This title appears in the Scientific Report :
2000
Please use the identifier:
http://hdl.handle.net/2128/20637 in citations.
Vergleich verschiedener Redox-Systeme zur trägerarmen in situ Radioiodierung aromatischer Verbindungen
Vergleich verschiedener Redox-Systeme zur trägerarmen in situ Radioiodierung aromatischer Verbindungen
Since radioiodinated tracers are widely used in life sciences applications for $\textit{in vitro}$ and $\textit{in vivo}$ applications, in this work new approaches for direct electrophilic n.c.a. radioiodination of deactivated arenas were studied, with special regard to mechanistic aspects. First di...
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Personal Name(s): | Mennicke, Eckart (Corresponding author) |
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Contributing Institute: |
Institut für Nuklearchemie; INC |
Imprint: |
Jülich
Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag
2000
|
Physical Description: |
III, 141 p. |
Dissertation Note: |
Köln, Univ., Diss., 2000 |
Document Type: |
Book Dissertation / PhD Thesis |
Research Program: |
Nukleare Daten und Radionuklidproduktion |
Series Title: |
Berichte des Forschungszentrums Jülich
3800 |
Subject (ZB): | |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Since radioiodinated tracers are widely used in life sciences applications for $\textit{in vitro}$ and $\textit{in vivo}$ applications, in this work new approaches for direct electrophilic n.c.a. radioiodination of deactivated arenas were studied, with special regard to mechanistic aspects. First direct n.c.a. radioiodination was examined using various metal salts in trifluoroacetic acid (TFA} as $\textit{in situ}$ oxidation agents. Two different types of metal salts were used comprising TFA-soluble (Pb(CH$_{3}$CO$_{2}$)$_{4}$, Mn(CH$_{3}$CO$_{2}$)$_{3}$, KMnO$_{4}$, Tl(CF$_{3}$CO$_{2}$)$_{3}$ AgCF$_{3}$SO$_{3}$ and TFA-insoluble (Ce(CF$_{3}$SO$_{3}$)$_{4}$), RuCl$_{3}$, FeBr$_{3}$, K$_{2}$Cr$_{2}$O$_{7}$) salts. Optimizing of both labelling systems has been performed using Pb(CH$_{3}$CO$_{2}$)$_{4}$, Ce(CF$_{3}$SO$_{3}$)$_{4}$ and benzene as model compound. At room temperature, the one-pot synthesis was completed within 15 min, resulting in a radiochemical yield (RCY) of 82% and 64% using Pb(CH$_{3}$CO$_{2}$)$_{4}$ or Ce(CF$_{3}$SO$_{3}$)$_{4}$, respectively. Radioiodination of weakly activated monosubstituted benzene derivatives led tp high RCY of about 80% and 60% of the corresponding ortho- and para- radioiodo-isomers using both salts. Weakly deactivated chlorobenzene could only be radioiodinated with Ce(CF$_{3}$SO$_{3}$)$_{4}$ as oxidant, forming exclusively the para-product with a RCY of about 35%. Using the optimized reaction parameters for the other TFA-soluble and - insoluble metal salts with benzene and toluene, good RCY were obtained in all cases except for manganese and silver salts. Apparently their oxidation power is not strong enough for the radioiodination of the non-activated benzenes. $\textit{In situ}$ formed trifluoroacetyl [$^{131}$I]hypoiodite was discussed with regard to the reaction mechanism, since the isomer distribution of the radioiodinated products of metal salts in TFA was typical of an electrophilic aromatic substitution mechanism and was identical for all metal salts used. Moreover, a high RCY could only be obtained in TFA as solvent. The concentration of the iodination agent or its electrophilic potential was probably dependent on the oxidation power of the metal salt in TFA, which led to varying total RCY. An other efficient method for the direct electrophilic n.c.a. radioiodination of even deactivated arenes has been developed using N-chlorosuccinimide (NCS)/radioiodide in trifluoromethanesulfonic acid (triflic acid). Optimization of the one pot labelling procedure using chlorobenzene as a model substrate resulted in a RCY of 75% within 15 min at room temperature. Radioiodination of weakly activated and deactivated monosubstituted benzene derivatives gave rise to a RCY of about 80% with an electrophilic substitution pattern. Strongly deactivated aromatic compounds were radioiodinated with high RCY of about 70% exclusively in their $\textit{meta}$-position using a reaction temperature of 75$^{\circ}$C and a reaction time of 1 h. The radioiodination probably followed a reaction pathway via $\textit{in situ}$ formed iodine(I)- trifluoromethanesulfonate (triflyl hypoiodite). In triflic acid as reaction solvent this acts in its protosolvated activated form as a de facto "superelectrophilic" iodinating species, which is even suitable for the radioiodination of strongly deactivated arenas. Both methods could be applied to the radioiodination of some interesting aromatic tracers. The electrophilic radioiodination of L-$\alpha$-methyltyrosine resulted in a RCY of 75% using NCS in triflic acid. Radioiodination with the metal salts led to the oxidative decomposition of the precursor. For the labelling of phenylpentadecanoic acid a high RCY of 70% could be obtained using metal salts in TFA. Ractioiodination with NCS in triflic acid led to a RCY of 40 %. Other molecules of interest, so far not available via direct electrophilic radioiodination, could also be labeled with the new methods. For example, radioiodinated 4-methoxy-N-methylbenzamide could be obtained in a RCY of 70 % using either NCS in triflic acid or metal salts under c.a. reaction conditions. Moreover, the radioiodination of the receptor ligands dexetimide and 3-([4-phenyl-piperazin-1-yl]-methyl}-1H-pyrrolo [2,3-b]-pyridine (L-750,667} was also possible, however, only with NCS in triflic acid and a RCY of about 40% for both compounds. |