Applications of Baylis-Idllman methodology in the synthesis of chromene derivatives
- Authors: Nocanda, Xolani Wittleton
- Date: 2001
- Subjects: Heterocyclic chemistry , Heterocyclic compounds -- Derivatives
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4556 , http://hdl.handle.net/10962/d1018257
- Description: The reaction of salicylaldehyde with various activated alkenes, viz., methyl vinyl ketone, ethyl vinyl ketone, phenyl vinyl sulfone, phenyl vinylsulfonate, acrolein and acrylonitrile, under Baylis-Hillman conditions, has been found to proceed with the chemoselective formation of chromene derivatives. The reaction conditions have been optimised and chromene derivatives have been obtained in isolated yields up to 87 %. The generality of the reaction, using 1,4-diazabicyclo[2.2.2]octane (DABCO), as the catalyst, and a heterogeneous (chloroform-water) solvent system, has been established using a range of salicylaldehyde derivatives,. including 2-hydroxynaphthaldehyde. The formation of chromene derivatives, under these conditions, has been assumed to proceed via an initial, Baylis-Hillman reaction, followed by cyclisation involving intramolecular conjugate addition, and subsequent dehydration. Evidence supporting this sequence has been obtained from the isolation ofBaylis-Hillman products from reactions involving the use of tertbutylclimethylsilyl-protected salicylaldehyde, 4-hydroxybenzaldehyde and tert-butyl acrylate as substrates. The potential of the ''Baylis-Hillman zwitterion" to participate as a donor species in Michael-type addition reactions has been explored and a series of climeric products has been isolated. The Baylis-Hillman methodology has also been successfully extended to the synthesis of sulfurcontaining heterocyclic systems, and a range of 3-substituted thiochromenes has been obtained in moderate yields, using 2,2'-dithiobenzaldehyde and various activated alkenes in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst. The electron-impact mass spectra of selected chromene and thiocbromene derivatives have been investigated permitting comparison of the fragmentation of the oxygen- and sulfur-containing analogues. In a study directed at the synthesis of potential HIV -1 protease inhibitors, chromene- and thiocbromene-containing analogues of the clinically useful drug, ritonavir, have been prepared. Thiochromene and chromene derivatives were converted to the corresponding 3 -carboxylic acids and coupled with a specially prepared, hydroxyethylene dipeptide isostere to afford ritonavir analogues containing cbromene and thiochromene termini in ca. 60% yield.
- Full Text:
- Date Issued: 2001
- Authors: Nocanda, Xolani Wittleton
- Date: 2001
- Subjects: Heterocyclic chemistry , Heterocyclic compounds -- Derivatives
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4556 , http://hdl.handle.net/10962/d1018257
- Description: The reaction of salicylaldehyde with various activated alkenes, viz., methyl vinyl ketone, ethyl vinyl ketone, phenyl vinyl sulfone, phenyl vinylsulfonate, acrolein and acrylonitrile, under Baylis-Hillman conditions, has been found to proceed with the chemoselective formation of chromene derivatives. The reaction conditions have been optimised and chromene derivatives have been obtained in isolated yields up to 87 %. The generality of the reaction, using 1,4-diazabicyclo[2.2.2]octane (DABCO), as the catalyst, and a heterogeneous (chloroform-water) solvent system, has been established using a range of salicylaldehyde derivatives,. including 2-hydroxynaphthaldehyde. The formation of chromene derivatives, under these conditions, has been assumed to proceed via an initial, Baylis-Hillman reaction, followed by cyclisation involving intramolecular conjugate addition, and subsequent dehydration. Evidence supporting this sequence has been obtained from the isolation ofBaylis-Hillman products from reactions involving the use of tertbutylclimethylsilyl-protected salicylaldehyde, 4-hydroxybenzaldehyde and tert-butyl acrylate as substrates. The potential of the ''Baylis-Hillman zwitterion" to participate as a donor species in Michael-type addition reactions has been explored and a series of climeric products has been isolated. The Baylis-Hillman methodology has also been successfully extended to the synthesis of sulfurcontaining heterocyclic systems, and a range of 3-substituted thiochromenes has been obtained in moderate yields, using 2,2'-dithiobenzaldehyde and various activated alkenes in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst. The electron-impact mass spectra of selected chromene and thiocbromene derivatives have been investigated permitting comparison of the fragmentation of the oxygen- and sulfur-containing analogues. In a study directed at the synthesis of potential HIV -1 protease inhibitors, chromene- and thiocbromene-containing analogues of the clinically useful drug, ritonavir, have been prepared. Thiochromene and chromene derivatives were converted to the corresponding 3 -carboxylic acids and coupled with a specially prepared, hydroxyethylene dipeptide isostere to afford ritonavir analogues containing cbromene and thiochromene termini in ca. 60% yield.
