and the following environmental pollution. Therefore, hydrazine's detecting techniques remains constantly under investigation. Herein, we report a ratiometric D-π-A fluorescent probe displaying NIR emission based on the ICT mechanism to detect N2H4. Other tested analytes have no observable interferences on the sensitivity and selectivity. The probe has sensitivity for N2H4 down to 1.29 µM with quick detection time (about 2.0 min). Moreover, the probe demonstrates solvatochromism with obvious emission varying from dull red to green, which implied high sensitivity to medium polarity. A portable smartphone platform for point-of-care detection of N2H4 in water samples is constructed. As a proof of real samples, the probe is successfully applied to sense N2H4 in water samples, to bioimage N2H4 in living cells and in plant cells with low cytotoxicity, suggesting significant potential application. This strategy opens up the preparation of new ratiometric fluorescence systems for bioimaging and environmental monitoring applications.

A highly branched macrocycle-based dual-channel sensor: Bodipy and pillar[5]arene combination for detection of Sn (II) &Hg (II) and bioimaging in living cells.

A highly branched pillar[5]arene-based sensor containing multiple BODIPY units has been designed and synthesized (B-P[5]arene). Systematical experiments on metal ion detection of B-P[5]arene in acetonitrile/water by emission and absorption spectra indicate that this macrocycle shows high sensitivity and selectivity to both Sn (II) and Hg(II) by dual-channels. Hg (II) ions quenched to the fluorescence intensity of B-P[5]arene, while Sn (II) caused a broader spectrum without any shifting in wavelength. The detection limits of B-P[5]arene for Hg (II) and Sn (II) were found to be 1.09 × 10-6 M and 3.18 × 10-7 M, respectively. For two complex interactions, the metal ion: ligand ratio was determined as 1:2. The complex interactions between the Hg (II)&Sn(II) metal ions and B-P[5]arene are generally stable in both basic and acidic media due to strong interaction.

A NIR fluorescent sensor based on thiazoline-isophorone with low cytotoxicity in living cells for Hg2+ detection through ICT associated hydrogen bonding effect.

Mercury (Hg) is a toxic pollutant and may cause serious health and environmental threats even at low concentrations. Thus, sensitive, efficient, and accurate techniques for the detection of Hg2+ ions in biological systems are in particular demand. In the current paper, a new, red emitting fluorescence probe (THI) based on electron deficient dicyanovinyl, electron-rich diethylamino, and receptor thiazoline toward Hg2+ has been developed. It has been determined that the recognition behavior of the probe toward Hg2+ is reversible with S2-. The probe not only shows perfect selectivity toward Hg2+ with a low detection limit over a series of metal ions, but it also displays positive solvato-chromism among the tested solvents via modulation of intramolecular energy transfer from the diethylamino to a dicyanovinyl moiety. Furthermore, it has been shown that the probe can be applied as a fluorescent probe for visualizing Hg2+ in living HeLa cells through a confocal laser scanning microscope. Also, the probe THI has not shown any toxic effect in cervical cancer and epithelial cells. Thus, the probe demonstrates high promise for Hg2+ detection in biomarker screening, disease diagnosis, and clinical medicine with low cytotoxicity.

Synthesis of calix[4]azacrown substituted sulphonamides with antioxidant, acetylcholinesterase, butyrylcholinesterase, tyrosinase and carbonic anhydrase inhibitory action.

A series of novel calix[4]azacrown substituted sulphonamide Schiff bases was synthesised by the reaction of calix[4]azacrown aldehydes with different substituted primary and secondary sulphonamides. The obtained novel compounds were investigated as inhibitors of six human (h) isoforms of carbonic anhydrases (CA, EC 4.2.1.1). Their antioxidant profile was assayed by various bioanalytical methods. The calix[4]azacrown substituted sulphonamide Schiff bases were also investigated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase enzymes, associated with several diseases such as Alzheimer, Parkinson, and pigmentation disorders. The new sulphonamides showed low to moderate inhibition against hCAs, AChE, BChE, and tyrosinase enzymes. However, some of them possessed relevant antioxidant activity, comparable with standard antioxidants used in the study.

Synthesis and evaluation of the antitumor activity of Calix[4]arene l-proline derivatives.

