Mitochondria-localising DNA-binding biscyclometalated phenyltriazole iridium(iii) dipyridophenazene complexes: syntheses and cellular imaging properties

Abstract

Two new biscyclometalated complexes [Ir(ptzR)2(dppz)]+ (dppz = dipyridophenazene; ptzRH = 4-phenyl-1-benzyl-1,2,3-triazole (1+) and 4-phenyl-1-propyl-1,2,3-triazole (2+)) have been prepared. The hexafluorophosphate salts of these complexes have been fully characterized and, in one case, the X-ray structure of a nitrate salt was obtained. The DNA binding properties of the chloride salts of the complexes were investigated, as well as their cellular uptake by A2780 and MCF7 cell lines. Both complexes display an increase in the intensity of phosphorescence upon titration with duplex DNA, indicating the intercalation of the dppz ligand and, given that they are monocations, the complexes exhibit appreciable DNA binding affinity. Optical microscopy studies reveal that both complexes are taken up by live cancer cell lines displaying cytosol based luminescence. Colocalization studies with commercial probes show high Pearson coefficients with mitotracker dyes confirming that the new complexes specifically localize on mitochondria.

Ir(III)-Based Agents for Monitoring the Cytochrome P450 3A4 Active Site Occupancy

“…We chose to examine Ir­(III) and Ru­(II) complexes as probes for CYP3A4 because they are powerful tools for monitoring biological activity. − Probes of this class have long luminescence lifetimes, ranging from hundreds of nanoseconds up to ∼100 μs, ,, which allows for time-resolved gating that can be used to exclude background emission from biomolecules and fluorogenic substrates. Thus, these compounds were expected to provide a distinct advantage over previous CYP3A4 probes containing organic-based fluorescent groups, whose low nanosecond lifetimes preclude the measurement of CYP activity in human liver microsomes, the gold standard in drug metabolism.…”

Electron‐donor substituents on the dppz‐based ligands to control luminescence from dark to bright emissive state in Ir(III) complexes

“…All complexes exhibit pseudo‐octahedral geometries at the S 0 state. The calculated bond lengths and angles are in agreement with the crystalline structures of similar cyclometalated Ir(III) complexes . Some bond lengths and angles appear at: d (Ir‐C 1 and Ir‐C 2 ) = 2.019 Å, d (Ir‐N 1 ) = 2.080‐2.081 Å, d (Ir‐N 3 ) = 2.208‐2.209 Å, < C 1 ‐Ir‐N 1 = 80.14‐80.15°, <N 3 ‐Ir‐N 4 = 75.67‐75.75°, <N 1 ‐Ir‐N 2 = 174.02‐174.18°, <C 1 ‐Ir‐N 4 = 172.61‐172.68, without larger differences between them.…”

“…The versatility that offer the different substitution positions of the dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz) ligand as well as prolongation of their π‐systems has allowed the synthesis of many dppz derivates and also of their respective coordination complexes with Ru(II), Cu(II), Re(I), Rh(III), Ir(III), Os(II), and Pd(II) . Nevertheless, main research involving dppz‐based complexes have focused in applications related to photosensitizers and intercalation into DNA to probe their cytotoxic properties . Dppz‐based ligands are easily synthesized through a Schiff‐base condensation between 1,10‐phenanthroline‐5,6‐dione and the corresponding diamine in ethanol and are isolated in high yield and purity .…”

Ru(II)-Dppz Derivatives and Their Interactions with DNA: Thirty Years and Counting

“…A wide variety of dppz-based complexes were designed, synthesized, and studied by modifying the bipyridine ancillary ligand or the dppz ligand [73][74][75][76][77][78], or changing the metal center to Re [79][80][81][82], Co [83,84], Cu [85,86], Rh [87][88][89][90], Os [91,92], Pt [31,[93][94][95], and Ir [96][97][98] cations.…”