An N2S2 bifunctional chelator for technetium-99m and rhenium: complexation, conjugation, and epimerization to a single isomer.
A bifunctional chelator 6 was prepared bearing an N2S2 core for binding rhenium or technetium and a carboxylic acid group for conjugation to amino groups of biomolecules. Complexation of 6 with rhenium(V) resulted in two kinetic isomers, anti-7 and syn-7, being formed in approximately equal amounts. Epimerization with 0.5 M NaOH yields a single isomer anti-7, as determined by NMR spectroscopy and single-crystal X-ray analysis. The 99mTc complex was prepared at the tracer level by reaction of the ligand with 99mTcO4-, tin(II) chloride and sodium gluconate giving a mixture of two isomers, but showing a preference for the anti isomer. Chelation in the presence of 1 M NaOH results in anti-8 being formed as the sole product. The bifunctional ability of the ligand was explored by amide formation with (S)-alpha-phenethylamine, either by direct DCC coupling or through the N-hydroxy succinimidyl ester 9 intermediate. The deprotected bioconjugate 11 was complexed with rhenium, yielding similar amounts of two isomeric rhenium complexes, anti-12 and syn-12, which were isolated and characterized by NMR spectroscopy. Treatment of the kinetic mixture of anti-12 and syn-12 with 1 M NaOH resulted in quantitative conversion to a single rhenium complex anti-12. With technetium-99m in 0.1 M sodium acetate, bioconjugate 11 yielded both technetium-99m complexes anti-13 and syn-13, in a 2:1 ratio, respectively. In contrast, complexation in the presence of 1 M NaOH gave only one technetium-99m complex, assigned the structure anti-13.
Luyt
L G
LG
Department of Chemistry, University of Western Ontario, London, Ontario, Canada N6A 5B7.
Jenkins
H A
HA
Hunter
D H
DH
D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000737:chemistry; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D015394:Molecular Structure; D012211:Rhenium / Q000737:chemistry*; D013237:Stereoisomerism; D013667:Technetium / Q000737:chemistry*
D002614:Chelating Agents; D003432:Cross-Linking Reagents; D012211:Rhenium; D013667:Technetium