Formation kinetics of pendant arm polyamine macrocycles with copper(II)

The complexation reaction between Cu(II) and a series of cyclam analogue macrocycles with dangling primary amine groups was investigated in aqueous solution. The pH dependence of the reaction was measured between pH 0 and 5.5 covering a range of different protonation stages of the ligands. The kinetics was observed by stopped-flow measurements followed at many wavelengths. An initial second order reaction results in an intermediate which isomerises to a stable complex. The observed rate constants for the initial step varied between 1.5 × 10^-2 M^-1 s^-1 at pH 0 and 6.3 × 10⁵ M^-1 s^-1 at pH 5.3; for the secondary step the rates varied between 2 × 10^-4 s^-1 at pH 1 and 24 s^-1 at pH 5.3. The pH dependence was successfully analysed in terms of the different reactivities for differently protonated ligands for the first step and differently protonated complexes for the second step. Ligands with unprotonated dangling primary amines react with rate constants of 10⁶–10⁷ M^-1 s^-1, the rates drop dramatically upon protonation of the arms to ca. 10–10² M^-1 s^-1 which are very similar to the rates of the parent cyclam ligand of equivalent protonation. The pH dependence of the secondary isomerisation reaction is explained in similar ways: protonated, dangling arms inhibit the isomerisation reaction completely.