Possible mechanisms of controlling the configuration, stability, and lipophilicity of [99mTcO]N3S and [ReO]N3S chelates

Abstract The relationship of structural characters of the tripeptidic amine–bisamido‐thiol (N 3 S type) chelators with the lipophilicity, configuration, and stability of four [ 99m TcO]N 3 S and one [ReO]N 3 S chelates is studied here. The results show that the hydroxymethyl group on the two N 3 S chelators, RP294 and RP435, has inhibited neither the formation nor interconversion of syn and anti stereoisomers of the chelates, while the tert ‐butyl group on RP455 and RP535 has prevented the anti isomer from converting to the syn one both in acidic and neutral solutions. The interconversion rates of a stereoisomer can be accelerated at higher pH. [ 99m TcO]RP455 is stable in pH 7.4 aqueous solution, while [ 99m TcO]RP535 undergoes decomposition at the same medium, suggesting the influence of a larger side‐chain on the stability of the chelate. Unlike [ 99m TcO]RP535, [ReO]RP535 is stable even in 0.1 N NaOH for 3 h without change. Combining factors of medium pH values, nature of substituents on a chelator's backbone, size of side‐chains, and property of central metal ions together determine the lipophilicity, configuration, and stability of [ 99m TcO]N 3 S and [ReO]N 3 S chelates. This information may be useful for a further design of [ 99m TcO]N 3 S or [ 186 ReO]N 3 S or [ 188 ReO]N 3 S chelates with predictable physicochemical properties favorable for the quality diagnosis of cancers. Copyright © 2008 John Wiley & Sons, Ltd.