The unique conformational properties, functionality, low toxicity, and low cost make calixarene-based compounds a valuable candidate against cancer. The aim of the present study is the synthesis of the upper rim and lower rim-functionalized l-proline-based calix[4]arene derivatives and evaluation of their cytotoxic potential for human cancerous cells as well as to determine the death mechanism. Synthesized calix[4]arene (3, 8a, 8b 13a, and 13b) derivatives were characterized by different spectroscopic techniques such as 1HNMR, 13CNMR, and FTIR. In vitro effects of compounds 3, 8a, 8b, 13a and 13b were tested on human cancerous cells (HEPG2, PC-3, A-549, and DLD-1) as well as human healthy epithelium cell (PNT1A). Results show that compounds 3, 8a, 8b and 13b have cytotoxic potential on human colorectal carcinoma cells (DLD-1) with IC50 values of 43 µM, 45.2 µM, 64.57 µM, and 29.35 µM respectively. Apoptosis ratios of cell death were investigated with flow cytometer using 7-AAD and Annexin-V as markers. Cytotoxic potential of 8a was found to be higher due to increased apoptosis, when compared with healthy cells the apoptotic cell death was significantly (p < 0.0001) increased up to 1.7-fold and 2.4-fold in DLD-1 and A549 cells, respectively. In conclusion, these l-proline derived calix[4]arenes with their selective cytotoxic potential on human cancerous cells may be a potential candidate for the treatment of human CRC and lung cancer.

Formation of the inclusion complex of water soluble fluorescent calix[4]arene and naringenin: solubility, cytotoxic effect and molecular modeling studies.

Naringenin is considered as an important flavonoid in phytochemistry because of its important effect on cancer chemoprevention. Unfortunately its poor solubility has restricted its therapeutic applications. In this study, an efficient water-soluble fluorescent calix[4]arene (compound 5) was synthesized as host macromolecule to increase solubility and cytotoxicity in cancer cells of water-insoluble naringenin as well as to clarify localization of naringenin into the cells. Complex formed by host-guest interaction between compound 5 and naringenin was analyzed with UV-visible, fluorescence, FTIR spectroscopic techniques and molecular modeling studies. Stern-Volmer analysis showed binding constant value of Ksv 3.5 × 107 M-1 suggesting strong interaction between host and guest. Binding capacity shows 77% of naringenin was loaded on compound 5. Anticarcinogenic effects of naringenin complex were evaluated on human colorectal carcinoma cells (DLD-1) and it was found that 5-naringenin complex inhibits proliferation of DLD-1 cells 3.4-fold more compared to free naringenin. Fluorescence imaging studies show 5-naringenin complex was accumulated into the cytoplasm instead of the nucleus. Increased solubility and cytotoxicity of naringenin with fluorescent calix[4]arene makes it one of the potential candidates as a therapeutic enhancer. For deep understanding of host-guest interaction mechanisms, complementary multiscale molecular modeling studies were also carried out.Communicated by Ramaswamy H. Sarma.

Environmental temperatures shape thermal physiology as well as diversification and genome-wide substitution rates in lizards.

Climatic conditions changing over time and space shape the evolution of organisms at multiple levels, including temperate lizards in the family Lacertidae. Here we reconstruct a dated phylogenetic tree of 262 lacertid species based on a supermatrix relying on novel phylogenomic datasets and fossil calibrations. Diversification of lacertids was accompanied by an increasing disparity among occupied bioclimatic niches, especially in the last 10 Ma, during a period of progressive global cooling. Temperate species also underwent a genome-wide slowdown in molecular substitution rates compared to tropical and desert-adapted lacertids. Evaporative water loss and preferred temperature are correlated with bioclimatic parameters, indicating physiological adaptations to climate. Tropical, but also some populations of cool-adapted species experience maximum temperatures close to their preferred temperatures. We hypothesize these species-specific physiological preferences may constitute a handicap to prevail under rapid global warming, and contribute to explaining local lizard extinctions in cool and humid climates.

Inclusion of Quercetin in Gold Nanoparticles Decorated with Supramolecular Hosts Amplifies Its Tumor Targeting Properties.

