A study on perfluorohexyloctane (F6H8) and perfluorobutylpentane (F4H5) through nuclear magnetic resonance

Abstract

The purpose of this thesis was to investigate and characterise basic physicochemical characteristics of short-chain SFAs (Semi Fluorinated Alkanes) and various SFA – excipient mixtures, to provide a foundation for the future use and application of these interesting compounds. Excipients are inactive substance that improve the overall effectiveness of a formulation. Only a handful of studies have been carried out on short chain SFA molecules with a majority of the work from molecular models and simulations. Therefore this thesis aims to provide novel analytical studies of SFA solution behaviour. This study uses predominantly nuclear magnetic resonance chemical shift and integral data with respect to excipient concentration to provide ternary phase diagrams, solubility and molecular interaction insights to further understand interactions of SFA molecules with themselves and with other small molecules. The interest in SFAs stems from their inert, hydrophobic and surfactant-like properties. The surfactant properties of SFAs are of interest because they do not contain a hydrophilic segment. NMR chemical shifts have been used to explore the molecular environmental changes in SFA mixtures mainly with respect to various organic excipients/additives, including ethanol, propanol, tetradecane, perfluorooctane, caprylic/capric triglyceride, isopropyl myristate, isopropyl palmitate, ethyl acetate, diethylene glycol monoethyl ether, dimethyl isosorbide and propylene glycol laurates, as well as temperature. These organic compounds were chosen as they provide a varied amount of functional groups and are used regularly as excipients. NMR integrals were used to determine compositions in phase separated samples with and without the addition of water to provide liquid – liquid equilibrium data to be used in order to provide miscibility boundary conditions and extraction behaviour in the presence of water. The chemical shift data indicated SFAs F6H8 and F4H5 exhibit preferential interactions in hydrocarbon and perfluorocarbons mixtures. Pure F6H8 was investigated separately by determining the temperature dependence of NMR chemical shifts and coupling constants, which when complemented with molecular simulations, indicated preferential interactions between the like-segments of SFAs at lower temperatures. The degree of association was less when SFAs were mixed with compounds containing long hydrocarbon chains and polar segments, such as caprylic/capric triglyceride, isopropyl myristate, and isopropyl palmitate, when compared to completely non polar tetradecane and perfluorooctane. In mixtures with smaller polar molecules like ethyl acetate, the NMR chemical shift changes were seen to be proportional to the additive concentration, which indicated close to ideal mixing with little preferential interactions. Furthermore, chemical environments of hydrogen diblocks of F6H8 and F4H5 changed much less with addition of excipients when compared to the perfluorocarbon diblocks suggesting that the driving force of association in the mixtures are the perfluorocarbon SFA segments. Ternary phase diagrams and liquid-liquid extraction data was used to derive empirical relations, to determine the saturated threshold water content reachable before phase separation would occur for F6H8 or F4H5 mixtures with either ethanol or propanol.

Date of Award	31 Dec 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Gordon Tiddy (Supervisor) & Robin Curtis (Supervisor)