Chemistry - Theses, Dissertations, and other Required Graduate Degree Essays

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“Click” cucurbit[7]uril hosts on self-assembled monolayers: Quantitative supramolecular complexation with ferrocene guests

Author: 
File(s): 
Date created: 
2022-04-06
Supervisor(s): 
Hogan Yu
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) M.Sc.
Abstract: 

Cucurbit[7]uril (CB[7]), a symmetrical pumpkin-shaped molecule with an internal volume that can encapsulate guest molecules of complementary shape and size at a 1:1 ratio, has attracted tremendous attention in diverse fields. Particularly, the outstanding in-solution binding affinity (Kf > 10^9 M^-1) of the host-guest inclusion complexation between cucurbit[7]uril molecule host and ferrocene derivatives molecule guests (Fc@CB[7]) enables their potential applications as conjugation/immobilization motifs for constructing biosensors and other molecular devices. However, their interfacial host-guest complexation behaviour has been rarely studied, partially due to the limitation of current CB[7] surface immobilization strategies (suffering from either poor stability or time-consuming and inconvenient procedure). In this thesis, it was shown that the well-known copper(I)-catalyzed azide-alkyne cycloaddition “click” reaction (CuAAC) can be used to chemically attach alkyne-functionalized CB[7] onto an azide-terminated self-assembled monolayer (SAM) on gold. The reaction time has been reduced from several hours to 30 min compared to conventional methods (e.g., the olefin metathesis reaction or the thiol-ene “click” reaction). Thus prepared CB[7]-tethered SAMs enabled the determination of complexation properties of CB[7] towards various Fc derivatives (e.g., neutral, positively charged and negatively charged substituents) on the surface via conventional cyclic voltammetry measurements. Particularly, the derived complexation thermodynamics (Kf = (1.6 ± 0.3) * 10^7 M^-1) for ferrocenemethanol (FcMeOH), and kinetics data (ka = (2.6 ± 0.4) * 10^3 M^-1s^-1, kd = (5.1 ± 0.3) * 10^-5 s^-1) confirms its strong interfacial host-guest binding with the surface-immobilized CB[7]. Moreover, the as-strong binding affinity of surface-bound CB[7] toward an anionic ferrocene derivative confirms the feasibility of employing Fc@CB[7] as the conjugation motif for immobilizing biological macromolecules (that are often negatively charged) to biochip surfaces.

Document type: 
Thesis

Metallocene-based bioactive agents

Author: 
Date created: 
2021-12-16
Supervisor(s): 
Charles Walsby
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.
Abstract: 

Metallocenes have demonstrated great potential as components of novel pharmaceuticals. Notable examples include ferrocene (Fc) compounds such as Ferrocifen and Ferroquine, which have shown clinical success as anticancer and antimalarial drugs respectively. In this work, metallocene conjugates have been developed to modify, enhance, and manipulate the activity of known drugs and biomolecules. The first study utilizes Fc as a bridge between two biologically-active molecules, biotin, a receptor targeting moiety, and chlorambucil, a chemotherapeutic, to give a novel trifunctional anticancer compound. Comparison of the activity of the resulting trifunctional molecule against the NCI-60 human-tumor cell-line screen with a series of control compounds, which had systematic absences of each of the three components, demonstrated that the Fc group increases anticancer activity. Furthermore, statistical analysis of patterns of activity in the NCI-60 data indicates that the Fc group likely exhibits activity due to the generation of reactive oxygen species (ROS). In the second study, Fc and receptor targeting moieties, biotin or estrone, were appended to an antimetastatic Ru(III) scaffold. The ligands of the compounds show promising cytotoxicity and selectivity, whereas the bimetallic complexes are less active, but still more cytotoxic than the parent Ru(III) complex. Spectroscopic and theoretical studies indicate a potential electrochemical interaction between the two redox-active metal centres. To further explore its ROS generating utility as a medicinal tool, Fc was also coupled to a series of uinolone-based antibiotics. Despite a design that aimed to allow the quinolone activity to be unencumbered by the Fc group, while allowing for ROS generation, the compounds showed little activity against a panel of bacterial pathogens. This suggested a fundamental harmacological issue with the compounds, possibly related to transport into cells. The fourth type of metallocene conjugate in this work installed ruthenocene-like tags to aromatic amino-acid side chains of human serum transferrin. These protein organometallics were studied for their ability to be transported into cancer cells, by comparing the tagged iron-loaded (holo) and iron-free (apo) forms of the protein. Circular Dichroism studies indicate that holo-transferrin maintains its secondary structure following modification, suggesting that the labelled protein could be transported via the transferrin receptor. Overall, the work in this thesis demonstrates the scope for diverse applications of metallocenes in medicinal chemistry.

