Synthetic analogues of the marine bisindole deoxytopsentin: potent selective inhibitors of MRSA pyruvate kinase
- Veale, Clinton G L, Zoraghi, Roya, Young, Ryan M, Morrison, James P, Pretheeban, Manoj, Lobb, Kevin A, Reiner, Neil E, Andersen, Raymond J, Davies-Coleman, Michael T
- Authors: Veale, Clinton G L , Zoraghi, Roya , Young, Ryan M , Morrison, James P , Pretheeban, Manoj , Lobb, Kevin A , Reiner, Neil E , Andersen, Raymond J , Davies-Coleman, Michael T
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448045 , vital:74693 , xlink:href="https://doi.org/10.1021/np500755v"
- Description: As part of an ongoing study to elucidate the SAR of bisindole alkaloid inhibitors against the evolutionary conserved MRSA pyruvate kinase (PK), we present here the synthesis and biological activity of six dihalogenated analogues of the naturally occurring sponge metabolite deoxytopsentin, including the naturally occurring dibromodeoxytopsentin. The most active compounds displayed potent low nanomolar inhibitory activity against MRSA PK with concomitant significant selectivity for MRSA PK over human PK orthologues. Computational studies suggest that these potent MRSA PK inhibitors occupy a region of the small interface of the enzyme tetramer where amino acid sequence divergence from common human PK orthologues may contribute to the observed selectivity.
- Full Text:
- Date Issued: 2015
- Authors: Veale, Clinton G L , Zoraghi, Roya , Young, Ryan M , Morrison, James P , Pretheeban, Manoj , Lobb, Kevin A , Reiner, Neil E , Andersen, Raymond J , Davies-Coleman, Michael T
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448045 , vital:74693 , xlink:href="https://doi.org/10.1021/np500755v"
- Description: As part of an ongoing study to elucidate the SAR of bisindole alkaloid inhibitors against the evolutionary conserved MRSA pyruvate kinase (PK), we present here the synthesis and biological activity of six dihalogenated analogues of the naturally occurring sponge metabolite deoxytopsentin, including the naturally occurring dibromodeoxytopsentin. The most active compounds displayed potent low nanomolar inhibitory activity against MRSA PK with concomitant significant selectivity for MRSA PK over human PK orthologues. Computational studies suggest that these potent MRSA PK inhibitors occupy a region of the small interface of the enzyme tetramer where amino acid sequence divergence from common human PK orthologues may contribute to the observed selectivity.
- Full Text:
- Date Issued: 2015
MRSA pyruvate kinase inhibitory activity of synthetically derived thiazole containing deoxytopsentin analogues
- Veale, Clinton G L, Zoraghi, Roya, Lobb, Kevin A, Reiner, Neil E, Andersen, Raymond J, Davies-Coleman, Michael T
- Authors: Veale, Clinton G L , Zoraghi, Roya , Lobb, Kevin A , Reiner, Neil E , Andersen, Raymond J , Davies-Coleman, Michael T
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448923 , vital:74771 , xlink:href="https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0034-1382365"
- Description: The health care crisis caused by methicillin resistant Staphylococcus aureus (MRSA) is due in part to a lack of fundamental drug discovery research into new antibiotics with novel modes of action. Marine bis-indole alkaloids have proved to be effective in vitro antibacterials. We present the synthesis of thiazole containing analogues of the marine natural product MRSA pyruvate kinase (PK) inhibitor, 6-bromodeoxytopsenin. The synthetic analogues showed moderate activity compared to the marine natural product against MRSA PK, an evolutionary conserved hub protein critical for bacterial survival. Our synthesis, via a Hantzsch thiazole condensation of α-oxo-1H-indole-3-thioacetamides with 2-bromo-1-(1H-indol-3-yl)-ethanones provided several challenges.
- Full Text:
- Date Issued: 2014
- Authors: Veale, Clinton G L , Zoraghi, Roya , Lobb, Kevin A , Reiner, Neil E , Andersen, Raymond J , Davies-Coleman, Michael T
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448923 , vital:74771 , xlink:href="https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0034-1382365"
- Description: The health care crisis caused by methicillin resistant Staphylococcus aureus (MRSA) is due in part to a lack of fundamental drug discovery research into new antibiotics with novel modes of action. Marine bis-indole alkaloids have proved to be effective in vitro antibacterials. We present the synthesis of thiazole containing analogues of the marine natural product MRSA pyruvate kinase (PK) inhibitor, 6-bromodeoxytopsenin. The synthetic analogues showed moderate activity compared to the marine natural product against MRSA PK, an evolutionary conserved hub protein critical for bacterial survival. Our synthesis, via a Hantzsch thiazole condensation of α-oxo-1H-indole-3-thioacetamides with 2-bromo-1-(1H-indol-3-yl)-ethanones provided several challenges.
