DOTA-M8 : an extremely rigid, high-affinity lanthanide chelating tag for PCS NMR spectroscopy

A new lanthanide chelating tag (M8) for paramagnetic labeling of biomolecules is presented, which is based on an eight-fold, stereoselectively methyl-substituted DOTA that can be covalently linked to the host molecule by a single disulfide bond. The steric overcrowding of the DOTA scaffold leads to an extremely rigid, kinetically and chemically inert lanthanide chelator. Its steric bulk restricts the motion of the tag relative to the host molecule. These properties result in very large pseudocontact shifts (<5 ppm) and residual dipolar couplings (<20 Hz) for Dy-M8 linked to ubiquitin, which are unprecedented for a small, single-point-attachment tag. Such large pseudocontact shifts should be well detectable even for larger proteins and distances beyond approximately 50 A. Due to its exceptionally high stability and lanthanide affinity M8 can be used under extreme chemical or physical conditions, such as those applied for protein denaturation, or when it is undesirable that buffer or protein react with excess lanthanide ions

Z-Selective Olefin Metathesis Reactions Promoted by Tungsten Oxo Alkylidene Complexes

Addition of LiOHMT (OHMT = O-2,6-dimesitylphenoxide) to W(O)(CH-t-Bu)(PMe[subscript 2]Ph)[subscript 2]Cl[subscript 2] led to WO(CH-t-Bu)Cl(OHMT)(PMe[subscript 2]Ph) (4). Subsequent addition of Li(2,5-Me[subscript 2]C[subscript 4]H[subscript 2]N) to 4 yielded yellow W(O)(CH-t-Bu)(OHMT)(Me[subscript 2]Pyr)(PMe[subscript 2]Ph) (5). Compound 5 is a highly effective catalyst for the Z-selective coupling of selected terminal olefins (at 0.2% loading) to give product in >75% yield with >99% Z configuration. Addition of 2 equiv of B(C[subscript 6]F[subscript 5])[subscript 3] to 5 afforded a catalyst activated at the oxo ligand by B(C[subscript 6]F[subscript 5])[subscript 3]. 5·B(C[subscript 6]F[subscript 5])[subscript 3] is a highly active catalyst that produces thermodynamic products (~20% Z).National Science Foundation (U.S.) (CHE-0841187)National Science Foundation (U.S.) (CHE-1111133)National Institutes of Health (U.S.) (Grant GM-59426)National Science Foundation (U.S.) (CHE-0946721