Document type: 
Thesis

Mechanistic studies of glycoside hydrolase substrates and inhibitors

Author: 
File(s): 
Date created: 
2021-10-15
Supervisor(s): 
Andrew Bennet
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.
Abstract: 

Glycoside hydrolases (GHs) are the enzymes that catalyze the cleavage of glycosidic bonds, which link carbohydrate units to other biomolecules. The work in this thesis comprises mechanistic studies of various GHs with experimental and computational methods. In Chapter 2, the transition state (TS) for the hydroxide-catalyzed hydrolysis of 4-nitrophenyl α-d-mannopyranoside in aqueous media was studied via kinetic isotope effect (KIE) measurements and computational methods. The findings were consistent with a mechanism involving formation of a transient oxirane intermediate. This mechanism supports the pre- viously proposed neigboring group participation mechanism for a GH99 mannosidase. Chapter 3 and 4 provides a mechanistic analysis of a GH36 α-galactosidase mechanism-based covalent inhibitor. Crystal structures of the enzyme-bound species demonstrate that the Michaelis complexes for intact inhibitor and product have half-chair conformations, while the covalent intermediate adopts a flattened half-chair conformation. QM/MM calculations confirm the structural and electronic properties of the enzyme-bound species and provide insight into active site interactions. TSs for covalent intermediate formation and hydrolysis were assessed using experimental KIEs and QM/MM calculations. The enzyme was found to stabilize TS charge development on a remote C5-allylic center of the reacting carbasugar, and catalysis proceeds via a loose SN 2 TS with no discrete cationic intermediate. In chapter 5 KIEs were measured for the hydrolysis of α-d-glucopyranosyl fluoride by two inverting GHs and compared to values computed with multiscale QM/MM methods for the hydrolysis of α-d-glucopyranosyl fluoride promoted by an inverting Aspergillus niger GH15 α-glucosidase to give β-d-glucopyranose. KIEs were also measured for catalysis of β-d-glucopyranosyl fluoride by the Trichoderma virens GH55 inverting β-glucosidase; this reaction occurs via the "Hehre resynthesis–hydrolysis mechanism" to give the hydrolysis product α-d-glucopyranose. The TSs for both reactions are essentially identical with fluoride ion departure occurring with active site stabilization of pyranosylium ion-like TSs, and with catalysis driven solely by enzymatic H-bonding assistance. In chapter 6 I present the design and synthesis of a cyclopropyl inactivator candidate for β-d- glucuronidase and α-l-iduronidase which was tested for activity with human βglucuronidase and human α-l-iduronidase but found no inhibition against the natural substrate.

Document type: 
Thesis

Plasmonic hot electron photovoltaics by internal photoemission

Author: 
Date created: 
2021-12-17
Supervisor(s): 
Gary W. Leach
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.
Abstract: 

The challenge of plasmonic hot electron science is in understanding and integrating the three pillars of device efficiency: (i) plasmonic excitation, (ii) plasmon decay and hot carrier transport, and (iii) rectification of the carrier’s energy across an interface. These three concepts were introduced and synthesized into a systematic experimental approach to the design and fabrication of silver-zinc oxide Schottky junction, plasmonic photovoltaic devices. Devices were built and tested to establish structure-function relationships that underpinned device performance. The high-throughput device optimization strategies employed allowed the fabrication of hundreds of test samples, iteratively achieving: (i) a novel deposition technique for the PVD evaporation of ultra-smooth, single-crystal silver thin films; (ii) a low-cost, single step, high fidelity nanopatterning technique; (iii) prism-coupled plasmonic photovoltaic devices that exhibited world best performance by the internal photoemission mechanism (11.2% IQE @ 543 nm); and (iv) a low-cost, free-space coupled, nanostructured design, that exhibited strong second order nonlinear second harmonic generation and two photon photoluminescence, as well as, optical absorbance that agreed well with models, informing the interpretation of the nanostructure’s photovoltaic response.

