{"id":{"repo_id":"baylor","oai_identifier":"oai:baylor-ir.tdl.org:2104/13850"},"canonical_url":"https://search.dev.ndltd.org/etd/baylor/oai:baylor-ir.tdl.org:2104/13850","repository":{"repo_id":"baylor","name":"Baylor University","base_url":"https://baylor-ir.tdl.org/server/oai/request"},"display":{"title":"Synthesis, characterization, and anticancer evaluation of novel gold(I) phosphine thiolate complexes : solubility, cellular uptake, and cytotoxicity.","abstract":"This dissertation describes the design, synthesis, characterization, and evaluation of novel gold(I) phosphine thiolate complexes as potential anticancer agents. Inspired by the activity of auranofin and the limitations of existing platinum-based drugs such as cisplatin, this research sought to explore the therapeutic potential of systematically varied gold(I) complexes. Ten complexes, comprising two series with either tri(2-furyl)phosphine (TFP) or triphenylphosphine (PPh3) and five different thiolate ligands, were synthesized and rigorously characterized. Spectroscopic (NMR, IR) and spectrometric (ESI-MS, ICP-MS) techniques, along with X-ray crystallography for four complexes, confirmed their identity, purity, and structural features. A critical, and often overlooked, aspect of drug development – accurate solubility determination – was addressed using ICP-MS. This technique allowed for direct measurement of gold concentration in saturated solutions, providing precise solubility values in both water and McCoy's 5A cell culture medium supplemented with 10% fetal bovine serum (FBS). The solubility of auranofin was found to be significantly lower (approximately four-fold) in cell culture media compared to water, underscoring the importance of measuring solubility in biologically relevant environments. Furthermore, the solubilities of the synthesized complexes varied considerably depending on the ligands. The addition of DMSO to aqueous solutions showed anticipated and substantial implications in determining the solubility of compounds. In vitro cytotoxicity assays, employing a range of breast cancer (SK-BR-3, MCF-7, MDA-MB-231) and non-cancerous (MCF 10A, HEK293T) cell lines, revealed that several of the synthesized complexes exhibited potent antiproliferative activity, comparable to that of auranofin and cisplatin. Notably, some complexes displayed selectivity towards cancer cells, particularly in the absence of DMSO. Cellular uptake studies in MCF-7 cells, using different drugs and media without additional cells introduced demonstrated a positive correlation between solubility in growth media and the amount of gold accumulated within cells, linking a compounds uptake rate in a cancerous cell line to cellular accumulation/retention. Overall, these measurements emphasize the crucial role of solubility measurements at different stages of any drug treatment development. These findings contribute to a deeper understanding of structure-activity-solubility relationships in gold(I) complexes and inform future efforts in the design and optimization of metal-based anticancer drugs.","abstract_html":"This dissertation describes the design, synthesis, characterization, and evaluation of novel gold(I) phosphine thiolate complexes as potential anticancer agents. Inspired by the activity of auranofin and the limitations of existing platinum-based drugs such as cisplatin, this research sought to explore the therapeutic potential of systematically varied gold(I) complexes. Ten complexes, comprising two series with either tri(2-furyl)phosphine (TFP) or triphenylphosphine (PPh3) and five different thiolate ligands, were synthesized and rigorously characterized. Spectroscopic (NMR, IR) and spectrometric (ESI-MS, ICP-MS) techniques, along with X-ray crystallography for four complexes, confirmed their identity, purity, and structural features. A critical, and often overlooked, aspect of drug development – accurate solubility determination – was addressed using ICP-MS. This technique allowed for direct measurement of gold concentration in saturated solutions, providing precise solubility values in both water and McCoy's 5A cell culture medium supplemented with 10% fetal bovine serum (FBS). The solubility of auranofin was found to be significantly lower (approximately four-fold) in cell culture media compared to water, underscoring the importance of measuring solubility in biologically relevant environments. Furthermore, the solubilities of the synthesized complexes varied considerably depending on the ligands. The addition of DMSO to aqueous solutions showed anticipated and substantial implications in determining the solubility of compounds. In vitro cytotoxicity assays, employing a range of breast cancer (SK-BR-3, MCF-7, MDA-MB-231) and non-cancerous (MCF 10A, HEK293T) cell lines, revealed that several of the synthesized complexes exhibited potent antiproliferative activity, comparable to that of auranofin and cisplatin. Notably, some complexes displayed selectivity towards cancer cells, particularly in the absence of DMSO. Cellular uptake studies in MCF-7 cells, using different drugs and media without additional cells introduced demonstrated a positive correlation between solubility in growth media and the amount of gold accumulated within cells, linking a compounds uptake rate in a cancerous cell line to cellular accumulation/retention. Overall, these measurements emphasize the crucial role of solubility measurements at different stages of any drug treatment development. These findings contribute to a deeper understanding of structure-activity-solubility relationships in gold(I) complexes and inform future efforts in the design and optimization of metal-based anticancer drugs.","abstract_has_math":false,"creators":["Wilhelm, Kyle L. (Kyle Logan), 1996-"],"institution":"Baylor University.","degree_name":"Ph.D.","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Solouki, Touradj, 1963-"],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-05","date_published":"2025-05","updated_at":"2026-07-24T01:07:49Z","subjects":["Chemistry.","Mass spectrometry.","Breast cancer.","Gold.","Solubility."],"languages":["en"],"rights":["Baylor University works are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact libraryquestions@baylor.edu for inquiries about permission."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2104/13850","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Solouki, Touradj, 1963-"]},{"key":"dc:creator","label":"Author","values":["Wilhelm, Kyle L. 