Excited state dynamics of bis-dehydroxycurcumin tert-butyl ester, a diketo-shifted derivative of the photosensitizer curcumin

Abstract

Bis-dehydroxycurcumin tert-butyl ester (K2T23) is a derivative of the natural spice curcumin. Curcumin is widely studied for its multiple therapeutic properties, including photosensitized cytotoxicity. However, the full exploitation of curcumin phototoxic potential is hindered by the extreme instability of its excited state, caused by very efficient non radiative decay by means of transfer of the enolic proton to the nearby keto oxygen. K2T23 is designed to exhibit a tautomeric equilibrium shifted toward the diketo conformers with respect to natural curcumin. This property should endow K2T23 with superior excited-state stability when excited in the UVB band, i.e., in correspondence of the diketo conformers absorption peaks, making this compound an interesting candidate for topical photodynamic therapy of, e.g., skin tumors or oral infections. In this work, the tautomeric equilibrium of K2T23 between the keto-enolic and diketo conformers is assessed in the ground state in several organic solvents by UV-visible absorption and by nuclear magnetic resonance. The same tautomeric equilibrium is also probed in the excited-state in the same environments by means of steady-state fluorescence and time-correlated single-photon counting measurements. These techniques are also exploited to elucidate the excited state dynamics and excited-state deactivation pathways of K2T23, which are compared to those determined for several other curcuminoids characterized in previous works of ours. The ability of K2T23 in photosensitizing the production of singlet oxygen is compared with that of curcumin.

Synthesis, Characterization and DNA-Binding Affinity of a New Zinc(II) Bis(5-methoxy-indol-3-yl)propane-1,3-dione Complex

“…The only exceptions to this rule are the excitation spectrum recorded with λ obs = 425 nm in DCM, which has a maximum at 326 nm due to the high prevalence of the diketo tautomers in this solvent, and the excitation spectrum with λ obs = 350 nm in DMF, which peaks at 280 nm, with a marked shoulder above 300 nm. Again by analogy with previously reported studies on curcumin analogues [49,50], this might indicate a non-trivial cis-/trans-tautomerism between the diketo tautomers in this solvent. Subtraction of out-of-peak excited fluorescence by the enolic species allowed to reconstruct the spectral features of the diketo emission (see Supplementary Materials Figure S5).…”

“…Subtraction of out-of-peak excited fluorescence by the enolic species allowed to reconstruct the spectral features of the diketo emission (see Supplementary Materials Figure S5). A similar behavior (red-shifted fluorescence in alcohols) was observed for several curcuminoids, and ascribed to tautomerism between the open cis-and trans-enol species [49,50,[52][53][54][55][56][57]. The quantum yield of 1 is generally low (see the values reported in Table 3).…”

“…A similar behavior (red-shifted fluorescence in alcohols) was observed for several curcuminoids, and ascribed to tautomerism between the open cisand trans-enol species [49,50,[52][53][54][55][56][57]. The quantum yield of 1 is generally low (see the values reported in Table 3).…”

“…Relying on previous experiences [ 49 , 50 ] as well as literature data [ 51 ] on other β-diketones, we attributed the 310 nm peaked band to the absorption of the BMIP ligands in the diketo tautomer, and the 395 nm peaked one to the absorption of those in the enol form. According to this interpretation, the coexistence of two peaks in all the solvents would support the picture offered by NMR, suggesting that both the diketo and the enol tautomers are able to chelate zinc(II) ions with comparable efficacy, and that the keto-enolic equilibrium is primarily dictated by solute–solvent interactions, rather than complexation.…”

Intramolecular Charge Transfer of Curcumin and Solvation Dynamics of DMSO Probed by Time-Resolved Raman Spectroscopy

“…Curcumin may exist either in diketo or enol form as expected from the molecular structures shown in Figure 1a. Many experimental and theoretical studies have confirmed that the enol form exists predominantly in the gas phase and various solution phases in a wide polarity range [5][6][7][8][9][10][11]. The enol form of curcumin may undergo the intramolecular proton transfer reaction in the hydrogen-bonded chelate center, resulting in the identical (symmetric) enol form as the product.…”