OpenUCT :: Browsing by Author "Smith, Gregory S"

Browsing by Author "Smith, Gregory S"

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Open Access
Alkylated PTA platforms for mono- and polynuclear pre-catalysts for the aqueous biphasic hydroformylation of 1-octene
(2018) Ramarou, Diteboho Selina; Smith, Gregory S; Makhubela, Banothile C E
A series of mono-, di- and trimeric alkylated PTA ligands were synthesised. These ligands were reacted with the dimeric rhodium precursor, [RhCl(COD)]2, to produce the corresponding mono-, di- and trinuclear Rh(I)-PTA complexes. These complexes were then reacted with carbon monoxide to substitute the COD ligands with CO ligands, yielding the carbonyl analogues of the complexes. The ligands and complexes were fully characterised using various spectroscopic and analytical techniques, which include 1H, 13C and 31P NMR spectroscopy, FTIR spectroscopy, mass spectrometry, and elemental analysis. The ligands were found to have good solubility in water at room temperature, while the complexes showed water solubility at elevated temperatures. All the complexes were evaluated as catalyst precursors in the aqueous biphasic hydroformylation of 1-octene. The hydroformylation reactions showed that the complexes (6 – 18) were all active when used as catalyst precursors in the aqueous biphasic hydroformylation of 1-octene to yield aldehydes (linear and branched) and iso-octenes as side products. All complexes exhibited good chemoselectivity for aldehydes with the COD complexes displaying better chemoselectivity towards aldehydes than the CO complexes. However, the CO complexes exhibited better regioselectivity for linear aldehydes than the COD complexes. The trinuclear complex displayed accelerated catalytic rates than the dinuclear complexes which, in turn, displayed faster rates than the mononuclear complexes. The complexes could be recycled three times with a marked decrease in the conversion of 1-octene after each run for each catalyst precursor. Leaching studies showed a significant loss of the metal catalysts into the organic layer after each catalytic run. Mercury poisoning studies were conducted and confirmed that, under the catalytic conditions, all complexes behaved entirely as homogeneous catalysts when evaluated as catalyst precursors for the aqueous biphasic hydroformylation of 1-octene.
Open Access
Aqueous phase catalysis using mono- and bimetallic transition metal complexes
(2015) Matsinha, Leah Charlie; Smith, Gregory S; Mapolie, Selwyn F; Venter, Gerhard A
The synthesis and characterization of monomeric and dimeric salicylaldimine water-soluble ligands is discussed. The salicylaldimine ligands (2.3-2.10) were synthesised via Schiff base condensation reactions of various amines with water-soluble sulfonated salicylaldehydes (2.1 and 2.2). The ligands were characterized using various analytical and spectroscopic techniques. Complexation reactions of these water-soluble ligands (2.3-2.10) with [Rh(COD)Cl]2 gave the corresponding water-soluble mononuclear (2.11-2.14) and binuclear (2.15-2.18) Rh(I) complexes. All the complexes were characterized using nuclear magnetic resonance spectroscopy, infrared spectroscopy, single crystal X-ray diffraction (for complex 2.14), mass spectrometry, elemental analysis and melting point determinations.
Open Access
Design, Synthesis and Catalytic Evaluation of Mono- and Polynuclear Organometallic Materials as Hydroformylation Catalysts
(2021) Omosun, Nikechukwu Nike; Smith, Gregory S
The hydroformylation reaction is an important homogeneous rhodium-catalyzed industrial process for the production of linear and branched aldehydes from readily available alkenes. The aldehydes produced serve as major building blocks for valuable chemical and pharmaceutical products. The fast-depleting and expensive, highly-active rhodium metal has triggered an interest in the design and synthesis of new, more efficient, selective and recyclable rhodium-based catalysts. The strategies of introducing hydrophilic substituents, multiple active sites and bulky dendritic ligands are currently explored to enhance catalyst performance and recyclability. This study investigated the synthesis, characterisation and catalytic potential of new water-soluble alpha-diimine Rh(I) complexes, alpha-diimine Rh(I) metallodendrimers and a water-soluble binuclear Rh(I) complex. New water-soluble disulfonated 1,4-diazabutadiene (DAD) ligands bearing either an ethyl or acenaphthene backbone were prepared. The alpha-diimine N,N-chelating ligands were synthesised via the Schiff base condensation reactions of 4-aminophenol with 1,2-ethanedione or acenapthenequinone, followed by sulfopropylation reactions with 1,3 propanesultone. Complexation of the water-soluble ligands with the rhodium precursor [Rh(COD)(MeCN)2]BF4 (where COD = 1,5-cyclooctadiene) yielded new water-soluble alphadiimine Rh(I) complexes. In addition, non-sulfonated 1,4-diazabutadiene (DAD) Rh(I) analogues were synthesised by complexation of the alpha-diimine Schiff base ligands with [Rh(COD)(MeCN)2]BF4. The complexes were fully characterised using 1H, 13C{1H} NMR spectroscopy, IR spectroscopy and electrospray ionisation mass spectrometry. The complexes were successfully evaluated as catalyst precursors in the hydroformylation of 1-octene. The reaction conditions were optimised at 75 ℃, 40 bar syngas pressure for 4 h with 2.87 x 10-3 mmol catalyst loading. The sulfonated 1,4-diazabutadiene Rh(I) complexes displayed excellent conversion of 1-octene (> 98%) and good chemoselectivity towards aldehydes (> 86%) while the non-sulfonated 1,4-diazabutadiene Rh(I) complexes displayed lower catalyst activity. Recyclability of the disulfonated 1,4-diazabutadiene Rh(I) complexes were successfully conducted over 4 cycles, with a loss in catalytic activity after the third cycle. Inductively coupled plasma optical spectrometry experiments confirmed negligible leaching of the catalyst precursors into the organic layer. Additionally, catalytic experiments in the presence of mercury show unsuppressed catalyst activity, thus suggesting that the