Structurally Characterized BODIPY-Appended Oxidovanadium(IV) β-Diketonates for Mitochondria-Targeted Photocytotoxicity

Abstract

Mixed-ligand oxidovanadium(IV) β-diketonates having NNN-donor dipicolylamine-conjugated to boron-dipyrromethene (BOD-IPY in L 1 ) and diiodo-BODIPY (in L 2 ) moieties, namely, [VO(L 1 )(acac)] Cl (1), [VO(L 2 )(acac)]Cl (2), and [VO(L 1 )(dbm)]Cl (3), where acac and dbm are monoanionic O,O-donor acetylacetone and 1,3-diphenyl-1,3propanedione, were prepared, characterized, and tested for their photoinduced anticancer activity in visible light. Complexes 1 and 2 were structurally characterized as their PF 6 − salts (1a and 2a) by X-ray crystallography. They showed V IV N 3 O 3 six-coordinate geometry with dipicolylamine base as the facial ligand. The non-iodinated BODIPY complexes displayed absorption maxima at ∼501 nm, while it is ∼535 nm for the di-iodinated 2 in 10% DMSO−PBS buffer medium (pH = 7.2). Complexes 1 and 3 being green emissive (λ em , ∼512 nm; λ ex , 470 nm; Φ F , ∼0.10) in 10% aqueous DMSO were used for cellular imaging studies. Complex 3 localized primarily in the mitochondria of the cervical HeLa cells with a co-localization coefficient value of 0.7. The nonemissive diiodo-BODIPY complex 2 showed generation of singlet oxygen (Φ Δ ≈ 0.47) on light activation. Annexin-V assay showed singlet oxygen-mediated cellular apoptosis, making this complex a targeted PDT agent.

Lysosomes Targeting pH Activable Imaging‐Guided Photodynamic Agents

“…Indeed, compared to the two latter producing respectively 1 O 2 in 87 % and 64 % quantum yields (see SI), the values are here lower. However, they are comparable to those reported for some bis‐iodo BODIPY derivatives with (or without) quenching functional groups, considering the different experimental conditions [40,41,51,75–77] . As expected, no 1 O 2 production was observed in the absence of protonation of the amino groups (see SI).…”

“…[28][29][30][31] The synthetic versatility of BODIPYs also allows to increase the selectivity towards the targeted tissues by conjugation to biomolecules for selective system delivery, [32][33][34][35][36][37][38] or by specific stimuli-responsive activation of the PS. [14][15][16] Indeed, the BODIPY molecular structure can be engineered with functional groups turning on or off specific spectroscopic signatures of molecules under specific physiological conditions and upon reaction with specific analytes allowing accumulation in targeted subcellular compartments, e. g., lysosomes, [39][40][41][42][43] lipidic membrane, [44][45][46][47][48] mitochondria, [43,[49][50][51][52][53][54][55][56][57] endoplasmic reticulum [43,58] and nucleus. [59][60][61] More specifically, targeting the lysosomes is a known strategy to develop efficient anticancer therapeutics, including PDT agents, fluorescent probes and theranostic agents.…”

BODIPY as a Multifunctional Theranostic Reagent in Biomedicine: Self‐Assembly, Properties, and Applications

“…BODIPY units can also participate in the formation of assemblies as PSs. For example, Chakravarty and co‐workers [ 246 ] reported a series of mixed‐ligand oxidovanadium(IV) complexes of β‐diketones. Tridentate dipicolylamine ligands contain noniodinated and di‐iodinated BODIPY moieties as pendants.…”

Self-Assembled BODIPY Nanoparticles for Near-Infrared Fluorescence Bioimaging

“…However, this may deteriorate its solubility and increase the difficulty in synthesizing BODIPY. The construction and modification of D-A structures on BODIPY have also been proven as efficient methods to achieve NIR emission, which not only red-shift the emission but also avoid the above-mentioned disadvantages [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. Additionally, in view of the main differences between the internal aqueous system of living organisms and the inherent hydrophobicity of BODIPY, it is particularly important to improve the water solubility of BODIPY through various modification methods [ 42 , 43 ].…”