Synthesis of two tartaric acid-derived host compounds and their behaviour in mixed pyridines and mixed heterocyclic guest compounds
- Authors: Recchia, Daniella Loridana
- Date: 2024-12
- Subjects: Complex compounds -- Synthesis , Chemistry , Chemistry, Organic
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/69445 , vital:77255
- Description: The host compounds (4R,5R)-bis(diphenylhydroxymethyl)-2-spiro-1’-cyclopentane-1,3-dioxolane (TADDOL5) and (4R,5R)-bis(diphenylhydroxymethyl)-2-spiro-1’-cyclohexane-1,3-dioxolane (TADDOL6) were successfully synthesized after initially reacting diethyl tartrate with either 1,1-dimethoxycyclopentane or 1,1-dimethoxycyclohexane to afford the intermediates diethyl 2-spiro-1’-cyclopentane-1,3-dioxolan-4,5-dicarboxylate or diethyl 2-spiro-1’-cyclohexane-1,3-dioxolan-4,5-dicarboxylate. These were then each subjected to a Grignard addition reaction with PhMgBr to furnish TADDOL5 and TADDOL6 in reasonably high yields (77 and 80%, respectively). Computational calculations were performed on TADDOL5 and TADDOL6 using the software programs Avogadro and ORCA. The optimised geometries of these host molecules were obtained using the MMFF94 force field in Avogadro, while ORCA was used to perform the computational modelling at the BLYP level using the 6-31G*, 6-31G**, 6-311G* and 6-311G** basis sets and, also, the B3LYP functional (with the same basis sets) to obtain the three lowest energy conformers. The final geometries of each conformer for both TADDOL5 and TADDOL6 at the B3LYP 6-311G* level were overlaid with the molecules obtained from their crystal structures. Significantly different geometries were thus noted for the calculated conformers compared with the guest-free TADDOL5 and TADDOL6 structures obtained from the SCXRD experiments. When TADDOL5 was crystallized independently from each of PYR, 2MP, 3MP and 4MP, 1:1 H:G inclusion complexes formed in each instance. This host compound was then investigated for its host separation ability of mixed pyridines through supramolecular chemistry protocols. These mixed guest experiments revealed that TADDOL5 possessed a notable selectivity towards 3MP and PYR (in the absence of 3MP) followed by 4MP and 2MP, and it was shown that TADDOL5 is a suitable host candidate for the separation of many of the mixed pyridines employed here. The results of the SCXRD analyses indicated that the only significant (host)π···π(guest) stacking interaction present was between TADDOL5 and the most favoured guest species PYR and 3MP. Furthermore, significantly shorter (host)O‒H···N(guest) iv hydrogen bonds were also observed in the complexes formed between this host compound and 3MP and PYR compared with these bonds involving disfavoured 4MP and 2MP. Hirshfeld surface considerations provided an explanation for the affinity of TADDOL5 for PYR (but not 3MP), while thermal analyses successfully explained this affinity: the 3MP-containing complex with the most preferred guest species was the most thermally stable one, followed by TADDOL5·PYR, as obtained through a consideration of the Ton values (the temperature at which the guest release event initiated) of the four complexes. As with TADDOL5, TADDOL6 formed 1:1 H:G inclusion compounds with each of the four pyridines. TADDOL6 was, furthermore, also assessed for its separation ability for mixed pyridines, and these guest competition experiments showed that the selectivity of TADDOL6 was for PYR and 3MP (in the absence of PYR), followed by 4MP and 2MP. (Interestingly, TADDOL5 preferred 3MP and then PYR, while both host compounds disfavoured 4MP and 2MP.) The results obtained in this work indicated that TADDOL6 may also serve as an efficient host candidate for the separation of many of these pyridyl solutions. SCXRD experiments demonstrated that the only significant (host)π···π(guest) stacking interactions were those between TADDOL6 and preferred PYR and 3MP, as was the case for TADDOL5. These experiments also revealed that the strongest (host)O‒H···N(guest) hydrogen bonds were between TADDOL6 and these favoured guest species. A consideration of Hirshfeld surfaces and quantification of the (guest)N···H(host) intermolecular interactions correlated with the host selectivity order, as did thermal analyses, where the Ton values confirmed that the thermal stabilities of these