Chitrangada Das Mukhopadhyay

Cd2+ Triggered the FRET “ON”: A New Molecular Switch for the Ratiometric Detection of Cd2+ with Live-Cell Imaging and Bound X-ray Structure

On the basis of the Förster resonance energy transfer mechanism between rhodamine and quinoline-benzothiazole conjugated dyad, a new colorimetric as well as fluorescence ratiometric probe was synthesized for the selective detection of Cd(2+). The complex formation of the probe with Cd(2+) was confirmed through Cd(2+)-bound single-crystal structure. Capability of the probe as imaging agent to detect the cellular uptake of Cd(2+) was demonstrated here using living RAW cells.

Unique Fluorogenic Ratiometric Fluorescent Chemodosimeter for Rapid Sensing of CN− in Water

A new benzimidazole-spiropyran conjugate chemosensor molecule (BISP) has been synthesized and characterized by (1)H NMR spectroscopy, mass spectrometry (ESI-MS), and elemental analysis. The two isomeric forms (BISP↔BIMC) were shown to be highly selective and sensitive to CN(-) among the ten anions studied in aqueous HEPES buffer, as shown by fluorescence and absorption spectroscopy and even by visual color changes, with a detection limit of 1.7 μM for BIMC. The reaction of CN(-) with BIMC was monitored by (1)H NMR spectroscopy, high-resolution mass spectrometry (HRMS), UV/Vis measurements, and fluorescence spectroscopy in HEPES buffer of pH 7.4. TDDFT calculations were performed in order to correlate the electronic properties of the chemosensor with its cyanide complex. Further, titration against thiophilic metal ions like Au(3+), Cu(2+), Ag(+), and Hg(2+) with [BIMC-CN] in situ showed that it acts as a secondary recognition ensemble toward Au(3+) and Cu(2+) by switch-on fluorescence. In addition, a reversible logic-gate property of BIMC has been demonstrated through a feedback loop in the presence of CN(-) and Au(3+) ions, respectively. Furthermore, the use of BIMC to detect CN(-) in live cells by fluorescence imaging has also been demonstrated. Notably, test strips based on BIMC were fabricated, which could serve as convenient and efficient CN(-) test kits.

A new ICT and CHEF based visible light excitable fluorescent probe easily detects in vivo Zn2

A new chelator and ICT donor based visible light excitable Zn2+ sensor was designed and developed by integrating quinoline and 2-hydroxy-3-(hydroxymethyl)-5-methylbenzaldehyde. The probe is sensitive towards Zn2+ in absorbance as well as in fluorescence experiments in 90% aqueous medium. The sensor demonstrates Zn2+-specific emission enhancement due to the ICT and CHEF process with the LOD in the range of 10−8 M. The fluorescence quantum yield of the chemosensor is only 0.02, and it increases almost 11-fold (0.22) after complexation with Zn2+. Interestingly, the introduction of other metal ions causes the fluorescence intensity to remain almost unchanged. Moreover, the ability of the probe (BQ) to sense Zn2+ in living cells has been explored.

A remarkable ratiometric fluorescent chemodosimeter for very rapid detection of hydrogen sulfide in the vapour phase and living cells

A ratiometric fluorescent and colorimetric probe for hydrogen sulfide has been developed by combining benzothiazole and the cyanine moiety. Due to its fast response and a large Stokes shift, it was used for sensitive and selective detection of hydrogen sulfide. Moreover, this probe detects SH− both in solid and vapor phases. Its potential for biological applications was confirmed by employing it for fluorescence imaging of SH− in living cells.

