Picosecond spectral relaxation of the excited state of curcumin in a binary solvent mixture of toluene and MeOH (or MeOH-d4) is reported with an instrument time resolution of ∼40 ps. With increasing mole fraction of MeOH (MeOH-d4) the fluorescence intensity and lifetime of curcumin increase to a maximum at a MeOH (MeOH-d4) mole fraction of 0.14 (0.40) and then decrease. In addition, fluorescence decays taken at the red edge of the emission spectrum started to show measurable rise times (170 to 30 ps), the magnitude of which decreased gradually with increasing alcohol mole fraction. This is attributed to the modulation of the nonradiative rates associated with the excited-state intermolecular H(D) bonding between the pigment and the polar protic solvent. As a consequence, the solvation times in the binary mixture were observed to slow down considerably (20-40 times) at certain solvent compositions compared to neat MeOH. The fact that three Gaussian components are needed to adequately represent the steady-state emission spectra and two isosbestic points are observed in the time-resolved area normalized emission (TRANE) spectra of the pigment suggests the existence of at least three species in the excited state. The observed results are rationalized with a scheme where ground state of the pigment exists in free and H-bonded (intermolecular) state. Optical excitation results in a mixture of these species in the excited state and the observed spectral relaxation correspond to the conversion of these two species in to a third species where dipolar solvation and intermolecular H-bonding have been optimized.
The diffusion kinetics of a hemicyanine dye, LDS-698, across model membrane bilayers was studied in real time by the surface specific second harmonic technique. Using liposomes made from different headgroups, it has been established that the diffusion is initiated by electrostatic adsorption of the positively charged dye to the outer surface of negatively charged liposomes and its time constant is affected by the rigidity of the bilayer. In the presence of the liphophilic drug curcumin (curcumin/lipid mole ratio ~ 0.2), the diffusion of LDS-698 was observed to be faster by ~56 times (from 780 to 14 s) at 25 °C. Under similar curcumin concentration, when cholesterol containing liposomes are used at 2 °C, the observed diffusion time constant increases from 14 to 65 s, showing that the effect of curcumin is superior to the effect of increasing bilayer rigidity on the diffusion process. Control experiments with other lipophilic molecules such as DPH and Nile Red showed that the effect of liposomal curcumin is superior. Consistent with previous reports of curcumin affecting the bilayer organization, this study additionally demonstrates increased permeability of liposomal curcumin, in particular against organic cations. It is speculated that origin of this enhanced membrane permeability by lipophilic molecules may depend upon the interaction of the molecule with the polar headgroup region of the lipid which, in turn, is expected to depend on the chemical structure of the molecule.
We have investigated the diffusion of the photosensitizer Chlorin-p(6) (Cp(6)) across a egg lecithin lipid bilayer at different pH by the Second Harmonic Generation (SHG) method. Cp(6) has three ionizable carboxylic acid groups, and consequently, neutral and several ionic forms of Cp(6) are expected to be present in the pH range 3-8. The absorption spectra of Cp(6) get considerably modified in the presence of liposomes as the pH is decreased indicating that the drug liposome binding is pH dependent. The first pK(a) of interconversion (D-C) has been identified at pH ~7.0 by fluorescence measurement in an earlier work. In this work, the second pK(a) of interconversion (C-B) has been identified at pH ~4.8 by the hyper-Rayleigh scattering method. At acidic pH (3, 4, and 5), where species A, B, and C are dominant, the addition of liposomes to a Cp(6) solution generates an instantaneous rise (less than 1 s) in the second harmonic (SH) signal followed by decays whose time constants ranged from ten to hundreds of seconds. The instantaneous rise is attributed to the adsorption of Cp(6) to the outer lipid bilayer, and the decay is attributed to the diffusion of the neutral and charged (A and B) species of the drug. The observed fast and slow time constants for diffusion in the pH range 3-5 are attributed to the neutral (A) and ionic form (B) of Cp(6), respectively. At pH 6, the intensity of the generated SH signals on the addition of liposome reduced, and at physiological pH, it was too weak to be detected. These results are consistent with previous studies that show that the interaction between Cp(6) and egg-PC liposomes is pH dependent. At lower pH due to the presence of the hydrophobic species (A and B) of Cp(6), its interaction with liposomes is strong, and at higher pH, the abundance of the negatively charged hydrophilic species (C and D) decreases the interaction with the like charged liposomes. We have also studied the effect of increasing the bilayer rigidity by decreasing the temperature of the medium or by incorporating 50 mol % cholesterol in the lipid bilayer and observed that lowering of temperature has more profound effect on the diffusion rates. The characteristics of the SH signal changed significantly when liposomes incorporating 50 mol % cholesterol were used at a low (3 °C) temperature. Under these conditions, the SH signal consisted of an instantaneous (<1s) followed by a slower rise (10-90s), and then, it decayed on a much longer time scale. This slow rise of the SH signal at pH 3 and 4 may be attributed to the temperature dependent adsorption of the anionic species (B) of Cp(6) with the liposomes. Further investigations are required in order to understand clearly the pH dependent diffusion of this drug across lipid bilayers.
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