David A Fulton Research Group

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Polymer-Scaffolded Dynamic Combinatorial Libraries

Can wholly synthetic macromolecules mimic the molecular recognition and catalytic properties of natural proteins?  To address this challenge, we are applying ideas from the field of dynamic combinatorial chemistry with the aim of developing a simple and rapid method to do just this.  We are developing libraries of macromolecules which have the potential to ‘reconfigure’ their structures in response to the addition of templates.  These libraries—which we have termed polymer-scaffolded dynamic combinatorial libraries—represent a conceptually new class of dynamic combinatorial library, and are ideally suited to the discovery of synthetic protein mimics.  Our most recent work has shown that templation of these libraries causes an increase in average association constants of the polymer library members with their templates as a consequence of being able to preferentially incorporate residues which promote binding and rejecting residues which do not.


The preparation and templation of a polymer-scaffolded dynamic combinatorial library.  Functionalized residues are grafted onto a synthetic polymer scaffold through dynamic covalent linkages.  The reversibility of these linkages allows residues to exchange with other residues and reshuffle their positions upon the polymer scaffold, presenting a mechanism for the system to adapt its primary structure.  Upon addition of the addition of a template, the PS-DCL will re-equilibrate to amplifying the concentration of library members which best bind the template.


Org. Biomol. Chem. 2015, 13, 2756-2761.

Chem. Sci. 20134, 3661-3666.

Polym. Sci. 2013, 4, 368-377.

Chem. Commun. 201147, 7209-7211.

Org. Lett. 200810, 3291-3294.

Responsive & Adaptive Polymeric Nanoparticles

Recent years have seen the utilization of dynamic bonds, whether they be non-covalent supramolecular interactions or so-called dynamic covalent bonds, to endow polymeric nanopartciles with the abilities to adapt their structures or compositions in response to an external stimuli.  When dynamic bonds are incorporated into polymeric systems, the reversible nature of bonds enables these systems to modify their architectures by reshuffling, incorporating or releasing their components, in effect providing a mechanism for polymer-based assemblies to reconfigure their molecular structures and therefore their functional or material properties. Within the DAF group we have incorporated dynamic covalent bonds into a range of polymeric nanoparticles, such as micelles, core-cross-linked star polymers and nanogels, and shown how the nanoparticles can undergo dramatic structural reconfigurations triggered by stimuli such as pH or the addition of  small organic molecules. This project at the interfaces of supramolecular, polymer and materials chemistries allows for the expression of a great deal of creativity, and we are confident our work will lead to the development of some exciting next-generation materials.



Polymers possessing aldehyde and amino groups cross-link at pH 11 to form CCS polymers. Any hydrophobic Nile Red present will be encapsulated within the hydrophobic core of the CCS polymer. The release of Nile Red can be triggered by pH-induced disassembly of the CCS polymer system, or temperature-induced loss of the hydrophobicity of the cross-linked core.  Both of these processes are reversible, and the Nile Red can be reencapsulated upon removal of the pH or temperature stimuli.


Polymer Chem. 20134, 31-45.

Angew. Chem. Int. Ed. 2013, 52, 956-959.

Macromolecules 2012, 45, 2699-2708.

Chem. Commun. 201147, 6807-6809.

Chem. Commun. 201046, 6051-6053.

Macromolecules 201043, 1069-1075.

