Four-electron deoxygenative reductive coupling of carbon monoxide at a single metal site

Carbon dioxide is the ultimate source of the fossil fuels that are both central to modern life and problematic: their use increases atmospheric levels of greenhouse gases, and their availability is geopolitically constrained. Using carbon dioxide as a feedstock to produce synthetic fuels might, in principle, alleviate these concerns. Although many homogeneous and heterogeneous catalysts convert carbon dioxide to carbon monoxide, further deoxygenative coupling of carbon monoxide to generate useful multicarbon products is challenging. Molybdenum and vanadium nitrogenases are capable of converting carbon monoxide into hydrocarbons under mild conditions, using discrete electron and proton sources. Electrocatalytic reduction of carbon monoxide on copper catalysts also uses a combination of electrons and protons, while the industrial Fischer–Tropsch process uses dihydrogen as a combined source of electrons and electrophiles for carbon monoxide coupling at high temperatures and pressures6. However, these enzymatic and heterogeneous systems are difficult to probe mechanistically. Molecular catalysts have been studied extensively to investigate the elementary steps by which carbon monoxide is deoxygenated and coupled, but a single metal site that can efficiently induce the required scission of carbon–oxygen bonds and generate carbon–carbon bonds has not yet been documented. Here we describe a molybdenum compound, supported by a terphenyl–diphosphine ligand, that activates and cleaves the strong carbon–oxygen bond of carbon monoxide, enacts carbon–carbon coupling, and spontaneously dissociates the resulting fragment. This complex four-electron transformation is enabled by the terphenyl–diphosphine ligand, which acts as an electron reservoir and exhibits the coordinative flexibility needed to stabilize the different intermediates involved in the overall reaction sequence. We anticipate that these design elements might help in the development of efficient catalysts for converting carbon monoxide to chemical fuels, and should prove useful in the broader context of performing complex multi-electron transformations at a single metal site

Blood vessel density correlates with the effects of targeted intra-arterial carboplatin infusion with concurrent radiotherapy for squamous cell carcinomas of the oral cavity and oropharynx

Our aim was first to evaluate the association between blood vessel density (BVD) and free platinum concentration in experimentally induced tumours in rabbits. We also investigated the association between tumour BVD and the clinical response of patients who had undergone targeted carboplatin intra-arterial (i.a.) chemoradiotherapy. VX2 carcinoma cells were transplanted into 46 inbred female Japanese white rabbits. In the i.a. group, carboplatin was infused into the lingual artery, and in the intravenous (i.v.) group, carboplatin was infused through the auricular vein. In the clinical study, we evaluated 19 patients with squamous cell carcinomas of the oral cavity and oropharynx, who had undergone targeted carboplatin i.a. chemoradiotherapy and had been administered i.a. tegafur/uracil chemotherapy before surgery. We quantified angiogenesis in both studies. Increased BVD was associated with a higher free platinum concentration in the tumour region in the i.a. group of rabbits. In the clinical study, using multivariate logistic regression analysis, only the BVD was related independently to the treatment effect. Therefore, BVD is a valid predictor of the effects of i.a. targeted carboplatin chemotherapy and concurrent radiotherapy for treating human oral and oropharyngeal squamous cell carcinomas

Metastasis Suppressors and the Tumor Microenvironment

The most dangerous attribute of cancer cells is their ability to metastasize. Throughout the process of metastasis, tumor cells interact with other tumor cells, host cells and extracellular molecules. This brief review explores how a new class of molecules – metastasis suppressors – regulate tumor cell–microenvironmental interactions. Data are presented which demonstrate that metastasis suppressors act at multiple steps of the metastatic cascade. A brief discussion for how metastasis suppressor regulation of cellular interactions might be exploited is presented