hydroformylation reaction is mediated by a molecularly-dispersed homogeneous species. A series of Fréchet-type dendrons with methyl ester groups at the periphery were subsequently prepared. The α-diimine (DAD) Schiff base ligands were synthesised and coupled to the Fréchet-type dendrons via a Williamson ether reaction to yield a new series of alpha-diimine poly(aryl ether) (PAE) dendrimers with methyl ester groups at the periphery. Complexation of the alpha-diimine poly(aryl ether) (PAE) dendrimers with the metal-precursor [Rh(COD)(MeCN)2]BF4 afforded the three generations of core-functionalised α-diimine Rh(I) metallodendrimers. The dendritic ligands and their corresponding Rh(I) metallodendrimers were fully characterised using standard spectroscopic and analytical techniques. The core-functionalised alpha-diimine rhodium(I) metallodendrimers were applied as catalyst precursors in the hydroformylation of 1-octene and styrene. For the hydroformylation of 1- octene, the metallodendrimers gave good conversions (> 81%) and good aldehyde chemoselectivity (> 83%) under optimum reaction conditions of 75 ℃, 40 bar syngas pressure over 4 h. With respect to regioselectivity, an increase in dendritic generation of the rhodium complexes increased the regioselectivity towards linear aldehydes. For the hydroformylation of aromatic-substituted olefin (styrene), the regioselectivity of the three generations of metallodendrimers were comparable. Therefore, the increased steric crowding around the metal centre had no effect in improving regioselectivity towards linear aldehyde for aromaticsubstituted olefinic substrates. Mercury poisoning experiments performed using the three generations of Rh(I) metallodendrimers displayed suppressed activity (< 52%). This is indicative of a catalytic system that follows a combination of homogeneous and heterogeneous pathway. Lastly, the synthesis and characterization of water-soluble tetrasulfonated tetraimine and disulfonated diimine ligands are described. The ligands were synthesized via the Schiff base condensation reactions of 4-hydroxybenzaldehyde with 3,3-diaminobenzidine or o-phenylenediamine, followed by nucleophilic reactions with 1,3 propanesultone. Complexation reactions of the water-soluble ligands with [Rh(COD)(MeCN)2]BF4 afforded water-soluble mononuclear and binuclear Rh(I) complexes. Both complexes displayed excellent water-solubility at room temperature. The compounds were characterised using an array of spectroscopic (1H, 13C{1H} NMR, FT-IR spectroscopy) and analytical (mass spectrometry) techniques. The sulfonated mononuclear and binuclear Rh(I) complexes were evaluated as catalyst precursors in the aqueous biphasic hydroformylation of 1-octene under hydroformylation conditions of 75 ℃, 40 bar syngas pressure for 4 h. Both catalyst precursors gave good catalytic conversion (> 96%) and aldehyde chemoselectivity (> 87%). Notably, the presence of an extra metal centre in the binuclear complex led to an increase in catalyst activity. Recyclability experiments were conducted over 4 cycles, with a significant drop in conversion after each cycle. The drop in catalyst performance may be attributed to catalyst degradation often associated with the reuse of the same catalyst containing phase.
Open Access
The design, synthesis and characterization of polynuclear materials for applications for catalysis
(2012) Makhubela, Banothile Charity Events; Smith, Gregory S; Jardine, Anwar
The synthesis and characterization of new chitosan- and 6-deoxy-6-amino chitosan-supported ligands is discussed. This was achieved via the reaction of either 2-pyridinecarboxaldehyde or 2-(diphenylphosphino)benzaldehyde with the accessible amino groups of chitosan to afford chitosan-supported Schiff base ligands (2.1-2.4) bearing iminopyridyl and iminophosphine functionalities on the surface. Complexation reactions with [PdCl2(COD)] and [RhCl(CO)2]2 gave the corresponding chitosan-supported complexes (2.5-2.8) and (2.13-2.14). These metal-containing materials and their precursors were isolated as air and moisture stable solids which proved insoluble in common organic solvents and have been characterized analytically and spectroscopically...
Open Access
Design, synthesis and characterization of water soluble heterobimetallic complexes and their evaluation as aqueous biphasic hydroformylation catalysts
(2015) Siangwata, Shepherd; Smith, Gregory S; Makhubela, Banothile C E
A series of new water-soluble N,O-chelating Schiff base ligands were synthesised. These ligands were reacted with ferrocenecarboxaldehyde through Schiff base condensation reactions, leading to new water-soluble ferrocenylimine mononuclear complexes. The mononuclear complexes were reacted with a dimeric rhodium precursor [RhCl(COD)]2 to produce a series of novel ferrocenylimine-Rh(I) heterobimetallic complexes. Both themononuclear and heterobimetallic complexes were found to have good solubility in water of up to 11 mg/mL. The complexes were characterised fully using various spectroscopic and analytical techniques including 1H NMR, 13C NMR spectroscopy, FT-IR spectroscopy, mass spectrometry and elemental analysis. In addition, mononuclear and heterobimetallic complexes were also synthesised as precursors to dendritic DAB-G1 structures. These were found to be water-soluble and they were also characterised using spectroscopic and analytical techniques. The two monometallic and two heterobimetallic complexes were evaluated as pre-catalysts for the aqueous biphasic hydro formylation of 1-octene.The mononuclear ferrocenyl complexes were inactive in the aqueous biphasic hydroformylation experiments. Hydroformylation using the heterobimetallic complexes showed that the pre-catalysts are active in 1-octene conversion, yielding aldehydes (linear and branched) as well as isomerisation products (cis and trans 2- and 3-octene). Linear aldehydes were more favoured with the tertiary-butyl analogue of the heterobimetallic complex. Although loss of metal from the aqueous layer was detected using ICP-OES, the catalysts exhibited good recyclability and could be reused up to 4 times.
