The development of rhenium(III) oxide nanoradiopharmaceuticals
- Authors: Joseph, Sinelizwi Veronica
- Date: 2018
- Subjects: Radiopharmaceuticals , Radiopharmaceuticals Rhenium
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/30507 , vital:30955
- Description: The study details the experimental work on the development of rhenium(III) oxide nanoradiopharmaceuticals for imaging and therapy of disease states. The nanoparticles (NPs) were capped with covalently linked tetraaminophthalocyanine-folate and ethylenediamine-folate to enhance their targeting ability. The capping agents were successfully synthesised and structurally characterised using Ultraviolet-Visible Spectroscopy (UV-Vis), Fourier Transform-Infrared Spectroscopy (FT-IR), Proton Nuclear Magnetic Resonance (1H-NMR), and Liquid Chromatography-Mass Spectroscopy (LC-MS). The nanoparticles were characterised using UV-Vis, spectrofluorimetry, Transmission Electron Microscopy (TEM), dynamic light scattering (DLS) and Zeta potential. Nanoparticles of sizes between 10 and 100 nm size were envisaged to be suitable for applications in biological systems. The preferred surface charge for the uptake of NPs must be between -30 and +30 mV, Re2O3 NPs capped with ethylenediamine were found to have a surface charge of -49 mV as compared with NPs capped with ethylenediamine-folate which gave -18.6 mV. The cytotoxicity studies of the nanoparticles were tested against four different cell lines: MDA-MB-468, MDA-MB-231, MCF-7, and MCF-10A. The cell survival rate after treatment was done with different capped rhenium(III) oxide nanoparticles obtained at a 10 μM concentration showed more than 80% cell viability. A comparison was conducted based on different nanoparticle sizes of capping agents across the four cell lines of varying folate receptor. All the cell lines were compared, and it was observed that MCF-7 had high percentage of cell viability especially with the cells treated with folate conjugated nanoparticles. Further investigation was done on the effects of folate conjugates and the effects of size. It was observed that the tetraaminophthalocyanine-folate favoured the MCF-7, for large-sized nanoparticles. However, further work is required to test the cancer cell internalisation of the nanoparticles using TEM as well as the correct size for endocytosis. Thereafter, the mice model study will be carried out for investigation of biodistribution of particles in tumour tissue using hot isotopes (186/188Re) and this will be done in a radiophamarceutical laboratory.
- Full Text:
- Date Issued: 2018
- Authors: Joseph, Sinelizwi Veronica
- Date: 2018
- Subjects: Radiopharmaceuticals , Radiopharmaceuticals Rhenium
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/30507 , vital:30955
- Description: The study details the experimental work on the development of rhenium(III) oxide nanoradiopharmaceuticals for imaging and therapy of disease states. The nanoparticles (NPs) were capped with covalently linked tetraaminophthalocyanine-folate and ethylenediamine-folate to enhance their targeting ability. The capping agents were successfully synthesised and structurally characterised using Ultraviolet-Visible Spectroscopy (UV-Vis), Fourier Transform-Infrared Spectroscopy (FT-IR), Proton Nuclear Magnetic Resonance (1H-NMR), and Liquid Chromatography-Mass Spectroscopy (LC-MS). The nanoparticles were characterised using UV-Vis, spectrofluorimetry, Transmission Electron Microscopy (TEM), dynamic light scattering (DLS) and Zeta potential. Nanoparticles of sizes between 10 and 100 nm size were envisaged to be suitable for applications in biological systems. The preferred surface charge for the uptake of NPs must be between -30 and +30 mV, Re2O3 NPs capped with ethylenediamine were found to have a surface charge of -49 mV as compared with NPs capped with ethylenediamine-folate which gave -18.6 mV. The cytotoxicity studies of the nanoparticles were tested against four different cell lines: MDA-MB-468, MDA-MB-231, MCF-7, and MCF-10A. The cell survival rate after treatment was done with different capped rhenium(III) oxide nanoparticles obtained at a 10 μM concentration showed more than 80% cell viability. A comparison was conducted based on different nanoparticle sizes of capping agents across the four cell lines of varying folate receptor. All the cell lines were compared, and it was observed that MCF-7 had high percentage of cell viability especially with the cells treated with folate conjugated nanoparticles. Further investigation was done on the effects of folate conjugates and the effects of size. It was observed that the tetraaminophthalocyanine-folate favoured the MCF-7, for large-sized nanoparticles. However, further work is required to test the cancer cell internalisation of the nanoparticles using TEM as well as the correct size for endocytosis. Thereafter, the mice model study will be carried out for investigation of biodistribution of particles in tumour tissue using hot isotopes (186/188Re) and this will be done in a radiophamarceutical laboratory.
