Sulphur-containing pyrrolidine-fused chlorins as potential candidates for photodynamic therapy: experimental and theoretical photophysical evaluation

Two novel sulphur-containing pyrrolidine-fused chlorin derivatives, Chlor-SH_trans and Chlor-CSH_trans, were synthesized through a 1,3-dipolar cycloaddition reaction of meso-tetrakis(pentafluorophenyl)porphyrin with azomethine ylides generated in situ through the condensation of paraformaldehyde with cysteine or l-thiazolidine-4-carboxylic acid (for Chlor-SH_trans) and homocysteine (for Chlor-CSH_trans). The synthesized chlorins were structurally characterized using various techniques, including nuclear magnetic resonance, UV-vis absorption and fluorescence spectroscopy and mass spectrometry. Density functional theory calculations confirmed that the trans isomer is the most stable for both chlorins, corroborating nuclear magnetic resonance findings. The reaction mechanisms were elucidated, revealing the potential formation of multiple products from the interaction of formaldehyde units with the amino acids cysteine or homocysteine. Chlor-CSH_trans exhibited enhanced stability, potentially due to the formation of a six-membered ring. In dimethylformamide, Chlor-CSH_trans demonstrated a slightly higher molar absorption coefficient at 650 nm, but a lower fluorescence quantum yield compared to Chlor-SH_trans. Interestingly, Chlor-SH_trans showed enhanced singlet oxygen production, attributed to a higher value of spin-orbit coupling and higher triplet state stability. Neither chlorin exhibited significant aggregation or photodegradation at the studied concentrations, indicating promising properties for photodynamic applications.