Hydrazones disulfide exchanges

The small-molecule-based machine conceived by von Delius, Geertsema, and Leigh [45] is a linear (for reviews, see [46], [100]) motor based on dynamic covalent chemistry [19-24] (forming, breaking, and reforming of dynamic covalent bonds with relatively fast equilibration in response to stimuli), namely on acyl-hydrazone and disulfide exchanges. The motor consists of a track that has four functional groups disposed alternately aldehyde-thiol-aldehyde-thiol which are the positions 1,2, 3, and 4 of the track, a walker NH2-NH-CO-(CH2)5-SH which has the feet A (hydrazide or acyl-hydrazine) and B (thiol), and a placeholder with a foot C of type thiol (Fig. 10). 

Fig. 10 (a) Operation of a linear motor based on hydrazone and disulfide exchanges the conversion between 37 and 38 occurs in the same conditions as that between 35 and 36, and that between 35 and 38 in the same conditions as that between 36 and 37 (b) stylized representation of the operation of the linear motor... 

Rodriguez-Docampo Z, Otto S (2008) Orthogonal or simultaneous use of disulfide and hydrazone exchange in dynamic covalent chemistry in aqueous solution. Chem Commun 2008 5301-5303... 

This molecular motor is an example that illustrates how the changes in configuration can have an influence on the exchanges of dynamic covalent bonds like -C=N- from acyl hydrazones and -S-S- (disulfides). 

Analysis of DCLs by a combination of high-performance liquid chromatography (HPLC) and MS (LC-MS) has proven very powerful, provided the library members are stable enough to allow chromatographic separation. LC-MS analysis can yield both the quantity and the identity of individual library members. Care should be taken that the exchange between library members is slow on the timescale of the experiment. This is usually the case for hydrazone and disulfide libraries, without requiring special precautions. It has recently been reported that even the composition of DCLs of hydrolytically labile imines can be analyzed directly by HPLC, provided an acidic mobile phase is used. Beau et al. successfully used a common reversed-phase HPLC solvent system based on acetonitrile/water mixtures containing 0.1% trifluoroacetic acid [10]. Imine hydrolysis is slow under these conditions because at low pH the zwitterionic hemi-aminal intermediate that is believed to be important in the hydrolysis process is more difficult to attain (Scheme 2.1). 

---