Imino–phenolic–azodye appended rhodamine as a primary fluorescence “off–on” chemosensor for tin (Sn 4+) in solution and in RAW cells and the recognition of sulphide by [AR–Sn]

A new azo-rhodamine based species, AR was developed to act as an ‘off–on’ reversible luminescent probe for Sn4+ detection. The chemosensing behavior of the AR has been demonstrated through fluorescence, absorption, visual fluorescence color changes, ESI MS and 1H NMR titrations. This chemosensor AR shows a significant visible color change and displays a remarkable luminescent switch on (>2300 fold) in the presence of Sn4+ ions. The chemosensor can be used as a ‘naked eye’ sensor. The roles of the fluorophore–photochrome (azodye) dyad platform as well as the iminophenolic binding core in ARs selective recognition of tin have been demonstrated by studying appropriate control molecules. Importantly, AR can selectively recognize Sn4+ in organo-aqueous media in the presence of other cations. The biological applications of AR were evaluated in RAW cells and it was found to exhibit low cytotoxicity and good membrane permeability for the detection of Sn4+. The development of practically viable colorimetric test strips of the chemosensor AR to detect Sn4+ was also reported. It has been possible to build an INHIBIT logic gate for two binary inputs viz., Sn4+ and S2− by monitoring the fluorescence emission band at 582 nm as output.

Catecholase activity, DNA binding and cytotoxicity studies of a Cu(II) complex of a pyridoxal schiff base: synthesis, X-ray crystal structure, spectroscopic, electrochemical and theoretical studies

A binuclear Cu(II) complex of formula [Cu(L1Hpy)Cl]2(ClO4)2 (1), where L1H2 is a new tridentate ligand, formed by condensation of 2-aminomethyl pyridine and pyridoxal (one of the forms of vitamin B6), has been synthesized. X-ray crystal structure determination shows that in this complex two Cu(II) ions are interconnected by complementary hydroxymethyl bridges of the two pyridoxal moieties, which is a very rare example in the literature. However, with a Cu⋯Cu separation of 6.574(1) A and Cu–O(H)CH2– distance of 2.289 A, the bridge is very weak, and DFT calculations, as well as ESI-MS data and solution spectral studies indicate that in a MeOH solution the complex exists predominantly as a mixture of monomers [Cu(L1Hpy)Cl]+ and [Cu(L1Hpy)(MeOH)]2+ with the former being the predominant form. The DFT calculations as well as EPR spectra suggest that the SOMO is a metal dx2−y2 orbital. The complex shows highly efficient catecholase activity with kcat = 3·46 × 105 h−1 and kcat/KM = 1.00 × 108 M−1 h−1, which are the best values reported in the literature, so far, for catecholase mimicking model complexes. DFT calculations show that the reduction of the Cu(II)/Cu(I) by the coordinated catechol and the resultant structural changes is the rate determining step in the catalytic cycle. The complex also binds DNA quite strongly with a binding constant of ∼105 M−1. DFT calculations suggest that the most probable binding mode of the complex is intercalation of the pyridine ring of the complex between two adenine or adenine and cytosine base pairs. The complex shows low cytotoxicity towards HCT and HeLa cells, though cytotoxicity towards the latter cell line is much more than the former. It was also found that the complex can be used as a fluorescence probe for imaging HCT cells.

Gene selection for designing optimal fuzzy rule base classifier by estimating missing value

Display Omitted Proposed estimating missing value method is improving classifier better training which increased classifier performance.Exploits structural information by selecting highly differentially expressed gene set.Enhance knowledge discovery and model interpretation.Optimum fuzzy rules used to classify disease and normal. DNA microarray technology, a high throughput technology evaluates the expression of thousands of genes simultaneously under different experimental conditions. Analysis of the gene expression data reveals that not all but few important genes are responsible for the diseases. However, the DNA microarray data set usually contain multiple missing value and therefore, selection of important genes using the incomplete data set may be erroneous, resulting misclassification in disease prediction. In the paper we propose an integrated framework, which first imputes the missing value and then in order to achieve maximum accuracy in classifying the patients a classifier has been designed to select the genes using the complete microarray data set.Here functionally similar genes are employed to estimate the missing value unlike the existing gene expression value based distance similarity measure. However, the functionally similar genes may differ in their protein production capacity and so the degree of similarity between the genes varies from gene to gene. The problem has been dealt by proposing a novel method to impute the missing value using the concept of fuzzy similarity. After imputing the missing value, the continuous gene expression matrix is discretized using fuzzy sets to distinguish the activation levels of different genes. The proposed fuzzy importance factor (FIf) of each gene represents its activation level or protein production capacity both in the disease and normal class. The importance of each gene is evaluated while optimizing the number of rules in the fuzzy classifier depending on the FIf. The methodology we propose has been demonstrated using nine different cancer data sets and compared with the state of the art methods. Analysis of experimental results reveals that the proposed framework able to classify the diseased and normal patients with improved accuracy.

