Debarati Ray

Binding Interaction and Rotational-Relaxation Dynamics of a Cancer Cell Photosensitizer with Various Micellar Assemblies

The present work demonstrates the photophysical characterization of the interaction of a promising cancer cell photosensitizer, harmane (HM), with biomimetic micellar nanocavities having varying surface charge characteristics. The polarity-sensitive prototropic transformation of HM is remarkably modified upon interaction with the macromolecular assemblies of micellar systems and is manifested through significant modulations on the absorption and emission profiles of HM. The ground- and excited-states prototropic equilibria of HM are found to be differentially modulated in various micellar assemblies. Out of various possibilities to assess the drug (HM)-micelle interaction mechanism, the postulate of varying extent of drug penetration into micellar units depending on the compactness of their headgroup arrangements is found to suitably rationalize and correlate different experimental findings, including the differences in binding constant (K) and free energy change (ΔG) of the interaction process. The micropolarity measurement has been exploited to evaluate the probable binding location of the drug which reveals that the cationic drug molecule does not penetrate deep into the micellar core region and the results are further substantiated from fluorescence quenching experiments. The work also pays proper attention to delineate the modulation in dynamical behaviors of the drug following interaction with the micellar systems. Wavelength-sensitive fluorescence parameters reveal the slower rate of solvent-relaxation around the excited probe within the micelle-encapsulated microheterogeneous environments. The enhancement of fluorescence anisotropy and rotational relaxation time of the drug in micellar environments from that in pure aqueous buffer suggests entrapment of the drug in motionally constrained regions introduced by the micelles.

Exploring the interaction of a micelle entrapped biologically important proton transfer probe with the model transport protein bovine serum albumin.

This article describes the interaction of a micelle entrapped pharmaceutically important isoindole fused imidazole derivative, namely, 1-(2-hydroxy-5-methyl-phenyl)-3,5-dioxo-1H-imidazo-[3,4-b] isoindole (ADII), with the model transport protein bovine serum albumin (BSA). Different spectroscopic techniques such as steady state absorption, emission, circular dichroism, dynamic light scattering, etc., have been employed to explore preferential interaction of this drug template with micelles and protein BSA. Binding of ADII with BSA is found to be enormously modified when it is released from the micellar environment. The binding constant of the ADII-BSA complex is reduced when the probe is released from anionic SDS micelle, whereas the binding is observed to be strengthened in cationic CTAB micellar medium due to the formation of a 1:2 complex (ADII-BSA). Time-resolved studies also support our steady state findings that the released drug from the micellar environment is found to be strongly bound with the protein BSA. Circular dichroism (CD) and dynamic light scattering (DLS) study reveals that the secondary structure of BSA gets some stabilization in SDS medium after binding of drug template to protein. The probable binding location of the probe within the protein cavity (hydrophilic subdomain IA) has been explored from an AutoDock-based blind docking simulation study.

Modulated photophysics of a cationic DNA-staining dye inside protein bovine serum albumin: Study of binding interaction and structural changes of protein

The binding affinity of cationic DNA-staining dye, propidium iodide, with transport protein, bovine serum albumin, has been explored using UV-vis absorption, fluorescence, and circular dichroism spectroscopy. Steady state and time resolved fluorescence studies authenticate that fluorescence quenching of bovine serum albumin by propidium iodide is due to bovine serum albumin-propidium iodide complex formation. Thermodynamic parameters obtained from temperature dependent spectral studies cast light on binding interaction between the probe and protein. Site marker competitive binding has been encountered using phenylbutazone and flufenamic acid for site I and site II, respectively. Energy transfer efficiency and distance between bovine serum albumin and propidium iodide have been determined using Förster mechanism. Structural stabilization or destabilization of protein by propidium iodide has been investigated by urea denaturation study. The circular dichroism study as well as FT-IR measurement demonstrates some configurational changes of the protein in presence of the dye. Docking studies support the experimental data thereby reinforcing the binding site of the probe to the subdomain IIA of bovine serum albumin.

Modulation in prototropism of the photosensitizer Harmane by host:guest interactions between β-cyclodextrin and surfactants

The present contribution demonstrates the photophysics of a prospective cancer cell photosensitizer Harmane (HM) belonging to the family of β-carboline in mixed microheterogeneous environments of β-cyclodextrin (β-CD) and surfactants having varying surface charges using steady-state and time-resolved fluorescence spectroscopic techniques. The remarkable modulations in prototropic activities of the micelle-bound drug in the presence of β-CD evinces for disruption of the micellar structural integrity by β-CD. The results are meticulously discussed in relevance to the effect of a potential drug delivery vehicle (CD) on the membrane-mimetic micellar system. Further, application of an extrinsic fluorescence probe for monitoring such interactions is fraught by the possibilities of no less than three equilibria that can operate simultaneously viz., (i) surfactant-cyclodextrin, (ii) surfactant-fluorophore and (iii) cyclodextrin-fluorophore. This aspect highlights the enormous importance of the issue of suitability of the fluorescence probe to study such complicated systems and interaction phenomena. Also the varying interaction scenario of β-CD with the nature of the surfactant highlights the importance of precise knowledge of the strength and locus of drug binding in delineating such complex interactions. The results of the present investigation advocate for the potential applicability of the drug (HM) itself as a fluorescence reporter in study of such complex microheterogeneous interactions.

Spectral properties of a simple azine Schiff base and its sensing ability towards protic environment through hydrogen bonding interaction

A simple azine linkage containing Schiff base p-N,N-diethylaminobenzaldazine (PDEAB) has been synthesized and its spectroscopic properties have been investigated using steady state absorption and fluorescence measurement. Both the absorption and emission studies indicate that the compound PDEAB forms intermolecular hydrogen bond with protic solvents. The formation of intermolecular hydrogen bond between PDEAB and protic solvents is further verified by Quantum chemical calculation using Density Functional Theory (DFT) (B3LYP/6-31++G(d,p)) and Natural Bond Orbital (NBO) analysis. The non-fluorescent nature (fluorescence off) of PDEAB in aprotic environment can be switched over to a fluorescent system (fluorescence on) in presence of protic solvents and hence this molecule can be used as highly sensitive fluorosensor for protic solvent in aprotic medium like ACN or DOX.

Modulation of Excited State Proton Transfer Dynamics of a Lactim–Lactam Tautomeric System in Different Block Copolymer–Surfactant Aggregates

The proton transfer (PT) process in 1-(2-hydroxy-5-chloro-phenyl)-3,5-dioxo-1H-imidazo-[3,4-b]isoindole (ADCL) has been studied in three different copolymer-surfactant supramolecular assemblies prepared in aqueous 1% P123 triblock copolymer micellar solution with varying concentrations of surfactants (sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and triton-X-100 (TX 100)). The aim of the present study is to monitor the modulation of the PT process by changing the degree of micellar hydration inside the P123 micelle with the addition of the three different surfactants (two ionic and one non ionic), that is, in P123-surfactant aggregates. Besides, a comparative study has been done with these results with those in water, pure P123 micellar medium and three different surfactants medium. The micropolarity measurement and time-resolved fluorescence anisotropic measurements have been performed to evaluate the binding location of the probe (ADCL) in the three different copolymer-surfactant supramolecular assemblies. It is found that the micropolarity at the binding site of the molecule in the various environments largely influences the PT rate of ADCL. The PT rate is found to be the slowest in the P123 medium and in P123-surfactant aggregates the rate becomes faster as the micropolarity around the binding locations of the molecule in these aggregates is higher in comparison to that in P123 micelle.