Nucleophilic Aromatic Substitution on Pentafluorophenyl-Substituted Dipyrranes and Tetrapyrroles as a Route to Multifunctionalized Chromophores for Potential Application in Photodynamic Therapy

Abstract

The application of porphyrinoids in biomedical fields like photodynamic therapy (PDT) requires the introduction of functional groups to adjust their solubility in the biological environment and to allow a coupling to other active moieties or carrier systems. A valuable motif in this regard is the pentafluorophenyl (PFP)- substituent, as the PFP-group easily undergoes a regiospecific nucleophilic replacement (SNAr) of the para-fluorine atom by a number of nucleophiles. Here, it is shown that - alternatively to an amino-substitution on the final porphyrinoid or BODIPY - the precursor 5-(PFP)-dipyrrane can be modified with amines (or alcohols). These dipyrranes were transformed into amino-substituted BODIPYs. Condensation of these dipyrranes with aldehydes gives access to trans-A2B2-porphyrins and -A2B-corroles. Using pentafluorobenzaldehyde another para-fluorine atom can be introduced enabling the synthesis of multifunctionalized tetrapyrroles. Furthermore, alkoxy- and amino-substituted dipyrranes were applied to the synthesis of A3B3-hexaphyrins. With this approach polar porphyrins can be prepared, which exhibit in vitro PDT activity against several tumor cell lines