Mobile Molecules: Reactivity Profiling Guides Faster Movement on a Cysteine Track.

We previously reported a molecular hopper, which makes sub-nanometer steps by thiol-disulfide interchange along a track with cysteine footholds within a protein nanopore. Here we optimize the hopping rate (ca. 0.1 s-1 in the previous work) with a view towards rapid enzymeless biopolymer characterization during translocation within nanopores. We first took a single-molecule approach to obtain the reactivity profiles of individual footholds. The pKa values of cysteine thiols within a pore ranged from 9.17 to 9.85, and the pH-independent rate constants of the thiolates with a small-molecule disulfide varied by up to 20-fold. Through site-specific mutagenesis and a pH increase from 8.5 to 9.5, the overall hopping rate of a DNA cargo along a five-cysteine track was accelerated 4-fold, and the rate-limiting step 21-fold.

Mobile Molecules: Reactivity Profiling Guides Faster Movement on a Cysteine Track.

We previously reported a molecular hopper, which makes sub-nanometer steps by thiol-disulfide interchange along a track with cysteine footholds within a protein nanopore. Here we optimize the hopping rate (ca. 0.1 s-1 in the previous work) with a view towards rapid enzymeless biopolymer characterization during translocation within nanopores. We first took a single-molecule approach to obtain the reactivity profiles of individual footholds. The pK a values of cysteine thiols within a pore ranged from 9.17 to 9.85, and the pH-independent rate constants of the thiolates with a small-molecule disulfide varied by up to 20-fold. Through site-specific mutagenesis and a pH increase from 8.5 to 9.5, the overall hopping rate of a DNA cargo along a five-cysteine track was accelerated 4-fold, and the rate-limiting step 21-fold.

Installing the "magic methyl"- C-H methylation in synthesis.

The selective and efficient C-H methylation of sp2 and sp3 carbon centres has become a powerful transformation in the synthetic toolbox. Due to the potential for profound changes to physicochemical properties attributed to the installation of a "Magic Methyl" group at a strategic site in a lead compound, such techniques have become highly desirable in modern drug discovery and synthesis programmes. This review will cover the diverse techniques that have been employed to enable the selective installation of the C-Me bond in a wide range of chemical structures, from simple building blocks to complex drug-like architectures.