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They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact libraryquestions@baylor.edu for inquiries about permission."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2104/13850"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["This dissertation describes the design, synthesis, characterization, and evaluation of novel gold(I) phosphine thiolate complexes as potential anticancer agents. Inspired by the activity of auranofin and the limitations of existing platinum-based drugs such as cisplatin, this research sought to explore the therapeutic potential of systematically varied gold(I) complexes. Ten complexes, comprising two series with either tri(2-furyl)phosphine (TFP) or triphenylphosphine (PPh3) and five different thiolate ligands, were synthesized and rigorously characterized. Spectroscopic (NMR, IR) and spectrometric (ESI-MS, ICP-MS) techniques, along with X-ray crystallography for four complexes, confirmed their identity, purity, and structural features. A critical, and often overlooked, aspect of drug development – accurate solubility determination – was addressed using ICP-MS. This technique allowed for direct measurement of gold concentration in saturated solutions, providing precise solubility values in both water and McCoy's 5A cell culture medium supplemented with 10% fetal bovine serum (FBS). The solubility of auranofin was found to be significantly lower (approximately four-fold) in cell culture media compared to water, underscoring the importance of measuring solubility in biologically relevant environments. Furthermore, the solubilities of the synthesized complexes varied considerably depending on the ligands. The addition of DMSO to aqueous solutions showed anticipated and substantial implications in determining the solubility of compounds. In vitro cytotoxicity assays, employing a range of breast cancer (SK-BR-3, MCF-7, MDA-MB-231) and non-cancerous (MCF 10A, HEK293T) cell lines, revealed that several of the synthesized complexes exhibited potent antiproliferative activity, comparable to that of auranofin and cisplatin. Notably, some complexes displayed selectivity towards cancer cells, particularly in the absence of DMSO. Cellular uptake studies in MCF-7 cells, using different drugs and media without additional cells introduced demonstrated a positive correlation between solubility in growth media and the amount of gold accumulated within cells, linking a compounds uptake rate in a cancerous cell line to cellular accumulation/retention. Overall, these measurements emphasize the crucial role of solubility measurements at different stages of any drug treatment development. These findings contribute to a deeper understanding of structure-activity-solubility relationships in gold(I) complexes and inform future efforts in the design and optimization of metal-based anticancer drugs."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Synthesis, characterization, and anticancer evaluation of novel gold(I) phosphine thiolate complexes : solubility, cellular uptake, and cytotoxicity."]}]}],"canonical_facts":{"dc:contributor.advisor":["Solouki, Touradj, 1963-"],"dc:creator":["Wilhelm, Kyle L. (Kyle Logan), 1996-"],"dc:date.accessioned":["2025-09-05T19:52:00Z"],"dc:date.issued":["2025-05"],"dc:description.abstract":["This dissertation describes the design, synthesis, characterization, and evaluation of novel gold(I) phosphine thiolate complexes as potential anticancer agents. Inspired by the activity of auranofin and the limitations of existing platinum-based drugs such as cisplatin, this research sought to explore the therapeutic potential of systematically varied gold(I) complexes. Ten complexes, comprising two series with either tri(2-furyl)phosphine (TFP) or triphenylphosphine (PPh3) and five different thiolate ligands, were synthesized and rigorously characterized. Spectroscopic (NMR, IR) and spectrometric (ESI-MS, ICP-MS) techniques, along with X-ray crystallography for four complexes, confirmed their identity, purity, and structural features. A critical, and often overlooked, aspect of drug development – accurate solubility determination – was addressed using ICP-MS. This technique allowed for direct measurement of gold concentration in saturated solutions, providing precise solubility values in both water and McCoy's 5A cell culture medium supplemented with 10% fetal bovine serum (FBS). The solubility of auranofin was found to be significantly lower (approximately four-fold) in cell culture media compared to water, underscoring the importance of measuring solubility in biologically relevant environments. Furthermore, the solubilities of the synthesized complexes varied considerably depending on the ligands. The addition of DMSO to aqueous solutions showed anticipated and substantial implications in determining the solubility of compounds. In vitro cytotoxicity assays, employing a range of breast cancer (SK-BR-3, MCF-7, MDA-MB-231) and non-cancerous (MCF 10A, HEK293T) cell lines, revealed that several of the synthesized complexes exhibited potent antiproliferative activity, comparable to that of auranofin and cisplatin. Notably, some complexes displayed selectivity towards cancer cells, particularly in the absence of DMSO. Cellular uptake studies in MCF-7 cells, using different drugs and media without additional cells introduced demonstrated a positive correlation between solubility in growth media and the amount of gold accumulated within cells, linking a compounds uptake rate in a cancerous cell line to cellular accumulation/retention. Overall, these measurements emphasize the crucial role of solubility measurements at different stages of any drug treatment development. These findings contribute to a deeper understanding of structure-activity-solubility relationships in gold(I) complexes and inform future efforts in the design and optimization of metal-based anticancer drugs."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/2104/13850"],"dc:language.iso":["en"],"dc:rights":["Baylor University works are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact libraryquestions@baylor.edu for inquiries about permission."],"dc:subject":["Chemistry.","Mass spectrometry.","Breast cancer.","Gold.","Solubility."],"dc:title":["Synthesis, characterization, and anticancer evaluation of novel gold(I) phosphine thiolate complexes : solubility, cellular uptake, and cytotoxicity."],"dc:type":["Thesis"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["Baylor University."]},"updated_at":"2026-07-24T01:07:49Z"}