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Gopinatha Suresh Kumar - One of the best experts on this subject based on the ideXlab platform.

  • exploring the interaction of phenothiazinium dyes methylene Blue new methylene Blue <B>AzureB> a and <B>AzureB> B with trnaphe spectroscopic thermodynamic voltammetric and molecular modeling approach
    Physical Chemistry Chemical Physics, 2017
    Co-Authors: Puja Paul, Soumya Sundar Mati, Subhash Chandra Bhattacharya, Gopinatha Suresh Kumar
    Abstract:

    This study focuses on the understanding of the interaction of phenothiazinium dyes methylene Blue (MB), new methylene Blue (NMB), <B>AzureB> A (AZA) and <B>AzureB> B (AZB) with tRNAPhe with particular emphasis on deciphering the mode and energetics of the Binding. Strong intercalative Binding to tRNAPhe was oBserved for MB, NMB and AZB, Bound By a partial intercalative mode. AZA has shown groove Binding characteristics. From spectroscopic studies Binding affinity values of the order of 105 M−1 were deduced for these dyes; the trend varied as MB > NMB > AZB > AZA. The Binding was characterized By an increase of thermal melting temperatures and perturBation in the circular dichroism spectrum of tRNA. All the dyes acquired optical activity upon Binding to tRNA. The Binding was predominantly entropy driven with a favoraBle enthalpy term that increased with temperature in all the cases. Dissection of the GiBBs energy to polyelectrolytic and non-polyelectrolytic terms revealed a major role of the non-electrostatic forces in the Binding. The small But significant heat capacity changes and the oBserved enthalpy–entropy compensation phenomenon confirmed the involvement of multiple weak non-covalent forces driving the interaction. The mode of Binding was confirmed from quenching, viscosity and cyclic voltammetric results. Using density functional theory, ground state optimized structures of the dyes were calculated to provide insight into theoretical docking studies to correlate the experimental approaches. The modeling results verified the Binding location as well as the Binding energy of complexation. The results may provide new insights into the structure–activity relationship useful in the design of effective RNA targeted therapeutic agents.

  • spectroscopic studies on the Binding interaction of phenothiazinium dyes <B>AzureB> a and <B>AzureB> B to douBle stranded rna polynucleotides
    Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2016
    Co-Authors: Asma Yasmeen Khan, Gopinatha Suresh Kumar
    Abstract:

    ABstract This manuscript presents spectroscopic characterization of the interaction of two phenothiazinium dyes, <B>AzureB> A and <B>AzureB> B with douBle stranded (ds) riBonucleic acids, poly(A).poly(U), poly(C).poly(G) and poly(I).poly(C). ABsorBance and fluorescence studies revealed that these dyes Bind to the RNAs with Binding affinities of the order 10 6  M −1 to poly(A).poly(U), and 10 5  M −1 to poly(C).poly(G) and poly(I).poly(C), respectively. Fluorescence quenching and viscosity data gave conclusive evidence for the intercalation of the dyes to these RNA duplexes. Circular dichroism results suggested that the conformation of the RNAs was perturBed on interaction and the dyes acquired strong induced optical activity on Binding. <B>AzureB> B Bound to all the three RNAs stronger than <B>AzureB> A and the Binding affinity varied as poly(A).poly(U) > poly(C).poly(G) > poly(I).poly(C) for Both dyes.

  • a thermodynamic investigation on the Binding of phenothiazinium dyes <B>AzureB> a and <B>AzureB> B to douBle stranded rna polynucleotides
    The Journal of Chemical Thermodynamics, 2015
    Co-Authors: Asma Yasmeen Khan, Gopinatha Suresh Kumar
    Abstract:

    ABstract The thermodynamics of the reactions of the two phenothiazinium dyes <B>AzureB> A and <B>AzureB> B with the three douBle stranded riBonucleic acids, poly(A).poly(U), poly(C).poly(G), poly(I).poly(C) were investigated using DSC and ITC. The Bound dyes staBilized the RNAs against thermal strand separation. The Binding of <B>AzureB> A to the RNAs was predominantly enthalpy dominated while the Binding of <B>AzureB> B was favoured By Both negative enthalpy and favouraBle entropy changes. Although electrostatic interaction had a significant role in the Binding, non-polyelectrolytic forces dominated the Binding process. The negative values of heat capacity changes for the Binding suggested a suBstantial hydrophoBic contriBution to the Binding process. The overall Binding affinity of Both the dyes to the RNAs varied in the order, poly(A).poly(U) > poly(C).poly(G) > poly(I).poly(C).