Document type: 
Thesis

Structural insights into f-block heterobimetallic dicyanoaurate coordination polymers

Author: 
Date created: 
2021-12-16
Supervisor(s): 
Daniel B. Leznoff
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.
Abstract: 

The first series of uranyl ([UO2]2+)-dicyanoaurate coordination polymers has been synthesized and characterized. The diversity of structures generated demonstrates the flexibility of uranyl and dicyanoaurate as building blocks. Small changes in solvent, reactions conditions, dicyanoaurate salt, and ancillary ligands lead to a wide range of structures, ranging from molecular compounds, to a series of one-dimensional chains (including a ladder with alternating aurophilic and peroxo rungs), to a two-dimensional network of aurophilic and hydrogen-bonds, and an unusual three-dimensional lattice of tetranuclear uranyl-oxo-nitrate clusters connected by dicyanoaurate linkers, with the rotation of the clusters providing the increased dimensionality. This final material undergoes a reversible single-crystal to single-crystal transformation on exposure to or removal from water vapour. The luminescence properties of these materials have been found to range from no detectable emission, to only the uranyl-based emission being detected, to both uranyl and either Au(I) or aurophilic emission being detected. Building on this f-block chemistry, a series of lanthanide-dicyanoaurate-2,2′-bipyridine dioxide (OOBipy) coordination polymers has been created with the formula Ln(OOBipy)2(H2O)x(Au(CN2)3)·yEtOH·zH2O, where x and y = 0–2, and z = 0–4. It is possible to convert between these coordination polymers by the addition of heat or water vapour. The coordination polymers containing Sm, Eu, and Tb were found to be emissive, and those with only Eu or Tb were found to have excellent quantum yields. Attempts to create blended materials of Eu and Tb lead to the quenching of Tb’s emission, and blending of Sm and Tb produced lackluster quantum yields. A procedure to export ellipsoidal crystallographic data to 3D printing file formats was documented. This method gives the ability to export structures from the CCDC’s Mercury to 3D printing file formats, allowing 3D ellipsoidal models to be printed quickly and easily. This has been demonstrated using the uranyl-peroxo coordination polymer mentioned above. Additionally, a method of 3D printing complex or challenging structures by breaking them into parts with connectors, printing each part separately, and then assembling the structure post-printing was developed. This has advantages such as multicoloured printing, framework optimization and reduction, print time reduction, and can be used to bypass print size limitations.

Document type: 
Thesis

Structural insights into f-block heterobimetallic dicyanoaurate coordination polymers

Author: 
Date created: 
2021-12-16
Supervisor(s): 
Daniel B. Leznoff
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.
Abstract: 

The first series of uranyl ([UO2]2+)-dicyanoaurate coordination polymers has been synthesized and characterized. The diversity of structures generated demonstrates the flexibility of uranyl and dicyanoaurate as building blocks. Small changes in solvent, reactions conditions, dicyanoaurate salt, and ancillary ligands lead to a wide range of structures, ranging from molecular compounds, to a series of one-dimensional chains (including a ladder with alternating aurophilic and peroxo rungs), to a two-dimensional network of aurophilic and hydrogen-bonds, and an unusual three-dimensional lattice of tetranuclear uranyl-oxo-nitrate clusters connected by dicyanoaurate linkers, with the rotation of the clusters providing the increased dimensionality. This final material undergoes a reversible single-crystal to single-crystal transformation on exposure to or removal from water vapour. The luminescence properties of these materials have been found to range from no detectable emission, to only the uranyl-based emission being detected, to both uranyl and either Au(I) or aurophilic emission being detected. Building on this f-block chemistry, a series of lanthanide-dicyanoaurate-2,2′-bipyridine dioxide (OOBipy) coordination polymers has been created with the formula Ln(OOBipy)2(H2O)x(Au(CN2)3)·yEtOH·zH2O, where x and y = 0–2, and z = 0–4. It is possible to convert between these coordination polymers by the addition of heat or water vapour. The coordination polymers containing Sm, Eu, and Tb were found to be emissive, and those with only Eu or Tb were found to have excellent quantum yields. Attempts to create blended materials of Eu and Tb lead to the quenching of Tb’s emission, and blending of Sm and Tb produced lackluster quantum yields. A procedure to export ellipsoidal crystallographic data to 3D printing file formats was documented. This method gives the ability to export structures from the CCDC’s Mercury to 3D printing file formats, allowing 3D ellipsoidal models to be printed quickly and easily. This has been demonstrated using the uranyl-peroxo coordination polymer mentioned above. Additionally, a method of 3D printing complex or challenging structures by breaking them into parts with connectors, printing each part separately, and then assembling the structure post-printing was developed. This has advantages such as multicoloured printing, framework optimization and reduction, print time reduction, and can be used to bypass print size limitations.

