Ultrafast molecular rotors (UMRs) are reported to be one of the best fluorescent sensors to study different microenvironments, including biomolecules. In the present work, we have explored the possibility of application of a julolidine-based neutral UMR, 9-(2,2-dicyano vinyl) julolidine (DCVJ), as a DNA sensor and studied its mode of binding with DNA in detail using spectroscopic and molecular docking techniques. Our spectroscopic studies indicate that association of DCVJ with DNA leads to a very large enhancement in its emission intensity. Detailed investigation reveals that, despite being a neutral molecule, binding of DCVJ with DNA is largely modulated in the presence of salt. Such an unusual salt effect has been explained by invoking the ion-dipole interaction between DCVJ and the phosphate backbone of DNA. The ion-dipole interaction has also been established by studying the interaction of DCVJ with nucleosides. Detailed time-resolved studies show that the twisting motion around the vinyl bond in DCVJ gets retarded to a great extent because of its association with DNA molecules. Through competitive binding studies, it has also been established that DCVJ also binds to DNA through intercalation. Finally, quantum chemical calculations and molecular docking studies have been performed to confirm the mode of binding of DCVJ with DNA.
Surfactants have often been employed for the sequestration of drugs from DNA. However, for an effective sequestration, the concentration of the surfactant needs to be higher than its critical micellar concentration (CMC). Use of such high concentrations of the surfactant may limit its practical usage as a sequestering agent due to its cytotoxicity. In the present study we have shown that sodium dodecyl sulfate (SDS) itself at a concentration less than its CMC failed to sequester a drug from DNA. However, the sequestration power of SDS at sub-CMC concentration could be enhanced to a significant extent when incorporated into Pluronic polymer micelles in the form of supramolecular assemblies. Such a sequestration process was monitored through detailed photophysical properties of a model drug using steady-state and time-resolved fluorescence techniques. It has also been demonstrated that unlike a conventional surfactant, the sequestration of drugs by SDS-polymer supramolecular assemblies can be controlled by their compositions. Two Pluronic polymers with different compositions have been used to understand the effect of polymer composition on the sequestration process. It has been shown that with the increase in the length of the hydrophilic blocks of the polymer, the extent of sequestration decreases due to the decrease in the sequestering force exerted on the intercalated drug. Most importantly, our in vitro cell viability studies show that the toxicity of the SDS surfactant is reduced to a remarkable extent due to its incorporation into the polymer micelles.
We have demonstrated that the drug sequestration power of cationic surfactant is enhanced and its protein denaturing capability is suppressed significantly through its incorporation in bio-compatible Pluronic micelles.
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