In Situ Ni(II) Complexation Induced Deprotonation of Bis-Thiourea-Based Tweezers in DMSO-Water Medium: An Approach toward Recognition of Fluoride Ions in Water with Organic Probe Molecules.

Recognition of fluoride in water through the fluoride-induced Brönsted acid-base deprotonation reaction of an organic probe molecule is still a challenging task owing to the lower basicity of fluoride ions and the instability of the conjugate base of the probe molecules in aqueous medium. Herein, we report a complementary strategy in which the conjugate base of the studied bis-thiourea molecule in dimethyl sulfoxide (DMSO) medium is simultaneously stabilized through chelation of the Ni(II) ion, which eventually facilitates the recognition of the fluoride ion in water samples. The recognition methodology is validated colorimetrically and electrochemically, and finally, the applicability of the approach is explored with water samples collected from fluoride-affected areas. The limit of detection value for the fluoride ion in water medium was found to be 0.2 and 0.3 ppm with UV-visible spectroscopy and differential pulse voltammetry measurements, respectively. The methodology is also demonstrated on a paper strip for the detection of the fluoride ion with the naked eye and a smartphone-based RGB sensor. The scheme has been shown to be effective in enhancing the aqueous fluoride recognition ability of the organic probe molecules with acidic hydrogen prone to deprotonation by the fluoride ion.

p-Thiocresol Functionalized Cesium Lead Bromide (PTC@CsPbBr3): A Fluorometric Sensing Probe for the Detection of Cholesterol.

Inorganic halide-based perovskites (e.g., cesium lead bromide) are tremendously useful semiconducting materials due to their unique optoelectronic properties. However, degradation of these perovskites under humid conditions is one of the major drawbacks to prevent their wide applications. Herein, passivated cesium lead bromide nanoparticles are synthesized using p-thiocresol as a passivating ligand, and this stable version of perovskite is later applied successfully as a sensor probe towards cholesterol detection. The designed sensor can detect cholesterol with a lower detection limit of 0.24 ppm and a fast response time of 10 s. The mechanism of quenching PTC@CsPbBr3 upon the gradual addition of cholesterol is discussed. Further, the sensor is successfully applied in the detection of cholesterol in real samples (blood serum). This work presents PTC@CsPbBr3 as a novel sensing platform for detecting cholesterol well in biomedical applications.

CsPbBr3 perovskites: A dual fluorescence sensor to distinguish ethanol from methanol.

In recent years, lead halide perovskites have emerged as a promising material with defect tolerance, thermally stable, and optoelectronic properties. However, the instability is the major factor which hinder their potential applications in various fields. This work demonstrates the chemical stability of Cesium Lead Bromide (CsPbBr3) under different passivation condition with an objective to develop alcohol sensor. Cetyltrimethyl ammonium bromide (CTAB) passivated CsPbBr3 demonstrated as a turn off fluorescent probe for alcohols and more significantly turn on fluorescent probe for ethanol. Herein, it is shown that CTAB passivated CsPbBr3 can effectively discriminate ethanol from methanol owing to its different mode of interaction with ethanol and methanol. The outstanding optical properties of halide perovskites with an ultra-low detection limit of 7.3 ppb was obtained for ethanol detection. The sensing performance of the material is also validated with petrol and cough syrup samples showing excellent performance for future implementation with practical applications.

Colorimetric detection of fluoride ions in aqueous medium using thiourea derivatives: a transition metal ion assisted approach.

This work explores the position of the hydroxyl moiety and its participation in intramolecular H-bonding towards dictating the fluoride selective colorimetric response in functionalized thiourea derivatives. The study reveals the pivotal aspect of the hydroxyl moiety in C2 towards attaining selectivity for fluoride over acetate and dihydrogenphosphate ion. Furthermore, a methodology employing stabilization of deprotonated thiourea through metal ion (Ni2+ and Cu2+) coordination is proposed for the colorimetric sensing of fluoride in water medium. The mechanism of interaction is thoroughly studied by UV-Vis, 1H NMR, ESR spectroscopy, electrochemical techniques and further validated by DFT calculations. This study reveals the formation of an in situ Ni2+ complex that shows greater stability in aqueous medium. The methodology is applied in the detection of fluoride in groundwater samples.

Revisiting the synthesis of aryl nitriles: a pivotal role of CAN.

Facilitated by the dual role of Ceric Ammonium Nitrate (CAN), herein we report a cost-effective approach for the cyanation of aryl iodides/bromides with CAN-DMF as an addition to the existing pool of combined cyanation sources. In addition to being an oxidant, CAN acts as a source of nitrogen in our protocol. The reaction is catalyzed by a readily available Cu(ii) salt and the ability of CAN to generate ammonia in the reaction medium is utilized to eliminate the additional requirement of a nitrogen source, ligand, additive or toxic reagents. The mechanistic study suggests an evolution of CN- leading to the synthesis of a variety of aryl nitriles in moderate to good yields. The proposed mechanism is supported by a series of control reactions and labeling experiments.

5,10-Diacylcalix[4]pyrroles: synthesis and anion binding studies.

5,10-Diacylcalix[4]pyrrole, a new positional isomer of the recently reported 5,15-diacylcalix[4]pyrrole, is synthesized as its two configurational isomers by acid catalysed condensation of meso-diacyltripyrrane with pyrrole. The solution phase anion binding of the two isomers of 5,10-diacylcalix[4]pyrrole was investigated by (1)H NMR spectroscopy in chloroform-d and isothermal titration calorimetry (ITC) in acetonitrile to gain insights into the positional and conformational effects of substituents on the macrocycle periphery towards anion binding. During the investigation, a functionalized, stable pyrrole-2-carbinol was isolated and subsequently converted to the corresponding tripyrrane in situ.