- Full Text:
- Date Issued: 2001
Chemical studies of chromone derivatives
- Authors: Sabbagh, Liezel Veronica
- Date: 2001
- Subjects: Benzopyrans Heterocyclic compounds -- Derivatives Coumarins
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4424 , http://hdl.handle.net/10962/d1006899
- Description:
This study has focussed on several aspects of chromone chemistry, viz., (i) the influence of remote substituents on the basicity of 2-(N,N-dimethylamino)chromones, (ii) MoritaBaylis-Hillman reactions of substituted chromone-3-carbaldehydes and (iii) an investigation into the application of chromone chemistry in the total synthesis of the marine natural product, Rietone A. Selected 2-(N,N-dimethylamino )chromones were prepared using two different methods; firstly, via cyclisation of salicylate-derived N,N-dimethyl-3;.(2-hydroxyphenyl)-3- oxopropanamide precursors and, secondly, via 2-hydroxyacetophenone boron difluoride complexes. ¹³C NMR analysis of the 6- and 7-methoxy-2-(N,N-dimethylamino)chromones confirmed that protonation occurs at the chromone carbonyl oxygen rather than the amino nitrogen - a conclusion supported by mol~cular orbital calculations. Potentiometric analysis of 2-(N,N-dimethylamino )chromones in ethanol-water afforded pKa (pK [subscript a]) values in the range 2.22 - 2.52. The observed trend has been rationalised in terms of substituent effects with the aid of molecular orbital calculations at the semi-empirical and ab initio levels, while hydrogen-bonding effects have been used to account for the apparently anomalous result obtained for the 6-nitro derivative. A series of seven substituted chromone-3-carbaldehydes, prepared by the application of Vilsmeier-Haack methodology to the corresponding 2-hydroxyacetophenones, have been examined as substrates for Morita-Baylis-Hillman reactions, using DABCO as the catalyst and three different activated alkenes, viz., methyl acrylate, methyl vinyl ketone and acrylonitrile. In all cases, with the exception of 6-nitrochromone-3-carbaldehyde, the reactions have been shown to afford the expected Morita-Baylis-Hillman products. Use of methyl acrylate and methyl vinyl ketone as the activated alkene has been observed to afford additional, unprecedented dimeric products, which have been unambiguously characterised using a combination of single crystal X-ray analysis and spectroscopic (high resolution MS and NMR) techniques. Different dimer-like adducts have been isolated from reactions in which acrylonitrile was used as the activated alkene, and the structures of these novel products have-been determined
- Full Text:
- Date Issued: 2001
- Authors: Sabbagh, Liezel Veronica
- Date: 2001
- Subjects: Benzopyrans Heterocyclic compounds -- Derivatives Coumarins
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4424 , http://hdl.handle.net/10962/d1006899
- Description:
This study has focussed on several aspects of chromone chemistry, viz., (i) the influence of remote substituents on the basicity of 2-(N,N-dimethylamino)chromones, (ii) MoritaBaylis-Hillman reactions of substituted chromone-3-carbaldehydes and (iii) an investigation into the application of chromone chemistry in the total synthesis of the marine natural product, Rietone A. Selected 2-(N,N-dimethylamino )chromones were prepared using two different methods; firstly, via cyclisation of salicylate-derived N,N-dimethyl-3;.(2-hydroxyphenyl)-3- oxopropanamide precursors and, secondly, via 2-hydroxyacetophenone boron difluoride complexes. ¹³C NMR analysis of the 6- and 7-methoxy-2-(N,N-dimethylamino)chromones confirmed that protonation occurs at the chromone carbonyl oxygen rather than the amino nitrogen - a conclusion supported by mol~cular orbital calculations. Potentiometric analysis of 2-(N,N-dimethylamino )chromones in ethanol-water afforded pKa (pK [subscript a]) values in the range 2.22 - 2.52. The observed trend has been rationalised in terms of substituent effects with the aid of molecular orbital calculations at the semi-empirical and ab initio levels, while hydrogen-bonding effects have been used to account for the apparently anomalous result obtained for the 6-nitro derivative. A series of seven substituted chromone-3-carbaldehydes, prepared by the application of Vilsmeier-Haack methodology to the corresponding 2-hydroxyacetophenones, have been examined as substrates for Morita-Baylis-Hillman reactions, using DABCO as the catalyst and three different activated alkenes, viz., methyl acrylate, methyl vinyl ketone and acrylonitrile. In all cases, with the exception of 6-nitrochromone-3-carbaldehyde, the reactions have been shown to afford the expected Morita-Baylis-Hillman products. Use of methyl acrylate and methyl vinyl ketone as the activated alkene has been observed to afford additional, unprecedented dimeric products, which have been unambiguously characterised using a combination of single crystal X-ray analysis and spectroscopic (high resolution MS and NMR) techniques. Different dimer-like adducts have been isolated from reactions in which acrylonitrile was used as the activated alkene, and the structures of these novel products have-been determined
- Full Text:
- Date Issued: 2001
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
Design, synthesis and evaluation of silver-specific ligands
- Authors: Daubinet, André
- Date: 2001
- Subjects: Ligands Ligands -- Design Ligands -- Analysis Ligands -- Evaluation Silver -- Metallurgy
