Photosensitizing effects and physicochemical properties of chlorophyll a derivatives with hydrophilic oligoethylene glycol fragments at the macrocycle periphery.

In this work, screening studies of the cytotoxic effect of chlorins with fragments of di-, tri-, and pentaethylene glycol at the macrocycle periphery in relation to HeLa, A549, and HT29 cells were performed. It is shown that, despite different hydrophobicity, all the compounds studied have a comparable photodynamic effect. The conjugate of chlorin e6 with pentaethylene glycol, which has the lowest tendency to association among the studied compounds with tropism for low density lipoproteins and the best characteristics of the formation of molecular complexes with Tween 80, has a significant difference in dark and photoinduced toxicity (ratio IC50(dark)/IC50(photo) approximately 2 orders of magnitude for all cell lines), which allows to hope for a sufficiently large "therapeutic window". A study of the interaction of this compound with HeLa cells shows that the substance penetrates the cell and, after red light irradiation induces ROS appearance inside the cell, associated, apparently, with the photogeneration of singlet oxygen. These data indicate that photoinduced toxic effects are caused by damage to intracellular structures as a result of oxidative stress. Programmed type of cell death characterized with caspase-3 induction is prevailing. So, the conjugate of chlorin e6 with pentaethylene glycol is a promising antitumor PS that can be successfully solubilized with Tween 80, which makes it suitable for further in vivo studies.

[Effects of hydrophilic and hydrophobic hydration in tetramethylbisurea and N,N'-dimethylpropyleneurea solutions].

The thermal effects of dissolving tetramethylbisurea in water at 298-318 K and N,N'-dimethylpropyleneurea at 293-313 K have been measured. It was shown that the standard heat of dissolution of tetramethylbisurea at 298 K was 3.58 +/- 0.04 kJ/mol, and that of N,N'-dimethylpropyleneurea was 22.8 +/- 0.01 kJ/mol. The standard heat capacities of urea derivatives at 298 K differed insignificantly: 167 +/- 10 J/(mol x K) and 149 +/- 5 J/(mol x K) for tetramethylbisurea and N,N'-dimethylpropyleneurea, respectively, indicating the moderately hydrophobic character of hydration of these compounds. It was found that, at temperatures close to the temperature of maximum density of water (277 K), the temperature dependence of Gibbs energy for tetramethylbisurea goes through the maximum.