  • photophysical and calorimetric investigation on the structural reorganization of poly a By phenothiazinium dyes <B>AzureB> a and <B>AzureB> B
    Photochemical and Photobiological Sciences, 2014
    Co-Authors: Puja Paul, Gopinatha Suresh Kumar
    Abstract:

    Poly(A) has significant relevance to mRNA staBility, protein synthesis and cancer Biology. The aBility of two phenothiazinium dyes <B>AzureB> A (AA) and <B>AzureB> B (AB) to Bind single-stranded poly(A) was studied By spectroscopic and calorimetric techniques. Strong Binding of the dyes and the higher affinity of AA over AB were ascertained from aBsorBance and fluorescence experiments. Significant perturBation of the circular dichroism spectrum of poly(A) in the presence of these molecules with formation of induced CD Bands in the 300–700 nm region was oBserved. Strong emission polarization of the Bound dyes and strong energy transfer from the adenine Base pairs of poly(A) suggested intercalative Binding to poly(A). Intercalative Binding was confirmed from fluorescence quenching experiments and was predominantly entropy driven as evidenced from isothermal titration calorimetry data. The negative values of heat capacity indicated involvement of hydrophoBic forces and enthalpy–entropy compensation suggested noncovalent interactions in the complexation for Both the dyes. Poly(A) formed a self-assemBled structure on the Binding of Both the dyes that was more favored under higher salt conditions. New insights in terms of spectroscopic and thermodynamic aspects into the self-structure formation of poly(A) By two new phenothiazinium dyes that may lead to structural and functional damage of mRNA are revealed from these studies.

  • thermodynamics of the dna Binding of phenothiazinium dyes toluidine Blue o <B>AzureB> a and <B>AzureB> B
    The Journal of Chemical Thermodynamics, 2013
    Co-Authors: Puja Paul, Gopinatha Suresh Kumar
    Abstract:

    ABstract The DNA Binding of toluidine Blue O (TBO), <B>AzureB> A and <B>AzureB> B was characterised By isothermal titration calorimetry, differential scanning calorimetry and thermal melting studies. The DNA Binding affinity of TBO was the highest followed By <B>AzureB> A and <B>AzureB> B. The Binding in each case was exothermic with a positive entropy change. The affinity of the Binding decreased as the [Na + ] concentration increased. The non electrostatic contriBution to the standard GiBBs energy remained the same over the range of (10 to 100) mM [Na + ]. The negative change in heat capacity of the Binding revealed a suBstantial hydrophoBic contriBution in the DNA Binding of these dyes. An enthalpy–entropy compensation was oBserved in each system. The Binding of these dyes staBilised the DNA against thermal strand separation. The energetics of the DNA Binding of these dyes correlate well with the structural data that suggest their utility as potential DNA targeting agents.

Puja Paul - One of the best experts on this subject based on the ideXlab platform.

  • exploring the interaction of phenothiazinium dyes methylene Blue new methylene Blue <B>AzureB> a and <B>AzureB> B with trnaphe spectroscopic thermodynamic voltammetric and molecular modeling approach
    Physical Chemistry Chemical Physics, 2017
    Co-Authors: Puja Paul, Soumya Sundar Mati, Subhash Chandra Bhattacharya, Gopinatha Suresh Kumar
    Abstract:

