استكشف المجموعة الواسعة من العناوين المتاحة.

Owing to the limited availability of natural sources, the widespread demand of the flavouring, perfume and pharmaceutical industries for unsaturated alcohols is met by producing them from α,β-unsaturated aldehydes, through the selective hydrogenation of the carbon-oxygen group (in preference to the carbon-carbon group). However, developing effective catalysts for this transformation is challenging, because hydrogenation of the carbon-carbon group is thermodynamically favoured. This difficulty is particularly relevant for one major category of heterogeneous catalyst: metal nanoparticles supported on metal oxides. These systems are generally incapable of significantly enhancing the selectivity towards thermodynamically unfavoured reactions, because only the edges of nanoparticles that are in direct contact with the metal-oxide support possess selective catalytic properties; most of the exposed nanoparticle surfaces do not. This has inspired the use of metal-organic frameworks (MOFs) to encapsulate metal nanoparticles within their layers or inside their channels, to influence the activity of the entire nanoparticle surface while maintaining efficient reactant and product transport owing to the porous nature of the material. Here we show that MOFs can also serve as effective selectivity regulators for the hydrogenation of α,β-unsaturated aldehydes. Sandwiching platinum nanoparticles between an inner core and an outer shell composed of an MOF with metal nodes of Fe , Cr or both (known as MIL-101; refs 19, 20, 21) results in stable catalysts that convert a range of α,β-unsaturated aldehydes with high efficiency and with significantly enhanced selectivity towards unsaturated alcohols. Calculations reveal that preferential interaction of MOF metal sites with the carbon-oxygen rather than the carbon-carbon group renders hydrogenation of the former by the embedded platinum nanoparticles a thermodynamically favoured reaction. We anticipate that our basic design strategy will allow the development of other selective heterogeneous catalysts for important yet challenging transformations.

Saturated aza-heterocycles are highly privileged building blocks that are commonly encountered in bioactive compounds and approved therapeutic agents. These N-heterocycles are also incorporated as chiral auxiliaries and ligands in asymmetric synthesis. As such, the development of methods to functionalize the α-methylene C-H bonds of these systems enantioselectively is of great importance, especially in drug discovery. Currently, enantioselective lithiation with (-)-sparteine followed by Pd(0) catalysed cross-coupling to prepare α-arylated amines is largely limited to pyrrolidines. Here we report a Pd(II)-catalysed enantioselective α-C-H coupling of a wide range of amines, which include ethyl amines, azetidines, pyrrolidines, piperidines, azepanes, indolines and tetrahydroisoquinolines. Chiral phosphoric acids are demonstrated as effective anionic ligands for the enantioselective coupling of methylene C-H bonds with aryl boronic acids. This catalytic reaction not only affords high enantioselectivities, but also provides exclusive regioselectivity in the presence of two methylene groups in different steric environments.

Copper-based compounds are promising entities for target-specific next-generation anticancer and NSAIDS therapeutics. In lieu of this, benzimidazole scaffold plays an important role, because of their wide variety of potential functionalizations and coordination modes. Herein, we report three copper complexes 1-3 with benzimidazole-derived scaffolds, a biocompatible molecule, and secondary ligands viz, 1-10-phenanthroline and 2,2'-bipyridyl. All the copper complexes have been designed, synthesized and adequately characterized using various spectroscopic techniques. In-vitro, human serum albumin (HSA) binding was also carried out using fluorescence technique and in-silico molecular modeling studies, which exhibited significant binding affinities of the complexes with HSA. Furthermore, copper complexes 1-3 were tested for biological studies, i.e., anticancer as well as NSAIDS. In vitro cytotoxicity results were carried out on cultured MCF-7 cell lines. To get the insight over the mechanism of action, GSH depletion and change in lipid peroxidation were tested and thus confirmed the role of ROS generation, responsible for the cytotoxicity of the complexes 1-3. Moreover, the copper complexes 1-3 were tested for potential to act as NSAIDS on albino rats and mice in animal studies in-vivo. Additionally, we also predicted the mechanism of action of the copper complexes 1-3 using molecular modeling studies with COX-2 inhibitor.

Radiation therapy can potentially induce immunogenic cell death, thereby priming anti-tumor adaptive immune responses. However, radiation-induced systemic immune responses are very rare and insufficient to meet clinical needs. Here, we demonstrate a synergetic strategy for boosting radiation-induced immunogenic cell death by constructing gadolinium-hemin based nanoscale coordination polymers to simultaneously perform X-ray deposition and glutathione depletion. Subsequently, immunogenic cell death is induced by sensitized radiation to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors. In conclusion, nanoscale coordination polymers-sensitized radiation therapy exhibits biocompatibility and therapeutic efficacy in preclinical cancer models, and has the potential for further application in cancer radio-immunotherapy.

The introduction of a trifluoromethyl (CF ) group can dramatically improve a compound's biological properties. Despite the well-established importance of trifluoromethylated compounds, general methods for the trifluoromethylation of alkyl C-H bonds remain elusive. Here we report the development of a dual-catalytic C(sp )-H trifluoromethylation through the merger of light-driven, decatungstate-catalysed hydrogen atom transfer and copper catalysis. This metallaphotoredox methodology enables the direct conversion of both strong aliphatic and benzylic C-H bonds into the corresponding C(sp )-CF products in a single step using a bench-stable, commercially available trifluoromethylation reagent. The reaction requires only a single equivalent of substrate and proceeds with excellent selectivity for positions distal to unprotected amines. To demonstrate the utility of this new methodology for late-stage functionalization, we have directly derivatized a broad range of approved drugs and natural products to generate valuable trifluoromethylated analogues. Preliminary mechanistic experiments reveal that a 'Cu-CF ' species is formed during this process and the critical C(sp )-CF bond-forming step involves the copper catalyst.

