Novel Cyclometalated Fe(II) Complex with NCN Pincer and BODIPY‐Appended 4'‐Ethynyl‐2,2':6',2”‐terpyridine as Mitochondria‐Targeted Photodynamic Anticancer Agents

Abstract

BODIPY (boron dipyrromethene) derivatives and iron complexes are two types of functional compounds that have found wide applications in the fields of biology and medicine. The new class of cyclometalated Fe(II) complex with NCN pincer and meso‐phenyl‐4'‐ethynyl‐2,2':6',2”‐terpyridine BODIPY ligands of formula [Fe(L)(tpy‐BODIPY)], 1, in which HL:5‐methoxy‐1,3‐bis (1‐methyl‐1H‐benzo[d]imidazol‐2‐yl)benzene, tpy‐BODIPY: 8‐(4‐phenyl‐4'‐ethynyl‐2,2':6',2”‐terpyridine) BODIPY, has been synthesized and studied as mitochondria‐targeted photodynamic therapy (PDT). Complex 1 showed photocytotoxicity in HeLa cells at 500 nm with low dark toxicity. The phototoxicity of complex 1 on the nontumorigenic MRC‐5 cell line showed the same trend observed for HeLa cells, that is moderately photocytotoxic against the nontumorigenic MRC‐5 cell line (IC50 = 36.21 μM). Moreover, complex 1 selectively localizes into mitochondria of the HeLa cells. The photophysical properties, cellular uptake, reactive oxygen species (ROS) generation, and cellular apoptosis of complex 1 have also been studied.Overall, the new Fe(II) complex with BODIPY moiety is significantly photocytotoxic in HeLa cells when irradiated with visible light of 500 nm giving as mitochondria targeting. Therefore, we present cyclometalated Fe(II) pincer complex induced mitochondria‐targeted PDT involving the BODIPY moiety that develops persuasively designed photoactivatable Fe(II) complexes.

Phototherapeutic anticancer strategies with first-row transition metal complexes: a critical review

“…76 A new type of Fe( ii ) complex was presented in 2018 by Tabrizi: it bears a tridentate ligand (which stabilizes the ferrous state as a pincer) appended with a BODIPY moiety known for its mitochondria-targeting, photodynamic and emissive properties ( Fe-3 ). 77 The complex displays good cytotoxicity upon 500 nm irradiation (1.06 μM in HeLa cells) while remaining essentially non-toxic in the dark. The BODIPY moiety allowed cellular imaging: the complex actually accumulates in the mitochondria.…”

Photodynamic Therapy of Inorganic Complexes for the Treatment of Cancer†

“…3. This resulted in a IC 50 values of 1.05 ± 0.3 µ m , against HeLa cells, and 36.21 ± 0.2 µ m , against noncancerous MRC‐5 cells, in the presence of a light source with λ = 500 nm (58).…”

Dibromine Promoted Transmetalation of an Organomercurial by Fe(CO)5: Synthesis, Properties, and Cytotoxicity of Bis(2-C6H4-2′-py-κC,N)dicarbonyliron(II)

“…Substitution Reactions. With the goal to convert complex 1 into species similar to RDCs and ODCs, which possess impressive anticancer activities, [15][16][17][18][19][20][21][22][23][24]53 an attempt was made to replace carbonyls by N or P donor ligands. First, the reaction between 1 and 4,4′-dimethyl-2,2′-bipyridine (N∩N) was explored at 20 °C in CH 2 Cl 2 .…”

“…Therefore, synthesis of phenylpyridine-based (phpyH) cyclometalated iron complexes seemed to be an undeniable way to new, more cytotoxic iron compounds that could bypass the need for caspase-dependent apoptosis. As a proof of this statement, the N–C–N pincer iron­(II) complex [Fe­(L)­(tpy-BODIPY)] + (L = 5-methoxy-1,3-bis­(1-methyl-1H-benzo­[d]­imidazol-2-yl)­benzene; tpy-BODIPY = 8-(4-phenyl-4′-ethynyl-2,2′:6′,2″-terpyridine) recently synthesized by Tabrizi et al showed a good photocytotoxicity in HeLa cancer cell line, particularly when activated by visible light . Unfortunately, there are no general methods of preparation of cyclometalated iron­(II/III) complexes.…”

“…As a proof of this statement, the N−C− N pincer iron(II) complex [Fe(L)(tpy-BODIPY)] + (L = 5methoxy-1,3-bis(1-methyl-1H-benzo[d]imidazol-2-yl)benzene; tpy-BODIPY = 8-(4-phenyl-4′-ethynyl-2,2′:6′,2″-terpyridine) recently synthesized by Tabrizi et al showed a good photocytotoxicity in HeLa cancer cell line, particularly when activated by visible light. 23 Unfortunately, there are no general methods of preparation of cyclometalated iron(II/III) complexes. A few have been previously prepared by activation of coordinated phosphines, imine, or diazo ligands.…”