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4308 , http://hdl.handle.net/10962/d1004966
- Description: Several series of ligands, designed to chelate silver(I) specifically in the presence of base metals, have been synthesised. The ligands include: - dithiodiamide compounds, prepared by the condensation of acetanilide derivatives with 1,2-dibromoethane; propanenitrile and propanoic ester derivatives prepared from pyridine-2-carbaldehyde via the Morita-Baylis-Hillman reaction; and novel malonamide ligands from the reaction of diethyl malonate with a range of primary amines. The malonamide derivatives were prepared under both conventional thermal and microwave-assisted conditions, the latter proving to be highly efficient. The ligands were all characterised using a combination of spectroscopic and, where appropriate, elemental analysis; in one case, the structural assignment was confirmed by single-crystal X-ray analysis. The fragmentation patterns in the electron-impact mass spectra of the malonamide derivatives have been explored using high-resolution and meta-stable peak scanning techniques. Complexes of the malonamide ligands with copper(II) and silver(I) have been synthesised, and examination of these complexes has revealed distinct differences in their co-ordination preferences towards silver(I) and copper(II). Tentative, computer-modelled structures for the complexes have been proposed using the available spectroscopic and elemental analysis data. Computer modelling, at the Molecular Mechanics level, has also been used to assess the capacity of the ligand systems to adopt conformations suitable for the chelation of tetrahedral silver(I). Solvent extraction studies have been undertaken using aqueous metal ion solutions and various organic solvents. The dithiodiamide derivatives typically presented solubility problems, but one of the ligands, N,N´-bis(3-chlorophenyl)-3,6-dithiaoctanediamide, exhibited significant but slow extraction of silver(I) into toluene. The malonamide derivatives, however, proved to be readily soluble in ethyl acetate and, in some cases, exhibited good to excellent selectivity for silver(I) in the presence of the base metals copper and lead. Atomic absorption analysis revealed rapid equilibration times (<15 min) and high extraction efficiencies over a wide pH range (2.78 - 9.0). Metal selectivity has been determined by ICP-MS analysis of the residual silver, copper and lead present in the aqueous phase after 15 min, and one of the ligands, N,N´-bis(2-benzylsulfanylethyl)malonamide, exhibits excellent (≥ 96 %) silver(I) specificity.
- Full Text:
- Date Issued: 2001
- Authors: Daubinet, André
- Date: 2001
- Subjects: Ligands Ligands -- Design Ligands -- Analysis Ligands -- Evaluation Silver -- Metallurgy
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4308 , http://hdl.handle.net/10962/d1004966
- Description: Several series of ligands, designed to chelate silver(I) specifically in the presence of base metals, have been synthesised. The ligands include: - dithiodiamide compounds, prepared by the condensation of acetanilide derivatives with 1,2-dibromoethane; propanenitrile and propanoic ester derivatives prepared from pyridine-2-carbaldehyde via the Morita-Baylis-Hillman reaction; and novel malonamide ligands from the reaction of diethyl malonate with a range of primary amines. The malonamide derivatives were prepared under both conventional thermal and microwave-assisted conditions, the latter proving to be highly efficient. The ligands were all characterised using a combination of spectroscopic and, where appropriate, elemental analysis; in one case, the structural assignment was confirmed by single-crystal X-ray analysis. The fragmentation patterns in the electron-impact mass spectra of the malonamide derivatives have been explored using high-resolution and meta-stable peak scanning techniques. Complexes of the malonamide ligands with copper(II) and silver(I) have been synthesised, and examination of these complexes has revealed distinct differences in their co-ordination preferences towards silver(I) and copper(II). Tentative, computer-modelled structures for the complexes have been proposed using the available spectroscopic and elemental analysis data. Computer modelling, at the Molecular Mechanics level, has also been used to assess the capacity of the ligand systems to adopt conformations suitable for the chelation of tetrahedral silver(I). Solvent extraction studies have been undertaken using aqueous metal ion solutions and various organic solvents. The dithiodiamide derivatives typically presented solubility problems, but one of the ligands, N,N´-bis(3-chlorophenyl)-3,6-dithiaoctanediamide, exhibited significant but slow extraction of silver(I) into toluene. The malonamide derivatives, however, proved to be readily soluble in ethyl acetate and, in some cases, exhibited good to excellent selectivity for silver(I) in the presence of the base metals copper and lead. Atomic absorption analysis revealed rapid equilibration times (<15 min) and high extraction efficiencies over a wide pH range (2.78 - 9.0). Metal selectivity has been determined by ICP-MS analysis of the residual silver, copper and lead present in the aqueous phase after 15 min, and one of the ligands, N,N´-bis(2-benzylsulfanylethyl)malonamide, exhibits excellent (≥ 96 %) silver(I) specificity.
