Monofunctional BODIPY-Appended Imidazoplatin for Cellular Imaging and Mitochondria-Targeted Photocytotoxicity

Abstract

Monofunctional platinum(II) complexes of formulation cis-[Pt(NH)(L)Cl](NO), where L is an imidazole base conjugated to 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) with emissive (L in 1) and nonemissive (L in 2) moieties were prepared and characterized, and their singlet oxygen-mediated photoinduced cytotoxicity was studied. The 1-methylimidazole (1-MeIm) complex 3 was prepared as a control and for structural characterization by X-ray crystallography. Complexes 1 and 2 showed strong visible absorption bands at 500 nm (ε = 2.7 × 10 M cm) and 540 nm (1.4 × 10 M cm). Complex 1 is emissive with a band at 510 nm (Φ = 0.09) in 1% dimethyl sulfoxide/Dulbecco's Modified Eagle's Medium (pH 7.2). Singlet oxygen generation upon photoirradiation with visible light (400-700 nm) was evidenced from 1,3-diphenylisobenzofuran titration experiments showing significant photosensitizing ability of the BODIPY complexes. Both 1 and 2 were remarkably photocytotoxic in visible light (400-700 nm, 10 J cm) in skin keratinocyte HaCaT and breast cancer MCF-7 cells giving IC values in nanomolar concentration. The complexes were, however, essentially nontoxic to the cells in the dark (IC > 80 μM). Complex 2 having a diiodo-BODIPY unit is nonemissive but an efficient photosensitizer with high singlet oxygen generation ability in visible light (400-700 nm). Confocal microscopy using the emissive complex 1 showed significant mitochondrial localization of the complex. Cell death via apoptotic pathway was observed from the Annexin-V-FITC/PI assay. The formation of Pt-DNA adducts was evidenced from the binding experiments of the complexes 1 and 2 with 9-ethylguanine as a model nucleobase from H NMR and mass spectral studies.

Bioactive Heterobimetallic Re(I)/Au(I) Complexes Containing Bidentate N-Heterocyclic Carbenes

“…1 The aim of this strategy is the compilation of information regarding the biodistribution and inner-interplay of drugs with the biological targets in order to design and deliver a sophisticated generation of anticancer metallodrugs. Within this framework several metallic structures combining well-known anticancer metal species such as cisplatin, 2 auranofin, 3 and RAPTA 4 analogues with either an organic chromophore or an emissive metallic species have already been described (see Figure 1A). However, a step forward would be the incorporation of an emissive species that is able to add extra antiproliferative value to the metallodrugs.…”

“…9 Therefore, it can be postulated that the combination of an NHC-Re(I) derivative with a metallodrug would be an excellent approach to maximize the therapeutic potential of a trackable metallodrug. Additionally, further substitution of L, which to the best of our knowledge has been only reported as a halogen for these types of Re(I) bidentate N-heterocyclic carbene derivatives 10 for a neutral N-donor ligand, will deliver high-potential mitochondrial bioprobes, as (1) cationic species present a greater predisposition to permeate those cellular membranes and (2) the N-donor ligand could be easily used as a linker to build the theranostic agents. Moreover, new grounds for the photophysical properties of these types of Re(I) complexes would be established.…”

Gold and platinum alkynyl complexes for biomedical applications

“…96 BODIPY is well-known for its versatile photosensitizing and photophysical 97 properties and it has been previously reported to be localized in the mitochondria of cancer cells. 98 Additionally, the use of an appending glucose to look for specific targeting is a common strategy to confer selectivity as many tumors have the glucose transporter GLUT-1 overexpressed. 99 In the present case, the photoinduced anticancer activity of 110 and its analogous complex lacking of the appended glucose moiety, complex 111, as well as the parent complex lacking also of BODIPY, complex 112, was investigated against HeLa, MCF-7 and A549 cells in dark and under red light (λ ¼ 600-720 nm).…”

Photodynamic Applications of New Imidazo[4,5‐f][1,10]phenanthroline Oxidovanadium(IV) Complexes: Synthesis, Photochemical, and Cytotoxic Evaluation

“…[13][14][15][16] Several transition metals complexes that release CO or NO and generate singlet oxygen or other reactive oxygen species (ROS) upon photoactivation are being explored for photochemotherapeutic applications. [17][18][19][20][21][22][23][24][25][26] Later transition metal complexes that absorb high-energy light (< 600 nm) are contraindicated for phototherapeutic applications. This is because high-energy light does not penetrate tumor tissue deeply, and heavy metals have some degree of inherent toxicity.…”