Open Access
Development of new bioorganometallic metallodendrimers as in vitro anticancer agents
(2014) Govender, Preshendren; Smith, Gregory S
The clinical success of cisplatin and its derivatives for the treatment of different cancers has had a profound effect on the use of metal-containing agents in medicine. Despite the successes, the drawbacks of platinum-based therapy, such as drug resistance, toxicity and the emergence of unwanted side effects, have bred a need for effective and novel anticancer agents. Hence, the design and study of bioorganometallic complexes as potential therapeutic agents may eventually lead to the identification of new drug candidates. The purpose of this study was to synthesize and characterize a series of polynuclear transition-metal-containing complexes based on a (poly)propyleneimine dendritic scaffold, and investigate the in vitro antiproliferative activity of these complexes.
Open Access
Development of organosilane-containing bioorganometallic compounds evaluated as antiparasitic agents against Plasmodium falciparum and Trichomonas vaginalis
(2016) Adams, Muneebah; Smith, Gregory S; Chibale, Kelly
Many successful initiatives have been employed to stem the spread of the diseases such as malaria and trichomonas's. However, in cases where infection has occurred, pharmaceutical treatments are required. A problem seen across the board is the development of resistance to known treatments. An even bigger problem has been the development of resistance to promising compounds during the clinical trial phase. This has led to the need for effective treatments which are able to overcome the resistance problem. This study investigated the synthesis, characterisation and pharmacological evaluation of new bioorganometallic organosilane-containing compounds based on thiosemicarbazone (TSC),quinoline and benzothiazole scaffolds. Selected thiosemicarbazone-containing ruthenium(II), rhodium(III) and palladium(II) metal complexes were also studied. The compounds were screened for antiplasmodial and antitrichomonal activity, along with their activity against A2780 human ovarian carcinoma and WHCO1 oesophageal cancer cell-lines.
Open Access
Development of quinoline and non-quinoline based organometallic complexes and their ligands conjugated to polyamine scaffolds as pharmacological agents
(2014) Stringer, Tameryn; Smith, Gregory S; Egan, Timothy J
Malaria remains a major global health problem and to date, hundreds of thousands of people die as a result of this disease every year. Malaria has been able to adapt and rebound despite various efforts made to combat the disease. The decrease in efficacy of many front-line drugs against malaria, due to increased resistance, prompts investigation into obtaining effective compounds that are able to overcome this resistance. This study investigated the synthesis, characterisation and biological evaluation of new quinoline as well as non-quinoline based compounds. Selected Rh(I) metal complexes thereof were also studied. The compounds were screened for antiplasmodial activity, in addition, their activity against WHCO1 oesophageal cancer cells and the parasite, Trichomonas vaginalis (T vaginalis) was also evaluated.
Open Access
Development, synthesis and anticancer evaluation of trinuclear Platinum Group Metal organometallic complexes
(2016) Burgoyne, Andrew R; Smith, Gregory S
Over the past few decades metals in medicine have played to play a significant role, especially after the discovery of the anticancer properties of cisplatin. However, acquired and intrinsic resistance, toxicity and a host of side-effects have encouraged the research for new metal based anticancer agents. Organometallic complexes have proved to be successful anticancer agents and several have commenced clinical trials. The aim of this study was to prepare and characterize trinuclear platinum group organometallic complexes and investigate their in vitro activity. The first series of ester containing complexes were prepared. The ligands were generated by the preparation of Schiff base ligands obtained from the condensation of 4-aminophenylmethanol and either benzaldehyde, 2-pyridinecarboxaldehyde or salicylaldehyde. Trimeric ester ligands were prepared from these monomeric ligands by reaction with trimesoyl chloride.
Open Access
Growth and chemical functionalization of SiC nanowires for biomedical applications in cardiology and oncology
(2019) Quaretti,Martina; Smith, Gregory S; Lazzarini, Laura; Rossi, Francesca
The current leading causes of death in the world are cardiovascular diseases (in particular myocardial infarctions) and cancer. In Italy in 2016 almost 400,000 people died because of these two pathologies. Despite the great progress made by medicine in recent decades, the road to cure these diseases is still long, and cancer and cardiac diseases remain a serious socio-economic problem for our society. For this reason, this PhD research focuses on these two main topics; called in the thesis the oncology project and the cardiology project. Both projects were devoted to the synthesis of Silicon Carbide Nanowires (SiC NWs), aiming to devise their new possible biomedical applications in the field of oncology and cardiology. This PhD, funded by Cariparma Crédit Agricole, is part of a Bilateral Agreement for Joint Philosophy Doctor (PhD) Degrees between the University of Parma and CNR-IMEM with the University of Cape Town. The synthesis of compounds for potential applications in cancer treatment was the main research topic of the oncology project during the period spent abroad in South Africa. Modern anti-tumor therapies are very invasive for the patient and often based on the administration of drugs, generally cisplatin derivatives, very cytotoxic and harmful to the human body. Furthermore, such treatments are often not fully selective and kill the diseased but also the healthy cells of the organism. Therefore, the aim of many scientists in the world is to design and synthesize new molecules with excellent anticancer properties but with fewer side effects compared to the drugs already currently in use, for example, less toxicity and greater selectivity for the cancer cells. Thiosemicarbazones (TSCs) are Schiff bases which in recent years have attracted considerable attention thanks to their promising anticancer properties. These compounds are very active also in the fight against malaria, moreover they are used as antifungal and antibacterial agents. TSCs are widely documented in literature, and a correlation has often been found between the efficacy of the antitumor activity of the molecule and the presence of aromatic groups in its structure. Furthermore, exploiting the presence in the TSCs of a set of donor atoms (N and S) able to coordinate various types of metal ions to form the related complexes, many studies emphasize the importance of the presence of metal ions bound to the molecule to further increase the antitumor efficacy. Unfortunately, TSCs have poor solubility in aqueous matrices. This behavior can make their administration as drugs more complex and create possible problems of precipitation (due to the insolubility) or