Document type: 
Thesis

Towards the fast neutron-induced isotope production of 99mTc via the 102Ru(n,α)99Mo reaction.

Author: 
File(s): 
Date created: 
2021-08-25
Supervisor(s): 
Daniel Leznoff
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) M.Sc.
Abstract: 

Radioactive isotopes are widely used in medicine for diagnostic and therapeutic procedures.The most commonly used isotope is technetium-99m (99mTc), a product of β-decay of a molybdenum-99 (99Mo) nucleus, which is currently commercially produced using nuclear reactors. An alternative method of medical grade radioisotope production is required to sustain the demand as nuclear reactors are decommissioned. The proposed method of isotope production which will be discussed in this thesis is to use fast neutrons (∼14.1 MeV) to induce an 102Ru(n,α)99Mo reaction. The Nuclear Science Laboratory (NSL) at Simon Fraser University (SFU) has a Deuterium-Tritium (D-T) Thermo Fisher P385 Neutron Generator (NG) which will be used for the neutron production, as well as ‘state of the art’ gamma ray spectrometers that will be used for experimental analysis. A series of experiments are discussed in this thesis to prove the viability of fast neutron induced isotope production.

Document type: 
Thesis

Structural insights into f-block heterobimetallic dicyanoaurate coordination polymers

Author: 
Date created: 
2021-12-16
Supervisor(s): 
Daniel B. Leznoff
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.
Abstract: 

The first series of uranyl ([UO2]2+)-dicyanoaurate coordination polymers has been synthesized and characterized. The diversity of structures generated demonstrates the flexibility of uranyl and dicyanoaurate as building blocks. Small changes in solvent, reactions conditions, dicyanoaurate salt, and ancillary ligands lead to a wide range of structures, ranging from molecular compounds, to a series of one-dimensional chains (including a ladder with alternating aurophilic and peroxo rungs), to a two-dimensional network of aurophilic and hydrogen-bonds, and an unusual three-dimensional lattice of tetranuclear uranyl-oxo-nitrate clusters connected by dicyanoaurate linkers, with the rotation of the clusters providing the increased dimensionality. This final material undergoes a reversible single-crystal to single-crystal transformation on exposure to or removal from water vapour. The luminescence properties of these materials have been found to range from no detectable emission, to only the uranyl-based emission being detected, to both uranyl and either Au(I) or aurophilic emission being detected. Building on this f-block chemistry, a series of lanthanide-dicyanoaurate-2,2′-bipyridine dioxide (OOBipy) coordination polymers has been created with the formula Ln(OOBipy)2(H2O)x(Au(CN2)3)·yEtOH·zH2O, where x and y = 0–2, and z = 0–4. It is possible to convert between these coordination polymers by the addition of heat or water vapour. The coordination polymers containing Sm, Eu, and Tb were found to be emissive, and those with only Eu or Tb were found to have excellent quantum yields. Attempts to create blended materials of Eu and Tb lead to the quenching of Tb’s emission, and blending of Sm and Tb produced lackluster quantum yields. A procedure to export ellipsoidal crystallographic data to 3D printing file formats was documented. This method gives the ability to export structures from the CCDC’s Mercury to 3D printing file formats, allowing 3D ellipsoidal models to be printed quickly and easily. This has been demonstrated using the uranyl-peroxo coordination polymer mentioned above. Additionally, a method of 3D printing complex or challenging structures by breaking them into parts with connectors, printing each part separately, and then assembling the structure post-printing was developed. This has advantages such as multicoloured printing, framework optimization and reduction, print time reduction, and can be used to bypass print size limitations.

