Design, Synthesis, Physicochemical Studies, Solvation, and DNA Damage of Quinoline-Appended Chalcone Derivative: Comprehensive Spectroscopic Approach toward Drug Discovery

Abstract

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.

ESIPT reaction of potential bioactive heterocyclic Schiff base: Atomic visualization coupled with in vitro spectroscopy

“…Moreover the weakening of the ÀOH peak in FTIR spectrum around the region of 3300-2700 cm À1 is consistent with the existence of strong intramolecular H-bonding in the enolimine form of the compound [24]. Thus 1 H, 13 C NMR and FTIR studies not only confirm the existence of the enol-imine form of CBMDP in the ground state but also attest a strong intramolecular H-bonding between phenolic hydrogen and azomethine nitrogen in the enolic form of the synthesized molecule.…”

“…The adopted design [23], amyloid specificity, metal ion chelation and other related biological activities of this synthesized CBMDP molecule have been communicated recently by our group elsewhere [21]. However the main focus of the present article is to explore the physicochemical behavior of the probe CBMDP, especially in terms of identification of the ground state geometry and the excited state intramolecular proton transfer reaction using 1 H, 13 C NMR, FTIR, X-ray crystallography, UV-vis absorbance, steady state fluorescence, and quantum chemical calculations to understand its photophysical behavior.…”

“…The higher chemical shift of phenolic proton may be due to its intramolecular H-bonding with azomethine nitrogen. 13 C NMR spectrum exhibits aromatic carbon peaks in the expected range of 100-165 ppm (Fig. S2).…”

“…Photoinduced electron transfer and proton transfer are important fundamental processes for many biochemical reactions and find numerous applications in scientific field [1][2][3][4][5][6][7][8][9][10][11][12][13]. Amongst all the photoinduced processes, excited state proton transfer are of special interest.…”

“…When a photoinduced proton transfer occurs from one atom to another atom within a single molecular framework, it is known as excited state intramolecular proton transfer (ESIPT) reaction. If a molecule possesses electron donor and acceptor group in the same skeleton, there is a strong possibility of excited state intramolecular charge transfer (ESICT) process to occur upon photoexcitation [13,14]. As a consequence, ESIPT processes are normally accompanied by intramolecular charge transfer process or vice versa [8].…”