Rebecca A. Kaner, Alan D. Faulkner, Suzanne E. Howson, Peter Scott
Dept. of Chemistry, University of Warwick, CV4 7AL, r.a.kaner@warwick.ac.uk
Protein α-helices in nature are key in many interations;
1 however as therapeutic agents they tend to display poor pharmacokinetics and so synthetic mimics are being developed.
2
Bis(bidentate) ligands ( AB
–
BA ) can be selfassembled over a metal scaffold to form helicates
3
(a) which are of an appropriate size shape and charge, and some examples bind to biomolecules,
4
but they rarely contain functional groups, form as a racemic mixture which is hard to separate and have high symmetry.
5
Recently we have developed a new system known as Flexicates , which do not rely on the helication principle. These highly symmetric compounds form in an optically pure manner, are water stable, easily functionalised and have shown great potential as both antimicrobial
7 and anticancer agents,
8
with the exact nature of the activity observed dependant on the structure of the ligand.
If however directional ligands ( AB
→
CD ) are employed, Head-to-Head-to-Head
[HHH] and Head-to-Head-to-Tail [HHT] configurations are possible.
9
We have recently reported a new [HHH] system which assembles C
3
-symmetric homohelical heterobimetallic helicates (b) using a chiral directional ligand.
10
Broadly speaking selective self-assembly, such as that required to make the optically pure C
1
-symmetric [HHT] helicate, presents a great challenge for (metallo)supramolecular chemistry.
Most excitingly we have devised functional C
1
-symmetric [HHT] triplex helicates (c) using a second carefully designed directional ligand. Triplex helicates are found to show exceptional selectivity and activity as anticancer agents, with some very interesting leads to possible modes of action.
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