- Full Text:
- Date Issued: 2014
Synthesis and MRSA PK inhibitory activity of thiazole containing deoxytopsentin analogues
- Veale, Clinton G L, Lobb, Kevin A, Zoraghi, Roya, Morrison, James P, Reiner, Neil E, Andersen, Raymond J, Davies-Coleman, Michael T
- Authors: Veale, Clinton G L , Lobb, Kevin A , Zoraghi, Roya , Morrison, James P , Reiner, Neil E , Andersen, Raymond J , Davies-Coleman, Michael T
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448028 , vital:74692 , xlink:href="https://doi.org/10.1016/j.tet.2014.09.007"
- Description: The public health care crisis caused by the emergence of drug resistant bacterial strains, e.g., methicillin resistant Staphylococcus aureus (MRSA) has underlined the urgent need to accelerate the discovery of new chemical entities active against antibiotic resistant bacteria. We report here the synthesis of a series thiazole containing deoxytopsentin analogues, which show moderate activity against a target MRSA pyruvate kinase enzyme: an evolutionary conserved hub protein critical for bacterial survival. A Hantzsch thiazole coupling between a-oxo-1H-indole-3-thioacetamides and 2-bromo-1-(1H-indol-3-yl)-ethanones provided facile access to the thiazole containing deoxytopsentin compounds.
- Full Text:
- Date Issued: 2014
- Authors: Veale, Clinton G L , Lobb, Kevin A , Zoraghi, Roya , Morrison, James P , Reiner, Neil E , Andersen, Raymond J , Davies-Coleman, Michael T
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448028 , vital:74692 , xlink:href="https://doi.org/10.1016/j.tet.2014.09.007"
- Description: The public health care crisis caused by the emergence of drug resistant bacterial strains, e.g., methicillin resistant Staphylococcus aureus (MRSA) has underlined the urgent need to accelerate the discovery of new chemical entities active against antibiotic resistant bacteria. We report here the synthesis of a series thiazole containing deoxytopsentin analogues, which show moderate activity against a target MRSA pyruvate kinase enzyme: an evolutionary conserved hub protein critical for bacterial survival. A Hantzsch thiazole coupling between a-oxo-1H-indole-3-thioacetamides and 2-bromo-1-(1H-indol-3-yl)-ethanones provided facile access to the thiazole containing deoxytopsentin compounds.
- Full Text:
- Date Issued: 2014
1H NMR-based kinetic-mechanistic study of the intramolecular trans-esterification of 2-exo-3-exo-dihydroxybornane monoacrylate esters
- Duggan, Andrew R, Mciteka, Lulama P, Lobb, Kevin A, Kaye, Perry T
- Authors: Duggan, Andrew R , Mciteka, Lulama P , Lobb, Kevin A , Kaye, Perry T
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448871 , vital:74767 , xlink:href="https://hdl.handle.net/10520/EJC135616"
- Description: A 1H NMR study of the acid-catalyzed, intramolecular trans-esterification between isomeric 2-exo-3-exo-dihydroxybornane monoacrylate esters has afforded insights into the reaction mechanism and permitted the determination of kinetic and thermodynamic parameters for the pseudo-first-order processes.
- Full Text:
- Date Issued: 2013
- Authors: Duggan, Andrew R , Mciteka, Lulama P , Lobb, Kevin A , Kaye, Perry T
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448871 , vital:74767 , xlink:href="https://hdl.handle.net/10520/EJC135616"
- Description: A 1H NMR study of the acid-catalyzed, intramolecular trans-esterification between isomeric 2-exo-3-exo-dihydroxybornane monoacrylate esters has afforded insights into the reaction mechanism and permitted the determination of kinetic and thermodynamic parameters for the pseudo-first-order processes.
- Full Text:
- Date Issued: 2013
Dual-Catalyst Acceleration of Tandem Disulfide Cleavage and Baylis–Hillman Synthesis of 2 H-1-Benzothiopyran Derivatives
- Nyoni, Dubekile, Lobb, Kevin A, Kaye, Perry T
- Authors: Nyoni, Dubekile , Lobb, Kevin A , Kaye, Perry T
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448898 , vital:74769 , xlink:href="https://doi.org/10.1080/00397911.2012.673449"
- Description: While both 1,8-diazabicyclo[5.4.0]undec-7-ene and triphenylphosphine catalyze tandem Baylis–Hillman reaction/disulfide cleavage of 2,2′-dithiodibenzaldehyde independently, when used together as a dual-catalyst system, the overall yields of the cyclized 2H-1-benzothiopyrans are consistently greater and the reaction time decreases dramatically.
