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

• Published in: Chemistry : a European journal Vol. 27; no. 21; pp. 6440 - 6459
• Main Authors: Hohlfeld, Benjamin F., Gitter, Burkhard, Kingsbury, Christopher J., Flanagan, Keith J., Steen, Dorika, Wieland, Gerhard D., Kulak, Nora, Senge, Mathias O., Wiehe, Arno
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 12-04-2021; John Wiley and Sons Inc
• Subjects: (dipyrrinato)iridium(III) complexes; Anti-Infective Agents; Antiinfectives and antibacterials; Antimicrobial agents; antimicrobial photodynamic inactivation; Chelation; Chemistry; Coordination Complexes - pharmacology; Coordination compounds; Crystal structure; dipyrrins; glycosylation; Inactivation; Iridium; Iridium compounds; Metal complexes; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents; glycosylation; antimicrobial photodynamic inactivation; dipyrrins; photodynamic therapy; (dipyrrinato)iridium(III) complexes
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202004776

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.
Heteroleptic dipyrrinato iridium complexes were synthesized and evaluated for their phototoxic activity against tumor cells and bacteria, the Gram‐positive germ S. aureus and the Gram‐negative Germ P. aeruginosa. Specifically, glycosylated phenylpyridyl‐dipyrrinato complexes showed a high phototoxic effect against cells and S. aureus. Certain cyclopentadienyl‐dipyrrinato complexes exerted a high phototoxic effect on S. aureus and P. aeruginosa.