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>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.
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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 (CcO) 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 CcO 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 OCH2 spacer in 1 and 2, which presumably does not encourage a favorable chelation conformation to be assumed.; Part II. Endohedral holmium metallofullerenes, 165Hox C82/84 (x = 1,2), have been prepared by carbon-arc methods and separated from empty fullerenes by HPLC techniques. The 165Ho metallofullerenes and empty C60 were then bombarded with neutrons under differing flux conditions to understand the various modes of compound degradation and to maximize yields of activated 166Hox C82/84 [165Ho(n,gamma) 166No]. C60 survived irradiation to a fairly high extent (>80%) at total neutron doses of 1018 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 C60. Furthermore, decomposition of the metal lofullerenes was shown to proceed primarily by fast-neutron damage instead of the predicted (n,gamma)-metal-atom recoil. Higher percentage thermal-neutron fluxes (96% and 99.7%) gave significantly improved metallofullerene survival (20---30% at total doses of 1015--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.
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