    This study focuses on the understanding of the interaction of phenothiazinium dyes methylene Blue (MB), new methylene Blue (NMB), <B>AzureB> A (AZA) and <B>AzureB> B (AZB) with tRNAPhe with particular emphasis on deciphering the mode and energetics of the Binding. Strong intercalative Binding to tRNAPhe was oBserved for MB, NMB and AZB, Bound By a partial intercalative mode. AZA has shown groove Binding characteristics. From spectroscopic studies Binding affinity values of the order of 105 M−1 were deduced for these dyes; the trend varied as MB > NMB > AZB > AZA. The Binding was characterized By an increase of thermal melting temperatures and perturBation in the circular dichroism spectrum of tRNA. All the dyes acquired optical activity upon Binding to tRNA. The Binding was predominantly entropy driven with a favoraBle enthalpy term that increased with temperature in all the cases. Dissection of the GiBBs energy to polyelectrolytic and non-polyelectrolytic terms revealed a major role of the non-electrostatic forces in the Binding. The small But significant heat capacity changes and the oBserved enthalpy–entropy compensation phenomenon confirmed the involvement of multiple weak non-covalent forces driving the interaction. The mode of Binding was confirmed from quenching, viscosity and cyclic voltammetric results. Using density functional theory, ground state optimized structures of the dyes were calculated to provide insight into theoretical docking studies to correlate the experimental approaches. The modeling results verified the Binding location as well as the Binding energy of complexation. The results may provide new insights into the structure–activity relationship useful in the design of effective RNA targeted therapeutic agents.

  • photophysical and calorimetric investigation on the structural reorganization of poly a By phenothiazinium dyes <B>AzureB> a and <B>AzureB> B
    Photochemical and Photobiological Sciences, 2014
    Co-Authors: Puja Paul, Gopinatha Suresh Kumar
    Abstract:

    Poly(A) has significant relevance to mRNA staBility, protein synthesis and cancer Biology. The aBility of two phenothiazinium dyes <B>AzureB> A (AA) and <B>AzureB> B (AB) to Bind single-stranded poly(A) was studied By spectroscopic and calorimetric techniques. Strong Binding of the dyes and the higher affinity of AA over AB were ascertained from aBsorBance and fluorescence experiments. Significant perturBation of the circular dichroism spectrum of poly(A) in the presence of these molecules with formation of induced CD Bands in the 300–700 nm region was oBserved. Strong emission polarization of the Bound dyes and strong energy transfer from the adenine Base pairs of poly(A) suggested intercalative Binding to poly(A). Intercalative Binding was confirmed from fluorescence quenching experiments and was predominantly entropy driven as evidenced from isothermal titration calorimetry data. The negative values of heat capacity indicated involvement of hydrophoBic forces and enthalpy–entropy compensation suggested noncovalent interactions in the complexation for Both the dyes. Poly(A) formed a self-assemBled structure on the Binding of Both the dyes that was more favored under higher salt conditions. New insights in terms of spectroscopic and thermodynamic aspects into the self-structure formation of poly(A) By two new phenothiazinium dyes that may lead to structural and functional damage of mRNA are revealed from these studies.

  • thermodynamics of the dna Binding of phenothiazinium dyes toluidine Blue o <B>AzureB> a and <B>AzureB> B
    The Journal of Chemical Thermodynamics, 2013
    Co-Authors: Puja Paul, Gopinatha Suresh Kumar
    Abstract:

    ABstract The DNA Binding of toluidine Blue O (TBO), <B>AzureB> A and <B>AzureB> B was characterised By isothermal titration calorimetry, differential scanning calorimetry and thermal melting studies. The DNA Binding affinity of TBO was the highest followed By <B>AzureB> A and <B>AzureB> B. The Binding in each case was exothermic with a positive entropy change. The affinity of the Binding decreased as the [Na + ] concentration increased. The non electrostatic contriBution to the standard GiBBs energy remained the same over the range of (10 to 100) mM [Na + ]. The negative change in heat capacity of the Binding revealed a suBstantial hydrophoBic contriBution in the DNA Binding of these dyes. An enthalpy–entropy compensation was oBserved in each system. The Binding of these dyes staBilised the DNA against thermal strand separation. The energetics of the DNA Binding of these dyes correlate well with the structural data that suggest their utility as potential DNA targeting agents.