Calix[2]bispyrrolylarenes: new expanded calix[4]pyrroles for fluorometric sensing of anions via extended π-conjugation.

Two new expanded calix[4]pyrroles 3 and 4 were synthesized by '2 + 2' cyclocoupling of easily prepared diboryldipyrromethane 7 (by Ir-catalyzed CH-bond activation) with appropriate diiodoarenes using the Suzuki protocol. Owing to the unique design, both macrocycles exhibited extended π-conjugation and enhanced fluorescence. Upon complexation with anions (fluoride and acetate), receptor 3 displayed turn-on sensing of fluorescence, whereas 4 showed turn-off sensing.

Colorimetric sensing of fluoride ion by new expanded calix[4]pyrrole through anion-π interaction.

Three new expanded calix[4]pyrroles were synthesized, where the two dialkylldipyrromethane units are linked via C-C double bonds. One of them, calix[2]bispyrrolylethene, colorimetrically senses fluoride ion only, owing to anion-π interaction in polar aprotic solvents.

Meso-diacylated calix[4]pyrrole: structural diversities and enhanced binding towards dihydrogenphosphate ion.

Meso-diacylated calix[4]pyrrole was obtained via acid catalysed condensation of meso-acylated dipyrromethane with acetone. Selective presence of flexible substituents at the calix[4]pyrrole periphery led to interesting structural motifs in the solid state along with enhanced binding towards anions, especially dihydrogenphosphate ion via anchoring.

MUC1* is a determinant of trastuzumab (Herceptin) resistance in breast cancer cells.

In the United States, 211,000 women are diagnosed each year with breast cancer. Of the 42,000 breast cancer patients who overexpress the HER2 growth factor receptor, <35% are responsive to treatment with the HER2-disabling antibody, called trastuzumab (Herceptin). Despite those statistics, women diagnosed with breast cancer are now tested to determine how much of this important growth factor receptor is present in their tumor because patients whose treatment includes trastuzumab are three-times more likely to survive for at least 5 years and are two-times more likely to survive without a cancer recurrence. Unfortunately, even among the group whose cancers originally respond to trastuzumab, 25% of the metastatic breast cancer patients acquire resistance to trastuzumab within the first year of treatment. Follow-on "salvage" therapies have prolonged life for this group but have not been curative. Thus, it is critically important to understand the mechanisms of trastuzumab resistance and develop therapies that reverse or prevent it. Here, we report that molecular analysis of a cancer cell line that was induced to acquire trastuzumab resistance showed a dramatic increase in the amount of the cleaved form of the MUC1 protein, called MUC1*. We recently reported that MUC1* functions as a growth factor receptor on cancer cells and on embryonic stem cells. Here, we show that treating trastuzumab-resistant cancer cells with a combination of MUC1* antagonists and trastuzumab, reverses the drug resistance. Further, HER2-positive cancer cells that are intrinsically resistant to trastuzumab became trastuzumab-sensitive when treated with MUC1* antagonists and trastuzumab. Additionally, we found that tumor cells that had acquired Herceptin resistance had also acquired resistance to standard chemotherapy agents like Taxol, Doxorubicin, and Cyclophosphamide. Acquired resistance to these standard chemotherapy drugs was also reversed by combined treatment with the original drug plus a MUC1* inhibitor.

A minimal fragment of MUC1 mediates growth of cancer cells.

The MUC1 protein is aberrantly expressed on many solid tumor cancers. In contrast to its apical clustering on healthy epithelial cells, it is uniformly distributed over cancer cells. However, a mechanistic link between aberrant expression and cancer has remained elusive. Herein, we report that a membrane-bound MUC1 cleavage product, that we call MUC1*, is the predominant form of the protein on cultured cancer cells and on cancerous tissues. Further, we demonstrate that transfection of a minimal fragment of MUC1, MUC1*(1110), containing a mere forty-five (45) amino acids of the extracellular domain, is sufficient to confer the oncogenic activities that were previously attributed to the full-length protein. By comparison of molecular weight and function, it appears that MUC1* and MUC1*(1110) are approximately equivalent. Evidence is presented that strongly supports a mechanism whereby dimerization of the extracellular domain of MUC1* activates the MAP kinase signaling cascade and stimulates cell growth. These findings suggest methods to manipulate this growth mechanism for therapeutic interventions in cancer treatments.

Regulation of the TCRalpha repertoire by the survival window of CD4(+)CD8(+) thymocytes.

T cell receptor (TCR) alpha alleles undergo primary and secondary rearrangement in double-positive (DP) thymocytes. By analyzing TCRalpha rearrangement in orphan nuclear receptor RORgamma-deficient mice, in which the DP lifespan is shorter, and in Bcl-x(L)-transgenic mice, in which the DP lifespan is extended, we show that the progression of secondary V(alpha) to J(alpha) rearrangements is controlled by DP thymocyte survival. In addition, because Bcl-x(L) induces a bias towards 3' J(alpha) usage in peripheral T cells, we conclude that the programmed cell death of DP thymocytes is not simply a consequence of failed positive selection. Rather, it limits the progression of rearrangement along the J(alpha) locus and the opportunities for positive selection, thereby regulating the TCRalpha repertoire.