title: 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, 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-A2B2-porphyrins and trans-A2B-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 A3B3-hexaphyrins. The polar porphyrins that were prepared by using this method exhibited in vitro PDT activity against several tumor cell lines.
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Fabeckstrasse 34/36, 14195, Berlin, Germany.|Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.|biolitec research GmbH, Otto-Schott-Str. 15, 07745, Jena, Germany.
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Gutsche
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Fabeckstrasse 34/36, 14195, Berlin, Germany.|Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.|biolitec research GmbH, Otto-Schott-Str. 15, 07745, Jena, Germany.
authors.forename: Marlene
authors.initials: M
authors.lastname: Ortwerth
authors.affiliation: biolitec research GmbH, Otto-Schott-Str. 15, 07745, Jena, Germany.
authors.forename: Susanna
authors.initials: S
authors.lastname: Gräfe
authors.affiliation: School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity Biomedical Sciences Institute, Trinity College Dublin, The University of Dublin, 152-160 Pearse Street, Dublin 2, Ireland.
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Flanagan
authors.affiliation: School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity Biomedical Sciences Institute, Trinity College Dublin, The University of Dublin, 152-160 Pearse Street, Dublin 2, Ireland.
authors.forename: Mathias O
authors.initials: MO
authors.lastname: Senge
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Reissig
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Fabeckstrasse 34/36, 14195, Berlin, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Kulak
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany. arno.wiehe@biolitec.de.|biolitec research GmbH, Otto-Schott-Str. 15, 07745, Jena, Germany. arno.wiehe@biolitec.de.
authors.forename: Arno
authors.initials: A
authors.lastname: Wiehe
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry; D001547:Benzaldehydes / Q000138:chemical synthesis / Q000737:chemistry; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D054879:Halogenation; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry*; D045725:Tetrapyrroles / Q000138:chemical synthesis / Q000737:chemistry*; D005464:Fluorobenzenes; D005466:Fluorocarbons
chemical_list: D000588:Amines; D001547:Benzaldehydes; D001896:Boron Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; D011758:Pyrroles; D045725:Tetrapyrroles; C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; C431863:corrole; C413389:pentafluorobenzaldehyde; D005464:Fluorobenzenes; D005466:Fluorocarbons
keywords: amines; fluorine; nucleophilic substitution; photodynamic therapy; porphyrinoids