- Full Text:
- Date Issued: 2013
- Authors: Nyoni, Dubekile , Lobb, Kevin A , Kaye, Perry T
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448898 , vital:74769 , xlink:href="https://doi.org/10.1080/00397911.2012.673449"
- Description: While both 1,8-diazabicyclo[5.4.0]undec-7-ene and triphenylphosphine catalyze tandem Baylis–Hillman reaction/disulfide cleavage of 2,2′-dithiodibenzaldehyde independently, when used together as a dual-catalyst system, the overall yields of the cyclized 2H-1-benzothiopyrans are consistently greater and the reaction time decreases dramatically.
- Full Text:
- Date Issued: 2013
Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors
- Bodill, Taryn, Conibear, Anne C, Mutorwa, Marius K, Goble, Jessica L, Blatch, Gregory L, Lobb, Kevin A, Klein, Rosalyn, Kaye, Perry T
- Authors: Bodill, Taryn , Conibear, Anne C , Mutorwa, Marius K , Goble, Jessica L , Blatch, Gregory L , Lobb, Kevin A , Klein, Rosalyn , Kaye, Perry T
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448912 , vital:74770 , xlink:href=""
- Description: DOXP-reductoisomerase (DXR) is a validated target for the development of antimalarial drugs to address the increase in resistant strains of Plasmodium falciparum. Series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts have been prepared as analogues of the potent DXR inhibitor fosmidomycin. The effects of the carboxamide N-substituents and the length of the methylene linker have been explored using in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays using both EcDXR and PfDXR. These studies indicate an optimal linker length of two methylene units and have confirmed the importance of an additional binding pocket in the PfDXR active site. Insights into the constraints of the PfDXR binding site provide additional scope for the rational design of DXR inhibitors with increased ligand–receptor interactions.
- Full Text:
- Date Issued: 2013
- Authors: Bodill, Taryn , Conibear, Anne C , Mutorwa, Marius K , Goble, Jessica L , Blatch, Gregory L , Lobb, Kevin A , Klein, Rosalyn , Kaye, Perry T
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448912 , vital:74770 , xlink:href=""
- Description: DOXP-reductoisomerase (DXR) is a validated target for the development of antimalarial drugs to address the increase in resistant strains of Plasmodium falciparum. Series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts have been prepared as analogues of the potent DXR inhibitor fosmidomycin. The effects of the carboxamide N-substituents and the length of the methylene linker have been explored using in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays using both EcDXR and PfDXR. These studies indicate an optimal linker length of two methylene units and have confirmed the importance of an additional binding pocket in the PfDXR active site. Insights into the constraints of the PfDXR binding site provide additional scope for the rational design of DXR inhibitors with increased ligand–receptor interactions.
- Full Text:
- Date Issued: 2013
The Formation of 2, 2, 4-Trimethyl-2, 3-dihydro-1 H-1, 5-Benzodiazepine from 1, 2-Diaminobenzene in the Presence of Acetone
- Odame, Felix, Kleyi, Phumelele, Hosten, Eric C, Betz, Richard, Lobb, Kevin A, Tshentu, Zenixole R
- Authors: Odame, Felix , Kleyi, Phumelele , Hosten, Eric C , Betz, Richard , Lobb, Kevin A , Tshentu, Zenixole R
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448952 , vital:74773 , xlink:href="https://doi.org/10.3390/molecules181114293"
- Description: In an attempt to synthesize a 2-substituted benzimidazole from the reaction of o-phenylenediamine and isophthalic acid in the presence of acetone and ethanol under microwave irradiation, a salt of the isophthalate ion and 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepin-5-ium ion was obtained. The condensation of two moles of acetone with the amine groups resulted in the formation of the benzodiazepine which crystallized as an iminium cation forming a salt with the isophthalate anion. The formation of benzodiazepine was also confirmed by performing the reaction of o-phenylenediamine with excess acetone in ethanol under conventional heating conditions. The compounds were characterized by NMR, FTIR, HRMS and microanalysis as well as X-ray crystallography. The reaction mechanism leading to the formation of benzodiazepine is also discussed.
- Full Text:
- Date Issued: 2013
- Authors: Odame, Felix , Kleyi, Phumelele , Hosten, Eric C , Betz, Richard , Lobb, Kevin A , Tshentu, Zenixole R
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448952 , vital:74773 , xlink:href="https://doi.org/10.3390/molecules181114293"
- Description: In an attempt to synthesize a 2-substituted benzimidazole from the reaction of o-phenylenediamine and isophthalic acid in the presence of acetone and ethanol under microwave irradiation, a salt of the isophthalate ion and 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepin-5-ium ion was obtained. The condensation of two moles of acetone with the amine groups resulted in the formation of the benzodiazepine which crystallized as an iminium cation forming a salt with the isophthalate anion. The formation of benzodiazepine was also confirmed by performing the reaction of o-phenylenediamine with excess acetone in ethanol under conventional heating conditions. The compounds were characterized by NMR, FTIR, HRMS and microanalysis as well as X-ray crystallography. The reaction mechanism leading to the formation of benzodiazepine is also discussed.
