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Type: Thesis
Title: Spectroscopic investigations on the molecular motions and solution chemistry of the medicinal pigment curcumin.
Author: Leung, Mandy Hei Man
Issue Date: 2015
School/Discipline: School of Physical Sciences
Abstract: Curcumin is the bioactive molecule in the pigments found in turmeric, a spice and traditional medicine in Asia for centuries. Research has shown that curcumin exhibits a number of medicinal benefits, in particular, anti-Alzheimer’s and anti-cancer properties. It has been shown that there is an elevated level of Cu(II) in amyloid plaques and tumours. In addition, curcumin has the ability to damage the DNA of cancer cells in the presence of Cu(II), which leads to apoptosis. Furthermore, the tautomerisation of curcumin is essential for the binding of amyloid aggregates, which is associated with Alzheimer’s disease. This thesis provides insight into the interaction between curcumin and copper ion and tautomerisation of curcumin, which are related to the proposed modes of action for curcumin. In addition, a method for stabilising of curcumin in an aqueous environment using biocompatible polyester nanoparticles is described in this thesis. These nanoparticles show potential applications as curcumin delivery systems in biological environment. As a part of the PhD thesis, the interaction between curcumin and Cu(II) has been investigated in methanol and the sodium dodecyl sulphate (SDS) micellar solution. The fluorescence quenching results show that curcumin forms both 1:1 and 1:2 Cu(II)−curcumin complexes and the binding constants are on the order of 10⁵ – 10⁸ M⁻¹, which indicate a strong binding between curcumin and Cu(II). The transient absorption spectroscopic results reveal that the strong interaction between curcumin and Cu(II) changes the electronic excited states of curcumin substantially. In addition, the decomposition of Cu(II)−curcumin complexes in a reducing environment has been studied. The UV-visible absorption values of the Cu(II)−curcumin complex in acetonitrile and in SDS micellar solution with ascorbic acid show a monotonic decrease as a function of time, indicating decomposition of curcumin in a reducing environment. In contrast, a lack of decomposition of Cu(II)−curcumin complex in methanol and curcumin in the presence of Cu(I) in acetonitrile was observed. The fluorescence results reveal that curcumin has a weaker interaction with Cu(I) than Cu(II). Therefore, the decomposition of curcumin is associated with the reduction of Cu(II) to Cu(I). The tautomerisation of curcumin in methanol, acetone and acetonitrile has been investigated by nuclear magnetic resonance spectroscopy. As tautomerisation of curcumin is the rate limiting step of the deuteration at the α-carbon position (Cα), the rate of tautomerisation is inferred from the rate of deuteration at the Cα of curcumin. The proton resonance peak corresponding to the hydrogen of Cα decays as a function of time, signifying a successful hydrogen-deuterium exchange. The rate constants of tautomerisation of curcumin have been measured at several temperatures and analysis using the Arrhenius equation has revealed that the activation energy of tautomerisation of curcumin is between 60 and 80 kJ mol⁻¹. The high activation energy values are attributable to the high energy barrier for disrupting the intramolecular hydrogen bonding and extended π-conjugation in the keto-enol tautomer of curcumin. Although curcumin has shown many medicinal effects, there are two major challenges regarding the utilisation of curcumin for disease treatments. These challenges are the poor solubility of curcumin in an aqueous environment and its lack of stability under physiological conditions. A one-step nanoprecipitation method to prepare curcumin-encapsulated polyester nanoparticles using polylactic acid, poly(lactide-coglycolide) and poly(ε-caprolactone) has been developed. The resulting nanoparticles have an average diameter less than 100 nm and a negative surface charge, which enables these nanoparticles to remain suspended in water. Furthermore, the UV-visible absorption values of the curcumin-polyester nanoparticles show only a minor decrease as a function of time, indicating that the polyester nanoparticles are able to prevent curcumin degradation. The results from studies using fluorescence upconversion spectroscopy reveal a lack of deuterium isotope effect of curcumin encapsulated in the polyester nanoparticles in the presence of D₂O. As a result of limited interaction between curcumin and water, the degradation of curcumin is suppressed. Overall, the polyester nanoparticles show significant potential as curcumin delivery agents.
Advisor: Kee, Tak W.
Lincoln, Stephen Frederick
Metha, Gregory Francis
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, School of Physical Sciences, 2015
Keywords: UV-visible; fluorescence; time-resolved spectroscopy; mass spectrometry; HPLC; NMR; nanoprecipitation; copper
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at:
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