Part I. Cytochrome c oxidase active-site modeling: Synthesis and characterization of new unsymmetrical tris(imidazole- and pyridine-appended) picket-fence porphyrins and their metal complexes. Part II. Toward fullerene-based radiopharmaceuticals: High-yield neutron activation of endohedral holmium-165 metallofullerenes

Part I . Two new unsymmetrical picket-fence porphyrin ligands 1 and 2 and their metal complexes have been prepared as potentially improved structural models for the binuclear (Fe/Cu) Cytochrome c Oxidase (C c O) active site. 1 and 2 have a naphthyl porphyrin superstructure which has been specifically designed to confer long-term configurational stability and allow synthetic manipulations to be easily performed without fear of atropisomer interconversions. The compounds also incorporate a covalently-linked, axially-offset tris(heterocycle) coordination site for a copper ion, like that found in the native C c O enzyme. Monometallic complexes [M = Zn(II), Ni(II), Cu(II), Fe(III)] of the imidazole- and pyridine-appended porphyrin ligands have been prepared and fully characterized. Only the Fe(III) hydroxide porphyrin complex reacted further with Cu(II) salts to form a heterobinuclear species of as yet unestablished structure. The unexpected difficulty of forming binuclear species is attributed to the conformational flexibility of the OCH 2 spacer in 1 and 2 , which presumably does not encourage a favorable chelation conformation to be assumed. Part II . Endohedral holmium metallofullerenes, 165 Ho x @C 82/84 (x = 1,2), have been prepared by carbon-arc methods and separated from empty fullerenes by HPLC techniques. The 165 Ho metallofullerenes and empty C 60 were then bombarded with neutrons under differing flux conditions to understand the various modes of compound degradation and to maximize yields of activated 166 Ho x @C 82/84 [ 165 Ho(n,γ) 166 No]. C 60 survived irradiation to a fairly high extent (>80%) at total neutron doses of <10 18 n cm –2 (75% thermal neutrons), but fast-neutron damage progressed rapidly thereafter, leaving only a few percent of surviving material. Under identical flux conditions, the metallofullerenes were degraded much more quickly and extensively (<10% survival) than was C 60 . Furthermore, decomposition of the metal lofullerenes was shown to proceed primarily by fast-neutron damage instead of the predicted (n,γ)-metal-atom recoil. Higher percentage thermal-neutron fluxes (96% and 99.7%) gave significantly improved metallofullerene survival (20—30% at total doses of 10 15 –10 16 n cm –2 ), and degradation under these conditions was demonstrated to proceed exclusively through the anticipated metal-recoil pathway. The present study establishes the general feasibility of developing radiopharmaceuticals based on neutron-activated endohedral metallofullerene materials.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Natural Sciences

Grantor

Rice University

Year dc:date.issued

1999

Author dc:creator

• Thrash, Thomas Pennix

Advisor dc:contributor.advisor

• Wilson, Lon J.

• Chemistry
• Nuclear chemistry
• Pharmacology
• Surgery
• Health and environmental sciences
• Pure sciences
• Cytochrome c oxidase
• Fullerene-based Holmium-165
• Metallofullerenes
• Neutron activation
• Picket-fence porphyrins
• Radiopharmaceuticals

Statement dc:rights

• Copyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1911/103630

OAI identifier oai:identifier

oai:repository.rice.edu:1911/103630