- Full Text:
- Date Issued: 2013
DBU-Mediated cleavage of aryl-and heteroaryl disulfides
- Nyoni, Dubekile, Lobb, Kevin A, Kaye, Perry T, Cairab, Mino R
- Authors: Nyoni, Dubekile , Lobb, Kevin A , Kaye, Perry T , Cairab, Mino R
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448884 , vital:74768
- Description: The capacity of the nitrogen nucleophile, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to reduce aryl- and heteroaryl disulfides to the corresponding mercaptans is demonstrated. While dicarboxylated disulfide analogues afford the mono-DBU disulfide salts, as confirmed by X-ray crystallography, the corresponding methyl esters are cleaved normally.
- Full Text:
- Date Issued: 2012
- Authors: Nyoni, Dubekile , Lobb, Kevin A , Kaye, Perry T , Cairab, Mino R
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448884 , vital:74768
- Description: The capacity of the nitrogen nucleophile, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to reduce aryl- and heteroaryl disulfides to the corresponding mercaptans is demonstrated. While dicarboxylated disulfide analogues afford the mono-DBU disulfide salts, as confirmed by X-ray crystallography, the corresponding methyl esters are cleaved normally.
- Full Text:
- Date Issued: 2012
Trends in the optical and redox properties of tetraphenyltetraphenanthroporphyrins
- Mack, John, Lobb, Kevin A, Nyokong, Tebello, Shen, Zhen, Kobayashi, Nagao
- Authors: Mack, John , Lobb, Kevin A , Nyokong, Tebello , Shen, Zhen , Kobayashi, Nagao
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/245809 , vital:51407 , xlink:href="https://doi.org/10.1142/S1088424612500885"
- Description: The results of TD-DFT calculations for a series of tetraaryltetraphenanthroporphyrins containing para-substituents with differing electron donating and accepting properties are compared to the observed optical and redox properties and Michl's perimeter model is used as a conceptual framework for analyzing the results.
- Full Text:
- Date Issued: 2012
- Authors: Mack, John , Lobb, Kevin A , Nyokong, Tebello , Shen, Zhen , Kobayashi, Nagao
- Date: 2012
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/245809 , vital:51407 , xlink:href="https://doi.org/10.1142/S1088424612500885"
- Description: The results of TD-DFT calculations for a series of tetraaryltetraphenanthroporphyrins containing para-substituents with differing electron donating and accepting properties are compared to the observed optical and redox properties and Michl's perimeter model is used as a conceptual framework for analyzing the results.
- Full Text:
- Date Issued: 2012
1H NMR-based kinetic and mechanistic study of unusual skeletal rearrangements of a spirobornyl tosylate derivative
- Lobb, Kevin A, Kaye, Perry T
- Authors: Lobb, Kevin A , Kaye, Perry T
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448858 , vital:74766 , xlink:href="https://doi.org/10.1002/poc.1699"
- Description: 1H NMR analysis of the kinetics of skeletal rearrangement of optically pure 3,3-xylyl-2-exo-bornyl tosylate in CDCl3 indicates the operation of tandem autocatalytic and pseudo-first-order transformations, leading sequentially to a pairof isomeric camphene derivatives and involving partial racemization. Changing the solvent system has been shown topermit the chemoselective isolation of either of the isomeric camphenes.
- Full Text:
- Date Issued: 2011
- Authors: Lobb, Kevin A , Kaye, Perry T
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448858 , vital:74766 , xlink:href="https://doi.org/10.1002/poc.1699"
- Description: 1H NMR analysis of the kinetics of skeletal rearrangement of optically pure 3,3-xylyl-2-exo-bornyl tosylate in CDCl3 indicates the operation of tandem autocatalytic and pseudo-first-order transformations, leading sequentially to a pairof isomeric camphene derivatives and involving partial racemization. Changing the solvent system has been shown topermit the chemoselective isolation of either of the isomeric camphenes.
- Full Text:
- Date Issued: 2011
Synthesis and evaluation of phosphonated N-heteroarylcarboxamides as DOXP-reductoisomerase (DXR) inhibitors
- Bodill, Taryn, Conibear, Anne C, Blatch, Gregory L, Lobb, Kevin A, Kaye, Perry T
- Authors: Bodill, Taryn , Conibear, Anne C , Blatch, Gregory L , Lobb, Kevin A , Kaye, Perry T
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448939 , vital:74772 , xlink:href="https://doi.org/10.1016/j.bmc.2010.11.062"
- Description: The diethyl esters and disodium salts of a range of heteroarylcarbamoylphosphonic acids have been prepared and evaluated as analogues of the highly active DOXP-reductoisomerase (DXR) inhibitor, fosmidomycin. Computer-simulated docking studies, Saturation Transfer Difference (STD) NMR analysis and enzyme inhibition assays have been used to explore enzyme-binding and -inhibition potential, while in silico analysis of the DXR active site has highlighted the importance of including a well-parameterised metal co-factor in docking studies and has revealed the availability of an additional binding pocket to guide future drug design.
