Synthesis and design of ligand copper complexes as anti-inflammatory drugs

Simple item page
dc.contributor.advisorJackson, Grahamen_ZA
dc.contributor.authorElmagbari, Fatin M Alien_ZA
dc.date.accessioned2015-12-10T09:35:10Z
dc.date.available2015-12-10T09:35:10Z
dc.date.issued2015en_ZA
dc.description.abstractRheumatoid arthritis is a debilitating disease for which there is no cure. Copper has been used for centuries to alleviate the inflammation associated with the disease. The aim of this research was to design and test new ligands which are able to promote the percutaneous absorption of copper and/or mobilize endogenous copper reserves. Formation constants of H+, Cu(II), Ni(II) and Zn(II) with five low molecular ligands 2-((2-aminoethyl)amino)-N-(pyridin-2- ylmethyl)acetamide) [H(555)NH2], 2-((2-dimethyl-amino)ethyl)amino)-N-(pyridin-2-ylmethyl) acetamide [H(555)NMe2], N-(2-aminoethyl)-N'-(pyridin-2-ylmethyl)ethanediamide [H2(555)NH2], 3-(2-aminoacetamido)-N-(pyridin-2-ylmethyl)propanamide [H2(565)NH2], 3-amino-N-(pyridin-2-lmethyl)-propanamide [H(56)NH2] were measured at 25±0.01oC and at an ionic strength of 0.15M (NaCl) using glass electrode potentiometry. The structures of the different Cu(II) species formed with these ligands were investigated using ultraviolet-visible (Uv-visible), nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography as well as molecular mechanics calculations. The Uv-visible spectra obtained for the different species in solution were typical of tetragonally distorted Cu(II) complexes. The active binding sites were identified as the pyridine nitrogen, the amide nitrogen and the terminal amino group. The pyridine nitrogen was involved in coordination first, followed by the amide and then the terminal amine groups. The X-ray crystal structure of two of the Cu(II) complexes were solved; one formed a rectangular pyramidal geometry and the other a distorted square planar geometry. Molecular mechanics was used to determine the lowest energy conformation of different possible geometries. Since the preferred route of administration is through the skin, the rate of dermal absorption and the bioavailability of copper are important. For this reason, the drugs were designed so that they could be administered dermally and be selective for Cu(II) so that they do not affect the speciation of other metal ions in blood plasma. Speciation calculations using a blood plasma model were used to estimate the complexing ability of the ligands in vivo. This result showed that [H(555)NH2] was the best at mobilising copper in vivo.en_ZA
dc.identifier.apacitationElmagbari, F. M. A. (2015). <i>Synthesis and design of ligand copper complexes as anti-inflammatory drugs</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/15767en_ZA
dc.identifier.chicagocitationElmagbari, Fatin M Ali. <i>"Synthesis and design of ligand copper complexes as anti-inflammatory drugs."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2015. http://hdl.handle.net/11427/15767en_ZA
dc.identifier.citationElmagbari, F. 2015. Synthesis and design of ligand copper complexes as anti-inflammatory drugs. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Elmagbari, Fatin M Ali AB - Rheumatoid arthritis is a debilitating disease for which there is no cure. Copper has been used for centuries to alleviate the inflammation associated with the disease. The aim of this research was to design and test new ligands which are able to promote the percutaneous absorption of copper and/or mobilize endogenous copper reserves. Formation constants of H+, Cu(II), Ni(II) and Zn(II) with five low molecular ligands 2-((2-aminoethyl)amino)-N-(pyridin-2- ylmethyl)acetamide) [H(555)NH2], 2-((2-dimethyl-amino)ethyl)amino)-N-(pyridin-2-ylmethyl) acetamide [H(555)NMe2], N-(2-aminoethyl)-N'-(pyridin-2-ylmethyl)ethanediamide [H2(555)NH2], 3-(2-aminoacetamido)-N-(pyridin-2-ylmethyl)propanamide [H2(565)NH2], 3-amino-N-(pyridin-2-lmethyl)-propanamide [H(56)NH2] were measured at 25±0.01oC and at an ionic strength of 0.15M (NaCl) using glass electrode potentiometry. The structures of the different Cu(II) species formed with these ligands were investigated using ultraviolet-visible (Uv-visible), nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography as well as molecular mechanics calculations. The Uv-visible spectra obtained for the different species in solution were typical of tetragonally distorted Cu(II) complexes. The active binding sites were identified as the pyridine nitrogen, the amide nitrogen and the terminal amino group. The pyridine nitrogen was involved in coordination first, followed by the amide and then the terminal amine groups. The X-ray crystal structure of two of the Cu(II) complexes were solved; one formed a rectangular pyramidal geometry and the other a distorted square planar geometry. Molecular mechanics was used to determine the lowest energy conformation of different possible geometries. Since the preferred route of administration is through the skin, the rate of dermal absorption and the bioavailability of copper are important. For this reason, the drugs were designed so that they could be administered dermally and be selective for Cu(II) so that they do not affect the speciation of other metal ions in blood plasma. Speciation calculations using a blood plasma model were used to estimate the complexing ability of the ligands in vivo. This result showed that [H(555)NH2] was the best at mobilising copper in vivo. DA - 2015 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Synthesis and design of ligand copper complexes as anti-inflammatory drugs TI - Synthesis and design of ligand copper complexes as anti-inflammatory drugs UR - http://hdl.handle.net/11427/15767 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15767
dc.identifier.vancouvercitationElmagbari FMA. Synthesis and design of ligand copper complexes as anti-inflammatory drugs. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2015 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/15767en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Chemistryen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherChemistryen_ZA
dc.titleSynthesis and design of ligand copper complexes as anti-inflammatory drugsen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
thesis_sci_2015_elmagbari_fatin_m_ali.pdf
Size:
3.85 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
PhD / Doctoral