Kinetics of formation of the 12-MC-4 metallacrown from (S)-α-Alanine hydroxamic acid and Copper(II) and its interaction with La(III)

Metallacrowns are a novel class of macrocyclic compounds, in which metal ions are an integral part of the macrocycle ring. The alfa-aminohydroxamates, which are derivatives of hydroxamic acids with an additional amino group as a potential coordinating group, are suitable ligands for metallacrown formation. These molecules form a metallamacrocycle ring with a metal-nitrogen-oxygen backbone in the presence of Copper (II) ions. A metallacrown with a five-membered chelating ring (15-MC-5) was firstly proposed for these ligands, but in 2001 it was established that alfa-aminohydroxamates can form also Copper(II) 12-MC-4 complexes in solution, that contain a four-membered chelating ring and for which a nonplanar and tensioned cup-like structure was suggested. The equilibria and the kinetics of the Copper(II)/(S)-alfa-alaninehydroxamate 12-MC-4 formation have been investigated by means of the stopped-flow tecnique, FAB-MS and UV-Vis spectrophotometric titrations of the ligand with CuCl2 solutions. A study of the trend of the kinetic parameters varying the pH, the ionic strength and the metal concentration has been performed, allowing an interpretation of the reaction mechanism. The reaction orders (r.o.) with respect to metal and ligand have been determined and their values, between 1 and 2, are in agreement with a complex reaction mechanism, that involves more than one step. The kinetic constants (k) for the metallacrown formation, measured at pH = 4.5 and T = 25°C, increase by a factor of about 50 on going from I=0.1 M to I=0.9 M (NaCl), revealing, according to the Debye-Hukel theory, that the rate determining step of the reaction involves ions with charges of the same sign. The kinetics of the of the replacement of the central copper atom by La(III) and the related conversion of Copper(II)/(S)-alfa-alaninehydroxamate 12-MC-4 to 15-MC- 5 has also been studied. The obtained biphasic kinetic curves reveal the presence of two reaction steps, that can likely be ascribed to the interaction of the 12-MC-4 with La(III) (fast effect) and to the rearrangement of the building block with an expansion of the metallamacrocycle (slow effect). The influence of pH and ligand concentration on the reaction has been analysed as well.