BODIPY-Ruthenium(II) Bis-Terpyridine Complexes for Cellular Imaging and Type-I/-II Photodynamic Therapy

Abstract

A series of multichromophoric ruthenium(II) complexes with the formulation [Ru(tpy-BODIPY)(tpy-R)]Cl 2 (1−4), having a heteroleptic Ru(II)-bis-tpy (tpy = 4′-phenyl-2,2′:6′,2″-terpyridine) moiety covalently linked to a boron-dipyrromethene (BODIPY) pendant, have been prepared and characterized and their application as a phototherapeutic and photodetection agent in cancer therapy has been explored. Ligand L 1 with a terpyridine-BODIPY moiety and complex 1 as its PF 6 salt (1a) have been structurally characterized by a single-crystal Xray diffraction study. Complex 1a has a distorted-octahedral RuN 6 core with a Ru(II)-bis-terpyridine unit that is covalently linked to one photoactive BODIPY unit. The complexes exhibit strong absorbance near 502 nm (ε ≈ (3.7−7.8) × 10 4 M −1 cm −1 ) and high singlet oxygen sensitization ability, giving singlet oxygen quantum yield (Φ Δ ) values ranging from 0.57 to 0.75 in DMSO. An emission-based study using complex 4 and Singlet Oxygen Sensor Green (SOSG) displays the formation of singlet oxygen inside the cells and also in the buffer medium upon light irradiation. DNA (pUC19) photocleavage experiments using ROS scavengers/stabilizers reveal photoinduced generation of singlet oxygen by a type-II process and of the superoxide anion radical by a type-I process. Complex 4 having a pendant biotin moiety as a cancer cell targeting group shows high photocytotoxicity with a remarkable phototherapeutic index (PI) value of >1400 in HeLa cancer cells with a low light dose activation (400−700 nm, 2.2 J cm −2 ). The complexes display reduced activity in noncancerous HPL1D cells. The emission property of the complexes is used for cellular imaging, thus making them suitable as next-generation theranostic PDT agents.

BODIPY-conjugated bis-terpyridine Ru(ii) complexes showing ultra-long luminescence lifetimes and applications to triplet–triplet annihilation upconversion

“…1 The chemical structures of the previously reported bodipy containing complexes. 20,43,[46][47][48]…”

“…[42][43][44][45][46] Fig. 1 summarizes some excellent examples of employing bodipy chromophores to regulate the excited states of metal complexes, 20,43,[46][47][48] including several recently reported terpyridine Ru(II) complexes. 20,48 The triplet state lifetimes were significantly prolonged to tens of microseconds.…”

“…1 summarizes some excellent examples of employing bodipy chromophores to regulate the excited states of metal complexes, 20,43,[46][47][48] including several recently reported terpyridine Ru(II) complexes. 20,48 The triplet state lifetimes were significantly prolonged to tens of microseconds. However, in most cases, the phosphorescence of both the coordination centre and bodipy unit was quenched, and the complexes were non-emissive, e.g., compounds 3 and 4.…”

“…11,12 The 3 IL state usually has a much longer lifetime but is often non-emissive due to the non-conjugated connection between the visible light-harvesting antenna and the coordination center which led to a weak heavy atom effect of the coordinated metal atoms. 20,21 Thus, the luminescence lifetime achieved in terpyridine complexes so far is still not satisfactory; 22,23 together with the weak absorption of the MLCT state, [Ru(tpy) 2 ] 2+ complexes have never been used as photosensitizers for TTA-UC so far.…”

How Computations Can Assist the Rational Design of Drugs for Photodynamic Therapy: Photosensitizing Activity Assessment of a Ru(II)-BODIPY Assembly

“…In order to overcome these limits, and thereby increasing the range of treatable cancers, many efforts were focused on developing systems that exhibit a red-shifted maximum absorption wavelength (λ max ). One way to shift λ max is the coordination of ligands with extended π-systems just such as BODIPYs [ 32 ]. This strategy allows for prolonging the lifetime of the Ru(II) triplet excited state due to a greater ISC and to obtain a higher singlet oxygen yield.…”