Photoinduced CO release, cellular uptake and cytotoxicity of a tris(pyrazolyl)methane (tpm) manganese tricarbonyl complex

Abstract

Cell viability studies of HT29 colon cancer cells treated with the CO-releasing compound [Mn(CO)(3)(tpm)]PF(6) revealed a significant photoinduced cytotoxicity comparable to that of established agent 5-fluorouracil (5-FU), while controls kept in the dark were unaffected at up to 100 microM.

PhotoCORMs: CO release moves into the visible

“…4). 46 This manganesebased system features a tris(pyrazolyl)methane (tpm) supporting ligand, leaving three sites on the metal filled by CO. Whilst this might be expected to allow the complex to deliver three equivalents of carbon monoxide, photolysis of 3 at 365 nm yielded only two photolabile CO molecules per metal centre. Nuernberger and co-workers later established using ultrafast laser spectroscopy that only one of the CO groups is liberated from the metal centre by the primary photochemical step.…”

“…65,67,75,80 Whilst these studies show that the compounds tests are not toxic, the potential of photoCORMs in active toxicity toward cancer cells has also been considered. 46,74 The latter studies focus on the possible 'turn on' of activity when irradiated.…”

Femtosecond Mid-Infrared Study of the Aqueous Solution Photochemistry of a CO-Releasing Molecule (CORM)

“…Suitable compounds have to be stable in air and in water, soluble in water, and specific to particular tissues. Recently synthesized metal carbonyl complexes can act as dark-stable prodrugs under physiological conditions [1,2]. One of them is the [Mn(CO) 3 (tpm)]Cl (tris(pyrazolyl)methane (tpm) manganese tricarbonyl) complex (Fig.…”

“…1a) investigated in this study. The complex undergoes photoinduced CO release upon UV irradiation and has been shown to be cytotoxic against cancer cells [2].…”

“…in [4][5][6]), the photolysis of CO in water-soluble CORMs with suitable properties for biological applications have so far only been studied on a macroscopic scale and at irradiation times of several minutes. For the CORM studied here, UV irradiation eventually leads to the release of two [2] or even all three CO ligands [3]. We have studied the primary processes of CO release from the CORM using UV/mid-IR transient absorption spectroscopy (for details on the experimental setup, cf.…”