Inactivation of photosensitizing merocyanine dyes by plasma, serum and serum components.

Merocyanine dyes with an oxygen in the electron donor heterocycle were rapidly degraded by plasma, serum and serum components. Replacement of the oxygen by a sulfur or selenium atom rendered the dyes refractory to degradation. The degradation of labile merocyanine dyes was temperature dependent and oxygen independent.

Structurally modified trimethine thiacarbocyanine dyes. Effect of N-alkyl substituents on antineoplastic behavior.

The effect of dye localization and dye distribution on the antineoplastic behavior of photosensitizers was investigated with a homologous series of trimethine thiacarbocyanine dyes in L1210 leukemia and A549 lung carcinoma cells. These dyes were synthesized with N-alkyl groups of different sizes (ethyl to octadecyl) to vary their lipophilic properties without compromising their photophysics. While dyes with smaller N-alkyl groups (ethyl to decyl) were already cytotoxic in the dark, longer chain cyanines exhibited antineoplastic activity only after exposure to light.

Potentiation of merocyanine 540-mediated photodynamic therapy by salicylate and related drugs.

Simultaneous exposure to merocyanine 540 (MC540) and light of a suitable wavelength kills leukemia, lymphoma and neuroblastoma cells but is relatively well tolerated by normal pluripotent hematopoietic stem cells. This differential phototoxic effect has been exploited in preclinical models and a phase I clinical trial for the extracorporeal purging of autologous bone marrow grafts. Salicylate is known to potentiate the MC540-mediated photokilling of tumor cells.

Merocyanine dyes: effect of structural modifications on photophysical properties and biological activity.

Merocyanine derivatives were prepared by structural alterations at the barbituric acid or chalcogenazole moieties. The photophysical properties of the dyes were markedly influenced by the presence of selenium rather than sulfur as a substituent at position 2 of the barbiturate. In methanol, quantum yields of both triplet state (phi T) and singlet oxygen sensitization (phi delta) were increased by over an order of magnitude, with a concomitant decrease in fluorescence, when selenium was present in the molecule.

Effects of structural modifications on the photosensitizing properties of dialkylcarbocyanine dyes in homogeneous and heterogeneous solutions.

The photophysical characterization of structurally modified symmetric dialkylthiacarbocyanine dyes in homogeneous and biomimetic media is reported. The aim of the two specific structural modifications was to increase singlet oxygen production, hence enhancing the photosensitizing properties of these cyanine dyes. Specifically, (1) the sulfur was exchanged with selenium in order to enhance intersystem crossing via an internal heavy atom effect and (2) substituents of differing size were introduced into the meso-position of the polymethine chain to reduce photoisomerization.