Despite the anticancer potential of natural products (NPs), their limited bioavailability necessitates laborious derivatization or covalent conjugation to delivery vehicles. To unleash their potential, we developed a nanohybrid delivery platform with a noncovalently tunable surface. Initially, the active compound was encapsulated in a macrocycle, p-sulfonatocalix[4]arene, enabling a 62 000-fold aqueous solubility amplification as also a 2.9-fold enhancement in its cytotoxicity with respect to the parent compound in SW-620 colon cancer cells. A pH stimuli responsive behavior was recorded for this formulate, where a programmable release of quercetin from the macrocycle was monitored in an acidic environment. Then, a nanoparticle gold core was decorated with calixarene hosts to accommodate noncovalently NPs. The loaded nanocarrier with the NP quercetin dramatically enhanced the cytotoxicity (>50-fold) of the parent NP in colon cancer and altered its cell membrane transport mode. In vivo experiments in a mouse 4T1 tumor model showed a reduction of tumor volume in mice treated with quercetin-loaded nanoparticles without apparent toxic effects. Further analysis of the tumor-derived RNA highlighted that treatment with quercetin-loaded nanoparticles altered the expression of 27 genes related to apoptosis.

Dose Ginger Have Preventative Effects on PONV-Related Eye Surgery? A Clinical Trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is considered a common complication of anesthesia, which, particularly in eye surgery, may exert pressure on stitches and open or leak the surgical wound, leading to bleeding. OBJECTIVES: We aimed to study the effect of ginger on PONV and changes in vital signs after eye surgery. METHODS: In this triple-blind randomized controlled trial, 120 candidate patients for eye surgery were divided into group A (n = 40) and group B (n = 40). Patients in group A received the capsules of ginger 1 g while patients in group B received a placebo one hour before the procedure with 30 mL water. The incidence of nausea and the frequency of vomiting were evaluated at 0, 15, 30 minutes, and 2 hours after the operation. Also, the vital signs of the participants were recorded at certain times. RESULTS: The results demonstrated a statistically significant difference in the frequency of nausea between group A and group B (P < 0.05). The severity of nausea was lower in group A than in group B immediately and 2 hours after recovery (P < 0.05). The incidence of vomiting was significantly lower in group A than in group B (P < 0.05). The vital signs were not significantly different between group A and group B (P > 0.05). CONCLUSIONS: Ginger was effective in the prevention of PONV after eye surgery but had no impact on vital signs. Hence, ginger is proposed to use as a low-cost, prophylactic measure for PONV reduction.

Comparative Venomics of the Vipera ammodytes transcaucasiana and Vipera ammodytes montandoni from Turkey Provides Insights into Kinship.

The Nose-horned Viper (Vipera ammodytes) is one of the most widespread and venomous snakes in Europe, which causes high frequent snakebite accidents. The first comprehensive venom characterization of the regional endemic Transcaucasian Nose-horned Viper (Vipera ammodytes transcaucasiana) and the Transdanubian Sand Viper (Vipera ammodytes montandoni) is reported employing a combination of intact mass profiling and bottom-up proteomics. The bottom-up analysis of both subspecies identified the major snake protein families of viper venoms. Furthermore, intact mass profiling revealed the presence of two tripeptidic metalloprotease inhibitors and their precursors. While previous reports applied multivariate analysis techniques to clarify the taxonomic status of the subspecies, an accurate classification of Vipera ammodytestranscaucasiana is still part of the ongoing research. The comparative analysis of the viper venoms on the proteome level reveals a close relationship between the Vipera ammodytes subspecies, which could be considered to clarify the classification of the Transcaucasian Nose-horned Viper. However, the slightly different ratio of some venom components could be indicating interspecific variations of the two studied subspecies or intraspecies alternations based on small sample size. Additionally, we performed a bioactivity screening with the crude venoms against several human cancerous and non-cancerous cell lines, which showed interesting results against a human breast adenocarcinoma epithelial cell line. Several fractions of Vipera a. transcaucasiana demonstrated a strong cytotoxic effect on triple negative MDA MB 231 breast cancer cells.

A New Piperidine Derivatized-Schiff Base Based "Turn-on" Cu2+Chemo-Sensor.

In this study, we report the synthesis of new Schiff base E-1-(((1-benzylpiperidin-4-yl)imino)methyl)naphthalenee-2-ol (L) and evaluation of its fluorescence response toward Cu2+ ion. Preliminary, solvent effect, metal selectivity and metal ligand ratio were analyzed through UV-Visible study. Fluorescence response toward Cu2+ was carried to assess the fluorescent property of synthesized Schiff base. The probe exhibited a higher fluorescence enhancement in the presence of Cu2+ over other metal ions (Ni2+, Zn2+, Hg2+, Co2+, Cd2+, Al3+, Fe2+, and Pb2+). The binding stoichiometry between L and Cu2+ has been investigated using Job's plot and Benesi-Hildebrand equation and it was found that ligand L can form 1:1 L-Cu2+ complex with binding constant (K a) of 4 × 104 LM-1.