{"id":{"repo_id":"auckland-ms","oai_identifier":"oai:researchspace.auckland.ac.nz:2292/75682"},"canonical_url":"https://search.dev.ndltd.org/etd/auckland-ms/oai:researchspace.auckland.ac.nz:2292/75682","repository":{"repo_id":"auckland-ms","name":"University of Auckland","base_url":"https://researchspace.auckland.ac.nz/server/oai/request"},"display":{"title":"Rational Design of Catalytic Metal Complexes for Potential Applications in Anticancer Chemotherapy","abstract":"Noncommunicable diseases, such as cancer and Alzheimer’s, are attributed to 74% of deaths worldwide in developing and developed nations, alike. Regrettably, many of these diseases are preventable assuming access to appropriate healthcare in addition to having a healthy lifestyle. Effective drug design is at the heart of the treatment of these and other diseases. The work described in this thesis seeks to contribute to the field of bioorthogonal research by developing metal-based pre-catalysts that could be utilised in a novel fashion as small-molecule artificial metalloenzyme-like drug candidates. Specifically, we were interested in disrupting the strict redox homeostasis found inside the intracellular environment of cancer cells. The research described herein details the development process of the small-molecule pre-catalyst structures, which afforded an understanding of the optimal donor ligand(s) and structural motif required for both effective catalytic activity in redox-based chemical transformations and long-term stability in strict biologically relevant conditions. Cancer cell death via a redox imbalance can be caused by either a reduction or oxidation pathway. The key pre-catalysts identified in the initial organic solvent trials were investigated in the reduction of critical biological co-factor NAD(P)+ achieved through transfer hydrogenation transformations in water. Similarly, the oxidation pathway was investigated in two ways, first through the catalytic oxidation of 1,4-NAD(P)H, and second by the catalytic formation of hydrogen peroxide. Catalytic testing in biologically relevant media was expanded on by repeating testing in the presence of common biological molecules including several amino acids and nucleobases. Further insight was gained after conducting interaction studies, monitored through 1H NMR spectroscopy, HR ESI-MS, and preliminary in vitro cancer cell studies. These studies demonstrated that the piano-stool complexes, whilst remaining catalytically active in the presence of biological molecules, lacked the lipophilicity required to achieve sufficient cellular uptake and accumulation, thus inhibiting their success in the intracellular environment. This thesis is concluded with the description of the biotinylation and adamantylation of the favoured bidentate pro-ligand structure, with the aim to increase lipophilicity of the resulting complexes. Unfortunately, despite successful ligand synthesis, complexation was unable to be achieved.","abstract_html":"Noncommunicable diseases, such as cancer and Alzheimer’s, are attributed to 74% of deaths worldwide in developing and developed nations, alike. Regrettably, many of these diseases are preventable assuming access to appropriate healthcare in addition to having a healthy lifestyle. Effective drug design is at the heart of the treatment of these and other diseases. The work described in this thesis seeks to contribute to the field of bioorthogonal research by developing metal-based pre-catalysts that could be utilised in a novel fashion as small-molecule artificial metalloenzyme-like drug candidates. Specifically, we were interested in disrupting the strict redox homeostasis found inside the intracellular environment of cancer cells. The research described herein details the development process of the small-molecule pre-catalyst structures, which afforded an understanding of the optimal donor ligand(s) and structural motif required for both effective catalytic activity in redox-based chemical transformations and long-term stability in strict biologically relevant conditions. Cancer cell death via a redox imbalance can be caused by either a reduction or oxidation pathway. The key pre-catalysts identified in the initial organic solvent trials were investigated in the reduction of critical biological co-factor NAD(P)+ achieved through transfer hydrogenation transformations in water. Similarly, the oxidation pathway was investigated in two ways, first through the catalytic oxidation of 1,4-NAD(P)H, and second by the catalytic formation of hydrogen peroxide. Catalytic testing in biologically relevant media was expanded on by repeating testing in the presence of common biological molecules including several amino acids and nucleobases. Further insight was gained after conducting interaction studies, monitored through 1H NMR spectroscopy, HR ESI-MS, and preliminary in vitro cancer cell studies. These studies demonstrated that the piano-stool complexes, whilst remaining catalytically active in the presence of biological molecules, lacked the lipophilicity required to achieve sufficient cellular uptake and accumulation, thus inhibiting their success in the intracellular environment. This thesis is concluded with the description of the biotinylation and adamantylation of the favoured bidentate pro-ligand structure, with the aim to increase lipophilicity of the resulting complexes. Unfortunately, despite successful ligand synthesis, complexation was unable to be achieved.","abstract_has_math":false,"creators":["Finlay, Connal"],"institution":"ResearchSpace@Auckland","degree_name":"PhD","degree_level":"Doctoral","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":[],"advisors":["Wright, James","Hartinger, Christian"],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025","date_published":"2025","updated_at":"2026-07-24T01:06:48Z","subjects":["Catalysis","Transfer Hydrogenation"],"languages":[],"rights":["Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated."],"rights_urls":["https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2292/75682","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Wright, James","Hartinger, Christian"]},{"key":"dc:creator","label":"Author","values":["Finlay, Connal"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-05-28T19:18:56Z"]},{"key":"dc:date.issued","label":"Date","values":["2025"]},{"key":"dc:publisher","label":"Institution","values":["ResearchSpace@Auckland"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["PhD"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Auckland"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Catalysis","Transfer Hydrogenation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated."]