Polymer Delivery Systems for the Effective Delivery of siRNA

Short interfering RNA (siRNA) are short double strands of RNA which can silence specific genes involved in disease, and thus hold great promise in the treatment of a range of conditions.5 A major obstacle to siRNA in the clinic is the challenge of delivering siRNA molecules in vivo as they are rapidly cleared from the body or degraded.  In addition to protecting siRNA from the harsh in vivo environment, a suitable delivery system must also be able to target siRNA molecules to the correct cells, facilitate the uptake of the siRNA inside the cells, escape from the endosome and then finally unravel to reveal their siRNA payload, all whilst presenting minimal toxicity to the cell.  These requirements present a series of formidable obstacles which have yet to be adequately overcome.  To address these challenges, the DAF group are developing polymer micelles—nanoparticles constructed from the aggregation of diblock copolymer chains—as new siRNA delivery systems.  Our work began in January 2011 and is performed in collaboration with the group of Dr Olaf Heidenreich of the Northern Institute of Cancer Research at Newcastle University, who are particularly interested in developing siRNA treatments for acute myloid leukaemia associated with the chromosomal translocation t(8;21).  The current treatment with cytotoxic and cytostatic compounds lacks tumour specificity, and is associated with significant acute and long-term side effects.  This project tackles a significant problem in medicine, and any successes in silencing the AML t(8;21) gene can then be translated to other diseases where siRNA therapies maybe promising.  The project benefits from the strong links which are developing between the chemistry/NICR groups.


Schematic of a polymer nanoparticle e designed to deliver siRNA to cells. The polymer nanoparticle can complex siRNA whilst sheilding it from its environment.  Antibody fragments conjugated onto the periphery of the nanoparticle will ensure its selective delivery to target cells.


J. Contr. Rel. 2013, 172, 939-945.

Anti-Biofouling Coatings

The unwanted fouling of surfaces by organisms presents a huge and largely unsolved problem.  From the fouling of medical implants to the hulls of container ships, fouling can lead to reduced performance and increased costs.  For example, the increased roughness on ships hulls can increase fuel consumption by 40%.  When one considers that there are over 90,000 vessels in the world fleet, with some of the largest ships consuming over 350 tonnes of fuel per day in normal cruising, the fuel savings the reduction on greenhouse gas emissions would be considerable if biofouling could be eliminated.

Image result for largest container ship

The Estelle Maersk, one of the largest container ships in the world.  It is estimated that the 15 largest ships now emit more pollution than the world 760 million cars combined.

At Newcastle the DAF group is working with partners across Europe, including leading marine paints manufacturer International Paints (part of the Akzo Nobel group), to develop next generation anti-biofouling coatings for marine applications.  This project started in 2014, and it is anticipated that our first work in this area will be submitted for publication in late 2015.


Polymer Nanoparticles by Emulsion Polymerisation

Emulsion polymerisation techniques present a remarkably quick and simple way to prepare nanoparticles.  At Newcastle we are interested in using emulsion polymerisations to encapsulate smaller molecules with the aim of protecting them from their surrounding environments.  Working with the group based in Newcastle medical school we have shown that a special dye, which can be used to measure concentrations of reactive oxygen species in live cells but is toxic, can be encapsulated within a polymer nanoparticle.  The encapsulation procedure reduces the toxicity of the dye whilst still allowing it to perform its measurement of the concentrations of reactive oxygen species.  We are now working with Dr Ben Horrocks within the School of Chemistry to encapsulate silicon quantum dots, a new class of interesting luminescent inorganic nanoparticle, within polymer nanoparticles.  These composite organic-inorganic nanoparticles will then allow us to exploit the properties of silicon quantum dots in new and useful ways.


(left)Alkylated silicon quantum dots can be encapsulated inside of polymer nanoparticles using emulsion polymerisation techniques.  These polymer nanoparticles display reactive aldehyde groups on their surfaces which allow them to be decorated with other molecules such as biomolecules or other polymers.  These luminescent conjugates will be useful in a wide variety of applications e.g. as intracellular biological probes, or as anti-counterfeiting markers.

(right) Transmission electron micrographs (TEM) of polymer nanoparticles (light grey) which contain encapsulated gold nanoparticles (black) and silicon nanoparticles.   Because silicon possesses a low scattering factor, the silicon nanoparticles are essentially invisible in TEM.


Chem. Commun. 2014, 50, 12389-12391.

Nanoscale, 2013, 5, 3817-3827.

Nanoscale, 20113, 4733-4741.

Biosensors and Bioelectronics, 200924, 3608-3614.