Exploring the interaction of phenothiazinium dyes methylene blue, new methylene blue,azure A and azure B with tRNA Phe: spectroscopic, thermodynamic, voltammetric and molecular modeling approach

Paul, Puja and Mati, Soumya Sundar and Bhattacharya, Subhash Chandra and Kumar, Gopinatha Suresh (2017) Exploring the interaction of phenothiazinium dyes methylene blue, new methylene blue,azure A and azure B with tRNA Phe: spectroscopic, thermodynamic, voltammetric and molecular modeling approach. PHYSICAL CHEMISTRY CHEMICAL PHYSICs, 19 (9). pp. 6636-6653.

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    Abstract

    This study focuses on the understanding of the interaction of phenothiazinium dyes methylene blue (MB), new methylene blue (NMB), azure A (AZA) and azure 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 4 NMB 4 AZB 4 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 nonelectrostatic forces in the binding. The small but significant heat capacity changes and the observed enthalpy–entropy compensation phenomenon confirmed the involvement of multiple weak noncovalent 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.

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/2641
    Subjects: Chemistry
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 12 May 2017 12:39
    Last Modified: 12 May 2017 12:39
    Official URL: http://dx.doi.org/10.1039/c6cp07888e
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