Role of H-bond formation in the photoreactivity of curcumin

Abstract

Curcumin is the main constituent of curry. In its ground state it shows chemo-preventive, chemo-therapeutic and anti-inflammatory effects. For its immunostimulating action it has been considered for the development of drugs suitable for treating AIDS and cystic fibrosis. Further biological action is induced in curcumin by photoactivation: in suitable environmental conditions electronically excited curcumin can act as a singlet oxygen generator. Moreover, cytotoxicity is enhanced by light exposure and antibacterial effects are photosensitized. This work is aimed to understand the photobiological action of curcumin by elucidating the deactivation mechanisms of its first excited singlet state. In particular we find evidence of the role of tautomerization in the excited state by measuring fluorescence lifetimes and quantum yields for such compound dissolved in solvents of different polarity and H-bonding capability. Degradation quantum yield and singlet oxygen generation efficiency were also measured in acetonitrile and methanol. The results emphasize the strong dependence of the deactivation processes from the environment. The deactivation phenomenology can be fully explained by postulating intramolecular proton transfer in thecisenol conformer to be the leading non-radiative deactivation pathway.

The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer

“…The tendency of the keto↔enol equilibrium to shift toward the enol tautomer in these solvent systems has been confirmed experimentally by Fourier transform infrared spectroscopy (FT-IR) (Kolev et al, 2005), nuclear magnetic resonance spectroscopy (NMR) (Roughley and Whiting, 1973;Unterhalt, 1980;Gorman et al, 1994;Khopde et al, 2000), fluorescence spectroscopy (Khopde et al, 2000;Nardo et al, 2008), and absorption spectroscopy (Khopde et al, 2000;Nardo et al, 2008) as well as computationally (Kolev et al, 2005;Balasubramanian, 2006;Payton et al, 2007;Galano et al, 2009). In nonpolar solvents, the steadystate absorption spectra of curcumin in cyclohexane (Nardo et al, 2008), toluene , benzene (Khopde et al, 2000), and others (Tønnesen et al, 1995) exhibit a concrete red band or shoulder, which has been ascribed to the diketo tautomer (Khopde et al, 2000;Nardo et al, 2008Nardo et al, , 2009. Curcumin hence adopts both the enol and diketo tautomeric form in nonpolar environments (Balasubramanian, 2006), albeit the diketo tautomer is quantitatively exiguous relative to the enol tautomer (Kolev et al, 2005), and exclusively the enol tautomeric form in solvents with increasing « r (Fig.…”

“…Accordingly, the conformation of the b-diketone is highly dependent on the chemical environment that in turn dictates intermolecular bonding behavior. In nonpolar solvents, curcumin primarily exists as a closed cis-enol tautomer, where the proton is believed to be symmetrical (Nardo et al, 2008) in an electrondelocalized system (Emsley, 1984;Balasubramanian, 2006) (Fig. 1B).…”

“…The enolic proton and carbonyl oxygen are therefore unavailable for H-bonding to other molecules. The intramolecular H-bonding is perturbed in weakly as well as strongly H-bonding solvents by the polar solvent molecules, as a result of which the enol tautomer adopts an open conformation (Emsley, 1984;Toullec, 1990;Khopde et al, 2000;Nardo et al, 2008), thereby abrogating the symmetry of the semiaromatic ring (Nardo et al, 2008(Nardo et al, , 2009 (Fig. 1B).…”

Excited-State Intramolecular Hydrogen Atom Transfer and Solvation Dynamics of the Medicinal Pigment Curcumin

“…12,[31][32][33][34] In all cases, these studies focused on excited-state intramolecular hydrogen atom transfer (ESIHT) of curcumin because this phenomenon has been associated with the medicinal properties of other pigment molecules, including hypericin and hypocrellin. [35][36][37][38][39] Two of these studies agree that the fluorescence lifetime of curcumin in methanol has a dominant component with a time constant of roughly 130 ps.…”

Effects of Fatty Acids on the Interfacial and Solution Behavior of Mixed Lipidic Aggregates Called Solid Lipid Nanoparticles

“…Emission spectra of curcumin in most of the solvents were unimodal except for n-hexane structured bands 44 . The absence of a significant difference between the emission spectra of curcumin in Tween 60 and in the prepared formulations confirmed that the molecularly dispersed curcumin molecules were in contact with the continuous medium of the SLNs as they got accumulated overthe surface.…”