New modular manganese(I) tricarbonyl complexes as PhotoCORMs: in vitro detection of photoinduced carbon monoxide release using COP-1 as a fluorogenic switch-on probe.

Five manganese(i) tricarbonyl complexes of the general formulae [Mn(bpea(N=CHC6H4R))(CO)3]PF6 and [Mn(bpea(NHCH2C6H4R))(CO)3]PF6 based on the tridentate bis(pyrazolyl)ethylamine (bpea) ligand, each containing a pendant 4-substituted phenyl group with R = H, I, and C≡C-H, were synthesized and fully characterized, including X-ray structure analysis for three compounds. All complexes are stable in the dark in aqueous buffer for an extended period of time. However, CO-release could be triggered by illumination at 365 nm, establishing these compounds as novel photoactivatable CO-releasing molecules (PhotoCORMs). The influence of the imine vs. amine group in the ligands on the electronic structure and the photophysical behavior was investigated with the aid of DFT and TDDFT calculations. Solution IR studies on selected compounds allowed identification of intermediates resulting from the photoreaction. Finally, light-induced CO release from a model compound was demonstrated both in PBS buffer and in vitro in human umbilical vein endothelial cells (HUVECs) using COP-1 as a fluorescent switch-on probe.

Iron metal-organic frameworks MIL-88B and NH2-MIL-88B for the loading and delivery of the gasotransmitter carbon monoxide.

Crystals of MIL-88B-Fe and NH2-MIL-88B-Fe were prepared by a new rapid microwave-assisted solvothermal method. High-purity, spindle-shaped crystals of MIL-88B-Fe with a length of about 2 µm and a diameter of 1 µm and needle-shaped crystals of NH2-MIL-88B-Fe with a length of about 1.5 µm and a diameter of 300 nm were produced with uniform size and excellent crystallinity. The possibility to reduce the as-prepared frameworks and the chemical capture of carbon monoxide in these materials was studied by in situ ultrahigh vacuum Fourier-transform infrared (UHV-FTIR) spectroscopy and Mössbauer spectroscopy. CO binding occurs to unsaturated coordination sites (CUS). The release of CO from the as-prepared materials was studied by a myoglobin assay in physiological buffer. The release of CO from crystals of MIL-88B-Fe with t(1/2) = 38 min and from crystals of NH2-MIL-88B-Fe with t(1/2) = 76 min were found to be controlled by the degradation of the MIL materials under physiological conditions. These MIL-88B-Fe and NH2-MIL-88B-Fe materials show good biocompatibility and have the potential to be used in pharmacological and therapeutic applications as carriers and delivery vehicles for the gasotransmitter carbon monoxide.

Ultrafast Photochemistry of a Manganese-Tricarbonyl CO-Releasing Molecule (CORM) in Aqueous Solution.

Ultraviolet irradiation of a manganese-tricarbonyl CO-releasing molecule (CORM) in water eventually leads to the liberation of some of the carbon monoxide ligands. By ultraviolet pump/mid-infrared probe femtosecond transient absorption spectroscopy in combination with quantum chemical calculations, we could disclose for the exemplary compound [Mn(CO)3(tpm)](+) (tpm = tris(2-pyrazolyl)methane) that only one of the three carbonyl ligands is photochemically dissociated on an ultrafast time scale and that some molecules may undergo geminate recombination.

Sonogashira and "Click" reactions for the N-terminal and side-chain functionalization of peptides with [Mn(CO)3(tpm)]+-based CO releasing molecules (tpm = tris(pyrazolyl)methane).

A recently identified photoactivatable CO releasing molecule (CORM) based on [Mn(CO)(3)(tpm)](+) was conjugated to functionalized amino acids and model peptides using the Pd-catalyzed Sonogashira cross-coupling and the alkyne-azide 1,3-dipolar cycloaddition ("Click reaction"). Both were found to be fully compatible with all functional groups present. The CORM-peptide conjugates were isolated in reasonable yield and high purity, as indicated by IR spectroscopy, ESI mass spectrometry and RP-HPLC. The myoglobin assay was used to demonstrate that they have CO release properties identical those of the parent compound. This work thus opens the way for a targeted delivery of CORMs to cellular systems.

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

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.

Cellular uptake, cytotoxicity, and metabolic profiling of human cancer cells treated with ruthenium(II) polypyridyl complexes [Ru(bpy)2(N--N)]Cl2 with N--N=bpy, phen, dpq, dppz, and dppn.

A series of five ruthenium(II) polypyridyl complexes [Ru(bpy)2(N--N)]Cl2 was tested against human HT-29 and MCF-7 cancer cell lines. Cellular uptake efficiency and cytotoxicity were found to increase with the size of the aromatic surface area of the N--N ligand. The most active compound carrying the dppn ligand exhibits a low micromolar IC(50) value against both cell lines comparable to that of cisplatin under similar conditions. Continuous measurement of oxygen consumption, extracellular acidification rate, and impedance of the cell layer with a chip-based sensor system upon exposure to the complexes showed only small changes for the first two parameters throughout the series. A significant and irreversible decrease in impedance was, however, found for the dppn compound. This suggests that its biological activity is related to modifications in cell morphology or cell-cell and cell-matrix contacts.