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Functionalised Metal-Organic Cages for Biomolecule Encapsulation


Project Description

In contrast to the plethora of examples of metal-organic cages that encapsulate, stabilise and activate small molecules a limited number of cages capable of encapsulating biomolecules have been reported. Challenges specific to biomolecule encapsulation include the increased size of many of these molecules in comparison to the organic and transition metal complexes more commonly encapsulated, as well as differential solubility’s. By default biomolecules are soluble in aqueous medium, while the vast majority of supramolecular cages are soluble in organic solvents such as acetonitrile. Furthermore, cages soluble in water frequently utilise the hydrophobic effect to drive host-guest encapsulation, implying that any guests should preferentially partition to a less polar environment.

Design and synthesis of ligands with polar moieties and specific biomolecule recognition motifs optimised for self-assembly in aqueous solution will provide access to host molecules with the appropriate features for biomolecule encapsulation. Initial studies will focus on construction cages capable of binding amino acids, short peptides and sugars, in a bid to develop a fundamental understanding of the properties required for biomolecule encapsulation. The ultimate goal of this research is to develop cages capable of encapsulating peptides for chemical interrogation or drug delivery applications.

The successful candidate will form part of an expanding research group and receive full training in inorganic synthesis and a variety of characterisation techniques that will enable them to design, synthesise and evaluate the outcome of metal self-assembly reactions in the presence of biomolecules. The candidate will use a variety of characterisation techniques including NMR spectroscopy (1D, 2D and multinuclear), mass spectrometry, X-ray crystallography and fluorescence spectroscopy and microscopy during the course of their research.

Contact for further Information
Imogen Riddell ([email protected] .ac.uk)
https://imogenriddell.wixsite.com/riddellgroup

Funding Notes

Applications are invited from self-funded students. For UK/EU tuition fees are £8,750 and International are £25,500 for 2019/20 academic year.

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or the overseas equivalent) in Chemistry and be interested in pursuing highly interdisciplinary research at the boundaries of inorganic chemistry and biochemistry. Potential applicants much have good laboratory skills, and experience working with biological reagents is advantageous. The successful candidate must also be highly motivated, capable of working independently and demonstrate good communication skills.

References

• L.L. K. Taylor, I. A. Riddell*, M. M. J. Smulders*, Self-assembly of functional discrete three-dimensional architectures in water. Angew. Chem. Int. Ed., 58, 1280 (2019).
• A. E. Czapar, Y-R. Zheng, I. A Riddell, S. Shukla, S. G. Awuah, S. J. Lippard, N. F. Steinmetz, Tobacco mosaic virus delivery of phenanthriplatin for cancer therapy. ACS Nano, 4, 4199 (2016).
• I. A. Riddell, M. M. J. Smulders, J. K. Clegg, J. R. Nitschke, Encapsulation, storage and controlled release of sulfur hexafluoride from a metal organic capsule. Chem. Comm. 47, 457–459 (2011).

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