Hypoxic tumours are a major problem for cancer photodynamic therapy. Here, we show that photoredox catalysis can provide an oxygen-independent mechanism of action to combat this problem. We have designed a highly oxidative Ir(III) photocatalyst, [Ir(ttpy)(pq)Cl]PF ([1]PF , where 'ttpy' represents 4'-(p-tolyl)-2,2':6',2''-terpyridine and 'pq' represents 3-phenylisoquinoline), which is phototoxic towards both normoxic and hypoxic cancer cells. Complex 1 photocatalytically oxidizes 1,4-dihydronicotinamide adenine dinucleotide (NADH)-an important coenzyme in living cells-generating NAD radicals with a high turnover frequency in biological media. Moreover, complex 1 and NADH synergistically photoreduce cytochrome c under hypoxia. Density functional theory calculations reveal π stacking in adducts of complex 1 and NADH, facilitating photoinduced single-electron transfer. In cancer cells, complex 1 localizes in mitochondria and disrupts electron transport via NADH photocatalysis. On light irradiation, complex 1 induces NADH depletion, intracellular redox imbalance and immunogenic apoptotic cancer cell death. This photocatalytic redox imbalance strategy offers a new approach for efficient cancer phototherapy.

Water oxidation catalysis constitutes the bottleneck for the development of energy-conversion schemes based on sunlight. To date, state-of-the-art homogeneous water oxidation catalysis is performed efficiently with expensive, toxic and earth-scarce transition metals, but 3d metal-based catalysts are much less established. Here we show that readily available, environmentally benign iron coordination complexes catalyse homogeneous water oxidation to give O(2), with high efficiency during a period of hours. Turnover numbers >350 and >1,000 were obtained using cerium ammonium nitrate at pH 1 and sodium periodate at pH 2, respectively. Spectroscopic monitoring of the catalytic reactions, in combination with kinetic studies, show that high valent oxo-iron species are responsible for the O-O forming event. A systematic study of iron complexes that contain a broad family of neutral tetradentate organic ligands identifies first-principle structural features to sustain water oxidation catalysis. Iron-based catalysts described herein open a novel strategy that could eventually enable sustainable artificial photosynthetic schemes.

The Fe-S clusters of nitrogenases carry out the life-sustaining conversion of N to NH . Although progress continues to be made in modelling the structural features of nitrogenase cofactors, no synthetic Fe-S cluster has been shown to form a well-defined coordination complex with N . Here we report that embedding an [MoFe S ] cluster in a protective ligand environment enables N binding at Fe. The bridging [MoFe S ] (μ-η :η -N ) complex thus prepared features a substantially weakened N-N bond despite the relatively high formal oxidation states of the metal centres. Substitution of one of the [MoFe S ] cubanes with an electropositive Ti metalloradical induces additional charge transfer to the N ligand with generation of Fe-N multiple-bond character. Structural and spectroscopic analyses demonstrate that N activation is accompanied by shortened Fe-S distances and charge transfer from each Fe site, including those not directly bound to N . These findings indicate that covalent interactions within the cluster play a critical role in N binding and activation.

The search for anticancer metal-based drugs alternative to platinum derivatives could not exclude zinc derivatives due to the importance of this metal for the correct functioning of the human body. Zinc, the second most abundant trace element in the human body, is one of the most important micro-elements essential for human physiology. Its ubiquity in thousands of proteins and enzymes is related to its chemical features, in particular its lack of redox activity and its ability to support different coordination geometries and to promote fast ligands exchange. Analogously to other trace elements, the impairment of its homeostasis can lead to various diseases and in some cases can be also related to cancer development. However, in addition to its physiological role, zinc can have beneficial therapeutic and preventive effects on infectious diseases and, compared to other metal-based drugs, Zn(II) complexes generally exert lower toxicity and offer few side effects. Zinc derivatives have been proposed as antitumor agents and, among the great number of zinc coordination complexes which have been described so far, this review focuses on the design, synthesis and biological studies of zinc complexes comprising N-donor ligands and that have been reported within the last five years.

The viability of building artificial metabolic pathways within a cell will depend on our ability to design biocompatible and orthogonal catalysts capable of achieving non-natural transformations. In this context, transition metal complexes offer unique possibilities to develop catalytic reactions that do not occur in nature. However, translating the potential of metal catalysts to living cells poses numerous challenges associated to their biocompatibility, and their stability and reactivity in crowded aqueous environments. Here we report a gold-mediated C-C bond formation that occurs in complex aqueous habitats, and demonstrate that the reaction can be translated to living mammalian cells. Key to the success of the process is the use of designed, water-activatable gold chloride complexes. Moreover, we demonstrate the viability of achieving the gold-promoted process in parallel with a ruthenium-mediated reaction, inside living cells, and in a bioorthogonal and mutually orthogonal manner.