complexes decreased in the guest order PYR > 3MP > 4MP > 2MP. The behaviour of TADDOL5 was further investigated in guest compounds DIO, PYR, PIP and MOR. Each guest solvent formed 1:1 H:G inclusion complexes with the host species, with the exception of DIO, which formed a 2:1 H:G complex. Mixed guest experiments revealed a clear preference for PIP and MOR, while PYR and DIO were less favoured. The host selectivity was demonstrated to be in the order PIP > MOR > PYR > DIO. SCXRD experiments showed that TADDOL5 formed a much shorter (and more linear) (host)O‒H···N(guest) hydrogen bond with the most favoured guest, PIP, compared to those involving MOR and PYR. A (host)O‒H···O(guest) hydrogen bond v was also observed in the DIO-containing inclusion complex. A consideration of the Hirshfeld surface interactions was not useful in explaining the host selectivity order for these heterocyclic guests, but thermal analyses confirmed that the most stable complex was the one with favoured PIP, followed by those with PYR, MOR and DIO. TADDOL6, on the other hand, formed 1:1 H:G inclusion compounds with all four of the heterocyclic guest solvents. Experiments in mixed guests showed that the selectivity of this host compound for these guests was in the order PYR > PIP > MOR > DIO, which differed from the TADDOL5 (which favoured PIP and then MOR). Interestingly, the strongest classical hydrogen bond was not formed with the most favoured guest PYR, but with PIP instead (this bond with TADDOL5 was also strongest with PIP, but PIP was favoured in that work). Hirshfeld surface investigations again were not useful in understanding the host selectivity behaviour. However, thermal analyses agreed with the observations made in the mixed guest experiments: the most stable complex was with PYR (favoured) and the least stable one was with DIO (least preferred). , Thesis (MSc) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2024
- Full Text:
- Date Issued: 2024-12
- Authors: Recchia, Daniella Loridana
- Date: 2024-12
- Subjects: Complex compounds -- Synthesis , Chemistry , Chemistry, Organic
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/69445 , vital:77255
- Description: The host compounds (4R,5R)-bis(diphenylhydroxymethyl)-2-spiro-1’-cyclopentane-1,3-dioxolane (TADDOL5) and (4R,5R)-bis(diphenylhydroxymethyl)-2-spiro-1’-cyclohexane-1,3-dioxolane (TADDOL6) were successfully synthesized after initially reacting diethyl tartrate with either 1,1-dimethoxycyclopentane or 1,1-dimethoxycyclohexane to afford the intermediates diethyl 2-spiro-1’-cyclopentane-1,3-dioxolan-4,5-dicarboxylate or diethyl 2-spiro-1’-cyclohexane-1,3-dioxolan-4,5-dicarboxylate. These were then each subjected to a Grignard addition reaction with PhMgBr to furnish TADDOL5 and TADDOL6 in reasonably high yields (77 and 80%, respectively). Computational calculations were performed on TADDOL5 and TADDOL6 using the software programs Avogadro and ORCA. The optimised geometries of these host molecules were obtained using the MMFF94 force field in Avogadro, while ORCA was used to perform the computational modelling at the BLYP level using the 6-31G*, 6-31G**, 6-311G* and 6-311G** basis sets and, also, the B3LYP functional (with the same basis sets) to obtain the three lowest energy conformers. The final geometries of each conformer for both TADDOL5 and TADDOL6 at the B3LYP 6-311G* level were overlaid with the molecules obtained from their crystal structures. Significantly different geometries were thus noted for the calculated conformers compared with the guest-free TADDOL5 and TADDOL6 structures obtained from the SCXRD experiments. When TADDOL5 was crystallized independently from each of PYR, 2MP, 3MP and 4MP, 1:1 H:G inclusion complexes formed in each instance. This host compound was then investigated for its host separation ability of mixed pyridines through supramolecular chemistry protocols. These mixed guest experiments revealed that TADDOL5 possessed a notable selectivity towards 3MP and PYR (in the absence of 3MP) followed by 4MP and 2MP, and it was shown that TADDOL5 is a suitable host candidate for the separation of many of the mixed pyridines employed here. The results of the SCXRD analyses indicated that the only significant (host)π···π(guest) stacking interaction present was between TADDOL5 and the most favoured