- Full Text:
- Date Issued: 2001
Extractives from six species of South African Marine Opisthobranch Molluscs
- Authors: McPhail, Kerry Lee
- Date: 2001
- Subjects: Mollusks -- Nutrition Mollusks -- Anatomy Marine fishes -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4433 , http://hdl.handle.net/10962/d1007412
- Description: The natural product chemistry of six species of South African opisthobranch molluscs and some of their dietary marine invertebrates was investigated. Nineteen previously undescribed secondary metabolites and twelve known compounds were isolated and their structures determined by a combination of spectroscopic and chemical methods. The circumtropical sea hares Aplysia parvula and A. dactylomela were found to contain halogenated red algal metabolites. 3Z-bromofucin (120), the Z analogue of a known Laurencia CIS acetogenin, was isolated from A. parvula. A. dactylomela yielded a series of novel non-aromatic cuparanes, the algoanes (121-123), the novel tricyclic Iaurane ether ibhayinol (124) and three known chamigrane sesquiterpenes, prepacifenol epoxide (101), pacif-7-enediol (104) and nidificene (125). A variety of new octocoral sesquiterpenes were isolated from the endemic South African arminacean nudibranch Leminda millecra including algoafuran (150), cubebenone (151), 8-hydroxycalamenene (152) and a series of seven triprenylated toluquinones and toluquinols (153-159). L. millecra also yielded the known sesquiterpenes millecrones A (142) and B (143) and isofuranodiene (149). Twenty eight voucher specimens and eighteen crude extracts of South African octocorals collected by the Coral Reef Research Foundation were screened by GC and GC-MS and 142 was found in Alcyonium fauri, while 143, 151 and possibly 149 were present in Leptogorgia palma. An investigation of southern African chromodorids yielded the known macrocyc1e latrunculin B (220) and two new spongiane diterpenes (221) and (222) from Chromodoris hamiltoni, while the known spongiane diterpene (210) was isolated from the endemic nudibranch Glossodoris sp. 4. The endemic nudibranch Hypselodoris capensis contained the known furanosesquiterpenes nakafuran-8 (223) and -9 (224) and the known furanosesterterpenes variabilin (195), 22-deoxyvariabilin (225) and furospinosulin (227) together with the new variant 22-deoxy-23-hydroxymethylvariabilin (226). Compounds 223 and 224 were also found in a Dysidea sponge, while the furanosesterterpenes 195, and 225-227 were present in a Fasciospongia sponge upon which H capensis specimens were found. The Dysidea dietary sponge of H capensis also yielded a new aromatic sesquiterpene, tsitsikarnmafuran (266), whose structure was confirmed by the synthesis of two possible regioisomers.
- Full Text:
- Date Issued: 2001
- Authors: McPhail, Kerry Lee
- Date: 2001
- Subjects: Mollusks -- Nutrition Mollusks -- Anatomy Marine fishes -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4433 , http://hdl.handle.net/10962/d1007412
- Description: The natural product chemistry of six species of South African opisthobranch molluscs and some of their dietary marine invertebrates was investigated. Nineteen previously undescribed secondary metabolites and twelve known compounds were isolated and their structures determined by a combination of spectroscopic and chemical methods. The circumtropical sea hares Aplysia parvula and A. dactylomela were found to contain halogenated red algal metabolites. 3Z-bromofucin (120), the Z analogue of a known Laurencia CIS acetogenin, was isolated from A. parvula. A. dactylomela yielded a series of novel non-aromatic cuparanes, the algoanes (121-123), the novel tricyclic Iaurane ether ibhayinol (124) and three known chamigrane sesquiterpenes, prepacifenol epoxide (101), pacif-7-enediol (104) and nidificene (125). A variety of new octocoral sesquiterpenes were isolated from the endemic South African arminacean nudibranch Leminda millecra including algoafuran (150), cubebenone (151), 8-hydroxycalamenene (152) and a series of seven triprenylated toluquinones and toluquinols (153-159). L. millecra also yielded the known sesquiterpenes millecrones A (142) and B (143) and isofuranodiene (149). Twenty eight voucher specimens and eighteen crude extracts of South African octocorals collected by the Coral Reef Research Foundation were screened by GC and GC-MS and 142 was found in Alcyonium fauri, while 143, 151 and possibly 149 were present in Leptogorgia palma. An investigation of southern African chromodorids yielded the known macrocyc1e latrunculin B (220) and two new spongiane diterpenes (221) and (222) from Chromodoris hamiltoni, while the known spongiane diterpene (210) was isolated from the endemic nudibranch Glossodoris sp. 4. The endemic nudibranch Hypselodoris capensis contained the known furanosesquiterpenes nakafuran-8 (223) and -9 (224) and the known furanosesterterpenes variabilin (195), 22-deoxyvariabilin (225) and furospinosulin (227) together with the new variant 22-deoxy-23-hydroxymethylvariabilin (226). Compounds 223 and 224 were also found in a Dysidea sponge, while the furanosesterterpenes 195, and 225-227 were present in a Fasciospongia sponge upon which H capensis specimens were found. The Dysidea dietary sponge of H capensis also yielded a new aromatic sesquiterpene, tsitsikarnmafuran (266), whose structure was confirmed by the synthesis of two possible regioisomers.