- Full Text:
- Date Issued: 2011
- Authors: Bodill, Taryn , Conibear, Anne C , Blatch, Gregory L , Lobb, Kevin A , Kaye, Perry T
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448939 , vital:74772 , xlink:href="https://doi.org/10.1016/j.bmc.2010.11.062"
- Description: The diethyl esters and disodium salts of a range of heteroarylcarbamoylphosphonic acids have been prepared and evaluated as analogues of the highly active DOXP-reductoisomerase (DXR) inhibitor, fosmidomycin. Computer-simulated docking studies, Saturation Transfer Difference (STD) NMR analysis and enzyme inhibition assays have been used to explore enzyme-binding and -inhibition potential, while in silico analysis of the DXR active site has highlighted the importance of including a well-parameterised metal co-factor in docking studies and has revealed the availability of an additional binding pocket to guide future drug design.
- Full Text:
- Date Issued: 2011
31P NMR kinetic study of the tandem cleavage of phosphonate esters by bromotrimethylsilane
- Conibear, Anne C, Lobb, Kevin A, Kaye, Perry T
- Authors: Conibear, Anne C , Lobb, Kevin A , Kaye, Perry T
- Date: 2010
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/449304 , vital:74810 , xlink:href="https://doi.org/10.1016/j.tet.2010.08.058"
- Description: 1H and 31P NMR methods have been used to access rate constants and activation parameters for each of the consecutive second-order silylation reactions involved in the overall transformation (1a→3a→4a), while computational optimisation of the rate constants obtained from the initial, linear phase of each reaction has permitted an excellent fit with the experimental data for the entire course of the reaction.
- Full Text:
- Date Issued: 2010
- Authors: Conibear, Anne C , Lobb, Kevin A , Kaye, Perry T
- Date: 2010
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/449304 , vital:74810 , xlink:href="https://doi.org/10.1016/j.tet.2010.08.058"
- Description: 1H and 31P NMR methods have been used to access rate constants and activation parameters for each of the consecutive second-order silylation reactions involved in the overall transformation (1a→3a→4a), while computational optimisation of the rate constants obtained from the initial, linear phase of each reaction has permitted an excellent fit with the experimental data for the entire course of the reaction.
- Full Text:
- Date Issued: 2010
Interaction between nickel hydroxy phthalocyanine derivatives with p-chlorophenol
- Khene, Samson, Lobb, Kevin A, Nyokong, Tebello
- Authors: Khene, Samson , Lobb, Kevin A , Nyokong, Tebello
- Date: 2010
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/248461 , vital:51688 , xlink:href="https://doi.org/10.1016/j.electacta.2010.10.007"
- Description: In this work the interaction between peripherally (β) substituted nickel tetrahydroxyphthalocyanines (β-NiPc(OH)4 and β-Ni(O)Pc(OH)4) with p-chlorophenol is theoretically rationalised by performing calculations at B3LYP/6-31G(d) level. Density functional theory (DFT) and molecular orbital theory are used to calculate the condensed Fukui function for phthalocyanine derivatives and p-chlorophenol, in order to determine the reactive sites involved when p-chlorophenol is oxidized, and to compare theoretically predicted reactivity to experimentally determined electrocatalytic activity. Electrocatalytic activities of adsorbed NiPc derivatives: ads-α-NiPc(OH)8-OPGE (OPGE = ordinary poly graphite electrode), ads-α-NiPc(OH)4-OPGE and ads-β-NiPc(OH)4-OPGE are compared with those of the polymerized counterparts: poly-α-Ni(O)Pc(OH)8-OPGE, poly-α-NiPc(OH)4-OPGE and poly-β-NiPc(OH)4-OPGE, respectively.
- Full Text:
- Date Issued: 2010
- Authors: Khene, Samson , Lobb, Kevin A , Nyokong, Tebello
- Date: 2010
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/248461 , vital:51688 , xlink:href="https://doi.org/10.1016/j.electacta.2010.10.007"
- Description: In this work the interaction between peripherally (β) substituted nickel tetrahydroxyphthalocyanines (β-NiPc(OH)4 and β-Ni(O)Pc(OH)4) with p-chlorophenol is theoretically rationalised by performing calculations at B3LYP/6-31G(d) level. Density functional theory (DFT) and molecular orbital theory are used to calculate the condensed Fukui function for phthalocyanine derivatives and p-chlorophenol, in order to determine the reactive sites involved when p-chlorophenol is oxidized, and to compare theoretically predicted reactivity to experimentally determined electrocatalytic activity. Electrocatalytic activities of adsorbed NiPc derivatives: ads-α-NiPc(OH)8-OPGE (OPGE = ordinary poly graphite electrode), ads-α-NiPc(OH)4-OPGE and ads-β-NiPc(OH)4-OPGE are compared with those of the polymerized counterparts: poly-α-Ni(O)Pc(OH)8-OPGE, poly-α-NiPc(OH)4-OPGE and poly-β-NiPc(OH)4-OPGE, respectively.
