{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/84084"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/84084","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Co(II), Fe(II), and Ni(II) Complexes for paraCEST Applications and a New Class of Fe(III) Macrocyclic Complexes as T1 MRI Contrast Agents","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Snyder, Eric; 0000-0002-7918-1603"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Morrow, Janet","Chemistry"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-06-21T15:47:46Z","date_published":"2022-06-21T15:47:46Z","updated_at":"2026-07-27T19:05:30Z","subjects":["inorganic chemistry","medical imaging"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/84084","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Morrow, Janet","Chemistry"]},{"key":"dc:creator","label":"Author","values":["Snyder, Eric; 0000-0002-7918-1603"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-06-21T15:47:46Z","2020"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["inorganic chemistry","medical imaging"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/84084"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","There is renewed interest in the development of MRI contrast agents which utilize first-row transition metal ions as alternatives to Gd(III)-based agents used in the clinic. Metal complexes of Co(II), Fe(II), and Ni(II) have shown favorable magnetic properties for utilization as paraCEST agents for MRI, while Fe(III) complexes increase the T1 relaxation of water protons, which is essential for T1-weighted MR imaging. Co(II) and Fe(II) complexes were prepared which utilize 4,10-Diaza-15-crown 5-Ether (N2O3) and triazole pendent groups. One of these complexes, Co(L3) produced exceptionally large paramagnetically shifted bulk water 1H resonances with a shift of 0.051 ppm/mM. Then, a series of Co(II) and Ni(II) azamacrocyclic complexes with either pendent alcohol or pendent amide groups, some of which contained a coordinated water ligand, were prepared. Complexes which contain a water ligand and those with alcohol pendent groups, were more effective in changing the water proton shift of bulk water 1H resonances in ppm/mM of complex for CEST agent applications. Furthermore, Co(II) analogs were superior to their Ni(II) analogs as shift agents, although the stability of the Ni(II) complexes was greater. Fe(III) complexes which contain two alcohol donor pendents on the 1,4,7-triazacyclononane macrocycle were studied as T1 MRI contrast agents. These complexes are remarkably stable under biologically relevant conditions as shown by the highly negative reduction potentials and minimal dissociation of the complex in the presence of 25 mM carbonate and 0.4 mM phosphate or in 100 mM HCl. One of these Fe(III) complexes produces more intense contrast in mice kidneys and liver at 30 minutes post injection than does a commercially used Gd(III) agent. MRI studies in mice show large in vivo differences between the Fe(III) complexes studied that correspond, in part, to their r1 relaxivity in phantoms. Furthermore, changes in overall charge of the complex and lipophilicity can modulate in vivo pharmacodynamic properties. Remarkably, the high T1 relaxivity of these complexes arises from second-sphere water exchange while complexes with comparable T1 relaxivity rely primarily on inner-sphere water exchange.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Co(II), Fe(II), and Ni(II) Complexes for paraCEST Applications and a New Class of Fe(III) Macrocyclic Complexes as T1 MRI Contrast Agents"]}]}],"canonical_facts":{"dc:contributor":["Morrow, Janet","Chemistry"],"dc:creator":["Snyder, Eric; 0000-0002-7918-1603"],"dc:date":["2022-06-21T15:47:46Z","2020"],"dc:description":["Ph.D.","There is renewed interest in the development of MRI contrast agents which utilize first-row transition metal ions as alternatives to Gd(III)-based agents used in the clinic. Metal complexes of Co(II), Fe(II), and Ni(II) have shown favorable magnetic properties for utilization as paraCEST agents for MRI, while Fe(III) complexes increase the T1 relaxation of water protons, which is essential for T1-weighted MR imaging. Co(II) and Fe(II) complexes were prepared which utilize 4,10-Diaza-15-crown 5-Ether (N2O3) and triazole pendent groups. One of these complexes, Co(L3) produced exceptionally large paramagnetically shifted bulk water 1H resonances with a shift of 0.051 ppm/mM. Then, a series of Co(II) and Ni(II) azamacrocyclic complexes with either pendent alcohol or pendent amide groups, some of which contained a coordinated water ligand, were prepared. Complexes which contain a water ligand and those with alcohol pendent groups, were more effective in changing the water proton shift of bulk water 1H resonances in ppm/mM of complex for CEST agent applications. Furthermore, Co(II) analogs were superior to their Ni(II) analogs as shift agents, although the stability of the Ni(II) complexes was greater. Fe(III) complexes which contain two alcohol donor pendents on the 1,4,7-triazacyclononane macrocycle were studied as T1 MRI contrast agents. These complexes are remarkably stable under biologically relevant conditions as shown by the highly negative reduction potentials and minimal dissociation of the complex in the presence of 25 mM carbonate and 0.4 mM phosphate or in 100 mM HCl. One of these Fe(III) complexes produces more intense contrast in mice kidneys and liver at 30 minutes post injection than does a commercially used Gd(III) agent. MRI studies in mice show large in vivo differences between the Fe(III) complexes studied that correspond, in part, to their r1 relaxivity in phantoms. Furthermore, changes in overall charge of the complex and lipophilicity can modulate in vivo pharmacodynamic properties. Remarkably, the high T1 relaxivity of these complexes arises from second-sphere water exchange while complexes with comparable T1 relaxivity rely primarily on inner-sphere water exchange.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/84084"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["inorganic chemistry","medical imaging"],"dc:title":["Co(II), Fe(II), and Ni(II) Complexes for paraCEST Applications and a New Class of Fe(III) Macrocyclic Complexes as T1 MRI Contrast Agents"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:30Z"}