- Full Text:
- Date Issued: 2001
Novel approaches to the synthesis of quinoline derivatives
- Authors: Klaas, Phindile Jonathan
- Date: 2001 , 2013-04-26
- Subjects: Quinoline--Synthesis
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4299 , http://hdl.handle.net/10962/d1004751 , Quinoline--Synthesis
- Description: The investigation has been concerned with the application of the Baylis-Hillman methodology to the synthesis of quinoline derivatives. An extensive range of novel Baylis-Hillman products has been prepared, typically in moderate to excellent yields, by condensing 2-nitrobenzaldehyde derivatives with various vinyl ketones and acrylic esters in the presence of diazabicyclo[2.2.2]octane (DABCO). Reduction of the nitro group in the Baylis-Hillman products was effected by catalytic hydrogenation in ethanol using a 10% palladium-on-carbon catalyst to afford quinoline, quinoline-N-oxide and quinolone derivatives. In all cases, it is apparent that cyclisation involves exclusive attack of nucleophilic nitrogen at the carbonyl centre, with acrylic ester derivatives affording quinolones and vinyl ketone derivatives affording quinolines and the corresponding quinoline-N-oxides. No products arising from a conjugate addition pathway were observed. The use of stannous chloride as an alternative reagent to effect reductive cyclisation of the Baylis-Hillman products has been explored, and found to favour the formation of 1,2- dihydroquinoline derivatives, with cyclisation occurring via a conjugate addition pathway. Isolation of the products, following work-up of the stannous chloride reactions, however, presented some difficulty. All compounds were characterised by spectroscopic (NMR and IR) and, where appropriate, elemental (high-resolution MS) analysis. Interconversion of the quinoline and quinoline-N-oxide derivatives has been explored and finally achieved in quantitative yields. Reduction of 2,3-dimethylquinoline-N-oxide to the corresponding quinoline was effected using phosphorus tribromide in DMF, and the reverse transformation with meta-chloroperbenzoic acid (MCPBA) in CHCl₃. Application of these methods to mixtures of 2,3-dimethylquinoline and its N-oxide has afforded, selectively, either the quinoline derivative or the corresponding N-oxide. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 2001
- Authors: Klaas, Phindile Jonathan
- Date: 2001 , 2013-04-26
- Subjects: Quinoline--Synthesis
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4299 , http://hdl.handle.net/10962/d1004751 , Quinoline--Synthesis
- Description: The investigation has been concerned with the application of the Baylis-Hillman methodology to the synthesis of quinoline derivatives. An extensive range of novel Baylis-Hillman products has been prepared, typically in moderate to excellent yields, by condensing 2-nitrobenzaldehyde derivatives with various vinyl ketones and acrylic esters in the presence of diazabicyclo[2.2.2]octane (DABCO). Reduction of the nitro group in the Baylis-Hillman products was effected by catalytic hydrogenation in ethanol using a 10% palladium-on-carbon catalyst to afford quinoline, quinoline-N-oxide and quinolone derivatives. In all cases, it is apparent that cyclisation involves exclusive attack of nucleophilic nitrogen at the carbonyl centre, with acrylic ester derivatives affording quinolones and vinyl ketone derivatives affording quinolines and the corresponding quinoline-N-oxides. No products arising from a conjugate addition pathway were observed. The use of stannous chloride as an alternative reagent to effect reductive cyclisation of the Baylis-Hillman products has been explored, and found to favour the formation of 1,2- dihydroquinoline derivatives, with cyclisation occurring via a conjugate addition pathway. Isolation of the products, following work-up of the stannous chloride reactions, however, presented some difficulty. All compounds were characterised by spectroscopic (NMR and IR) and, where appropriate, elemental (high-resolution MS) analysis. Interconversion of the quinoline and quinoline-N-oxide derivatives has been explored and finally achieved in quantitative yields. Reduction of 2,3-dimethylquinoline-N-oxide to the corresponding quinoline was effected using phosphorus tribromide in DMF, and the reverse transformation with meta-chloroperbenzoic acid (MCPBA) in CHCl₃. Application of these methods to mixtures of 2,3-dimethylquinoline and its N-oxide has afforded, selectively, either the quinoline derivative or the corresponding N-oxide. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 2001
Photosensitizing properties of non-transition metal porphyrazines towards the generation of singlet oxygen
- Seotsanyana-Mokhosi, Itumeleng
- Authors: Seotsanyana-Mokhosi, Itumeleng
- Date: 2001 , 2013-05-02
- Subjects: Phthalocyanines , Photosensitization, Biological , Active oxygen -- Physiological effect , Photosensitizing compounds
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4395 , http://hdl.handle.net/10962/d1006086 , Phthalocyanines , Photosensitization, Biological , Active oxygen -- Physiological effect , Photosensitizing compounds
- Description: Metallophthalocyanine complexes containing non-transition metals are very useful as sensitizers for photodynamic therapy, a cure for cancer that is based on visible light activation of tumour localized photo sensitizers. Excited sensitizers generate singlet oxygen as the main hyperactive species that destroy the tumour. Water soluble sensitizers are sought after for the convenience of delivery into the body. Thus, phthalocyanine (pc), tetrapyridinoporphyrazines (tppa) and tetramethyltetrapyridinoporphyrazines (tmtppa) with non-transition central metal atoms of Ge, Si, Sn and Zn were studied. First was the synthesis of these complexes, followed by their characterisation. The characterisation involved the use of ultraviolet and visible absorption spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, electrochemical properties and elemental analysis. Photochemical properties of the complexes were then investigated. Photolysis of these macrocycles showed two processes; -reduction of the dye and photobleaching, which leads to the disintegration of the conjugated chromophore structure of the dye. Photobleaching is the reductive quenching of the excited state of the sensitizers. The intensity of the quenching decreased progressively from tmtppa, tppa to pc metal complexes with photobleaching quantum yields, 6.6 x 10.5⁻¹, 1.8 x 10.5⁻¹ and 5.4 x 10⁻⁶ for Zntmtppa, Zntppa and Znpc, respectively. Efficiency of singlet oxygen sensitization is solvent dependent with very different values obtained for the same compound in different solvents, for example, 0.25 and 0.38 were observed as singlet oxygen quantum yields for Gepc complex in DMSO and DMF respectively. In DMSO the efficiency of ¹O₂ generation decrease considerably from pc to tppa and finally tmtppa. In water Getmtppa exhibits much higher singlet oxygen quantum yield, hence promising to be effective as a sensitizer for photodynamic therapy.