- Full Text:
- Date Issued: 2018
Design, synthesis and characterization of novel rhenium(V) and technetium(V) complexes as potential radiopharmaceuticals
- Authors: Hlabela, Patrick Simon
- Date: 2001
- Subjects: Radiopharmaceuticals , Rhenium , Technetium
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4306 , http://hdl.handle.net/10962/d1004964 , Radiopharmaceuticals , Rhenium , Technetium
- Description: A number of bidentate N, N-diethyl-N' -(R ')benzoylthiourea ligands (where R' = H,CH₃,CI,OCH₃ and N0₂) have been synthesized, as well as the three Re(V) precursor complexes, ReOCl₃(PPh₃)₂,[ReO₂(py)₄]CI and [n-Bu₄N] [ReOCI₄J. The reaction of N,N-diethyl-N'-benzoylthiourea (LH) with these three metal precursor complexes in methanol in the presence of a base gave a novel mixed-ligand complex bis(N,N-diethyl-N'-benzoylthioureato)methoxyoxorhenium(V), [ReO(L)₂(OMe)] (1). In the absence of a base and under an inert atmosphere, the reaction between [n-Bu₄N][ReOCI₄] and LH yielded bis(N,N-diethyl-N'-benzoylthioureato)chlorooxorhenium(V), [ReO(L)₂CI] (lb). The reaction of LH with [ReO₂(py)₄]CI in ethanol and iso-propanol in the presence of sodium acetate gave the novel mixed ligand complexes bis(N,N-diethyl-N'benzoylthioureato) ethoxyoxorhenium(V), [ReO(L)₂(OEt)] (6) and bis(N,N-diethyl-N'benzoylthioureato)(iso-propoxy)oxorhenium(V), [ReO(L)₂(OiPr)] (7), respectively. An oxygen bridged dirhenium complex, [(L)₂0Re-O-ReO(L)₂] (15) was obtained when the reaction was carried out in acetonitrile. A series of mixed ligand Re(V)-oxo complexes using N, N-diethyl-Nʾ-(R' )benzoylthiourea (LR'),N,N-morpholino-N' -(R')benzoylthiourea (morph-LR') and 8-(N-(R')benzoylthiocarbamoyl)-1,4-dioxa-8-azaspiro[4.5]decane ligands (spiro-LR') (where R' = H,CH₃,CI, OCH₃ and N0₂) ((1)(14) have been prepared by the reaction of [ReO₂(py)₄]CI and the ligand in the presence of sodium acetate in methanol. The solution state chemistry of these complexes has shown that complexes(1)-(14) (with the exception of (1b)) undergo dimerization in solution to give complex (15) in the presence of water. Preliminary ¹H NMR kinetics studies of the dimerization of (1), (6) and (7) to (15) have shown that the rate of dimerization decreases in the order (7) > (6) > (1). The rate of dimerization has also been compared for complexes (1), [ReO(morph-L)₂(OMe)] (8) and [ReO(spiro-L)₂(OMe)] (13) and the rate of dimerization was found to be fastest for (13). The crystal structures of (1), [ReO(LN0₂)₂(OMe)] (4), (6) and (15) have been determined. The Re(V)-oxo complexes (1), (4) and (6) have a slightly distorted octahedral geometry with the two acylthiourea ligands binding in a cis arrangement in the equatorial plane of the octahedron. The alkoxy and oxo ligands occupy the axial positions and are situated trans to each other. The crystal and molecular structure of complex (15), consist of two slightly distorted octahedral [ReO(L)₂] moieties bridged by an oxygen atom with a Re-O-Re bond angle of 175.2(2)°. The preliminary studies done in the present study have indicated that the complexation chemistry of technetium(V) with the N,N-diethyl-benzoylthiourea is different to that of rhenium (V). The reaction between [n-BuN₄][TcOCl₄] and N,N-diethyl-N'-benzoylthiourea yielded the square pyramidal cationic complex [TcO(L)₂]Cl. By contrast the octahedral methoxy complex [ReO(L )₂( OMe)] was obtained when the analogous Re(V)-oxo precursor, [n-Bu₄N] [ReOCI₄], was reacted with N,N-diethyl-N'-benzoylthiourea under the same reaction conditions.