guest species PYR and 3MP. Furthermore, significantly shorter (host)O‒H···N(guest) iv hydrogen bonds were also observed in the complexes formed between this host compound and 3MP and PYR compared with these bonds involving disfavoured 4MP and 2MP. Hirshfeld surface considerations provided an explanation for the affinity of TADDOL5 for PYR (but not 3MP), while thermal analyses successfully explained this affinity: the 3MP-containing complex with the most preferred guest species was the most thermally stable one, followed by TADDOL5·PYR, as obtained through a consideration of the Ton values (the temperature at which the guest release event initiated) of the four complexes. As with TADDOL5, TADDOL6 formed 1:1 H:G inclusion compounds with each of the four pyridines. TADDOL6 was, furthermore, also assessed for its separation ability for mixed pyridines, and these guest competition experiments showed that the selectivity of TADDOL6 was for PYR and 3MP (in the absence of PYR), followed by 4MP and 2MP. (Interestingly, TADDOL5 preferred 3MP and then PYR, while both host compounds disfavoured 4MP and 2MP.) The results obtained in this work indicated that TADDOL6 may also serve as an efficient host candidate for the separation of many of these pyridyl solutions. SCXRD experiments demonstrated that the only significant (host)π···π(guest) stacking interactions were those between TADDOL6 and preferred PYR and 3MP, as was the case for TADDOL5. These experiments also revealed that the strongest (host)O‒H···N(guest) hydrogen bonds were between TADDOL6 and these favoured guest species. A consideration of Hirshfeld surfaces and quantification of the (guest)N···H(host) intermolecular interactions correlated with the host selectivity order, as did thermal analyses, where the Ton values confirmed that the thermal stabilities of these complexes decreased in the guest order PYR > 3MP > 4MP > 2MP. The behaviour of TADDOL5 was further investigated in guest compounds DIO, PYR, PIP and MOR. Each guest solvent formed 1:1 H:G inclusion complexes with the host species, with the exception of DIO, which formed a 2:1 H:G complex. Mixed guest experiments revealed a clear preference for PIP and MOR, while PYR and DIO were less favoured. The host selectivity was demonstrated to be in the order PIP > MOR > PYR > DIO. SCXRD experiments showed that TADDOL5 formed a much shorter (and more linear) (host)O‒H···N(guest) hydrogen bond with the most favoured guest, PIP, compared to those involving MOR and PYR. A (host)O‒H···O(guest) hydrogen bond v was also observed in the DIO-containing inclusion complex. A consideration of the Hirshfeld surface interactions was not useful in explaining the host selectivity order for these heterocyclic guests, but thermal analyses confirmed that the most stable complex was the one with favoured PIP, followed by those with PYR, MOR and DIO. TADDOL6, on the other hand, formed 1:1 H:G inclusion compounds with all four of the heterocyclic guest solvents. Experiments in mixed guests showed that the selectivity of this host compound for these guests was in the order PYR > PIP > MOR > DIO, which differed from the TADDOL5 (which favoured PIP and then MOR). Interestingly, the strongest classical hydrogen bond was not formed with the most favoured guest PYR, but with PIP instead (this bond with TADDOL5 was also strongest with PIP, but PIP was favoured in that work). Hirshfeld surface investigations again were not useful in understanding the host selectivity behaviour. However, thermal analyses agreed with the observations made in the mixed guest experiments: the most stable complex was with PYR (favoured) and the least stable one was with DIO (least preferred). , Thesis (MSc) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2024
- Full Text:
- Date Issued: 2024-12
New platinum and palladium complexes: their anticancer application
- Authors: Louw, Marissa
- Date: 2010
- Subjects: Complex compounds -- Synthesis , Ligands (Biochemistry) , Antineoplastic antibiotics
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10424 , http://hdl.handle.net/10948/d1016218