- Full Text:
- Date Issued: 2001
- Authors: Seotsanyana-Mokhosi, Itumeleng
- Date: 2001 , 2013-05-02
- Subjects: Phthalocyanines , Photosensitization, Biological , Active oxygen -- Physiological effect , Photosensitizing compounds
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4395 , http://hdl.handle.net/10962/d1006086 , Phthalocyanines , Photosensitization, Biological , Active oxygen -- Physiological effect , Photosensitizing compounds
- Description: Metallophthalocyanine complexes containing non-transition metals are very useful as sensitizers for photodynamic therapy, a cure for cancer that is based on visible light activation of tumour localized photo sensitizers. Excited sensitizers generate singlet oxygen as the main hyperactive species that destroy the tumour. Water soluble sensitizers are sought after for the convenience of delivery into the body. Thus, phthalocyanine (pc), tetrapyridinoporphyrazines (tppa) and tetramethyltetrapyridinoporphyrazines (tmtppa) with non-transition central metal atoms of Ge, Si, Sn and Zn were studied. First was the synthesis of these complexes, followed by their characterisation. The characterisation involved the use of ultraviolet and visible absorption spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, electrochemical properties and elemental analysis. Photochemical properties of the complexes were then investigated. Photolysis of these macrocycles showed two processes; -reduction of the dye and photobleaching, which leads to the disintegration of the conjugated chromophore structure of the dye. Photobleaching is the reductive quenching of the excited state of the sensitizers. The intensity of the quenching decreased progressively from tmtppa, tppa to pc metal complexes with photobleaching quantum yields, 6.6 x 10.5⁻¹, 1.8 x 10.5⁻¹ and 5.4 x 10⁻⁶ for Zntmtppa, Zntppa and Znpc, respectively. Efficiency of singlet oxygen sensitization is solvent dependent with very different values obtained for the same compound in different solvents, for example, 0.25 and 0.38 were observed as singlet oxygen quantum yields for Gepc complex in DMSO and DMF respectively. In DMSO the efficiency of ¹O₂ generation decrease considerably from pc to tppa and finally tmtppa. In water Getmtppa exhibits much higher singlet oxygen quantum yield, hence promising to be effective as a sensitizer for photodynamic therapy.
- Full Text:
- Date Issued: 2001
Synthesis and characterisation of novel platinum (II) complexes potential chemotherapeutic drugs
- Authors: Datt, Michael Steven
- Date: 2001
- Subjects: Chemotherapy Platinum
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4366 , http://hdl.handle.net/10962/d1005031
- Description: The present study involves the preparation of novel mixed-ligand platinum(II) complexes in the hope of expanding the range of platinum(II) complexes that exhibit anticancer activity and which are less toxic and have a broader spectrum of activity than cisplatin and its analogues. To this end, N-(3-R-benzoyl)-N’,N’-diethylthiourea, N-(3-R-benzoyl)-N’-morpholinothiourea, N-(3-Rbenzoyl)-N’,N’-di(2-hydroxyethyl)thiourea (R = NO2, Cl, H, CH3, OCH3), N,N-diethyl-N’-menthyloxycarbonylthiourea and N-menthyloxycarbonyl-N’-morpholinothiourea ligands, and their corresponding mixed-ligand platinum(II) complexes of the type [PtCl(L)(RR’SO)], were synthesised and characterised by elemental analyses, IR, 1H and 195Pt NMR spectroscopy and, in some cases, X-ray crystallography. Dimethylsulfoxide complexes were prepared using all the ligands, while complexes containing unsymmetrically substituted sulfoxides were prepared using the N-benzoyl-N’,N’-diethylthiourea and ,N-diethyl-’-(-)-(3R)-menthyloxycarbonylthiourea ligands only. The molecular structures of cis-(S,S)-[PtCl(DMSO)(L)] (where L = N-benzoyl-N’,N’-diethylthioureato, N-(+)-(3S)-menthyloxycarbonyl-N’-morpholinothioureato), cis-(S,S)-[Pt(N-benzoyl-N’,N’-diethylthioureato)Cl(MPSO)] and cis-[Pt(N-benzoyl-N’,N’-diethylthioureato)2] were determined by X-ray crystallography. The X-ray crystal structure of