Dipyrrinato-Iridium(III) Complexes for Application in Photodynamic Therapy and Antimicrobial Photodynamic Inactivation.

Affiliation

Hohlfeld BF(1)(2), Gitter B(2), Kingsbury CJ(3), Flanagan KJ(3), Steen D(2), Wieland GD(2), Kulak N(1)(4), Senge MO(3)(5), Wiehe A(1)(2).
Author information:
(1)Institut für Chemie u. Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
(2)biolitec research GmbH, Otto-Schott-Str. 15, 07745, Jena, Germany.
(3)Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, Trinity College Dublin, The University of Dublin, St James's Hospital, Dublin, 8, Ireland.
(4)Institut für Chemie, Otto-von-Guericke-Universität Magdeburg, Universitätsplatz 2, 39106, Magdeburg, Germany.
(5)Institute for Advanced Study
(TUM-IAS), Technical University of Munich, Lichtenbergstrasse 2a, 85748, Garching, Germany.

Abstract

The generation of bio-targetable photosensitizers is of utmost importance to the emerging field of photodynamic therapy and antimicrobial (photo-)therapy. A synthetic strategy is presented in which chelating dipyrrin moieties are used to enhance the known photoactivity of iridium(III) metal complexes. Formed complexes can thus be functionalized in a facile manner with a range of targeting groups at their chemically active reaction sites. Dipyrrins with N- and O-substituents afforded (dipy)iridium(III) complexes via complexation with the respective Cp*-iridium(III) and ppy-iridium(III) precursors (dipy=dipyrrinato, Cp*=pentamethyl-η5 -cyclopentadienyl, ppy=2-phenylpyridyl). Similarly, electron-deficient [IrIII (dipy)(ppy)2 ] complexes could be used for post-functionalization, forming alkenyl, alkynyl and glyco-appended iridium(III) complexes. The phototoxic activity of these complexes has been assessed in cellular and bacterial assays with and without light; the [IrIII (Cl)(Cp*)(dipy)] complexes and the glyco-substituted iridium(III) complexes showing particular promise as photomedicine candidates. Representative crystal structures of the complexes are also presented.