- Full Text:
- Date Issued: 2001
- Authors: Hlabela, Patrick Simon
- Date: 2001
- Subjects: Radiopharmaceuticals , Rhenium , Technetium
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4306 , http://hdl.handle.net/10962/d1004964 , Radiopharmaceuticals , Rhenium , Technetium
- Description: A number of bidentate N, N-diethyl-N' -(R ')benzoylthiourea ligands (where R' = H,CH₃,CI,OCH₃ and N0₂) have been synthesized, as well as the three Re(V) precursor complexes, ReOCl₃(PPh₃)₂,[ReO₂(py)₄]CI and [n-Bu₄N] [ReOCI₄J. The reaction of N,N-diethyl-N'-benzoylthiourea (LH) with these three metal precursor complexes in methanol in the presence of a base gave a novel mixed-ligand complex bis(N,N-diethyl-N'-benzoylthioureato)methoxyoxorhenium(V), [ReO(L)₂(OMe)] (1). In the absence of a base and under an inert atmosphere, the reaction between [n-Bu₄N][ReOCI₄] and LH yielded bis(N,N-diethyl-N'-benzoylthioureato)chlorooxorhenium(V), [ReO(L)₂CI] (lb). The reaction of LH with [ReO₂(py)₄]CI in ethanol and iso-propanol in the presence of sodium acetate gave the novel mixed ligand complexes bis(N,N-diethyl-N'benzoylthioureato) ethoxyoxorhenium(V), [ReO(L)₂(OEt)] (6) and bis(N,N-diethyl-N'benzoylthioureato)(iso-propoxy)oxorhenium(V), [ReO(L)₂(OiPr)] (7), respectively. An oxygen bridged dirhenium complex, [(L)₂0Re-O-ReO(L)₂] (15) was obtained when the reaction was carried out in acetonitrile. A series of mixed ligand Re(V)-oxo complexes using N, N-diethyl-Nʾ-(R' )benzoylthiourea (LR'),N,N-morpholino-N' -(R')benzoylthiourea (morph-LR') and 8-(N-(R')benzoylthiocarbamoyl)-1,4-dioxa-8-azaspiro[4.5]decane ligands (spiro-LR') (where R' = H,CH₃,CI, OCH₃ and N0₂) ((1)(14) have been prepared by the reaction of [ReO₂(py)₄]CI and the ligand in the presence of sodium acetate in methanol. The solution state chemistry of these complexes has shown that complexes(1)-(14) (with the exception of (1b)) undergo dimerization in solution to give complex (15) in the presence of water. Preliminary ¹H NMR kinetics studies of the dimerization of (1), (6) and (7) to (15) have shown that the rate of dimerization decreases in the order (7) > (6) > (1). The rate of dimerization has also been compared for complexes (1), [ReO(morph-L)₂(OMe)] (8) and [ReO(spiro-L)₂(OMe)] (13) and the rate of dimerization was found to be fastest for (13). The crystal structures of (1), [ReO(LN0₂)₂(OMe)] (4), (6) and (15) have been determined. The Re(V)-oxo complexes (1), (4) and (6) have a slightly distorted octahedral geometry with the two acylthiourea ligands binding in a cis arrangement in the equatorial plane of the octahedron. The alkoxy and oxo ligands occupy the axial positions and are situated trans to each other. The crystal and molecular structure of complex (15), consist of two slightly distorted octahedral [ReO(L)₂] moieties bridged by an oxygen atom with a Re-O-Re bond angle of 175.2(2)°. The preliminary studies done in the present study have indicated that the complexation chemistry of technetium(V) with the N,N-diethyl-benzoylthiourea is different to that of rhenium (V). The reaction between [n-BuN₄][TcOCl₄] and N,N-diethyl-N'-benzoylthiourea yielded the square pyramidal cationic complex [TcO(L)₂]Cl. By contrast the octahedral methoxy complex [ReO(L )₂( OMe)] was obtained when the analogous Re(V)-oxo precursor, [n-Bu₄N] [ReOCI₄], was reacted with N,N-diethyl-N'-benzoylthiourea under the same reaction conditions.
- Full Text:
- Date Issued: 2001
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