Synthesis and characterisation of ferrocenylalkoxy-functionalised polyphosphazenes for biomedical applications
| dc.contributor.advisor | Muller, E. | |
| dc.contributor.advisor | Swarts, J. C. | |
| dc.contributor.author | Govender, Maheshini | |
| dc.date.accessioned | 2020-12-15T05:44:40Z | |
| dc.date.available | 2020-12-15T05:44:40Z | |
| dc.date.issued | 2020-01 | |
| dc.description.sponsorship | A series of known ferrocene-containing alcohols of the type Fc(CH2)mOH, where m = 1, 2, 3, and 4 and Fc = FeII[(η5 – C5H5) (η5 – C5H4)], were obtained in multiple synthetic steps and characterised with the aid of infra-red (IR) spectroscopy and 1H nuclear magnetic resonance (NMR) spectroscopy. A series of new poly[tris(2,2,2-trifluoroethoxy)(ferrocenylalkoxy)phosphazene] derivatives, [(P(OCH2CF3)2=N)-(P(OCH2CF3)(O(CH2)mFc)=N]- with m = 1, 2, 3, or 4, were also synthesised in yields of 11.6 %, 13.5 %, 12.2 %, and 10.3 %, respectively. All synthesised ferrocenylalkoxyfunctionalised polyphosphazenes were characterised with IR spectroscopy, and 1H, 19F, and 31P NMR spectroscopy. Gel permeation chromatography (GPC) was used to determine number average molecular masses relative to poly(methylmethacrylate) standards for the new poly[tris(2,2,2-trifluoroethoxy)- (ferrocenylalkoxy)phosphazene] derivatives; they were determined to be 6307 (m = 1), 3410 (m = 2), 7421 (m = 3), and 3310 (m = 4) daltons respectively. Increasing monomer to initiator ratios of Cl3P=N(SiMe3):PCl5 = 33:1, 50:1 and 100:1 generated polymer molecular masses of 126 554, 168 475, and 213 731 daltons respectively against polystyrene standards. Dilute solution viscometry measurements were used to determine the Mark-Houwink constants “a” and “K” for poly[tris(2,2,2-trifluoroethoxy)(ferrocenylalkoxy)phosphazenes] in the equation [η] = K𝑀���visa; “a” was determined to be 0.87 and “K” was determined to be 0.0000634 dl/gm. X-ray photoelectron spectroscopic (XPS) analyses of the synthesised ferrocenylalkoxy-functionalised polyphosphazenes resulted in elemental compositions of P2.0N2.1O4.2F7.8C9.4HxFe0.7 (theoretical P2N2O4F9C17H17Fe), P2.0N2.0O3.4F9.3C5.6HxFe0.6 (theoretical P2N2O4F9C18H19Fe), P2.0N2.1O3.7F9.0C6.7HxFe0.7 (theoretical P2N2O4F9C19H21Fe) and P2.0N2.1O2.3F7.4C3.9HxFe0.5 (theoretical P2N2O4F9C20H23Fe) for ferrocenylalkoxy chain lengths of m = 1, 2, 3, and 4, respectively. XPS cannot measure hydrogen and the lower than expected carbon content is amongst others ascribed to the evaporation of cyclopentadienyl fragments that are liberated during irradiation while the analysis takes place. The full width at half maximum value for phosphorus and nitrogen photoelectron lines (P 2p and N 1s) were observed to be directly proportional to the alkyl chain length of the ferrocenylalkoxy groups. Results were consistent with greater polymer conformation flexibility in polymers with longer ferrocenylalkoxy side chain lengths. An electrochemical study of the poly[tris(2,2,2-trifluoroethoxy)(ferrocenylalkoxy)phosphazene] derivatives resulted in ferrocenyl formal reduction potentials of E°' = 23.5, -24.5, -35.5, and -51.1 mV versus FcH/FcH+ for m = 1, 2, 3, and 4 respectively. Electrochemical reversibility (expressed as a function of ∆Ep values) for this redox process was found to decrease as the alkyl chain length on the ferrocenylalkoxy groups increased. Chemical reversibility of these ferrocenyl-based redox processes were observed to be directly proportional to the alkyl chain length of the ferrocenylalkoxy groups implying that as the alkyl