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

摘要

The application of porphyrinoids in biomedical fields, such as photodynamic therapy (PDT), requires the introduction of functional groups to tune their solubility for 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, which can easily undergo a regiospecific nucleophilic replacement (SNAr) of its para-fluorine atom by a number of nucleophiles. Here, it is shown that, instead of amino-substitution on the final porphyrinoid or BODIPY (boron dipyrromethene), 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 gave access to trans-A(2)B(2)-porphyrins and trans-A(2)B-corroles. By using pentafluorobenzaldehyde, it was possible to introduce another para-fluorine atom, which enabled the synthesis of multifunctionalized tetrapyrroles. Furthermore, alkoxy-and amino-substituted dipyrranes were applied to the synthesis of A(3)B(3)-hexaphyrins. The polar porphyrins that were prepared by using this method exhibited in vitro PDT activity against several tumor cell lines.