Document type: 
Thesis

Structural insights into f-block heterobimetallic dicyanoaurate coordination polymers

Author: 
Date created: 
2021-12-16
Supervisor(s): 
Daniel B. Leznoff
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.
Abstract: 

The first series of uranyl ([UO2]2+)-dicyanoaurate coordination polymers has been synthesized and characterized. The diversity of structures generated demonstrates the flexibility of uranyl and dicyanoaurate as building blocks. Small changes in solvent, reactions conditions, dicyanoaurate salt, and ancillary ligands lead to a wide range of structures, ranging from molecular compounds, to a series of one-dimensional chains (including a ladder with alternating aurophilic and peroxo rungs), to a two-dimensional network of aurophilic and hydrogen-bonds, and an unusual three-dimensional lattice of tetranuclear uranyl-oxo-nitrate clusters connected by dicyanoaurate linkers, with the rotation of the clusters providing the increased dimensionality. This final material undergoes a reversible single-crystal to single-crystal transformation on exposure to or removal from water vapour. The luminescence properties of these materials have been found to range from no detectable emission, to only the uranyl-based emission being detected, to both uranyl and either Au(I) or aurophilic emission being detected. Building on this f-block chemistry, a series of lanthanide-dicyanoaurate-2,2′-bipyridine dioxide (OOBipy) coordination polymers has been created with the formula Ln(OOBipy)2(H2O)x(Au(CN2)3)·yEtOH·zH2O, where x and y = 0–2, and z = 0–4. It is possible to convert between these coordination polymers by the addition of heat or water vapour. The coordination polymers containing Sm, Eu, and Tb were found to be emissive, and those with only Eu or Tb were found to have excellent quantum yields. Attempts to create blended materials of Eu and Tb lead to the quenching of Tb’s emission, and blending of Sm and Tb produced lackluster quantum yields. A procedure to export ellipsoidal crystallographic data to 3D printing file formats was documented. This method gives the ability to export structures from the CCDC’s Mercury to 3D printing file formats, allowing 3D ellipsoidal models to be printed quickly and easily. This has been demonstrated using the uranyl-peroxo coordination polymer mentioned above. Additionally, a method of 3D printing complex or challenging structures by breaking them into parts with connectors, printing each part separately, and then assembling the structure post-printing was developed. This has advantages such as multicoloured printing, framework optimization and reduction, print time reduction, and can be used to bypass print size limitations.

Document type: 
Thesis

Structural insights into f-block heterobimetallic dicyanoaurate coordination polymers

Author: 
Date created: 
2021-12-16
Supervisor(s): 
Daniel B. Leznoff
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.
Abstract: 

The first series of uranyl ([UO2]2+)-dicyanoaurate coordination polymers has been synthesized and characterized. The diversity of structures generated demonstrates the flexibility of uranyl and dicyanoaurate as building blocks. Small changes in solvent, reactions conditions, dicyanoaurate salt, and ancillary ligands lead to a wide range of structures, ranging from molecular compounds, to a series of one-dimensional chains (including a ladder with alternating aurophilic and peroxo rungs), to a two-dimensional network of aurophilic and hydrogen-bonds, and an unusual three-dimensional lattice of tetranuclear uranyl-oxo-nitrate clusters connected by dicyanoaurate linkers, with the rotation of the clusters providing the increased dimensionality. This final material undergoes a reversible single-crystal to single-crystal transformation on exposure to or removal from water vapour. The luminescence properties of these materials have been found to range from no detectable emission, to only the uranyl-based emission being detected, to both uranyl and either Au(I) or aurophilic emission being detected. Building on this f-block chemistry, a series of lanthanide-dicyanoaurate-2,2′-bipyridine dioxide (OOBipy) coordination polymers has been created with the formula Ln(OOBipy)2(H2O)x(Au(CN2)3)·yEtOH·zH2O, where x and y = 0–2, and z = 0–4. It is possible to convert between these coordination polymers by the addition of heat or water vapour. The coordination polymers containing Sm, Eu, and Tb were found to be emissive, and those with only Eu or Tb were found to have excellent quantum yields. Attempts to create blended materials of Eu and Tb lead to the quenching of Tb’s emission, and blending of Sm and Tb produced lackluster quantum yields. A procedure to export ellipsoidal crystallographic data to 3D printing file formats was documented. This method gives the ability to export structures from the CCDC’s Mercury to 3D printing file formats, allowing 3D ellipsoidal models to be printed quickly and easily. This has been demonstrated using the uranyl-peroxo coordination polymer mentioned above. Additionally, a method of 3D printing complex or challenging structures by breaking them into parts with connectors, printing each part separately, and then assembling the structure post-printing was developed. This has advantages such as multicoloured printing, framework optimization and reduction, print time reduction, and can be used to bypass print size limitations.

Document type: 
Thesis