A study of the incorporation of antischistosomiasis drugs into polyheterocycles and DFT calculations on polymer precursors

  • Yanhong Li

Student thesis: Doctoral Thesis


There is great interest beginning to be shown in conducting polymers, such as polypyrrole (PPy), for use in the area of drug delivery systems. The main aim of the project was to produce PPy containing antischistosomal compounds and to study their release under electrochemical control. Schistosomiasis is the second most prevalent typical disease in the world, affecting millions of people, the majority of whom are young children. Once affected, parasites live inside the body, causing several terrible symptomatic diseases, such as hepatic fibrosis, ascites and granuloma formation.
Antischistosomal compounds investigated for incorporation were niclosamide, niclosamide ethanolamine salt (NES), praziquantel and trichlorfon. All these, apart from NES, were found be to electrochemically inactive in the potential window used to prepare PPy. The conducting polymer grown in the presence of niclosamide was found to have quite different topography to that electrodeposited in its absence, as indicated by light microscopy and scanning electron microscopy (SEM). X-ray photoelectron spectroscopy (XPS) studies, however, did not show any peaks associated with niclosamide. This, together with the very poor solubility of niclosamide in a range of electrolytes (e.g., aqueous Na2SO4 (0.1 mol dm-3); tetrabutylammonium tetrafluoroborate, TBABF4 (0.01 mol dm-3) / acetonitrile; TBABF4 (0.01 mol dm-3) / methanol) suggested that niclosamide was not a suitable candidate for incorporation into this conducting polymer. Nucleation and growth behaviour (chronoamperometry) showed that the presence of praziquantel and trichlorfon in the electrolyte did not alter PPy formation. Light microscopy and SEM investigations showed that no changes in film topography occured when these two drugs were added to the electrolyte. PPy was found to be electrodeposited at the surface of reticulated vitreous carbon (RVC) electrodes and did not penetrate far into the bulk of the material. Thicker films (7 – 11 μm) and slightly greater penetration was achieved by stepping the potential to +800 mV vs. SCE for 15 min, rather than using potential cycling.
Subsequent studies were focused on trichlorfon due to its solubility in aqueous systems and hence greater promise for use in delivery devices to be used in aquatic systems. The presence of trichlorfon in PPy was not evidenced from Fourier-transform infra-red spectroscopy (FTIR) investigations, although this was probably due to the low concentration of the compound, since it was detected by XPS. These studies showed that one trichlorfon molecule was incorporated for every 765 pyrrole units when RVC was used as the substrate, and for every 103 pyrrole units when ITO glass was used. The former substrate has a much larger surface area, however, and so more trichlorfon overall will be incorporated than for PPy on ITO. XPS also showed that one sulphate anion was detected for every 4.6 to 6.4 pyrrole units. Trichlorfon release from PPy was successfully followed by GCMS, where ca. twice as much trichlorfon was released when the PPy/trichlorfon/RVC electrode was held at -300 mV vs. SCE compared to open circuit conditions (no applied potential). At -400 mV vs. SCE, a similar amount of trichlorfon (6.43 μmol) was released after just 60 min compared to that released at -300 mV vs. SCE after 24 h (6.93 μmol). When the potential was too negative (-500 mV vs. SCE), a reduced amount of trichlorfon (4.72 μmol) was released after 60 min compared to the film at -400 mV vs. SCE (6.43 μmol), although it was greater than that released at -300 mV vs. SCE (2.87 μmol) and with no applied potential (1.09 μmol). Thus, trichlorfon was successfully incorporated into PPy and could be released in a controlled fashion by varying the potential. The PPy/trichlorfon/RVC system showed promise for the construction of delivery devices for controlled release of trichlorfon, potentially for use in vivo or in aquatic environments.
The last part of the work used computational chemistry techniques to investigate growing conducting polymer chains. Density functional theory (DFT) was used to calculate the unpaired π-electron spin density distribution of oligopyrrole and oligothiophene radical cations using VWN, BLYP and B3LYP functionals. For the oligomers investigated, α,α'-linkages were maintained, which preserve conjugation and hence conductivity. Pendant monomer units, however, joined via α,β'-linkages along the linear chain, were also predicted. The frequency of these pendent groups was dependent on the functional used, with more accurate B3LYP calculations suggesting a higher frequency than those performed using VWN. The time required to perform DFT calculations on long-chain oligomers (ca. 10 monomer units) was still practicable using the high-level B3LYP functional owing to the use of parallel processing. Since the frequency of pendant monomer units along the chain was dependent on the functional used, calculations using the B3LYP functional are recommended over more rapid computations using the VWN functional.
Date of AwardAug 2010
Original languageEnglish
Awarding Institution
  • University of Portsmouth
SupervisorJames Smith (Supervisor)

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