Polypyridyl iron(II) complexes showing remarkable photocytotoxicity in visible light

Abstract

Iron(II) complexes of polypyridyl ligands (B), viz. [Fe(B) 2 ]Cl 2 (1 and 2) of N, N, N-donor 2-(2-pyridyl)-1,10-phenanthroline (pyphen in 1) and 3-(pyridin-2-yl)dipyrido[3,2-a:2',3'-c]phenazine (pydppz in 2), are prepared and characterized. They are 1:2 electrolytes in aqueous DMF. The diamagnetic complexes exhibit metal to ligand charge transfer band near 570 nm in DMF. The complexes are avid binders to calf thymus DNA giving binding constant (K b ) values of ∼10 6 M −1 suggesting significant intercalative DNA binding of the complexes due to presence of planar phenanthroline bases. Complex 2 exhibits significant photocytotoxicity in immortalized human keratinocyte cells HaCaT and breast cancer cell line MCF-7 giving IC 50 values of 0.08 and 13 μM in visible light (400-700 nm). Complex 2 shows only minor dark toxicity in HaCaT cells but is non-toxic in dark in MCF-7 cancer cells. The light-induced cellular damage follows apoptotic pathway on generation of reactive oxygen species as evidenced from the dichlorofluorescein diacetate (DCFDA) assay.

Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand

“…The LD50 values for complex 1 in HeLa cells are 0.2 μM with light and 1.6 μM without, giving a photo-index of 8. It is worth noting that while other compounds have been shown to have values of up to 3 magnitudes higher 22 23 , many other small metal complexes are reported with similar photo-indexes of <10 16 17 21 26 .…”

“…In several cancer cell models complex 1 has been demonstrated to behave as a promising photosensitizer under visible light (405 nm light, light dose 3.6 J cm −2 ). The typical light dose range used in PDT with small metal complexes is ~2–30 J cm −2 , demonstrating that complex 1 -induced photosensitizion can be caused by comparatively low doses of light 13 16 21 22 23 24 26 . The LD50 values for complex 1 in HeLa cells are 0.2 μM with light and 1.6 μM without, giving a photo-index of 8.…”

“…Recently, several examples of transition metal complexes as either oxygen dependent or independent photosensitizers in PDT have been reported, including Ru(II), Re(I) and Pt(IV) 9 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 . Here, we demonstrate the potential of a small, low-weight Pt(II) complex for PDT.…”

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

“…The same team published another diamagnetic Fe( ii ) complex bearing ligands, which induces apoptosis in cancer cells with significant phototoxicity under visible light irradiation ( Fe-2 ). 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.…”

Synthesis, Characterization, and Biological Evaluation of Red-Absorbing Fe(II) Polypyridine Complexes

“…A recent study has also demonstrated the use of pyridyldipyridophenazine substituted Fe(II) complexes as partial DNA intercalative binders. The complexes had phototoxicity upon visible light irradiation, in addition to a low dark toxicity [53]. Inspired from the works described above, we have decided to investigate the potential of Fe(II) polypyridyl complexes as chemotherapeutic agents and PDT PSs.…”