Jump to main content
Jump to site search

Issue 12, 2019
Previous Article Next Article

Enhancing the kinetics of hydrazone exchange processes: an experimental and computational study

Author affiliations

Abstract

The capacity of hydrazone bonds to readily undergo component exchange processes sees their extensive utilization in dynamic combinatorial chemistry. The kinetics of hydrazone exchange are optimal at pH ∼4.5, which limits the use of hydrazone-based dynamic combinatorial libraries, particularly for biological targets which are only stable at near-neutral pH values. It would thus be advantageous if hydrazone exchange proceeded with faster rates at pH values closer to neutral. We experimentally and computationally evaluated the hypothesis that hydrazones possessing neighbouring acidic or basic functional groups within the carbonyl-derived moitety of the hydrazone would enhance exchange rates. Our work suggests that judiciously placed N- or O-hydrogen bond acceptors within the carbonyl-derived moiety of the hydrazone stabilize transition states via hydrogen bonding interactions, providing a valuable boost to exchange kinetics at near-neutral pH values. We anticipate these findings will be of interest in dynamic combinatorial chemistry, dynamic covalent polymers/materials, functionalized nanoparticles and interlocked molecules, all of which may benefit from hydrazone exchange processes able to operate at near-neutral pH values.

Graphical abstract: Enhancing the kinetics of hydrazone exchange processes: an experimental and computational study

Back to tab navigation

Supplementary files

Article information


Submitted
09 Jan 2019
Accepted
25 Feb 2019
First published
26 Feb 2019

Org. Biomol. Chem., 2019,17, 3218-3224
Article type
Paper

Enhancing the kinetics of hydrazone exchange processes: an experimental and computational study

P. L. Higgs, A. J. Ruiz-Sanchez, M. Dalmina, B. R. Horrocks, A. G. Leach and D. A. Fulton, Org. Biomol. Chem., 2019, 17, 3218
DOI: 10.1039/C9OB00058E

Social activity

Search articles by author

Spotlight

Advertisements