The design and synthesis of fluorinated model compounds to investigate the influence of fluorination on lipophilicity and hydrogen bonding

Lead Research Organisation: University of Southampton
Department Name: School of Chemistry

Abstract

Fluorination of organic molecules causes modification of a wide range of properties. In our group we study the influence of fluorination on hydrogen bonding properties of adjacent functional groups, on lipophilicity and on conformation. Hydrogen bonding (H-bonding) is one of the main transient intermolecular interactions involved in biological recognition events, and lipophilicity is regarded as one of the most important physical properties relevant to drug efficacy (next to potency).
We are currently particularly interested in hydroxylated substrates, but we wish to broaden our substrate range to amines and amides. The student will undertake the synthesis and lipophilicity measurements of a range of stereochemically defined rigid and flexible fluorinated amines of increasing complexity, followed by rationalisation of the obtained results. In addition, we aim to achieve further improvements in our lipophilicity measurement methodology, including the adaptation to measure logD values.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509747/1 01/10/2016 30/09/2021
1934815 Studentship EP/N509747/1 28/09/2017 30/09/2021 Hannah Felstead
 
Description We have explored a number of chemical modifications that medicinal chemists can use as part of the drug development process, especially towards optimising the physical properties of drug candidates. The focus has mainly been on optimising lipophilicity of compounds. Importantly, we have not only studied this using the conventional octanol solvent, but also using toluene in order to investigate intramolecular hydrogen bonding effects.
Exploitation Route This will be of interest for pharmaceutical scientists
Sectors Pharmaceuticals and Medical Biotechnology

 
Description ESBOC-glycobiology, Gregynog 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invityed speaker at the annual ESBOC-glycobiology meeting, this time in Gregynog, "Exploring physical properties of carbohydrate derivatives: lipophilicities of fluorinated monosaccharides"
Year(s) Of Engagement Activity 2019
 
Description GlycoBasque meeting March 19 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited speaker at the annual GlycoBasque meeting, CIC bioGUNE, Bilbao (Spain), "How fluorination modifies carbohydrate hydrogen bonding properties and lipophilicity"
Year(s) Of Engagement Activity 2019
 
Description Poster presentations at national conferences 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Presented poster in national conference (two occasions), one with majority audience industry, one with majority audience postgraduate students. Sparked discussion about topic and relevance of application, people were engaged with the topic and interested. Discussions led to further ideas for this research and progression of direction.
Year(s) Of Engagement Activity 2019
 
Description Presentation at CARBO XXXIV 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited presentation at the International Carbohydrate Conference CARBO - XXXIV, Lucknow (India), "Insights in carbohydrate lipophilicity"
Year(s) Of Engagement Activity 2019
 
Description Presentation at EUROCARB 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Speaker at EUROCARB XX, Leiden (NL), "Lipophilicities of fluorinated carbohydrates and derivatives"
Year(s) Of Engagement Activity 2019
 
Description Presentation at IITB 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited presentation at Institute of Indian Technology Bombay (IITB), Mumbai (India), "The Influence of Fluorination on Aliphatic Lipophilicity"
Year(s) Of Engagement Activity 2019