accumulation inside the human body. For this reason, in the oncology project of this PhD research a series of aromatic-TSCs were synthetized and then anchored on the chemically modified surface of SiC NWs, employed as carriers. According to previous results obtained by my research group at IMEM-CNR, these SiC-based NWs are biocompatible and can be conjugated with several organic molecules (e.g. porphyrins). The target of these new nanomaterial-drug systems are solid tumors, e.g. affecting breast, lungs, pancreas and liver, where they can be injected and be active to reduce the tumor mass in view of later surgical removal. To anchor these thiosemicarbazones to the nanowires, SiC NWs coated with a thin external layer of silica (nanomaterials called core-shell SiC/SiO2 NWs) were chosen. In fact, this external layer of silica can be chemically functionalized by appropriate silane linkers. The silane linkers used are (3-aminopropyl)triethoxysilane (APTES) and triethoxy(3-isothiocyanatopropyl) silane (Si-NCS). These alkoxysilanes react with the silica surface and covalently bind to the NWs. Thus, it was possible introduce on the NWs surface amino or isothiocyanate groups, able to react with proper TSCs in the anchoring step. To conjugate the NWs with TSCs, it was required the synthesis of thiosemicarbazones having suitable functional groups able to react with the groups present on NWs surface. In this way thiosemicarbazone molecule was anchored by covalent bonds to the surface of the nanowires. During the time spent at the University of Cape Town, working on the oncology project, various TSCs-metal complexes were prepared and successively anchored to NWs previously decorated with amino groups. Literature is rich in examples of platinum (and related metals) complexes with excellent anticancer activity. Therefore, reactions between the TSCs bound to the NWs surface and platinum, ruthenium and rhodium salts were carried out to obtain NWs functionalized with these complexes. Unfortunately, it was observed that this approach has a drawback due to the ability of the amino groups to give competitive complexes with transition metals. Therefore, the attention of the oncology project was focused on a specific thiosemicarbazone compound (Triapine), on a way to find a new procedure to anchor it to NWs and subsequently on the evaluation of the antitumor activity of this new nano-system by in vitro tests. Triapine is an α-(N)-heterocyclic thiosemicarbazone, which successfully passed Phase II of Clinical Trial. Currently, Triapine is tested as an anticancer drug in human patients. The precursor of Triapine was synthetized, with a suitable functional group able to react with the Si-NCS linker anchored to the NWs. In this way the NWs surface was covered by Triapine molecules connected to the SiC/SiO2 structure through a carbon chain as linker. Then, the anchored Triapine was used as a ligand to coordinate metal ions; specifically copper, a metal with low toxicity to the human body. Subsequently, these nano-systems (NWs-Triapine and NWs-Triapine-Cu complex) and the free molecules (Triapine and Triapine-Cu complex without NWs) were tested on A549 human lung adenocarcinoma cell line to evaluate their antitumor efficacy. The free molecules showed good IC50 values – in the micromolar range - with greater antitumor activity of the free complex compared to the free ligand in the first 24 h, but situation reversed in the subsequent 48 h and 72 h. Vice versa, about the compounds anchored to the NWs, only the NWs-complex has proved active, suggesting that the free molecules and the molecules anchored to the NWs have different mechanisms of action and different interactions with cancer cells. The mechanisms of action were better investigated studying the cell cycle. Regarding the other research topic of this PhD thesis, the problem of myocardial infarction has been addressed in the cardiology project. Infarction is the death (necrosis) of part of the heart muscle tissue (myocardium) due to the lack of adequate oxygenation by the arterial blood flow (ischemia). After the infarction, the affected area is no longer able to contract due to the death of cardiomyocytes, the cardiac cells responsible for the generation and transmission of the electro-cardiac pulse. The dead cardiac cells cannot be regenerated and are replaced by a fibrous connective tissue (collagen fibers) that forms a scar area in which the electrical pulse is no longer able to be diffused. Therefore, an insulating area is generated in the heart, with drastic consequences for the health of the organ and for the correct cardiac functioning. Previous in vitro experiments on cardiomyocytes had shown that SiC NWs (semiconductive nanowires, without the external shell of silica) were able to connect two distant cardiac cells, previously isolated from each other. Thanks to the presence of SiC NWs, the two cells, previously silent, were able to propagate the electric pulse to each other and to synchronize their action potential. Based on these results, in collaboration with a medical research team of the University of Parma, in this cardiology project SiC NWs were tested in vivo on infarcted rats' hearts, to verify if the SiC NWs semiconductive properties were able to restore, even partially, the normal propagation of the cardiac electrical pulse, interrupted after the infarction in the ischemic tissues area. For this purpose, in ten rats the myocardial infarction was induced by creating an ischemic zone in the left ventricle through three different protocols: injection of formaldehyde solution at different concentrations (4% and 38%), deposition of a drop of formaldehyde 38% solution on the heart surface and cryoinjury (creation of a necrotic area by selective burning of cardiac tissues using a metal tip cooled by liquid nitrogen). Before and after the infarction the electro-cardiac activity was monitored with a special high-resolution electrode grid. This accurate epicardial mapping of the affected area showed important changes in the values related to the EGs parameters (waves and intervals) and in the isochrone maps (velocity and direction of propagation of the pulse wavefront) before and after the infarction. These data also allowed to understand that cryoinjury was the best technique in creating an effective ischemic zone, with well-defined edges, easily reproducible in rats. Subsequently, a saline solution containing SiC NWs was injected into the infarcted area and the cardiac signals were collected and analyzed. The aim of this cardiology project is to compare the cardiac functioning after the injection of semiconductive SiC NWs with the pre-infarction conditions to evaluate whether the use of SiC NWs helps restore normal cardiac functioning, lost as a result of a myocardial infarction. Based on preliminary data, in some rats after the injection of SiC NWs some important physioelectric parameters show promising changes compared to the values recorded after the infarction, returning similar to the normal pre-infarction conditions. However, the absence of significant statistical series makes it difficult to assert more specific statements.
