Metal-metal cooperativity is emerging as an important strategy in catalysis. This requires appropriate ligand scaffolds that can support two metals in close proximity. Here we report nickel-promoted formation of a dinucleating planar macrocyclic ligand that can support bimetallic dinickel(II) and dinickel(I) complexes. Reaction outcomes can be tuned by variation of the substituents and reaction conditions to favour dinucleating macrocyclic, mononucleating macrocyclic or conventional pincer architectures.

An expanded pincer ligand tBu-PONNOP (2,7-bis(di-tert-butylphosphinito)-1,8-naphthyridine) has been synthesised and its coordination to coinage metals has been studied. Bimetallic complexes were produced with metal halide salts of the type [M2X2(tBu-PONNOP)]...

Protein conformational changes can facilitate the binding of noncognate substrates and underlying promiscuous activities. However, the contribution of substrate conformational dynamics to this process is comparatively poorly understood. Here, we analyze human (hMAT2A) and Escherichia coli (eMAT) methionine adenosyltransferases that have identical active sites but different substrate specificity. In the promiscuous hMAT2A, noncognate substrates bind in a stable conformation to allow catalysis. In contrast, noncognate substrates sample stable productive binding modes less frequently in eMAT owing to altered mobility in the enzyme active site. Different cellular concentrations of substrates likely drove the evolutionary divergence of substrate specificity in these orthologues. The observation of catalytic promiscuity in hMAT2A led to the detection of a new human metabolite, methyl thioguanosine, that is produced at elevated levels in a cancer cell line. This work establishes that identical active sites can result in different substrate specificity owing to the effects of substrate and enzyme dynamics.

Protein conformational change can facilitate the binding of non-cognate substrates and underlie promiscuous activities. However, the contribution of substrate conformational dynamics to this process is comparatively poorly understood. Here we analyse human (hMAT2A) and Escherichia coli (eMAT) methionine adenosyltransferases that have identical active sites but different substrate specificity. In the promiscuous hMAT2A, non-cognate substrates bind in a stable conformation to allow catalysis. In contrast, non-cognate substrates rarely sample stable productive binding modes in eMAT owing to increased mobility of an active site loop. Different cellular concentrations of substrate likely drove the evolutionary divergence of substrate specificity in these orthologs. The observation of catalytic promiscuity in hMAT2A led to the detection of a new human metabolite, methyl thioguanosine, that is produced at elevated level in a cancer cell line. This work establishes that identical active sites can result in different substrate specificity owing to the combined effects of both enzyme and substrate dynamics.

The ditungstaoctatetrayne [(Tp*)(CO)2WCCCCCCW(CO)2(Tp*)] (Tp* = hydrotris(dimethylpyrazolyl)borate) regioselectively adds extraneous metal–ligand fragments to the internal CC or terminal WC triple bonds leading to new tri-, tetra- or hexametallic assemblies.