Design, Synthesis, and Proticity Inclined Conformational Modulation in a Highly Fluorescent Bichromophoric Naphthalimide Derivative: Hint Directed from RICT Perspective

Abstract

The present study embodies design, in silico DNA interaction, synthesis of benzothiazole containing naphthalimide derivative, 2-(6-chlorobenzo[d]thiazol-2-yl)-1H-benzo[de] isoquinoline-1,3(2H)-dione (CBIQD) along with its systematic photophysics, solvatochromic behavior, and solvation dynamics using an experimental and theoretical spectroscopic approach. Steady-state dual emission and biexponential fluorescence decay reveals the formation of two different excited species. Ground- and excited-state optimized geometry and the potential-energy curve obtained from DFT and TD-DFT calculation ascertained the existence of nonplanar and planar conformation. When the solvent polarity is changed from nonpolar to protic polar, the feebly emissive emission band highly intensifies probably due to the reversal of n, π*-π, π* emissive state along with consequent modulation of their energy gap that is induced by H-bonding. Excluding nonpolar solvents, in all other solvents, the Stokes shift correlates linearly with orientation polarizability, whereas in water, the story remains intriguing. With photoexcitation, intermolecular H-bonding stimulates the pyramidalization tendency of imide "N" with subsequent conformational change of GS nonplanar geometry to a coplanar one through acceptor rehybridization generating a rehybridized intramolecular charge transfer (RICT) state that caused a dramatic fluorescence upsurge. This allosteric modulation is promoted by excited-state H-bonding dynamics especially in strong H-bond donor water. A close interplay between preferential solvation and the proximity effect is evident in the emission behavior in a benzene (Bn)-ethanol (EtOH) binary mixture. Molecular docking analysis delineates considerable noncovalent sandwiched π-π stacking interactions of CBIQD with the pyrimidine rings as well as with imidazole rings of dG 6 and dG 2 base pairs of B-DNA double helix, which probably suffices the design strategy adopted. Overall, a strategic design to synthesize a highly fluorescent and potential bioactive agent is executed to revolutionize the fluorophore field due its enormous progressive importance in biochemical applications.

Unveiling the Potential of Unfused Bichromophoric Naphthalimide To Induce Cytotoxicity by Binding to Tubulin: Breaks Monotony of Naphthalimides as Conventional Intercalators

“…However, CBIQD does not show any considerable emission in the region of protein fluorescence. 24 The new bands in the red region are out of scope of the present discussion. The SV plot shows a slight upward curvature toward the y axis at higher concentrations of the guest molecule (Figure 5B, inset), so the data points at lower ligand concentrations following linearity (Figure 5B) are used to determine an SV quenching constant of 3.56 × 10 4 L mol −1 , which may suggest involvement of static quenching process only.…”

“…In Figure 5A, quenching is accompanied with simultaneous formation of a new band around 375 nm with a shoulder around 395 nm and the intensity rises with subsequent increase in [CBIQD]. This could be because of the fact that CBIQD also has an appreciable absorption near the excitation wavelength (280 nm) as well as in the range 340 nm 24 where the protein emits. However, CBIQD does not show any considerable emission in the region of protein fluorescence.…”

“…CBIQD (Scheme 1) used for the present study is designed and synthesized by our group and is reported elsewhere. 24 Colchicine (Col), 4′,6-diamidino-2-phenyl-indole (DAPI), vinblastine, bis-8-anilinonaphthalene-1-sulfonate (bis-ANS), and 5,5′-dithiobis-2-nitrobenzoic acid (DTNB) are procured from Sigma-Aldrich and used as received. Tubulin protein (>99%, bovine), guanosine 5′-triphosphate sodium salt (GTP), and general tubulin buffer (GTB) (lyophilized powder) are acquired from Cytoskeleton Inc. GTB powder constituting appropriate amounts of 80 mM piperazine-N,N'-bis(2-ethanesulfonic acid) (PIPES), 2 mM MgCl 2 , and 1 mM ethylene glycol tetraacetic acid (EGTA) is resuspended in 100 mL of Millipore water to give 1× strength buffer and is further used for experiments.…”

“…To identify the CBIQD binding site inside the tubulin scaffold, the competitive binding with the standard site markers colchicine and vinblastine is experimented by measuring the change in the fluorescence of tubulin−CBIQD complex. CBIQD exhibits intense emission in aqueous medium on account of its RICT state 24 and so this emission can be probed to decipher its binding location in tubulin in the presence of increasing concentrations of site markers (colchicine and vinblastine). The extent of CBIQD emission quenching in the presence of site markers may give a direct measure of its binding location in tubulin protein.…”

A simple sensor based on 1,8-naphthalimide with large Stokes shift for detection of hypochlorous acid in living cells

“…The electron donor capacity of benzothizole increased the uorescence quantum yield of the probe molecule. 40 Upon reaction to HOCl, the uorescence intensity of Probe 1 decreased and signicant change with the solution colour (yellow-green to colourless), which could be used as a uorometric or colorimetric indicator for HOCl. This molecular probe features a thioether group (MeS) uorescent modulator that is integrated into naphthalimide.…”