- Description: Novel non-leaving groups were employed in this dissertation to synthesize platinum complexes which can assist in the understanding or improvement of anticancer action. Emphasis was placed on (NS)-chelate and (NN)-chelate platinum complexes. Bidentate (NS)-donor ligands were used as non-leaving ligands in the synthesis of platinum(II) complexes with iodo, chloro, bromo and oxalato groups as leaving groups. These complexes were synthesized and studied since many questions regarding the interaction of sulfur-donors and platinum still exist. These relate to thermodynamic and kinetic factors and their influence on anticancer action. In this dissertation the properties of novel platinum(II) complexes of a bidentate ligand having an aromatic nitrogen-donor atom in combination with a thioethereal sulfur atom capable of forming a five-membered ring with platinum(II) were studied. The general structure of the (NS)-ligands used was 2-((alkylthio)methyl)pyridine. Alkyl groups used were methyl, ethyl, propyl, benzyl and phenyl. Amine complexes of platinum have been studied extensively in the past. However, attention was given to novel aspects of substituted pyridine and imidazole ligands and their corresponding complexes. Amongst these are 2-(2-methylaminoethyl)pyridine, 1-methyl-2-methylaminoethylimidazole and 1-methyl-2-methylaminobenzylimidazole. The leaving groups included chloro, bromo and oxalato. Mononitroplatinum(IV) complexes were prepared using novel synthetic methods. Selected platinum(II) amine complexes were used as starting materials for this synthesis. Some of these compounds exhibit promising anticancer behaviour. (Trans-(R,R)-1,2-diaminocyclohexane)(oxalato)(mononitrochloro)platinum(IV) is a particularly good anticancer agent and has been patented internationally. All these complexes were characterized using mass spectrometry, chromatography, thermogravimetric analysis, kinetic aspects such as ligand exchange rates and finally their anticancer action against three different cancer cell lines was evaluated via cytotoxicity assays. Some of the compounds exhibited particularly good anticancer potential.
- Full Text:
- Date Issued: 2010
- Authors: Louw, Marissa
- Date: 2010
- Subjects: Complex compounds -- Synthesis , Ligands (Biochemistry) , Antineoplastic antibiotics
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10424 , http://hdl.handle.net/10948/d1016218
- Description: Novel non-leaving groups were employed in this dissertation to synthesize platinum complexes which can assist in the understanding or improvement of anticancer action. Emphasis was placed on (NS)-chelate and (NN)-chelate platinum complexes. Bidentate (NS)-donor ligands were used as non-leaving ligands in the synthesis of platinum(II) complexes with iodo, chloro, bromo and oxalato groups as leaving groups. These complexes were synthesized and studied since many questions regarding the interaction of sulfur-donors and platinum still exist. These relate to thermodynamic and kinetic factors and their influence on anticancer action. In this dissertation the properties of novel platinum(II) complexes of a bidentate ligand having an aromatic nitrogen-donor atom in combination with a thioethereal sulfur atom capable of forming a five-membered ring with platinum(II) were studied. The general structure of the (NS)-ligands used was 2-((alkylthio)methyl)pyridine. Alkyl groups used were methyl, ethyl, propyl, benzyl and phenyl. Amine complexes of platinum have been studied extensively in the past. However, attention was given to novel aspects of substituted pyridine and imidazole ligands and their corresponding complexes. Amongst these are 2-(2-methylaminoethyl)pyridine, 1-methyl-2-methylaminoethylimidazole and 1-methyl-2-methylaminobenzylimidazole. The leaving groups included chloro, bromo and oxalato. Mononitroplatinum(IV) complexes were prepared using novel synthetic methods. Selected platinum(II) amine complexes were used as starting materials for this synthesis. Some of these compounds exhibit promising anticancer behaviour. (Trans-(R,R)-1,2-diaminocyclohexane)(oxalato)(mononitrochloro)platinum(IV) is a particularly good anticancer agent and has been patented internationally. All these complexes were characterized using mass spectrometry, chromatography, thermogravimetric analysis, kinetic aspects such as ligand exchange rates and finally their anticancer action against three different cancer cell lines was evaluated via cytotoxicity assays. Some of the compounds exhibited particularly good anticancer potential.