Open Access
Iminophosphine complexes of palladium and platinum: catalysis and metallacycloalkanes synthesis
(2012) Mahamo, Tebello; Smith, Gregory S; Lammertsma, Koop; Mapolie, Selwyn F; Slootweg, J Chris; Ehlers, Andreas W
A series of N-functionalized 2-diphenylphosphinobenzaldimino ligands (3.1 â 3.6) bearing pendant groups on the imine moiety were prepared by the Schiff-base condensation reaction of 2-diphenylphosphinibenzaldehyde and appropriate primary amines. The ligands were subsequently used to synthesize a range of palladium complexes of the types [Pd(P^N)Cl2] (3.7 â 3.12) and [Pd(P^N)(Me)Cl)] (3.13 â 3.18) from precursor complexes [Pd(COD)Cl2] and [Pd(COD)(Me)Cl], respectively. Platinum complexes of the type [Pt(P^N)Cl2] (3.19 â 3.24) were synthesized by the ligand displacement reaction between [Pt(COD)Cl2] and ligands 3.1 â 3.6. All compounds were characterized by multinuclear NMR and infrared spectroscopies as well as elemental analysis. In addition, the structure of complex 3.14 was determined by x-ray crystallography. Palladium complexes 3.8 â 3.10 and 3.16 were evaluated as pre-catalysts in the Suzuki- Miyaura coupling reaction. These complexes were found to be highly active and tolerant of a wide range of reaction conditions and functional groups on substrates. Low catalyst loadings (0.1 mol% Pd) were required, while high conversions and short reaction times were maintained. Having a substituent bearing a donor atom on the imine moiety of the ligand (ligands 3.3 and 3.4) was found to enhance catalytic activity. Palladium methyl chloride complexes were found to show slightly more activity than their palladium dichloride counterparts. Reaction of [Pt(P^N)Cl2] complexes with BrMg(CH2)4MgBr in an attempt to synthesize platinacycloalkane complexes resulted in the formation of bromobutyl complexes [Pt(P^N)(C4H9)Br] (3.25 and 3.26) instead. Successful synthesis of platinacyclopentane complexes, 5.1 â 5.6, and platinacycloheptane complexes, 5.7 â 5.12, was achieved by the reaction of [Pt(COD)Cl2] with appropriate di-Grignard reagents, followed by ligand displacement with the iminophosphine ligands. All complexes were fully characterized using various NMR spectroscopies, mass spectrometry and elemental analysis. Crystal structures of the bromobutyl and platinacyclopentane complexes 3.25 and 5.1 were determined. Studies on the thermal decomposition of the platinacycloalkane complexes were carried out. Platinacyclopentane complexes 5.1 â 5.6 were found to be markedly stable, with the decomposition reaction requiring temperatures higher than 100 Â°C. Reaction temperature and duration were found to have a significant influence on the organic product distribution obtained. These reactions gave 1-butene (for the platinacyclopentane complexes) and 1- hexene (for the platinacycloheptane complexes) as major products. Kinetic data obtained for the decomposition of 5.1 and 5.7 shows that the decomposition reaction follows first order kinetics for the initial 30% of the decomposition reaction. Thereafter, reaction order deviates from first order behaviour, indicating increasing involvement of products in the reaction mechanism. The generally accepted Î²-hydride elimination/reductive elimination reaction mechanism for the decomposition of metallacycloalkanes was investigated using DFT methods. The simplified complex, 5.13B, was used as a model for platinacyclopentane complexes. Results from these calculations show that intramolecular Î²-hydride elimination from the carbocyclic ring of platinacyclopentane complexes is unlikely to occur as this process requires an extremely high energy barrier (>64 kcal.mol-1). Furthermore, these calculations reveal that ligand hemilability is energetically disfavoured in the Î²-elimination reaction while it is favoured in the reductive elimination reaction.
Open Access
An investigation into the alkene hydroformylation reaction using platinum complexes
(2009) Kistamurthy, Deshen; Moss, John R; Smith, Gregory S
Hydroformylation is the most widely applied homogeneous catalysis reaction used in industry. The aldehyde product is an important commodity in both the bulk and specialty chemical industry. Platinum catalysts have shown significant chemo- and regioselectivities in alkene hydroformylation. This thesis investigates the activity as well as selectivity of platinum complexes containing bidentate ligands in the hydroformylation reaction.
Open Access
Mono- and multinuclear PGM complexes containing thiosemicarbazones synthesis, characterization and antiplasmodial evaluation
(2012) Adams, Muneebah; Smith, Gregory S
Four aryl- and ferrocenyl-derived thiosemicarbazone ligands have been synthesized and characterized using NMR, infrared (IR) spectroscopy and mass spectrometry. These ligands were used towards the synthesis of three series of mono- and multinuclear complexes, in which the thiosemicarbazone ligands chelate in either a bidentate (N,S) or tridentate (C,N,S) mode.