- Full Text:
- Date Issued: 2010
Introducing chemistry students to the “real world” of chemistry
- Brown, Michael E, Cosser, Ronald C, Davies-Coleman, Michael T, Kaye, Perry T, Klein, Rosalyn, Lamprecht, Emmanuel, Lobb, Kevin A, Nyokong, Tebello, Sewry, Joyce D, Tshentu, Zenixole R, Van der Zeyde, Tino, Watkins, Gareth M
- Authors: Brown, Michael E , Cosser, Ronald C , Davies-Coleman, Michael T , Kaye, Perry T , Klein, Rosalyn , Lamprecht, Emmanuel , Lobb, Kevin A , Nyokong, Tebello , Sewry, Joyce D , Tshentu, Zenixole R , Van der Zeyde, Tino , Watkins, Gareth M
- Date: 2010
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/449360 , vital:74814 , xlink:href="https://doi.org/10.1021/ed8001539"
- Description: A majority of chemistry graduates seek employment in a rapidly changing chemical industry. Our attempts to provide the graduates with skills in entrepreneurship and the ability to understand and communicate with their chemical engineering colleagues, in addition to their fundamental knowledge of chemistry, are described. This is done at second-year level with practical projects in which student teams formulate and prepare relatively simple chemical products for marketing, followed a year later by a more advanced study of the feasibility of producing and marketing a fine chemical on a commercial scale.
- Full Text:
- Date Issued: 2010
- Authors: Brown, Michael E , Cosser, Ronald C , Davies-Coleman, Michael T , Kaye, Perry T , Klein, Rosalyn , Lamprecht, Emmanuel , Lobb, Kevin A , Nyokong, Tebello , Sewry, Joyce D , Tshentu, Zenixole R , Van der Zeyde, Tino , Watkins, Gareth M
- Date: 2010
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/449360 , vital:74814 , xlink:href="https://doi.org/10.1021/ed8001539"
- Description: A majority of chemistry graduates seek employment in a rapidly changing chemical industry. Our attempts to provide the graduates with skills in entrepreneurship and the ability to understand and communicate with their chemical engineering colleagues, in addition to their fundamental knowledge of chemistry, are described. This is done at second-year level with practical projects in which student teams formulate and prepare relatively simple chemical products for marketing, followed a year later by a more advanced study of the feasibility of producing and marketing a fine chemical on a commercial scale.
- Full Text:
- Date Issued: 2010
Towards the synthesis of coumarin derivatives as potential dual-action HIV-1 protease and reverse transcriptase inhibitors
- Olomola, Temitope O, Klein, Rosalyn, Lobb, Kevin A, Sayed, Yasien, Kaye, Perry T
- Authors: Olomola, Temitope O , Klein, Rosalyn , Lobb, Kevin A , Sayed, Yasien , Kaye, Perry T
- Date: 2010
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448963 , vital:74774 , xlink:href="https://doi.org/10.1016/j.tetlet.2010.09.121"
- Description: 3-(Chloromethyl)coumarins, obtained via acid-catalysed cyclisation of salicylaldehyde-derived Baylis– Hillman adducts, have been treated with propargylamine; reaction of the resulting 3-alkynylmethylcoumarins with azidothymidine (AZT) in the presence of a Cu(I) catalyst has afforded a series of cycloaddition products for evaluation, in their own right, as potential dual-action HIV-1 protease and non-nucleoside reverse transcriptase inhibitors, and as scaffolds for further structural elaboration.
- Full Text:
- Date Issued: 2010
- Authors: Olomola, Temitope O , Klein, Rosalyn , Lobb, Kevin A , Sayed, Yasien , Kaye, Perry T
- Date: 2010
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448963 , vital:74774 , xlink:href="https://doi.org/10.1016/j.tetlet.2010.09.121"
- Description: 3-(Chloromethyl)coumarins, obtained via acid-catalysed cyclisation of salicylaldehyde-derived Baylis– Hillman adducts, have been treated with propargylamine; reaction of the resulting 3-alkynylmethylcoumarins with azidothymidine (AZT) in the presence of a Cu(I) catalyst has afforded a series of cycloaddition products for evaluation, in their own right, as potential dual-action HIV-1 protease and non-nucleoside reverse transcriptase inhibitors, and as scaffolds for further structural elaboration.