N,N-diethyl-N’- (-)-(3R)-menthyloxycarbonylthiourea was also determined. The spectroscopic and crystallographic data are consistent with complexes containing a (S,O)-chelated ligand and a sulfur-bonded sulfoxide ligand. However, the 1H and 195Pt NMR studies showed that the alkoxycarbonylthioureato complexes exist as geometric isomers with the sulfoxide coordinated either in a cis-(S,S) or trans-(S,S) arrangement with respect to the sulfur donor atom of the chelated ligand, whereas the acylthioureato complexes yielded only cis-(S,S)-[PtCl(L)(RR’SO)] complexes. The difference in the coordination chemistry of the acylthiourea and alkoxycarbonylthiourea ligands was examined further by treatment of the [PtCl(DMSO)(L)] complexes, where L = Nbenzoyl-N’,N’-diethylthioureato, N-benzoyl-N’-morpholinothioureato, N,N-diethyl-N’-(-)-(3R)- menthyloxycarbonylthioureato and N-(+)-(3S)-menthyloxycarbonyl-N’-morpholinothioureato, with PPh3 to give the corresponding [PtCl(L)(PPh3)] and [Pt(L)(PPh3)2]+ complexes. 31P NMR studies of these complexes reveal that the alkoxycarbonylthioureato ligands bind less strongly than the acylthioureato ligands, which is consistent with the crystallographic studies. The morpholine derivatives of the acylthioureato and alkoxycarbonylthioureato ligand systems also appear to bind less tightly than the diethyl derivatives. The weaker binding properties of the alkoxycarbonylthioureato ligands might be a possible explanation for the observed geometric isomerisation of these complexes, with the mechanism of isomerisation involving a chelate ringiv opening step. Furthermore, crystallographic and 31P NMR studies suggest that the acylthioureato carbonyl oxygen donor atom is relatively softer and therefore has a greater trans-influence than the carbonyl oxygen donor atom of the alkoxycarbonylthioureato ligand. The substitution kinetics of the chloride and sulfoxide leaving groups by azide, iodide, thiocyanate, triphenylphosphine, 2-mercaptobenzimidazole, 4-(dimethylamino)pyridine and thiourea, from selected cis-(S,S)-[PtCl(N,N-dialkyl-N’-(3-R-benzoyl)thioureato)(RR’SO)] complexes, in methanol, were evaluated to determine if variation of the electronic properties of the chelated ligand and variation of the sulfoxide have a significant influence on the reactivity of these complexes. Two consecutive reactions were observed. It was found that neutral nucleophiles initially substitute the dimethylsulfoxide, while anionic nucleophiles substituted the chloride ligand. For all the nucleophiles studied, the first substitution step was evaluated, except for triphenylphosphine and 4-(dimethylamino)pyridine, where the second step was also evaluated. The overall order of reactivity for the first substitution step was; N3 - < DMAP < I- < SCN- < MBI < thiourea < PPh3, with the rate varying three orders of magnitude. The substitution of the dimethylsulfoxide ligand by PPh3 from cis-(S,S)-[Pt(N-benzoyl-N’,N’-diethylthioureato)Cl-(DMSO)] to form cis-(S,P)-[Pt(N-benzoyl-N’,N’-diethylthioureato)Cl(PPh3)] was confirmed by X-ray crystallography. In general, manipulation of the chelating moiety, as well as interchanging the sulfoxide did not alter the reactivity of these complexes to a great extent. The anticancer activity of all the platinum(II) sulfoxide complexes were evaluated against a HeLa cell line, of which three complexes, cis-(S,S)-[PtCl(DMSO)(N,N-diethyl-N’-(3-nitrobenzoyl)- thioureato)], cis-(S,S)-[PtCl(DMSO)(N-morpholino-N’-(3-nitrorobenzoyl)thioureato)] and cis-(S,S)-[PtCl(DMSO)(N-(3-methoxybenzoyl)-N’-morpholinothioureato)] exhibited a concentration dependent anti-proliferative effect, but were less potent than cisplatin. These three complexes displayed a similar dose response in a MCF-7 cell line. Preliminary morphology studies with the three biologically active complexes in a HeLa cell line suggest that they induce cell death by apoptosis. Preliminary pBR322 plasmid DNA binding studies of selected [Pt(acylthioureato)Cl(RR’SO)]complexes clearly indicate that these complexes have a different mode of binding to DNA than cisplatin.