Open Access
Mono- and polynuclear Ferrocenyl-derived complexes: synthesis, characterisation and biological evaluation as antimycobacterial and antiplasmodial agents
(2015) Baartzes, Nadia; Smith, Gregory S
Ferrocene-containing precursors, vinylferrocene and (E)-4-vinylferrocenylbenzaldehyde were prepared, by a Wittig olefination reaction and Heck cross-coupling reaction, respectively. Mononuclear ferrocenyl-derived imino complexes were synthesised by Schiff-base condensation reactions of (E)-4-vinylferrocenylbenzaldehyde with various amines. This included the preparation of a silicon-containing derivative and its carbon analogue, to determine the effect of the lipophilic moiety on the biological activity. In addition, polynuclear ferrocenyl-derived imino complexes based on the tris(2-aminoethyl)amine scaffold and the polypropyleneimine (PPI) first- and second-generation scaffolds were also synthesised using Schiff-base chemistry. These polynuclear complexes were prepared using template chemical procedures to that of the mononuclear complexes. The corresponding mono- and polynuclear ferrocenyl-derived amino complexes were synthesised via reductive amination reactions from the (E)-4-vinylferrocenylbenzaldehyde. The imine moiety was hydrogenated in order to compare the effect on the biological activity. The imino and amino complexes were isolated in moderate to high yields. A second series of ferrocenyl complexes was also prepared incorporating a thiosemicarbazone moiety, as this is a known pharmacophore and may confer favourable properties in terms of biological activity as well as solubility. Methyl hydrazinecarbodithioate was synthesised and reacted with the previously synthesised (E)-4-vinylferrocenylbenzaldehyde by a Schiff-base condensation reaction to afford a ferrocenyl dithiocarbamate. The dithiocarbamate was reacted with various amines via nucleophilic substitution reactions to give mono- and polynuclear ferrocenylthiosemicarbazone complexes. These complexes were isolated in low to moderate yields.
Open Access
Monometallic and multimetallic complexes as precatalysts in the hydroformylation of olefins
(2020) Siangwata, Shepherd; Smith, Gregory S; Goosen, Neill J
A series of new aryl ether salicylaldimine-based monomeric, dimeric, trimeric and hexameric triazolyl ligands have been synthesised. The N,O-chelating ligands were synthesised via Schiff base condensation reactions of salicylaldehyde with the bromopropylamine hydrobromide salt, followed by the azidation of the resultant N-3-bromopropylsalicylaldimine. Click chemistry reactions of the azido propyl salicylaldimine with the appropriate phenolic-alkyne afforded the mono-, di-, tri- and hexameric aryl ether salicylaldimine-based triazolyl ligands. The ligands were characterised using various analytical and spectroscopic techniques. Complexation of the monomeric and trimeric ligands with the dimeric rhodium precursor [RhCl(COD)]2 yielded new aryl ether N,O-chelate mononuclear and trinuclear Rh(I) complexes. The complexes were characterised using nuclear magnetic resonance spectroscopy, infrared spectroscopy, mass spectrometry and melting point determinations. The mononuclear and trinuclear complexes were successfully evaluated as catalyst precursors in the hydroformylation of higher olefins. The reaction conditions were optimised using the mononuclear precatalyst at 85 ℃, 40 bar syngas pressure for 4 h with 2.87 x 10-3 mmol Rh loading and a substrate (1-octene) to catalyst ratio of 2500 : 1. These conditions gave good aldehyde chemoselectivity (90%), excellent conversion of the substrate (99%) and good catalytic activity (554 h-1 ). Comparable catalytic performance of both precatalysts was obtained when milder reaction conditions (85 ℃, 20 bar for 4 h) were adopted in the evaluation of the mononuclear complex against the low generation dendritic trinuclear complex. The mercury poisoning experiments revealed a dual catalytically influenced system, emanating from a combination of homogeneous and heterogeneous catalytic species. The mononuclear catalyst precursor was also evaluated successfully in the hydroformylation of internal olefins 7- tetradecene and trans-4-octene. The catalyst precursor gave good conversions of both internal olefins (> 80%) under the optimum reaction conditions (85 ℃, 40 bar for 4 h). Catalyst recyclability studies in the hydroformylation of 1-octene conducted using the Organic Solvent Nanofiltration (OSN) strategy demonstrated five successful recycles with consistently good catalytic performance from both catalyst precursors. Inductively coupled plasma optical emission spectrometry (ICP-OES) experiments revealed a near perfect (99%) membrane retention of the rhodium metal. Kinetic studies using the mononuclear precatalyst were investigated by evaluating the effect of temperature, syngas total pressure and catalyst loading on the rate of hydroformylation. The activation energy for the hydroformylation of 1-octene was calculated to be 62 kJ mol-1 and the experimental rate constants were found to be in good agreement with the predicted rate data obtained using a modified fundamental mechanismbased rate model. The synthesis and characterisation of new water-soluble, sulfonated aryl ether salicylaldiminebased mono- and trimeric ligands has also been described. The ligands were prepared following a series of amine and Boc-protection and deprotection procedures, Schiff base condensation reactions and Williamson ether synthesis. The water-soluble N,O-chelating aryl ether ligands were characterised using various spectroscopic and analytical techniques. Subsequently, complexation reactions of the ligands with the dimeric [RhCl(COD)]2 gave the corresponding new water-soluble mononuclear and trinuclear Rh(I) complexes. The complexes were characterised using nuclear magnetic resonance spectroscopy, infrared spectroscopy, mass spectrometry and melting point determinations. The complexes show appreciably good solubility in water, 15.7 mg/mL (mononuclear complex) and 8.6 mg/mL (trinuclear complex). The new water-soluble mono- and trinuclear complexes were successfully evaluated as precursors in the aqueous biphasic hydroformylation of higher olefins. Optimisation experiments using the mononuclear precatalyst gave the best results at 85 ℃, 50 bar syngas pressure for 4 h with 2.87 x 10-3 mmol Rh loading and a substrate (1-octene) to catalyst ratio of 2500 : 1. Both catalyst precursors gave near quantitative catalytic conversion of 1-octene, good activities (> 550 h -1 ) and attractive aldehyde chemoselectivity (> 85%). A substrate and product-distribution time study showed a positive dendritic effect in relation to the trinuclear complex over the mononuclear complex. The mercury poisoning experiments were suggestive of a system that is catalysed by a dual effect of homogeneous and heterogeneous catalytic species. Recyclability experiments were successfully conducted over 5 cycles, with a gradual decline in catalytic performance for both complexes. The dendrimer stabilised trinuclear precatalyst showed improved recyclability in “neat”, monophasic hydroformylation experiments, while the mononuclear precatalyst showed a reduced overall performance. The bias towards the linear aldehyde for the dendritic trinuclear complex was tunable by addition of excess bulkier trimeric water-soluble ligand into the catalytic system. Inductively coupled plasma optical emission spectrometry experiments showed moderate losses of the metal from the aqueous phase to the organic layer. Both catalyst precursors also showed good catalytic activity (> 450 h-1 ) and a total bias to aldehyde chemoselectivity (no hydrogenation products) in the aqueous biphasic hydroformylation of styrene.