- Full Text:
- Date Issued: 2010
Characterization of nickel tetrahydroxy phthalocyanine complexes and the electrocatalytic oxidation of 4-chlorophenol
- Khene, Samson M, Lobb, Kevin A, Nyokong, Tebello
- Authors: Khene, Samson M , Lobb, Kevin A , Nyokong, Tebello
- Date: 2009
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/263308 , vital:53616 , xlink:href="https://doi.org/10.1016/j.ica.2009.08.019"
- Description: This work reports on the use of nickel(II) tetrahydroxy (NiPc(OH)4) and (poly-Ni(OH)Pc(OH)4) phthalocyanine complexes as films on ordinary poly graphite electrode (OPGE) for the electrochemical oxidation of 4-chlorophenol (4-CP). The NiPc(OH)4 film was electrotransformed to Ni(OH)Pc(OH)4 film in aqueous 0.1 M NaOH solution to the ‘O–Ni–O oxo’ bridge form. The result showed that the Ni(OH)Pc(OH)4 film on OPGE was more electroactive in terms of increase in current and less catalytic in terms of potential compared to the adsorbed NiPc(OH)4 on OPGE. The reactivity of the two molecules was explained by theoretical calculations. The energies of the frontier orbitals of NiPc(OH)4, Ni(OH)Pc(OH)4 and 4-chlorophenol were calculated using density functional theory (DFT) method. The inter molecular hardness (η) and donor–acceptor hardness (ηDA) of Ni(OH)Pc(OH)4, NiPc(OH)4, Ni(OH)Pc(OH)4/4-chlorophenol and NiPc(OH)4/4-chlorophenol were estimated. The Ni(OH)Pc(OH)4, showed stronger interaction with 4-chlorophenol than NiPc(OH)4. DFT method was also used to model IR and Raman spectrum of H2Pc(OH)4 and NiPc(OH)4.
- Full Text:
- Date Issued: 2009
- Authors: Khene, Samson M , Lobb, Kevin A , Nyokong, Tebello
- Date: 2009
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/263308 , vital:53616 , xlink:href="https://doi.org/10.1016/j.ica.2009.08.019"
- Description: This work reports on the use of nickel(II) tetrahydroxy (NiPc(OH)4) and (poly-Ni(OH)Pc(OH)4) phthalocyanine complexes as films on ordinary poly graphite electrode (OPGE) for the electrochemical oxidation of 4-chlorophenol (4-CP). The NiPc(OH)4 film was electrotransformed to Ni(OH)Pc(OH)4 film in aqueous 0.1 M NaOH solution to the ‘O–Ni–O oxo’ bridge form. The result showed that the Ni(OH)Pc(OH)4 film on OPGE was more electroactive in terms of increase in current and less catalytic in terms of potential compared to the adsorbed NiPc(OH)4 on OPGE. The reactivity of the two molecules was explained by theoretical calculations. The energies of the frontier orbitals of NiPc(OH)4, Ni(OH)Pc(OH)4 and 4-chlorophenol were calculated using density functional theory (DFT) method. The inter molecular hardness (η) and donor–acceptor hardness (ηDA) of Ni(OH)Pc(OH)4, NiPc(OH)4, Ni(OH)Pc(OH)4/4-chlorophenol and NiPc(OH)4/4-chlorophenol were estimated. The Ni(OH)Pc(OH)4, showed stronger interaction with 4-chlorophenol than NiPc(OH)4. DFT method was also used to model IR and Raman spectrum of H2Pc(OH)4 and NiPc(OH)4.
- Full Text:
- Date Issued: 2009
Chromone Studies. Part 17. Tricyclic Scaffolds from Reactions of chromone-3-carbaldehydes and methyl vinyl ketone under Baylis–Hillman conditions
- Ganto, Mlungiseleli M, Molefe, Duduzile M, Lobb, Kevin A, Kaye, Perry T
- Authors: Ganto, Mlungiseleli M , Molefe, Duduzile M , Lobb, Kevin A , Kaye, Perry T
- Date: 2009
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/449321 , vital:74811 , xlink:href="https://doi.org/10.3184/030823409X4652"
- Description: Reaction of a series of chromone-3-carbaldehydes with methyl vinyl ketone under Baylis–Hillman conditions, using 3-hydroxyquinuclidine in chloroform or DABCO in 1-methyl-2-pyrrolidinone, affords unprecedented tricylic chromone derivatives which, depending on the conditions, may be accompanied by the normal Baylis–Hillman products or their respective tricyclic dimers.
- Full Text:
- Date Issued: 2009
- Authors: Ganto, Mlungiseleli M , Molefe, Duduzile M , Lobb, Kevin A , Kaye, Perry T
- Date: 2009
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/449321 , vital:74811 , xlink:href="https://doi.org/10.3184/030823409X4652"
- Description: Reaction of a series of chromone-3-carbaldehydes with methyl vinyl ketone under Baylis–Hillman conditions, using 3-hydroxyquinuclidine in chloroform or DABCO in 1-methyl-2-pyrrolidinone, affords unprecedented tricylic chromone derivatives which, depending on the conditions, may be accompanied by the normal Baylis–Hillman products or their respective tricyclic dimers.
