Time-domain evaluation of drug–solvent interactions of the photosensitizers TPCS 2a and TPPS 2a as part of physicochemical characterization

Abstract

The patented photosensitizer meso-tetraphenyl chlorin disulphonate (TPCS 2a) is intended for use in the technology of photochemical internalization (PCI). The compound is advantageous with respect to the related meso-tetraphenyl porphyrin disulphonate (TPPS 2a), due to its high absorption in the red part of the absorption spectrum ( λ abs ≈ 650 nm). We report a time-resolved fluorescence study of TPCS 2a aimed to elucidate the susceptibility of the photosensitizer's excited state dynamics to properties of its environment, such as polarity and hydrogen bond formation. TPPS 2a is used as a reference compound. Fluorescence decays with <30 ps temporal resolution of TPCS 2a and TPPS 2a in 14 organic solvents of varying polarity and amphiprotic properties were measured by time-correlated single-photon counting (TCSPC). Both compounds show triple exponential fluorescence decays in non-polar environment, i.e. τ L ∼ 7 ns, τ I ∼ 2 ns and τ S ∼ 0.5 ns. The two shorter decay components, τ I and τ S, which we associated with two different intramolecular charge transfer mechanisms, readily disappear when the solvent polarity is slightly increased. The fluorescence decays of both compounds in any solvent of dielectric constant ɛ > 7.58 are well fitted by a single exponential model, with decay time roughly constant, τ L ∼ 10 ns, and independent of the amphiprotic properties of the solvents. The present results allow concluding that the fluorescence decay pathways of TPCS 2a and TPPS 2a are only slightly affected by the environmental properties under consideration, as previously probed by steady-state measurements (Lilletvedt et al. [1]). Singlet oxygen ( 1O 2) generation of the two photosensitizers were measured indirectly in water by applying the singlet oxygen sensor green (SOSG) reagent. Both photosensitizers generate 1O 2 to some extent upon excitation in vitro.