A synthetic molecular pentafoil knot

Knots are being discovered with increasing frequency in both biological and synthetic macromolecules and have been fundamental topological targets for chemical synthesis for the past two decades. Here, we report on the synthesis of the most complex non-DNA molecular knot prepared to date: the self-assembly of five bis-aldehyde and five bis-amine building blocks about five metal cations and one chloride anion to form a 160-atom-loop molecular pentafoil knot (five crossing points). The structure and topology of the knot is established by NMR spectroscopy, mass spectrometry and X-ray crystallography, revealing a symmetrical closed-loop double helicate with the chloride anion held at the centre of the pentafoil knot by ten CH···Cl⁻ hydrogen bonds. The one-pot self-assembly reaction features an exceptional number of different design elements—some well precedented and others less well known within the context of directing the formation of (supra)molecular species. We anticipate that the strategies and tactics used here can be applied to the rational synthesis of other higher-order interlocked molecular architectures.6 page(s

Nucleophilic catalysis of acylhydrazone equilibration for protein-directed dynamic covalent chemistry

Dynamic covalent chemistry uses reversible chemical reactions to set up an equilibrating network of molecules at thermodynamic equilibrium, which can adjust its composition in response to any agent capable of altering the free energy of the system. When the target is a biological macromolecule, such as a protein, the process corresponds to the protein directing the synthesis of its own best ligand. Here, we demonstrate that reversible acylhydrazone formation is an effective chemistry for biological dynamic combinatorial library formation. In the presence of aniline as a nucleophilic catalyst, dynamic combinatorial libraries equilibrate rapidly at pH 6.2, are fully reversible, and may be switched on or off by means of a change in pH. We have interfaced these hydrazone dynamic combinatorial libraries with two isozymes from the glutathione S-transferase class of enzyme, and observed divergent amplification effects, where each protein selects the best-fitting hydrazone for the hydrophobic region of its active site