chain length increased, the ferrocenyl redox processes became more chemically reversible. The ipc/ipa ratios for poly[tris(2,2,2trifluoroethoxy)(ferrocenylalkoxy) phosphazenes], with alkyl chain lengths of m = 1, 2, 3, and 4, were determined to be 0.288, 0.387, 0.676, and 0.839 respectively at a scan rate of 100 mV s-1. UV/Vis spectroscopy was used to investigate the kinetics of hydrolysis of poly[tris(2,2,2trifluoroethoxy)(ferrocenylmethoxy)phosphazene] into 2,2,2-trifluoroethanol, ferrocenylmethanol, phosphates and ammonia. Pseudo first order reaction conditions were used whereby THF polymer solutions with a polymer concentration of 2.377 mM were allowed to react with THF solutions with an H2O content of 18.51 M. Kinetic results are consistent with three equivalents of 2,2,2-trifluoroethanol being cleaved first from the polymeric main chain followed by hydrolysis of the ferrocenylmethoxy group. Observed pseudo first order rate constants are 2.0x10-4 and 1.29x10-4 s-1 respectively. The remaining polymer main chain fragments then isomerises and recoils into a new folding pattern. Finally, the remaining polymer main chain fragments hydrolyse to (NH4)3PO4 with kobs = 2.6x10-6 s-1. The second order rate constant for this main chain hydrolysis is 1.38x10-7 M-1s-1. Increasing the concentration of water from 18.52 M to 27.28 M increased the rate of main chain hydrolysis by an order of magnitude. Differential scanning calorimetry (DSC) was utilised to evaluate the thermal properties of poly[bis(2,2,2-trifluoroethoxy)phosphazene] and poly[tris(2,2,2-trifluoroethoxy)(ferrocenylalkoxy) phosphazene] derivatives. Poly[bis(2,2,2-trifluoroethoxy)phosphazene] exhibited thermoplastic properties with indications of thermal cracking of the polymer main chain after multiple heating and cooling cycles. A glass transition temperature of 220 K was estimated. The onset melting temperature of this polymer was 68.46 °C. DSC thermograms for poly[tris(2,2,2-trifluoroethoxy)(ferrocenylalkoxy)phosphazene] derivatives exhibited melting temperatures at 38.3 (m = 1), 42.4 (m = 2), 70.1 (m = 3), and 38.7 °C (m = 4) respectively. Phase separation between higher and lower molecular mass fractions of poly[tris(2,2,2-trifluoroethoxy)(ferrocenylbutoxy)phosphazene] was also observed. Cytotoxicity studies for all poly[tris(2,2,2-trifluoroethoxy)(ferrocenylalkoxy)phosphazene] derivatives against a human HeLa cervical cancer cell line resulted in half maximal inhibitory concentrations (IC50) of 18.24 (m = 1), 40.15 (m = 2), 67.85 (m = 3), and 59.09 μM (m = 4) respectively. The IC50 value of cisplatin under the same conditions was 1.21 μM. It is concluded that polyphosphazenes are successful in acting as drug delivery devices, although cisplatin is 15 – 50 times more effective. | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11660/10895 | |
| dc.language.iso | en | en_ZA |
| dc.publisher | University of the Free State | en_ZA |
| dc.rights.holder | University of the Free State | en_ZA |
| dc.subject | Thesis (Ph.D. (Chemistry))--University of the Free State, 2020 | en_ZA |
| dc.subject | Polyphosphazene | en_ZA |
| dc.subject | Ferrocene | en_ZA |
| dc.subject | Gel permeation chromatography | en_ZA |
| dc.subject | Mark-houwink | en_ZA |
| dc.subject | Electrochemistry | en_ZA |
| dc.subject | Hydrolysis kinetics | en_ZA |
| dc.subject | Cytotoxicity | en_ZA |
| dc.title | Synthesis and characterisation of ferrocenylalkoxy-functionalised polyphosphazenes for biomedical applications | en_ZA |
| dc.type | Thesis | en_ZA |