},{"key":"dc:rights.uri","label":"Rights URI","values":["https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2292/75682"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Noncommunicable diseases, such as cancer and Alzheimer’s, are attributed to 74% of deaths worldwide in developing and developed nations, alike. Regrettably, many of these diseases are preventable assuming access to appropriate healthcare in addition to having a healthy lifestyle. Effective drug design is at the heart of the treatment of these and other diseases. The work described in this thesis seeks to contribute to the field of bioorthogonal research by developing metal-based pre-catalysts that could be utilised in a novel fashion as small-molecule artificial metalloenzyme-like drug candidates. Specifically, we were interested in disrupting the strict redox homeostasis found inside the intracellular environment of cancer cells. The research described herein details the development process of the small-molecule pre-catalyst structures, which afforded an understanding of the optimal donor ligand(s) and structural motif required for both effective catalytic activity in redox-based chemical transformations and long-term stability in strict biologically relevant conditions. Cancer cell death via a redox imbalance can be caused by either a reduction or oxidation pathway. The key pre-catalysts identified in the initial organic solvent trials were investigated in the reduction of critical biological co-factor NAD(P)+ achieved through transfer hydrogenation transformations in water. Similarly, the oxidation pathway was investigated in two ways, first through the catalytic oxidation of 1,4-NAD(P)H, and second by the catalytic formation of hydrogen peroxide. Catalytic testing in biologically relevant media was expanded on by repeating testing in the presence of common biological molecules including several amino acids and nucleobases. Further insight was gained after conducting interaction studies, monitored through 1H NMR spectroscopy, HR ESI-MS, and preliminary in vitro cancer cell studies. These studies demonstrated that the piano-stool complexes, whilst remaining catalytically active in the presence of biological molecules, lacked the lipophilicity required to achieve sufficient cellular uptake and accumulation, thus inhibiting their success in the intracellular environment. This thesis is concluded with the description of the biotinylation and adamantylation of the favoured bidentate pro-ligand structure, with the aim to increase lipophilicity of the resulting complexes. Unfortunately, despite successful ligand synthesis, complexation was unable to be achieved."]},{"key":"dc:title","label":"Title","values":["Rational Design of Catalytic Metal Complexes for Potential Applications in Anticancer Chemotherapy"]}]}],"canonical_facts":{"dc:contributor.advisor":["Wright, James","Hartinger, Christian"],"dc:creator":["Finlay, Connal"],"dc:date.accessioned":["2026-05-28T19:18:56Z"],"dc:date.issued":["2025"],"dc:description.abstract":["Noncommunicable diseases, such as cancer and Alzheimer’s, are attributed to 74% of deaths worldwide in developing and developed nations, alike. Regrettably, many of these diseases are preventable assuming access to appropriate healthcare in addition to having a healthy lifestyle. Effective drug design is at the heart of the treatment of these and other diseases. The work described in this thesis seeks to contribute to the field of bioorthogonal research by developing metal-based pre-catalysts that could be utilised in a novel fashion as small-molecule artificial metalloenzyme-like drug candidates. Specifically, we were interested in disrupting the strict redox homeostasis found inside the intracellular environment of cancer cells. The research described herein details the development process of the small-molecule pre-catalyst structures, which afforded an understanding of the optimal donor ligand(s) and structural motif required for both effective catalytic activity in redox-based chemical transformations and long-term stability in strict biologically relevant conditions. Cancer cell death via a redox imbalance can be caused by either a reduction or oxidation pathway. The key pre-catalysts identified in the initial organic solvent trials were investigated in the reduction of critical biological co-factor NAD(P)+ achieved through transfer hydrogenation transformations in water. Similarly, the oxidation pathway was investigated in two ways, first through the catalytic oxidation of 1,4-NAD(P)H, and second by the catalytic formation of hydrogen peroxide. Catalytic testing in biologically relevant media was expanded on by repeating testing in the presence of common biological molecules including several amino acids and nucleobases. Further insight was gained after conducting interaction studies, monitored through 1H NMR spectroscopy, HR ESI-MS, and preliminary in vitro cancer cell studies. These studies demonstrated that the piano-stool complexes, whilst remaining catalytically active in the presence of biological molecules, lacked the lipophilicity required to achieve sufficient cellular uptake and accumulation, thus inhibiting their success in the intracellular environment. This thesis is concluded with the description of the biotinylation and adamantylation of the favoured bidentate pro-ligand structure, with the aim to increase lipophilicity of the resulting complexes. Unfortunately, despite successful ligand synthesis, complexation was unable to be achieved."],"dc:identifier.uri":["https://hdl.handle.net/2292/75682"],"dc:publisher":["ResearchSpace@Auckland"],"dc:rights":["Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated."],"dc:rights.uri":["https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm"],"dc:subject":["Catalysis","Transfer Hydrogenation"],"dc:title":["Rational Design of Catalytic Metal Complexes for Potential Applications in Anticancer Chemotherapy"],"dc:type":["Thesis"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["PhD"],"thesis:institution_name":["The University of Auckland"]},"updated_at":"2026-07-24T01:06:48Z"}