Ruthenium– and cobalt–based artificial metalloenzymes for photocatalytic water oxidation in artificial photosynthesis

Producing green energy has become the main goal in our society in the search of reducing or eliminating the carbon emission from fossil fuels. In this project, proteins were used as a tool to develop an artificial system capable of promoting the most demanding reaction in photosynthesis, water oxidation, as a new concept of producing energy from a green source. For this purpose, a screening study of the interaction between selected proteins and a library photocatalytic ruthenium and cobalt complexes was carried out. The results from such study allowed the production of two types of artificial metalloenzymes (ArM) which were proven to be able to perform water oxidation reaction via blue light irradiation. As well, an unusual interaction between proteins which promote the photocatalytic O2 evolution from water. These findings lead to develop ruthenium and cobalt metalloenzymes as promising candidates for artificial photosynthesis in bio-inspired systemsMetals in Catalysis, Biomimetics & Inorganic Material

An artificial metalloenzyme that can oxidize water photocatalytically: design, synthesis, and characterization

Metals in Catalysis, Biomimetics & Inorganic MaterialsSolid state NMR/Biophysical Organic ChemistryBiological and Soft Matter Physic

A screening method for binding synthetic metallo-complexes to haem proteins

The introduction of a second coordination sphere, in the form of a protein scaffold, to synthetic catalysts can be beneficial for their reactivity and substrate selectivity. Here we present semi-native polyacrylamide gel elec-trophoresis (semi-native PAGE) as a rapid screening method for studying metal complex-protein interactions. Such a screening is generally performed using electron spray ionization mass spectrometry (ESI-MS) and/or UV-Vis spectroscopy. Semi-native PAGE analysis has the advantage that it does not rely on spectral changes of the metal complex upon protein interaction and can be applied for high-throughput screening and optimization of complex binding. In semi-native PAGE non-denatured protein samples are loaded on a gel containing sodium dodecyl sulphate (SDS), leading to separation based on differences in structural stability. Semi-native PAGE gel runs of catalyst-protein mixtures were compared to gel runs obtained with native and denaturing PAGE. ESI-MS was additionally realised to confirm protein-complex binding. The general applicability of semi-native PAGE was investigated by screening the binding of various cobalt-and ruthenium-based compounds to three types of haem proteins.Metals in Catalysis, Biomimetics & Inorganic MaterialsSolid state NMR/Biophysical Organic Chemistr

Cyclic ruthenium-peptide conjugates as integrin-targeting phototherapeutic prodrugs for the treatment of brain tumors

To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Ph2phen)2(OH2)2]2+, was conjugated to the RGD-containing Ac-MRGDH-NH2 peptide by direct coordination of the M and H residues to the metal. This design afforded two diastereoisomers of a cyclic metallopeptide, Λ-[1]Cl2 and Δ-[1]Cl2. In the dark, the ruthenium-chelating peptide had a triple action. First, it prevented other biomolecules from coordinating with the metal center. Second, its hydrophilicity made [1]Cl2 amphiphilic so that it self-assembled in culture medium into nanoparticles. Third, it acted as a tumor-targeting motif by strongly binding to the integrin (Kd = 0.061 μM for the binding of Λ-[1]Cl2 to αIIbβ3), which resulted in the receptor-mediated uptake of the conjugate in vitro. Phototoxicity studies in two-dimensional (2D) monolayers of A549, U87MG, and PC-3 human cancer cell lines and U87MG three-dimensional (3D) tumor spheroids showed that the two isomers of [1]Cl2 were strongly phototoxic, with photoindexes up to 17. Mechanistic studies indicated that such phototoxicity was due to a combination of photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) effects, resulting from both reactive oxygen species generation and peptide photosubstitution. Finally, in vivo studies in a subcutaneous U87MG glioblastoma mice model showed that [1]Cl2 efficiently accumulated in the tumor 12 h after injection, where green light irradiation generated a stronger tumoricidal effect than a nontargeted analogue ruthenium complex [2]Cl2. Considering the absence of systemic toxicity for the treated mice, these results demonstrate the high potential of light-sensitive integrin-targeted ruthenium-based anticancer compounds for the treatment of brain cancer in vivo.Metals in Catalysis, Biomimetics & Inorganic MaterialsAnimal science

Ruthenium– and cobalt–based artificial metalloenzymes for photocatalytic water oxidation in artificial photosynthesis

Producing green energy has become the main goal in our society in the search of reducing or eliminating the carbon emission from fossil fuels. In this project, proteins were used as a tool to develop an artificial system capable of promoting the most demanding reaction in photosynthesis, water oxidation, as a new concept of producing energy from a green source. For this purpose, a screening study of the interaction between selected proteins and a library photocatalytic ruthenium and cobalt complexes was carried out. The results from such study allowed the production of two types of artificial metalloenzymes (ArM) which were proven to be able to perform water oxidation reaction via blue light irradiation. As well, an unusual interaction between proteins which promote the photocatalytic O2 evolution from water. These findings lead to develop ruthenium and cobalt metalloenzymes as promising candidates for artificial photosynthesis in bio-inspired systems</p