- Title
- Mechanistic aspects of molecular imprinting by precipitation polymerisation
- Creator
- Lim, Kosta Fremielle
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2018
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- This study aims to further understand the mechanistic aspects of the non-covalent approach of molecular imprinting produced by precipitation polymerisation, with emphasis on the effect of the nature of template, temperature, the formulation and nature of porogen on the properties and binding performance of the microspheres as literature has demonstrated that precipitation imprinting is susceptible to changes in polymerisation conditions. Additionally, we have successfully utilized NMR as the main tool for quantitative measurements, which, to the best of our knowledge the first time that NMR has been applied to the full extent for MIP characterisation. Throughout the course of this study, azobisisobutyronitrile (AIBN) and acetonitrile (ACN) were employed as initiator and porogen, respectively, with the porogen:monomer ratio for all precipitation imprinting experiments maintained at 10-12 mL per mmol of total monomer. Reaction temperature was set at 60oC except during photochemical initiation when it was recorded to be 27-35oC. The effects of the feed formulation, i.e. template:functional monomer (T:FM) ratio, functional monomer: cross-linker (FM:XL) ratio and initiator:total monomer (I:TM) ratio, as well as temperature (60oC vs 27-35oC) were exemplified by investigating microspheres imprinted with xanthine derivatives caffeine (CAF) and theophylline (THP) and phenolic targets 3,5-dimethylphenol (1OH), 5-methylbenzene-1,3-diol (2OH) and 1,3,5-benzenetriol (3OH). Our results suggest that FM:XL ratios should be maintained between 1:5-1:10 in order to get rigid MIPs that can favourably form higher number of template-functional monomer (T-FM) complexes during the imprinting process but lower NIP binding. Interestingly, regardless of the T:FM ratio and level of template incorporation, comparable template rebinding was obtained for MIPs as well as for NIPs resulting in comparable imprinting factors. Our results yielded no preference to T:FM ratios between 1:2 to 1:8 for MIP synthesis by precipitation polymerisation. Higher concentration of initiator (I:TM = 1:5), and hence, faster rate of polymerisation, was found to favour template incorporation and rebinding of both CAF and THP when the FM:XL ratio was kept at 1:5 while moderate level of initiator (I:TM = 1:100) was sufficient at higher concentration of crosslinker (FM:XL = 1:10). In contrast with the xanthine derivatives, higher template incorporation, rebinding and IF (due to comparable NIP binding across all tested I:TM ratios) were observed with MIPs for phenolic targets 3,5-dimethylphenol (1OH) and 1,3,5-benzenetriol (3OH) synthesized at lower concentration of initiator (I:TM = 1:100) and equivalent FM:XL ratio of 1:5. These contrasting results indicate that various templates require different times to reach optimum equilibrium concentration of T-FM complex and should be a primary consideration for precipitation imprinting. It would seem that, overall, MIP performance can improved by keeping the following feed formulation: T:FM ratios of 1:2 to 1:8, FM:XL ratios of 1:5 to 1:10 and I:TM ratios of 1:5 to 1:100. In all cases, the incorporation and binding efficiency of THP are higher than CAF signifying a stronger interaction with the functional monomer. Template incorporation for these systems were 20-75% but, interestingly, this has not been efficiently translated to high fidelity binding sites showing only 5-10% binding conversions. Both 1OH and 3OH MIPs gave high IF’s (1.8) and N (2.3 µmol/g). Cross-reactivity studies, however, demonstrated that 3OH MIP is the most selective towards its template giving selectivity indices of 0.58 and 0.67 for 1OH and 2OH, respectively, indicating the formation of higher fidelity binding sites due to stronger 3OH-MAA interaction. While thermal initiation at 60oC only showed evidence of dimerisation for 2OH, in photochemical initiation (27-35oC), all three phenolic templates demonstrated evidence of dimerisation. Thus, while photochemical initiation at lower temperature has the potential to yield better performing MIPs, potential side reactions limit its applicability. Particle sizes, surface areas and porosities of the microspheres imprinted with the xanthine derivatives (CAF and THP) and phenolic templates (1OH, 2OH and 3OH) was demonstrated to be affected by the nature of the template. Results obtained for selected phenolic templated MIPs also provided evidence of the effect of the concentration of initiator on particle size, surface area and porosity of the microspheres. Further investigation is warranted in order to deduce a more evident correlation. With the use of a stoichiometric functional monomer, 2,6-bis(acryl)amido pyridine (BAAPy), capable of forming an array of H-bond interactions (donor-acceptor-donor/acceptor-donor-acceptor, DAD/ADA) with an imide-containing template, 2’,3’,5’-tri-O-acetyl uridine (TAU) in this study, more binding efficient polymers were produced, exhibiting IFs (3.0) and N higher than those generated using the non-stoichiometric functional monomer MAA. Interestingly, the stoichiometric 1:1 T:FM ratio, observed in bulk imprinting, has not been maintained in precipitation polymerisation and an optimal TAU:BAAPy ratio of 1:2.5 was obtained due to the additional hydrogen bond interaction with the acetyl groups of TAU. While a moderate initiator concentration, (I:TM ratio of 1:131), resulted in high template incorporation (60%), template rebinding was only 3-4% of the incorporated template. The application of a room temperature ionic liquid (IL) 1-butyl-3-imidazolium hexafluorophosphate (bmimPF6) as porogen in precipitation imprinting of propranolol (PNL) was further explored using TRIM as cross-linker, MAA as functional monomer, and a T:FM:XL ratio of 1:1.5:4. Both ACN and IL gave comparable template incorporation (64%) while IF for IL, with respect to mass, was lower due to high IL NIP binding which could be attributed to its surface area, average pore volume and size being significantly higher that the IL MIP. Binding capacities normalised with respect to surface area, however, were comparable for both ACN and IL microspheres resulting in equivalent IFs (~2.5). Both ACN and IL systems exhibited similar microstructure while the glass transition temperatures (Tg‘s) of their MIPs were observed to be lower than those of their NIPs as an expected consequence of an efficient imprinting process.Molecular imprinting technology is becoming a widespread technology.
- Subject
- molecularly imprinted polymers; MIPs; precipitation polymerisation; microspheres; molecular imprinting; 2,6-bis(acryl)amidopyridine; stoichiometric non-covalent imprinting; ionic liquid; bmImPF6
- Identifier
- http://hdl.handle.net/1959.13/1355278
- Identifier
- uon:31445
- Rights
- Copyright 2018 Kosta Fremielle Lim
- Language
- eng
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