Elucidation of the Relationships between H-Bonding Patterns and Excited State Dynamics in Cyclovalone

Abstract

Cyclovalone is a synthetic curcumin derivative in which the keto-enolic system is replaced by a cyclohexanone ring. This modification of the chemical structure might in principle result in an excited state that is more stable than that of curcumin, which in turn should produce an enhanced phototoxicity. Indeed, although curcumin exhibits photosensitized antibacterial activity, this compound is characterized by very fast excited-state dynamics which limit its efficacy as a photosensitizer. In previous works we showed that the main non-radiative decay pathway of keto-enolic curcuminoids is through excited-state transfer of the enolic proton to the keto-oxygen. Another effective deactivation pathway involves an intermolecular charge transfer mechanism occurring at the phenyl rings, made possible by intramolecular H-bonding between the methoxy and the hydroxyl substituent. In this paper we present UV-Vis and IR absorption spectra data with the aim of elucidating the intramolecular charge distribution of this compound and its solvation patterns in different environments, with particular focus on solute-solvent H-bonding features. Moreover, we OPEN ACCESSMolecules 2014, 19 13283 discuss steady state and time-resolved fluorescence data that aim at characterizing the excited-state dynamics of cyclovalone, and we compare its decay photophysics to that of curcumin. Finally, because during the characterization procedures we found evidence of very fast photodegradation of cyclovalone, its photostability in four organic solvents was studied by HPLC and the corresponding relative degradation rates were calculated.

Characterization and antimicrobial phototoxicity of curcumin dissolved in natural deep eutectic solvents

“…There seems to be a difference in emission spectrum and thereby the network Curcumin has been reported to be protonated just below pH 1 followed by an increase in aqueous solubility and a shift in the absorption maximum to 540 nm, as demonstrated in Figure 4. 40 The pH was measured to 0.6 in undiluted MC3 and curcumin should therefore be protonated. However, no spectral change was observed.…”

“…36 Absorption in this wavelength range is ascribed to the conjugation between the aromatic rings in curcumin via the enol-form involving an intramolecular H-bond and the planar conformation of the molecule(Figure 1) 37,38. The absorption maximum at 370 nm can be ascribed to the formation of the polar diketo conformer of the curcumin molecule which leads to a substantial reduction in conjugation (Figure 1) 39,40. That NADES may induce conformational changes in solubilized phenolic compounds has also been observed byDai et al (2014) 41.…”

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

“…However, cyclovalone was extremely photolabile, thus CURC resulted a more performing photosensitizer even at moderate light doses [25]. …”

Anti-Inflammatory and Antioxidant Activity of Synthesized Mannich Base Derivatives of (2e,6e)-2-[(4-Hydroxy-3-Methoxyphenyl)methylidene]-6-(Phenyl Methylidene)cyclohexan-1-One

“…Various MACs have been synthesized in an attempt to improve the biological activity and other properties [3][4][5][6][7][8]. The recent study reported that AMACs containing a morpholine Mannich base substituted into the phenolic ring and various substituents at para position on another phenyl ring exhibited low antioxidant activity, whereas the compounds containing methoxy or fluoro substituents at the para position on another phenyl ring exhibited potent anti-inflammatory activity that was almost comparable to that of the standard, diclofenac sodium [9].…”

“…Several series of symmetrical monocarbonyl analogs of curcumin (MACs), containing a cyclohexanone or cyclopentanone linker between the two phenyl rings, reportedly have superior anti-inflammatory and antioxidant activity, higher chemical stability, and improved pharmacokinetic profiles compared to curcumin [3,4]. On the other hand, several asymmetrical MAC (AMACs) reportedly exhibit potent anti-inflammatory, antioxidant, and antitumor activities [5][6][7][8]. Finally, our group reported that, while AMACs containing a morpholine Mannich base exhibit low antioxidant activity, two compounds exhibit potent anti-inflammatory activity [9].…”