- Full Text:
- Date Issued: 2001
- Authors: Datt, Michael Steven
- Date: 2001
- Subjects: Chemotherapy Platinum
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4366 , http://hdl.handle.net/10962/d1005031
- Description: The present study involves the preparation of novel mixed-ligand platinum(II) complexes in the hope of expanding the range of platinum(II) complexes that exhibit anticancer activity and which are less toxic and have a broader spectrum of activity than cisplatin and its analogues. To this end, N-(3-R-benzoyl)-N’,N’-diethylthiourea, N-(3-R-benzoyl)-N’-morpholinothiourea, N-(3-Rbenzoyl)-N’,N’-di(2-hydroxyethyl)thiourea (R = NO2, Cl, H, CH3, OCH3), N,N-diethyl-N’-menthyloxycarbonylthiourea and N-menthyloxycarbonyl-N’-morpholinothiourea ligands, and their corresponding mixed-ligand platinum(II) complexes of the type [PtCl(L)(RR’SO)], were synthesised and characterised by elemental analyses, IR, 1H and 195Pt NMR spectroscopy and, in some cases, X-ray crystallography. Dimethylsulfoxide complexes were prepared using all the ligands, while complexes containing unsymmetrically substituted sulfoxides were prepared using the N-benzoyl-N’,N’-diethylthiourea and ,N-diethyl-’-(-)-(3R)-menthyloxycarbonylthiourea ligands only. The molecular structures of cis-(S,S)-[PtCl(DMSO)(L)] (where L = N-benzoyl-N’,N’-diethylthioureato, N-(+)-(3S)-menthyloxycarbonyl-N’-morpholinothioureato), cis-(S,S)-[Pt(N-benzoyl-N’,N’-diethylthioureato)Cl(MPSO)] and cis-[Pt(N-benzoyl-N’,N’-diethylthioureato)2] were determined by X-ray crystallography. The X-ray crystal structure of N,N-diethyl-N’- (-)-(3R)-menthyloxycarbonylthiourea was also determined. The spectroscopic and crystallographic data are consistent with complexes containing a (S,O)-chelated ligand and a sulfur-bonded sulfoxide ligand. However, the 1H and 195Pt NMR studies showed that the alkoxycarbonylthioureato complexes exist as geometric isomers with the sulfoxide coordinated either in a cis-(S,S) or trans-(S,S) arrangement with respect to the sulfur donor atom of the chelated ligand, whereas the acylthioureato complexes yielded only cis-(S,S)-[PtCl(L)(RR’SO)] complexes. The difference in the coordination chemistry of the acylthiourea and alkoxycarbonylthiourea ligands was examined further by treatment of the [PtCl(DMSO)(L)] complexes, where L = Nbenzoyl-N’,N’-diethylthioureato, N-benzoyl-N’-morpholinothioureato, N,N-diethyl-N’-(-)-(3R)- menthyloxycarbonylthioureato and N-(+)-(3S)-menthyloxycarbonyl-N’-morpholinothioureato, with PPh3 to give the corresponding [PtCl(L)(PPh3)] and [Pt(L)(PPh3)2]+ complexes. 31P NMR studies of these complexes reveal that the alkoxycarbonylthioureato ligands bind less strongly than the acylthioureato ligands, which is consistent with the crystallographic studies. The morpholine derivatives of the acylthioureato and alkoxycarbonylthioureato ligand systems also appear to bind less tightly than the diethyl derivatives. The weaker binding properties of the alkoxycarbonylthioureato ligands might be a possible explanation for the observed geometric isomerisation of these complexes, with the mechanism of isomerisation involving a chelate ringiv opening step. Furthermore, crystallographic and 31P NMR studies suggest that the acylthioureato carbonyl oxygen donor atom is relatively softer and therefore has a greater trans-influence than the carbonyl oxygen donor atom of the alkoxycarbonylthioureato ligand. The substitution kinetics of the chloride and sulfoxide leaving groups by azide, iodide, thiocyanate, triphenylphosphine, 2-mercaptobenzimidazole, 4-(dimethylamino)pyridine and thiourea, from selected cis-(S,S)-[PtCl(N,N-dialkyl-N’-(3-R-benzoyl)thioureato)(RR’SO)] complexes, in methanol, were evaluated to determine if variation of the electronic properties of the chelated ligand and variation of the sulfoxide have a significant influence on the reactivity of these complexes. Two consecutive reactions were observed. It was found that neutral nucleophiles initially substitute the dimethylsulfoxide, while anionic nucleophiles substituted the chloride ligand. For all the nucleophiles studied, the first substitution step was evaluated, except for triphenylphosphine and 4-(dimethylamino)pyridine, where the second step was also evaluated. The overall order of reactivity for the first substitution step was; N3 - < DMAP < I- < SCN- < MBI < thiourea < PPh3, with the rate varying three orders of magnitude. The substitution of the dimethylsulfoxide ligand by PPh3 from cis-(S,S)-[Pt(N-benzoyl-N’,N’-diethylthioureato)Cl-(DMSO)] to form cis-(S,P)-[Pt(N-benzoyl-N’,N’-diethylthioureato)Cl(PPh3)] was confirmed by X-ray crystallography. In general, manipulation of the chelating moiety, as well as interchanging the sulfoxide did not alter the reactivity of these complexes to a great extent. The anticancer activity of all the platinum(II) sulfoxide complexes were evaluated against a HeLa cell line, of which three complexes, cis-(S,S)-[PtCl(DMSO)(N,N-diethyl-N’-(3-nitrobenzoyl)- thioureato)], cis-(S,S)-[PtCl(DMSO)(N-morpholino-N’-(3-nitrorobenzoyl)thioureato)] and cis-(S,S)-[PtCl(DMSO)(N-(3-methoxybenzoyl)-N’-morpholinothioureato)] exhibited a concentration dependent anti-proliferative effect, but were less potent than cisplatin. These three complexes displayed a similar dose response in a MCF-7 cell line. Preliminary morphology studies with the three biologically active complexes in a HeLa cell line suggest that they induce cell death by apoptosis. Preliminary pBR322 plasmid DNA binding studies of selected [Pt(acylthioureato)Cl(RR’SO)]complexes clearly indicate that these complexes have a different mode of binding to DNA than cisplatin.
- Full Text:
- Date Issued: 2001
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