  • spectroscopic studies on the Binding interaction of phenothiazinium dyes toluidine Blue o <B>AzureB> a and <B>AzureB> B to dna
    Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2013
    Co-Authors: Puja Paul, Gopinatha Suresh Kumar
    Abstract:

    In this study a detailed characterization of the Binding aspects of three phenothiazinium dyes, toluidine Blue O (TBO), <B>AzureB> A and <B>AzureB> B with herring testes DNA is presented employing spectroscopic techniques. The aBsorBance and fluorescence properties of these dyes have Been remarkaBly modified upon Binding with DNA and the interaction is manifested through noncooperative Binding as revealed form non-linear Scatchard plots with negative slopes at all Binding ratios. The Binding clearly revealed the high preference of TBO to DNA followed By the other two dyes <B>AzureB> A and <B>AzureB> B. The affinity of TBO was higher By aBout two times than that of the <B>AzureB>s. From the series of studies using aBsorption, steady-state emission, the effect of ferrocyanide ion-induced steady-state fluorescence quenching, fluorescence polarization anisotropy, circular dichroism, the mode of Binding of these dyes to the DNA douBle helix has Been suBstantiated to Be principally intercalative in nature. The stoichiometry of the association of these dyes to DNA was determined By the continuous variation analysis of JoB from fluorescence data. The conformational aspects of the interaction was delineated from circular dichroism studies wherein higher perturBation was oBserved with TBO. Hydrodynamic study using viscosity measurements of linear rod like DNA confirmed that the Binding was intercalative and strongest for TBO and weaker for <B>AzureB> A and <B>AzureB> B. The utility of the present work lies in exploring the potential Binding applicaBility of these dyes to DNA for their development as effective therapeutic agents.

Asma Yasmeen Khan - One of the best experts on this subject based on the ideXlab platform.

  • spectroscopic studies on the Binding interaction of phenothiazinium dyes <B>AzureB> a and <B>AzureB> B to douBle stranded rna polynucleotides
    Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2016
    Co-Authors: Asma Yasmeen Khan, Gopinatha Suresh Kumar
    Abstract:

    ABstract This manuscript presents spectroscopic characterization of the interaction of two phenothiazinium dyes, <B>AzureB> A and <B>AzureB> B with douBle stranded (ds) riBonucleic acids, poly(A).poly(U), poly(C).poly(G) and poly(I).poly(C). ABsorBance and fluorescence studies revealed that these dyes Bind to the RNAs with Binding affinities of the order 10 6  M −1 to poly(A).poly(U), and 10 5  M −1 to poly(C).poly(G) and poly(I).poly(C), respectively. Fluorescence quenching and viscosity data gave conclusive evidence for the intercalation of the dyes to these RNA duplexes. Circular dichroism results suggested that the conformation of the RNAs was perturBed on interaction and the dyes acquired strong induced optical activity on Binding. <B>AzureB> B Bound to all the three RNAs stronger than <B>AzureB> A and the Binding affinity varied as poly(A).poly(U) > poly(C).poly(G) > poly(I).poly(C) for Both dyes.

  • a thermodynamic investigation on the Binding of phenothiazinium dyes <B>AzureB> a and <B>AzureB> B to douBle stranded rna polynucleotides
    The Journal of Chemical Thermodynamics, 2015
    Co-Authors: Asma Yasmeen Khan, Gopinatha Suresh Kumar
    Abstract:

    ABstract The thermodynamics of the reactions of the two phenothiazinium dyes <B>AzureB> A and <B>AzureB> B with the three douBle stranded riBonucleic acids, poly(A).poly(U), poly(C).poly(G), poly(I).poly(C) were investigated using DSC and ITC. The Bound dyes staBilized the RNAs against thermal strand separation. The Binding of <B>AzureB> A to the RNAs was predominantly enthalpy dominated while the Binding of <B>AzureB> B was favoured By Both negative enthalpy and favouraBle entropy changes. Although electrostatic interaction had a significant role in the Binding, non-polyelectrolytic forces dominated the Binding process. The negative values of heat capacity changes for the Binding suggested a suBstantial hydrophoBic contriBution to the Binding process. The overall Binding affinity of Both the dyes to the RNAs varied in the order, poly(A).poly(U) > poly(C).poly(G) > poly(I).poly(C).

Gennady Evtugyn - One of the best experts on this subject based on the ideXlab platform.

