Cyclocurcumin (CC), a turmeric curcuminoid with potential therapeutic properties, is also a natural photoswitch that may undergo E/Z photoisomerization under UV light. To be further exploited in relevant biological applications, photoactivation under near-infrared (NIR) irradiation is required. Such requirement can be met through opportune chemical modifications, by favoring two-photon absorption (TPA) probability. Herein, a general and efficient synthesis of a biomimetic 2,6disubstituted-γ-pyrone analogue of CC is described, motivated by the fact that molecular modeling previews an order of magnitude increase of its NIR TPA compared to CC. Three retrosynthetic pathways have been identified (i) via an aryl-oxazole intermediate or via aryl-diynone through (ii) a bottom-up or (iii) a top-down approach. While avoiding the passage through unstable synthons or low-yield intermediate reactions, only the latest approach could conveniently afford the 2,6-disubstituted-γ-pyrone analogue of CC, in ten steps and with an overall yield of 18%. The photophysical properties of our biomimetic analogue have also been characterized showing an improved photoisomerization yield over the parent natural compound. The potentially improved nonlinear optical properties, as well as enhanced stability, may be correlated to the enforcement of the planarity of the pyrone moiety leading to a quadrupolar D−π−A−π−D system.
Cyclocurcumin is a natural compound extracted from turmeric and showing, in addition to antiinfective, antibacterial, and intinflammatory capabilities, solvent-dependent phtoswitching ability. The solvent-dependent photochemistry of cyclocurcumin has been rationalized on...
We report the synthesis and characterization of a novel photoswitch based on biomimetic cyclocurcumin analogous and interacting with the lipid bilayer, which can be used in the framework of oxygen-independent lightinduced therapy. More specifically, by using molecular dynamics simulations and free energy techniques, we show that the inclusion of hydrophobic substituents is needed to allow insertion in the lipid membrane. After having confirmed experimentally that the substituents do not preclude the efficient photoisomerization, we show through UV−vis and dynamic light scattering measurements together with compression isotherms that the chromophore is internalized in both lipid vesicles and monomolecular film, respectively, inducing their fluidification. The irradiation of the chromophore-loaded lipid aggregates modifies their properties due to the different organization of the two diastereoisomers, E and Z. In particular, a competition between a fast structural reorganization and a slower expulsion of the chromophore after isomerization can be observed in the kinetic profiles recorded during E to Z photoisomerization. This report paves the way for future investigations in the optimization of biomimetic photoswitches potentially useful in modern light-induced therapeutic strategies.
The use of photoswitches which may be activated by suitable electromagnetic radiation is an attractive alternative to conventional photodynamic therapy. Here, we report all-atom molecular dynamics simulation of a biomimetic photoswitch derived from cyclocurcumin and experiencing E/Z photoisomerization. In particular, we show that the two isomers interact persistently with a lipid bilayer modeling a cellular membrane. Furthermore, the interaction with the membrane is strongly dependent on the concentration, and a transition between ordered and disordered arrangements of the photoswitches is observed. We also confirm that the structural parameters of the bilayer are differently affected by the two isomers and hence can be modulated through photoswitching, offering interesting perspectives for future applications.
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