Open Access
Multinuclear PGM complexes of thiosemicarbazones : synthesis, characterisation and biological activity
(2010) Stringer, Tameryn; Smith, Gregory S
A series of mono- and dithiosemicarbazone ligands were prepared by simple Schiff-base condensation reactions between thiosemicarbazides and various substituted salicylaldehydes.
Open Access
Quinoline-triazole half-sandwich iridium(III) complexes: Synthesis, antiplasmodial activity and preliminary transfer hydrogenation studies
(2020) Melis, Diana; Smith, Gregory S
Malaria is a devastating and pervasive infectious disease and continues to be a major global health issue, with over half the world's population being at risk of transmission. In the absence of a suitable vaccine, efforts to eradicate the disease rely heavily on clinically available drugs. Plasmodium falciparum, the deadliest species of malaria, has however become resistant to most conventional antimalarial treatments, resulting in the worldwide search for new, effective drugs. Amongst other requirements, these drugs should target resistant parasitic strains in an attempt to curb the escalation of the disease. In this regard, the incorporation of a metal into the organic framework of a biologically active compound has become an increasingly popular method of enhancing antiplasmodial activity in the drug-resistant parasite strains. Two series of 7-chloroquinoline-1,2,3-triazole ligands, one with the direct attachment of the triazole to the quinoline and one where the two entities are separated by an aminopropyl linker, were synthesised. Coordination of selected ligands with [IrCl(μ-Cl)(Cp*)]₂ yielded six neutral, cyclometallated and two cationic,N,N-chelated iridium complexes. Computational analysis revealed that metal coordination to the quinoline nitrogen occurs first, forming an unstable kinetic product that, upon heating over time, forms the stable, cyclometallated, thermodynamic product. All of the compounds were fully characterised using an array of spectroscopic (¹H, ¹³C{¹H}, ¹⁹F{¹H}, ³¹P{¹H} NMR and FT-IR spectroscopy) and analytical (mass spectrometry and melting point analysis) techniques. Single crystal X-ray diffraction confirmed the proposed molecular structure and a pseudo-tetrahedral geometry around the metal centre for the cyclometallated and monodentate, quinoline nitrogen-coordinated complexes. The ligand series containing the propyl chain linker displayed superior in vitro antiplasmodial activity against the chloroquine-sensitive NF54 strain of P. falciparum in comparison with the series having thetriazole directly attached to the quinoline moiety. Upon complexation with iridium, the activity of selected ligands is significantly enhanced (0.247< IC₅₀ (μM)< 2.34), with some complexes being over one hundred times more active than their respective ligands. For most of these compounds, their antiplasmodial activity is lower in the chloroquine-resistant K1 strain, however, their calculated RI values suggest that they likely only experience mild cross-resistance, not to the same extent of chloroquine. Selected complexes were tested against the healthy, mammalian Chinese Hamster Ovarian (CHO) cell line and were found not to be cytotoxic. They were also determined to be more selective towards the parasite than healthy cells. An “IC₅₀ speed assay” using the three most active complexes against the chloroquine-sensitive NF54 strain found the two neutral, cyclometallated complexes to be fast-acting compounds which reach their lowest IC₅₀ values within 24 hours, while the active cationic complex was determined to be slow-acting, only reaching its lowest IC₅₀ value after 48 hours. To gain insight into the possible mechanisms of action of these compounds, selected ligands and complexes were tested for their ability to inhibit the formation β-haematin(the synthetic form of haemozoin), sinceone of the mechanisms of 7-chloroquinoline-containing compounds is the inhibition of haemozo information. All five of the tested compounds were found to inhibit β-haematin formation to some extent but were, in general, less effective β-haematin inhibitors than chloroquine itself. Interestingly, the aminopropyl-containing cationic complex which displayed the lowest antiplasmodial activity exhibited far greater β-haematin inhibitory activity (IC₅₀ 9.65 μM) than chloroquine(IC₅₀ 65.3 μM).Finally, three of the most active complexes were evaluated for their ability to facilitate transfer hydrogenation, by reducing β-nicotinamide adenine dinucleotide (NAD+) to NADH in the presence of hydrogen source, sodium formate. Through preliminary qualitative and quantitative cell-free experiments, it was found that the two most active neutral, cyclometallated complexes tested may be capable of acting as transfer hydrogenation catalysts while the active, cationic complex tested did not indicate reduction of NAD+ to NADH over 4 hours.