- Full Text:
- Date Issued: 2010
Synthesis and characterization of novel platinum complexes : their anticancer behaviour
- Authors: Myburgh, Jolanda
- Date: 2009
- Subjects: Complex compounds -- Synthesis , Platinum compounds , Antineoplastic agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10429 , http://hdl.handle.net/10948/d1018621
- Description: In this dissertation novel non-leaving groups were employed to synthesize platinum complexes which can contribute to the understanding or improvement of anticancer action. These complexes basically consist of (NS)-chelate and amineplatinum complexes. Bidentate (NS)-donor ligands were used as non-leaving ligands in the syntheses of platinum(II) complexes with iodide, chloride, bromide and oxalate anions as leaving groups. These complexes were synthesized and studied since many questions regarding the interaction of sulfur donors and platinum still exists. These relate to thermodynamic and kinetic factors and their influence on anticancer action. In this dissertation the properties of novel platinum(II) complexes of a bidentate ligand having an aromatic nitrogen-donor atom in combination with a thioethereal sulfur atom capable of forming a five membered ring with platinum(II) were studied. The general structure of the (NS) -ligands used were N-alkyl-2-methylthioalkyl imidazole. Alkyl groups used were methyl, ethyl and propyl. Although amine complexes of platinum have been extensively studied there are some new aspects of these that are worthwhile investigating. In this dissertation amines having planar attachments which will be at an angle with the coordination plane viz. benzylamine and amines having cyclic aliphatic groups namely cyclopropyl and cyclohexyl were investigated. Some of the (NS) - and amineplatinum(II) complexes were oxidised to their mononitroplatinum(IV) analogues . The motivation for the synthesis of these complexes was the greater kinetic stability of platinum(IV) and recent research has shown that a specific type of platinum(IV) compound shows suitable properties as an anticancer agent. These complexes were characterised by a variety of spectral means (IR, NMR, mass spectroscopy) as well as elemental analysis, solubility determinations, thermal analysis (TGA), ionization studies and finally their anticancer behaviour towards three different cell lines(Hela, MCF 7, Ht29) and in this process they were compared to the behaviour of cisplatin as a reference. A few have shown promising anticancer behaviour.
- Full Text:
- Date Issued: 2009
- Authors: Myburgh, Jolanda
- Date: 2009
- Subjects: Complex compounds -- Synthesis , Platinum compounds , Antineoplastic agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10429 , http://hdl.handle.net/10948/d1018621
- Description: In this dissertation novel non-leaving groups were employed to synthesize platinum complexes which can contribute to the understanding or improvement of anticancer action. These complexes basically consist of (NS)-chelate and amineplatinum complexes. Bidentate (NS)-donor ligands were used as non-leaving ligands in the syntheses of platinum(II) complexes with iodide, chloride, bromide and oxalate anions as leaving groups. These complexes were synthesized and studied since many questions regarding the interaction of sulfur donors and platinum still exists. These relate to thermodynamic and kinetic factors and their influence on anticancer action. In this dissertation the properties of novel platinum(II) complexes of a bidentate ligand having an aromatic nitrogen-donor atom in combination with a thioethereal sulfur atom capable of forming a five membered ring with platinum(II) were studied. The general structure of the (NS) -ligands used were N-alkyl-2-methylthioalkyl imidazole. Alkyl groups used were methyl, ethyl and propyl. Although amine complexes of platinum have been extensively studied there are some new aspects of these that are worthwhile investigating. In this dissertation amines having planar attachments which will be at an angle with the coordination plane viz. benzylamine and amines having cyclic aliphatic groups namely cyclopropyl and cyclohexyl were investigated. Some of the (NS) - and amineplatinum(II) complexes were oxidised to their mononitroplatinum(IV) analogues . The motivation for the synthesis of these complexes was the greater kinetic stability of platinum(IV) and recent research has shown that a specific type of platinum(IV) compound shows suitable properties as an anticancer agent. These complexes were characterised by a variety of spectral means (IR, NMR, mass spectroscopy) as well as elemental analysis, solubility determinations, thermal analysis (TGA), ionization studies and finally their anticancer behaviour towards three different cell lines(Hela, MCF 7, Ht29) and in this process they were compared to the behaviour of cisplatin as a reference. A few have shown promising anticancer behaviour.
- Full Text:
- Date Issued: 2009
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