Acid Catalysed Hydrolysis of β -sultam Vicky Sutcliffe Supervisors; Prof Mike Page, Dr Andy Laws Studies are currently being carried out in a European collaborative effort (involving several members from the University of Huddersfield) into the use of taurine as a treatment of neurodegenerative conditions [1]. β -sultam may act as a taurine pro-drug, crossing the blood-brain barrier in its cyclised form and hydrolysing to release taurine in situ. β-sultam peak at 1329cm -1 Taurine peak at 1034cm -1 NH 2 peak CH 2 - NH 2 peaks CH 2 - SO 2 peaks Chlorine Preparation Apparatus High performance anion exchange chromatography with pulsed amperometric detection was used to separate mixtures of taurine and β -sultam. The retention times of the two components were significantly different (see left) and the area of the peaks correlated with the component concentrations. This method needs refining but shows promise for the analysis of mixtures taken from the hydrolysis reaction at set times. High performance anion exchange chromatography with pulsed amperometric detection was used to separate mixtures of taurine and β -sultam. The retention times of the two components were significantly different (see left) and the area of the peaks correlated with the component concentrations. This method needs refining but shows promise for the analysis of mixtures taken from the hydrolysis reaction at set times. Initial data for the acid-catalysed hydrolysis of β -sultam has not been reliable enough to provide actual rate data for the reaction. The work has shown, however, that both ReactIR and HPAEC-PAD are valid techniques for monitoring this reaction. Further work will be carried out using ReactIR as this technique is real-time, whilst HPAEC- PAD requires sampling of the reaction and dilution to stop the reaction before analysis can be run. Hydrolysis of β -sultam to yield taurine Chromatogram of 3:1 β -sultam:taurine solution Overlaid IR spectra of taurine and β-sultam 1 H NMR of β-sultam Overlaid spectra for mixed solutions of taurine and β -sultam in water showing the change in absorbance (y-axis) at characteristic wavenumbers (x-axis). References: [1] Biochemical Pharmacology, 2011, R.J.Ward, [2] Thesis – The Mechanism of Reactions of β -sultams, Nicholas J. Baxter 1998 [3] Le Berre, A., Petit, J., Tetrahedron Letters No. 3, 1972, H2OH2O 2 Cl 2 EtOH 2 Na 2 CO 3 β- sultam The synthesis was carried out in two steps according to the procedure first described by Le Berre [3] and adopted by previuos members of the research group. The first step required the production of chlorine gas (as shown left). β -sultam was synthesised at an overall yield of 67% and confirmed by 1 H NMR. β-sultam Taurine The IR spectra of taurine and β -sultam in aqueous solution are dominated by the absorbance due to water. Characteristic absorbance peaks are present though with taurine showing absorbance at 1047cm -1 and 1200cm -1 whilst β -sultam has characteristic absorbance peaks at 1154cm -1, 1258cm -1 and 1303cm -1. The combined graph (right) shows the trends in absorbance at these wavenumbers for mixed solutions of β -sultam and taurine between 0.1 and 0.7mol dm -3. The IR spectra of taurine and β -sultam in aqueous solution are dominated by the absorbance due to water. Characteristic absorbance peaks are present though with taurine showing absorbance at 1047cm -1 and 1200cm -1 whilst β -sultam has characteristic absorbance peaks at 1154cm -1, 1258cm -1 and 1303cm -1. The combined graph (right) shows the trends in absorbance at these wavenumbers for mixed solutions of β -sultam and taurine between 0.1 and 0.7mol dm -3.