Details of Grant 

EPSRC Reference:	EP/C536347/1
Title:	The C-F bond as a conformational Tool in Biological and Materials Chemistry
Principal Investigator:	O'Hagan, Professor D
Other Investigators:
Researcher Co-Investigators:
Project Partners:	Merck KGaA
Department:	Chemistry
Organisation:	University of St Andrews
Scheme:	Standard Research (Pre-FEC)
Starts:	22 August 2005	Ends:	21 August 2008	Value (£):	288,539
EPSRC Research Topic Classifications:	Biological & Medicinal Chem. Chemical Synthetic Methodology Materials Synthesis & Growth
EPSRC Industrial Sector Classifications:	Chemicals Electronics Pharmaceuticals and Biotechnology
Related Grants:
Panel History:
Summary on Grant Application Form
The research will explore the C-F bond as a substituent in organic molecules to examine if it can can influence the conformation/shape of such molecules. The shape of molecules is extremely important in the performance of that molecule in a given situation. Thus the conformation of a peptide will determine its biological activity, because it has to fit into a receptor. Also for materials such as liquid crystals, that are used in lap top computer displays and mobile phone displays, it is extremely important that these molecules orientate with respect to each other and that they have strong and oriented dipoles. The C-F bond, if it is strategically placed should be able to do this, more so than any other bond in organic chemistry, because the C-F bond is extremely polar, due to the high electronegitivity of fluorine (the highest at 4, on the Pauling scale) but the fluorine does not get involved in Hbonding and is not 'sticky' in any way that new and complicating interactions are introduced unlike eg the C-OH bond.The programme will make molecules where C-F bonds are lined up next to each other on adjacent carbons. The plan is to make systems with two, three and four such C-F bond in individual molecules. The fluorines are just a little bigger than hydrogen and such modifications will not have a dramatic steric effect. So these molecules will be sterically similar to the all hydrogen analogues (hydrocarbons). However the C-F bonds are expected to sense each others presence and orientate gauche (-60 degrees) to each other, following from the well described gauche effect. So it follows that by placing the C-F bonds along the carbon chain with different stereochemistries, should allow us to predict which stereochemistries will turn and which will be linear. We will test these hypotheses.It is pained too to exploit the effect that a C-F bond placed anti to an amide wants to sit anti to the carbonyl and syn to the N-H bond. This very strong preference in energy terms will be exploited to influence the conformation of peptides and a specific case study will use the effect to explore the shape of a neurotransmitter receptor ( the vanoilid receptor) a current target in analgesia. We can use the C-F bond to influence the shapes of molecules that bind to this receptor (agonists) and that will provide important information on the shape of the receptor, which can then be used for the design of good and better analgesics.The' research will require that these molecules are made in the laboratory by the methods of organic synthesis, and that each of the isomers is made individually. We are very well equipped in St Andrews for this type of activity, however to succeed at the project we will need to recruit skilled synthesis chemists. We plan to have our molecules tested by interactions with liquid crystal experts in industry.We will also explore our molecules by molecular modelling to anticipate their behaviour to help us design which ones to make and assist us in understanding the experimental phenomenon that we see.
Key Findings
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Organisation Website:	http://www.st-and.ac.uk