Synthesis, Structures, and CO Release Capacity of a Family of Water-Soluble PhotoCORMs: Assessment of the Biocompatibility and Their Phototoxicity toward Human Breast Cancer Cells

Abstract

Two manganese(I) carbonyl complexes derived from 2-(pyridyl)benzothiazole (pbt) and 1,10-phenanthroline (phen) release carbon monoxide (CO) under low-power broad-band visible-light illumination. CO photorelease from [Mn(CO)(pbt)(PTA)]CFSO (1, where PTA = 1,3,5-triaza-7-phosphaadamantane) is accompanied by an emergence of a strong fluorescence around 400 nm from almost nonfluorescent preirradiated 1. However, [Mn(CO)(phen)(PTA)]CFSO (2) showed no such phenomenon upon prolonged illumination under similar experimental conditions. The two analogous rhenium(I) complexes, namely, [Re(CO)(pbt)(PTA)]CFSO (3) and [Re(CO)(phen)(PTA)]CFSO (4), have also been synthesized and characterized to compare their photo properties with the manganese congeners. Complexes 3 and 4 exhibit moderate CO release upon irradiation with low-power UV light. All four complexes are highly soluble in anaerobic/aerobic aqueous media and are also considerably more stable when kept under dark conditions. The inherently luminescent rhenium complex 3 was utilized to demonstrate cellular internalization of these types of compounds by MDA-MB-231 (human breast cancer) cells, while the two biocompatible manganese(I) complexes (1 and 2) have been applied to assess the cell viability of these malignant cells upon CO delivery.

CO-Induced apoptotic death of colorectal cancer cells by a luminescent photoCORM grafted on biocompatible carboxymethyl chitosan

“…CO delivered from such discrete complexes has been shown to eradicate human breast and cervical cancer cells quite effectively in a dose-dependent manner. 10,11 However, site-specific delivery of these CO releasing prodrugs remains as a tantalizing challenge. Moreover systemic toxicity that might arise from the photoproduct(s) is another major concern.…”

Tracking CO Release in Cells via the Luminescence of Donor Molecules and/or their By‐Products

“…The luminescence properties of 7 thus allow for tracking of both the localization of the compound in cells and the CO release reaction. The water soluble [Re(CO) 3 (pbt)(PTA)]O 3 SCF 3 ( 8 , PTA=1,3,5‐triaza‐7‐phosphaadamantane) and [Re(CO) 3 (phen)(PTA)]O 3 SCF 3 ( 9 ) (Figure ) exhibit similar CO release and turn‐off emissive properties (λ em ∼550 nm), with the former having also been evaluated in MDA‐MB‐231 cells …”

“…A more insightful approach to assess CO delivery is via the use of photoCORMs that exhibit trackable luminescence with turn‐off behaviour upon CO release. Examples of Re(I) compounds of this type have been recently developed ,. The first example was reported in the context of designing metal carbonyl‐loaded mesoporous silica nanoparticles for CO delivery .…”

“…Several Mn(I) complexes containing a chelate fluorescent ligand and the [Mn(I)(CO) 3 ] unit have been shown to act as turn‐on photoCORMs for tracking CO release. Mascharak and co‐workers reported that the Mn(I) photoCORMs 10 and 11 (Figure ) exhibit turn‐on luminescence behaviour upon visible light‐induced CO release ,. The appearance of luminescence in these complexes is associated with the oxidation of Mn(I) to Mn(II) and the release of the bidentate 2‐(2‐pyridyl)‐benzothiazole (pbt) ligand, which exhibits a blue emission (λ em =400 nm) as a free organic molecule.…”

“…This change also corresponds to the release of all three CO ligands. To date, the feasibility of 10 as a turn‐on photoCORM in cells has not been reported . Toxicity studies show that 10 does exhibit CO‐induced dose‐dependent eradication of MDA‐MB‐231 cells (∼50 % at 100 μM).…”