Solvent Effect on the Photophysical Properties of the Anticancer Agent Ellipticine

Abstract

This paper investigates how solution conditions, especially solvent polarity and hydrogen bonding, affect the fluorescence of ellipticine, a natural plant alkaloid with anticancer activity. A total of 16 solvents that cover a wide range of polarities were tested. The ultraviolet (UV) absorption and fluorescence emission of ellipticine were found to be solvent dependent. The absorption and emission maximum shifted to higher wavelengths (red shift) with increased solvent polarity. The difference in absorption and emission maximum (Stokes' shift) was large, approximately 10,000-11,000 cm-1, in polar solvents (with orientation polarizability Deltaf>0.2) but unusually small, approximately 8900 cm-1, in nonpolar solvents (hexane and cyclohexane). Large Stokes' shifts were due to an intramolecular charge transfer (ICT), which was enabled by large solvent polarity and hydrogen bonding of ellipticine with the solvents. Two transitions were found in the Lippert-Mataga plot between (1) nonpolar and semipolar solvents and between (2) semipolar and polar solvents. The first transition reflected the formation of hydrogen bonds between ellipticine and the solvents whereas the second transition indicated that ellipticine underwent an ICT. In addition, the larger extinction coefficients and the longer lifetime of ellipticine obtained in protic solvents were attributed to the formation of stronger hydrogen bonds. The photophysical response of ellipticine to changes in solvent polarity and hydrogen bond formation could be used to infer the location of ellipticine in a heterogeneous medium, namely liposomes in aqueous solution. A relatively large red shift of emission in liposomes indicated that ellipticine may be in a more polar environment with respect to the lipid bilayer, possibly close to the hydrophilic interface.

Amino Acid Pairing for De Novo Design of Self‐Assembling Peptides and Their Drug Delivery Potential

“…[ 30 ] Second, the fl uorescent properties of ellipticine make it easy to be characterized for its encapsulation and release. [ 22 ] Third, the challenges encountered during early clinical trials of its derivatives suggest a strong need of an effective delivery system. [30][31][32] The complexation of ellipticine with APP8 at different peptide concentrations (4.4-436 μ M ) was fi rst studied by examining the ellipticine emission fl uorescence spectra ( Figure 4 ).…”

Self‐Assembling Peptide as a Potential Carrier for Hydrophobic Anticancer Drug Ellipticine: Complexation, Release and In Vitro Delivery

“…[23] Second, ellipticine is extremely hydrophobic, with a low water solubility of $0.62 mM at neutral pH, [24] which is comparable with that of the model hydrophobic compound pyrene. [25] Third, its great anticancer activity makes ellipticine one of the promising candidates in cancer chemotherapy.…”

The origin of the dual fluorescence of protonated ellipticine in water

“…The constituents have planar geometry and anti-parallel orientations allowing interactions between the benzene rings of the two EH + molecules. Since no dimerization is observed in organic solvents [3], hydrophobic interaction may play essential role in (EH + ) 2 formation. The changes in the structure of the hydrate shells and the redistribution of the water network around the solutes significantly contribute to the driving force of dimerization also in the case of other compounds [14].…”

“…To gain a deeper understanding of the factors controlling the excited state relaxation processes, the fluorescent behavior of E was examined in organic solvents of a wide range of polarities and hydrogen bonding capabilities [3]. Selfassembling peptides was found to stabilize this alkaloid in water [4,5].…”