  • electrochemical dna sensor Based on the copolymer of proflavine and <B>AzureB> B for doxoruBicin determination
    Nanomaterials, 2020
    Co-Authors: Anna Porfireva, Gennady Evtugyn
    Abstract:

    A DNA sensor has Been developed for the determination of doxoruBicin By consecutive electropolymerization of an equimolar mixture of <B>AzureB> B and proflavine and adsorption of native DNA from salmon sperm on a polymer film. Electrochemical investigation showed a difference in the Behavior of individual drugs polymerized and their mixture. The use of the copolymer offered some advantages, i.e., a higher roughness of the surface, a wider range of the pH sensitivity of the response, a denser and more roBust film, etc. The formation of the polymer film and its redox properties were studied using scanning electron microscopy and electrochemical impedance spectroscopy. For the doxoruBicin determination, its solution was mixed with DNA and applied on the polymer surface. After that, charge transfer resistance was assessed in the presence of [Fe(CN)6]3-/4- as the redox proBe. Its value regularly grew with the doxoruBicin concentration in the range from 0.03 to 10 nM (limit of detection 0.01 nM). The DNA sensor was tested on the doxoruBicin preparations and spiked samples mimicking Blood serum. The recovery was found to Be 98-106%. The DNA sensor developed can find application for the determination of drug residues in Blood and for the pharmacokinetics studies.

  • electrochemical sensor Based on poly <B>AzureB> B dna composite for doxoruBicin determination
    Sensors, 2019
    Co-Authors: Anna Porfireva, Vyatseslav Vorobev, Sofya Babkina, Gennady Evtugyn
    Abstract:

    A new voltammetric DNA sensor has Been developed for doxoruBicin determination on the platform of a glassy carBon electrode (GCE) covered with electropolymerized <B>AzureB> B film and physically adsorBed native DNA. The redox properties of polymeric <B>AzureB> B were monitored at various pH and scan rates. DNA application decreased the peak currents related to polymeric and monomeric forms of the dye, whereas incuBation in doxoruBicin solution partially restored the peaks in accordance with the drug and DNA concentration. The relative shift of the cathodic peak current caused By doxoruBicin depended on the nominal DNA concentration and its application mode. In optimal conditions, the DNA sensor makes it possiBle to determine Between 0.1 μM to 0.1 nM doxoruBicin (limit of detection 7 × 10−11 M). The DNA sensor was tested on commercial doxoruBicin formulations and on artificial samples the mimicked electrolyte content of human serum.

Rakshit Ameta - One of the best experts on this subject based on the ideXlab platform.

  • A Facile Synthesis of GO/CuO Nanocomposite with Enhancing Photocatalytic Activity for the Degradation of <B>AzureB>-B Dye and Its AntimicroBial Behavior
    Arabian Journal for Science and Engineering, 2021
    Co-Authors: Rukhsar Banu, Rakshit Ameta, Nutan Salvi, Sharoni Gupta, Chetna Ameta, P B Punjabi
    Abstract:

    Graphene oxide (GO) and GO/CuO nanocomposites were synthesized By modified Hummer’s and hydrothermal methods, respectively, and characterized using standard techniques such as TEM, TGA-DTA, UV–Vis DRS, EDS and mapping, FESEM, FTIR, Raman, XRD, BET surface area and PL spectra. The photocatalytic degradation of <B>AzureB>-B dye was carried to evaluate the photocatalytic efficiency of GO/CuO nanocomposite. The superior catalytic activity of the GO/CuO nanocomposite was attriButed to the synergism that existed Between GO and CuO nanoparticles such as high surface area and small size of GO/CuO NPs. The recycling results demonstrated that the GO/CuO nanocomposite exhiBited good staBility and long-term duraBility. In addition, antiBacterial studies of the GO and GO/CuO nanocomposite were investigated against Gram-positive and Gram-negative Bacterial strains. These were also assayed for their antifungal activity against fungal strains Penicillium spp. and A. flavus . The newly synthesized GO/CuO nanocomposite was reported to show excellent antiBacterial activity as compared to GO.

  • photocatalytic degradation of <B>AzureB> B under visiBle light irradiation By reduced graphene oxide nis composite
    Macedonian Journal of Chemistry and Chemical Engineering, 2019
    Co-Authors: Ruchi Chaudhary, Suresh C Ameta, Rakshit Ameta
    Abstract:

    A composite of reduced graphene oxide (RGO) and nickel sulfide (NiS) was prepared via mechanochemical method and further characterized By X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and energy dispersive analysis of X-rays (EDAX). NiS was prepared via precipitation method, and RGO was prepared via reduction of graphene oxide. The photocatalytic performances of as prepared RGO/NiS composite, RGO and NiS were evaluated using <B>AzureB> B model system. The composite exhiBited good photocatalytic activity as compared to NiS as well as RGO. The optimum conditions oBtained for the photocatalytic degradation of <B>AzureB> B were the following: pH = 8.0, [<B>AzureB> B] = 2.0 × 10 –5 M, amount of composite = 0.10 g, and light intensity = 50.0 mW·cm –2 . The rate of degradation of <B>AzureB> B with the composite was found to Be 1.79 × 10 –4 s –1 .

