The present study epitomizes the design, synthesis, photophysics, solvation, and interaction with calf-thymus DNA of a potential antitumor, anticancer quinoline-appended chalcone derivative, (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ) using steady state absorption and fluorescence spectroscopy, molecular modeling, molecular docking, Fourier-transform infrared spectroscopy (FTIR), molecular dynamics (MD) simulation, and gel electrophoresis studies. ADMQ shows an unusual photophysical behavior in a variety of solvents of different polarity. The dual emission has been observed along with the formation of twisted intramolecular charge transfer (TICT) excited state. The radiationless deactivation of the TICT state is found to be promoted strongly by hydrogen bonding. Quantum mechanical (DFT, TDDFT, and ZINDO-CI) calculations show that the ADMQ is sort of molecular rotor which undergoes intramolecular twist followed by a complete charge transfer in the optimized excited state. FTIR studies reveals that ADMQ undergoes important structural change from its native structure to a β-hydroxy keto form in water at physiological pH. The concentration-dependent DNA cleavage has been identified in agarose gel DNA electrophoresis experiment and has been further supported by MD simulation. ADMQ forms hydrogen bond with the deoxyribose sugar attached with the nucleobase adenine DA-17 (chain A) and result in significant structural changes which potentially cleave DNA double helix. The compound does not exhibit any deleterious effect or toxicity to the E. coli strain in cytotoxicity studies. The consolidated spectroscopic research described herein can provide enormous information to open up new avenues for designing and synthesizing chalcone derivatives with low systematic toxicity for medicinal chemistry research.
Due
to its numerous applications, triplet formation and resulting
phosphorescence remain a frontier area of research for over eight
decades. Facile intersystem crossing (ISC) is the primary requirement
for triplet formation and observation of phosphorescence. The incorporation
of a heavy atom in molecules is one of the common approaches employed
to facilitate ISC. A detailed study of the excited state dynamics
that governs ISC is necessary to understand the mechanism of heavy
atom effect (HAE). Incorporation of iodine at the 3 position of coumarin-1
reduces fluorescence quantum yield (ϕ
f
) drastically as expected, whereas bromine substitution at
the same position increased the ϕ
f
. Such a contrasting effect of the two heavy atoms suggests that
there are other features yet to be discovered to fully understand
the HAE. Detailed steady state and femtosecond transient absorption
studies along with theoretical calculations suggest that the C3-X
(X = Br, I) bond vibration plays an important role in the ISC process.
The study reveals that while in the case of the iodo-derivative there
is no energy barrier in the singlet triplet crossing path, there is
a barrier in the case of the bromo-derivative, which slows the ISC
process. Such an unexpected phenomenon is not limited to halocoumarins
as this rationalizes the photobehavior of 1-bromo-/iodo-substituted
naphthalenes as well.
The development of Photoremovable protecting groups (PRPGs), which can be activated in the ʽphototherapeutic windowʼ for biological applications, is highly challenging. Only PRPGs based on BODIPY dye have been developed so far, which can be excited ≥600 nm. Herein, we developed for the first time NIR dye hydroxystyryl dicyanomethylene-4H-pyran (DCM) as a PRPG that can be operated in the phototherapeutic window. Ours easily synthesized DCM photocages efficiently released aromatic and aliphatic carboxylic acids in an aqueous solution on irradiation using the light of wavelength ≥600 nm and 650 nm, separately. As an application, we used our DCM-PRPG as a single component nanocarrier drug delivery system (DDS) to uncage valproic acid (a known histone deacetylase inhibitor) for cancer treatment. In vitro studies revealed that our DDS, hydroxystyryl dicyanomethylene-4H-pyran valproic acid conjugate nanoparticles (DCM-VPA-NPs) exhibited good cellular internalization, biocompatibility, and enhanced cytotoxicity upon irradiation.
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