Open Access
Recent Advances in the Biological Investigation of Organometallic Platinum-Group Metal (Ir, Ru, Rh, Os, Pd, Pt) Complexes as Antimalarial Agents
(2020-11-12) Mbaba, Mziyanda; Golding, Taryn M; Smith, Gregory S
In the face of the recent pandemic and emergence of infectious diseases of viral origin, research on parasitic diseases such as malaria continues to remain critical and innovative methods are required to target the rising widespread resistance that renders conventional therapies unusable. The prolific use of auxiliary metallo-fragments has augmented the search for novel drug regimens in an attempt to combat rising resistance. The development of organometallic compounds (those containing metal-carbon bonds) as antimalarial drugs has been exemplified by the clinical development of ferroquine in the nascent field of Bioorganometallic Chemistry. With their inherent physicochemical properties, organometallic complexes can modulate the discipline of chemical biology by proffering different modes of action and targeting various enzymes. With the beneficiation of platinum group metals (PGMs) in mind, this review aims to describe recent studies on the antimalarial activity of PGM-based organometallic complexes. This review does not provide an exhaustive coverage of the literature but focusses on recent advances of bioorganometallic antimalarial drug leads, including a brief mention of recent trends comprising interactions with biomolecules such as heme and intracellular catalysis. This resource can be used in parallel with complementary reviews on metal-based complexes tested against malaria.
Open Access
Synthesis and characterisation of small molecule and macromolecular photoredox catalysts for radical thiol-ene reactions
(2021) Motimani, Nozuko; Smith, Gregory S
The use of polynuclear complexes is attracting significant attention, offering several advantages over mononuclear analogues. In the context of this project, the presence of several photoactive centres can lead to a multi-electron transfer in a single step and offering other modalities. With the aim to improve the reactivity and stability of photoredox catalysts, multinuclear photoredox catalysts were developed. Consequently, bipyridyl monomeric and trimeric ligands functionalised with imine and amine functionalities were synthesised via Schiff base condensation and reductive amination reactions, respectively. The ligands were then reacted with cis-dichlorobis (2,2'-bipyridine) ruthenium (II) to afford two new mononuclear and two new trinuclear Ru(II)-based complexes. The resulting complexes were then fully characterised by various spectroscopic and analytical techniques such as 1H NMR, 13C{1H} NMR, FT-IR spectroscopy and mass spectrometry. Furthermore, electrochemical, electronic absorption and emission studies for the complexes were conducted and the collected data displayed the effects of ligand modifications on the photophysical and redox properties of the complexes. All the ligand-modified complexes exhibited red shifted emission spectra (614−633 nm) relative to the [Ru(bpy)3](PF6)2 complex (609 nm) and this emission band was attributed to the transition from the triplet MLCT excited state (3MLCT) to the ground state. The excited state redox potentials for the ligand-modified complexes were comparable to that of the known complex thus displaying promising photocatalytic activity. The photoexcited [Ru(bpy)3] 2+ complex had the most positive excited state reduction potential (Ered (2+*/+) = +0.350 V vs Ag/Ag+), making it a more powerful oxidant than the photoexcited states of the ligand-modified complexes. The complexes were then evaluated as photoredox catalysts in the radical hydrothiolation reaction of olefins (thiol-ene reactions) to produce thioethers, which are valuable starting materials in the pharmaceutical industry, material and polymer science, and in the synthesis of various drug molecules. The isolated yields, from the reaction between thiophenol and styrene, were higher for the [Ru(bpy)3](PF6)2 complex (54%) in comparison to the ligand-modified mononuclear complexes (8–24%). This result was expected since [Ru(bpy)3](PF6)2 exhibited the most positive excited state reduction potential (Ered (2+*/+) = +0.350 V vs Ag/Ag+ ), making the photoexcited state of this complex more readily quenched by the thiophenol. Control reactions carried out in the absence of the photocatalyst resulted in either significantly lower yields (6%) or no product formation thus showing the role of the complexes as photoredox catalysts in the reactions. Varying the substrates by using styrene and 1-butanethiol afforded the desired coupled thioether product, while the reaction between thiophenol and allyl alcohol resulted in the formation of the disulfide product. However, when allyl alcohol was reacted with 1- butanethiol, the desired anti-Markovnikov thioether product was formed and this indicated the importance of substrate choice and compatibility with the photoexcited catalyst when designing a photocatalytic system. The reactions carried out using trinuclear complexes (Ered (2+*/+) = +0.300 V vs Ag/Ag+ for each metal centre) resulted in a three-fold increase in isolated yields (26%, 73%) when compared to their respective mononuclear analogues (8%, 22%). This demonstrated the benefits of having a multinuclear photocatalyst with several photoactive centres.
Open Access
Synthesis and characterization of nickel, palladium and chromium complexes as olefin oligomerization catalysts
(2009) Mogorosi, Moses Mokgolela; Moss, John R; Smith, Gregory S
New N-functionalized 2-phosphinobenzaldimino (P^N) ligands (L) bearing 3-picolyl (41), furfuryl (42), thiophene-2-methyl (43), thiophene-2-ethyl (44), and benzyl (45) groups have been prepared in good yield. In addition, 2-iminopyridyl (N^N) (46), 2-bromobenzaldimino (47), and 2-phenoxyimino (O^N) (48) ligands and precursors, bearing furfuryl groups, were prepared in good yield. The amino analogues of 47 and 48 were obtained by reduction of the imine bonds using sodium borohydride. All compounds were fully characterized using spectroscopic and analytical techniques, including melting point, ¹H, ¹³C, and ³¹P NMR, IR spectroscopy, MS, and elemental analysis. These ligands (L) were reacted with appropriate metal precursors to give the corresponding metal complexes of the type PdLMeCl (51 – 55), PdLCl₂ (56 – 63), NiLBr₂ (75 – 82), and CrL(THF)Cl₃ (83 – 88).