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

The relationship of structural characters of the tripeptidic amine-bisamido-thiol (N3S type) chelators with the lipophilicity, configuration, and stability of four [(99m)Tc0]N3S and one [ReO]N3S chelates is studied here. The results show that the hydroxymethyl group on the two N3S 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. [(TcO)-Tc-99m]RP455 is stable in pH 7.4 aqueous solution, while [(TcO)-Tc-99m]RP535 undergoes decomposition at the same medium, suggesting the influence of a larger side-chain on the stability of the chelate. Unlike [(TcO)-Tc-99m]RPS35, [ReO]RP535 is stable even in 0.1 N NaOH for 3h 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 [(TcO)-Tc-99m]N3S and [ReO]N3S chelates. This information may be useful for a further design of [(TcO)-Tc-99m]N3S or [(ReO)-Re-186]N3S Or [(ReO)-Re-188]N3S chelates with predictable physicochemical properties favorable for the quality diagnosis of cancers.