- Full Text:
- Date Issued: 2009
Synthesis and structure determination of 8-and 9-iodocamphorquinone bis (ethylene ketal)
- Magqi, Nceba, Lobb, Kevin A, Kaye, Perry T, Caira, Mino R
- Authors: Magqi, Nceba , Lobb, Kevin A , Kaye, Perry T , Caira, Mino R
- Date: 2007
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/449399 , vital:74817 , xlink:href="https://doi.org/10.3184/030823407X209"
- Description: The structures of 8- and 9-iodocamphorquinone bis(ethylene ketal) have been confirmed by spectroscopic and single crystal X-ray analysis. The unexpected formation of the latter isomer is attributed to intramolecular rearrangement of the camphor skeleton, the mechanistic details of which have been explored using coset analysis.
- Full Text:
- Date Issued: 2007
- Authors: Magqi, Nceba , Lobb, Kevin A , Kaye, Perry T , Caira, Mino R
- Date: 2007
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/449399 , vital:74817 , xlink:href="https://doi.org/10.3184/030823407X209"
- Description: The structures of 8- and 9-iodocamphorquinone bis(ethylene ketal) have been confirmed by spectroscopic and single crystal X-ray analysis. The unexpected formation of the latter isomer is attributed to intramolecular rearrangement of the camphor skeleton, the mechanistic details of which have been explored using coset analysis.
- Full Text:
- Date Issued: 2007
Transformations of manool. Tri-and tetracyclic norditerpenoids with in vitro activity against plasmodium falciparum
- van Wyk, Albert W W, Lobb, Kevin A, Mino, Caira R, Hoppe, Heinrich C, Davies-Coleman, Michael T
- Authors: van Wyk, Albert W W , Lobb, Kevin A , Mino, Caira R , Hoppe, Heinrich C , Davies-Coleman, Michael T
- Date: 2007
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/450511 , vital:74956 , xlink:href="https://doi.org/10.1021/np0701071"
- Description: The known 17-norisopimar-15-ene-8‚,13‚-diol (5) and five new semisynthetic norditerpenoids, ethyl 17-norabiet-13-(15)-E-en-8‚-ol-16-oate (6), ethyl 17-norabiet-13(15)-Z-en-8‚-ol-16-oate (7), 17-norpimaran-13R-ethoxy-8,16-olactone(8), 17-norisopimarane-8‚,15-diol (9), and 17-norarabiet-13(15)-ene-8‚,16-diol (10), were prepared from manool (11).Standard spectroscopic data including X-ray crystal analysis were used to determine the structures of5-10. All fivecompounds exhibited in Vitroantiplasmodial activity against the malarial parasitePlasmodium falciparumat varyingÌgmL-1concentrations.
- Full Text:
- Date Issued: 2007
- Authors: van Wyk, Albert W W , Lobb, Kevin A , Mino, Caira R , Hoppe, Heinrich C , Davies-Coleman, Michael T
- Date: 2007
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/450511 , vital:74956 , xlink:href="https://doi.org/10.1021/np0701071"
- Description: The known 17-norisopimar-15-ene-8‚,13‚-diol (5) and five new semisynthetic norditerpenoids, ethyl 17-norabiet-13-(15)-E-en-8‚-ol-16-oate (6), ethyl 17-norabiet-13(15)-Z-en-8‚-ol-16-oate (7), 17-norpimaran-13R-ethoxy-8,16-olactone(8), 17-norisopimarane-8‚,15-diol (9), and 17-norarabiet-13(15)-ene-8‚,16-diol (10), were prepared from manool (11).Standard spectroscopic data including X-ray crystal analysis were used to determine the structures of5-10. All fivecompounds exhibited in Vitroantiplasmodial activity against the malarial parasitePlasmodium falciparumat varyingÌgmL-1concentrations.
- Full Text:
- Date Issued: 2007
Crystallographic Analysis and Structural Revision of a Spiroterpenoid Rearrangement Product
- Lobb, Kevin A, Kaye, Perry T
- Authors: Lobb, Kevin A , Kaye, Perry T
- Date: 2003
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/449335 , vital:74812 , xlink:href="https://www.ajol.info/index.php/sajc/article/view/122435"
- Description: Single crystal X-ray analysis of a spiroterpenoid rearrangement product has revealed that its structure is, in fact, isomeric with the structure proposed previously – an observation that has significant mechanistic implications.
- Full Text:
- Date Issued: 2003
- Authors: Lobb, Kevin A , Kaye, Perry T
- Date: 2003
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/449335 , vital:74812 , xlink:href="https://www.ajol.info/index.php/sajc/article/view/122435"
- Description: Single crystal X-ray analysis of a spiroterpenoid rearrangement product has revealed that its structure is, in fact, isomeric with the structure proposed previously – an observation that has significant mechanistic implications.
- Full Text:
- Date Issued: 2003