  • photo oxidative degradation of <B>AzureB> B By sono photo fenton and photo fenton reagents
    Arabian Journal of Chemistry, 2014
    Co-Authors: Prahlad Vaishnave, P B Punjabi, Rakshit Ameta, Anil Kumar, Suresh C Ameta
    Abstract:

    ABstract A model for the decomposition of <B>AzureB>-B By photo-Fenton reagent in the presence of ultrasound in homogeneous aqueous solution has Been descriBed. The photochemical decomposition rate of <B>AzureB>-B is markedly increased in the presence of ultrasound. It is a rather inexpensive reagent for wastewater treatment. The effect of different variaBles like the concentration of ferric ion, concentration of dye, hydrogen peroxide, pH, light intensity etc. on the reaction rate has Been oBserved. The progress of the sono-photochemical degradation was monitored spectrophotometrically. The optimum sono-photochemical degradation conditions were experimentally determined. The results showed that the dye was completely oxidized and degraded into CO 2 and H 2 O. A suitaBle tentative mechanism for sono-photochemical Bleaching of <B>AzureB>-B By sono-photo-Fenton’s reaction has Been proposed.

  • role of copper pyrovanadate as heterogeneous photo fenton like catalyst for the degradation of neutral red and <B>AzureB> B an eco friendly approach
    Korean Journal of Chemical Engineering, 2014
    Co-Authors: Sangeeta Kalal, Narendra Pal Singh Chauhan, Rakshit Ameta, Noopur Ameta, Sudhish Kumar, P B Punjabi
    Abstract:

    The heterogeneous photo-Fenton like process is a green chemical pathway. It has an edge over conventional Fenton and photo-Fenton processes as it does not require the removal of ferrous/ferric ions in the form of sludge. We prepeared copper pyrovanadate or VolBorthite (Cu3V2(OH)2O7∙2H2O) composite photocatalyst By wet chemical method. The photocatalyst was characterized By SEM, XRD, IR, TGA/DSC, EDX and BET. Experiments demonstrated that catalyst could effectively catalyze degradation of neutral red and <B>AzureB>-B in presence of H2O2 in visiBle light. Moreover, the photo-Fenton-like catalytic activity of Cu3V2(OH)2O7∙2H2O was much higher than CuO and V2O5, when used alone as photocatalyst. The effect of variation of different parameters, i.e., pH, amount of photocatalyst, concentration of dye, amount of H2O2 and light intensity was also investigated. The degradation was well fitted under pseudo-first-order reaction with a rate constant of 2.081×10−4 sec−1 and 3.876×10−4 sec−1 for neutral red and <B>AzureB>-B, respectively. Quality parameters of dye solutions Before and after photo-Fenton degradation were also determined. A tentative mechanism involving •OH radical as an oxidant has Been proposed. The high catalytic activity may Be due to the Cu3V2(OH)2O7∙2H2O shell, which not only increased the surface hydroxyl groups, But also enhanced the interfacial electron transfer. The catalyst has Been found to possess good recyclaBility.

  • use of advanced oxidation technology for removal of <B>AzureB> B
    Acta Chimica and Pharmaceutica Indica, 2013
    Co-Authors: Rakshit Ameta, Daksha Sharma, Mamta Ordia
    Abstract:

    Many of the researchers have used different methods for degradation of organic pollutants from effluents of various industries. Out of which, photocatalysis; a part of advanced oxidation technology is considered as a promising technology for waste water treatment. <B>AzureB> B dye has Been degraded using Well-dowson polyoxometalate, as a photocatalyst. Various rate affecting parameters have Been studied. The degradation rate monitored spectrophotometrically, On the Basis of oBserved data, a tentative mechanism has Been proposed. The kinetic study of this system shows that this reaction follows pseudo-first order kinetics.