Dimension Reduction of Gene Expression Data for Designing Optimized Rule Base Classifier

The paper highlights the need of dimension reduction of voluminous gene expression microarray data for developing a robust classifier to predict patients with cancerous genes. The proposed algorithm builds a fuzzy rule based classifier with optimized rule set without much sacrificing classification accuracy. The gene expression matrix is first discretized using linguistic values. The importance factor of each gene is then evaluated representing the degree of presence of a unique linguistic value of the gene both in disease and nondisease classes. Initial fuzzy rule base consists higher ranking genes and gradually other genes are included in the rule base in order to achieve maximum classification accuracy. Thus optimum rule set is built with important genes for classification of test data set. The methodology proposed here has been successfully demonstrated for the lung cancer classification problem, which includes 97 smokers with lung cancer and 90 without lung cancer gene expression data. The results are promising even though maximum number of genes are removed from the original data.

Functional amyloids: interrelationship with other amyloids and therapeutic assessment to treat neurodegenerative diseases

ABSTRACTMisfolded β-sheet structures of proteins leading to neurodegenerative diseases like Alzheimers disease (AD) and Parkinsons disease (PD) are in the spotlight since long. However, not much ...ABSTRACT Misfolded β-sheet structures of proteins leading to neurodegenerative diseases like Alzheimers disease (AD) and Parkinsons disease (PD) are in the spotlight since long. However, not much was known about the functional amyloids till the last decade. Researchers have become increasingly more concerned with the degree of involvement of these functional amyloids in human physiology. Interestingly, it has been found that the human body is exposed to a tremendous systemic amyloid burden, especially, during aging. Although many findings regarding these functional amyloids come up every day, some questions still remain unanswered like do these functional amyloids directly involve in the fibrillization of amyloid beta (Aβ) 42 peptide or enhance the Aβ42 aggregation rate; whether functional bacterial amyloids (FuBA) co-localize with the senile plaques of AD or not. A detailed review of the latest status regarding the interrelationship between functional amyloids, pathogenic amyloids and misfolded prions and therapeutic assessment of functional amyloids for the treatment of neurodegenerative diseases can help identify an alternative medication for neurodegeneration. A unique mathematical model is proposed here for alteration of Aβ42 aggregation kinetics in AD to carve out the future direction of therapeutic consideration.

Role of Curcumin in Treatment of Alzheimer Disease

A lot of research findings support that curcumin (diferuloyl methane) has antioxidant, anti-inflammatory and antitumor activity. In India, curcumin has a widespread use as food additive and herbal medicine for human diseases without any side effect. Though curcumin is well established as an anticancer agent but there are a few reports about its promising role against amyloid diseases. According to recent finding curcumin play a crucial inhibitory role in pathophysiology of Alzheimer’s disease (AD). Oral administration of curcumin or its metabolites has shown the inhibition of Aβ deposition, Aβ oligomerization and tau phosphorylation in the brain of AD animal model including behavioural improvement. But still it is unknown whether the curcumin is directly involved in those processes or enhance those mechanisms. Thus in this review we want to focus on overall mechanism of curcumin in AD. Some strategies to overcome the problem of low absorption and fast clearance of curcumin nanoparticles have also been proposed.