New tetraaza macrocyclic ligands with acetate pendant arms: Synthesis and studies of transition metal and lanthanide ion complexes

Title: New tetraaza macrocyclic ligands with acetate pendant arms: Synthesis and studies of transition metal and lanthanide ion complexes

Abstract
Tetraaza macrocycles are excellent ligands for the complexation of metal ions, thus having been widely studied in the last few decades, and those containing donor pendant arms can further enhance that capability. Cyclam (1,4,8,11-tetraazacyclotetradecane) and its derivatives is one of the most prominent groups of macrocyclic ligands because of the high thermodynamic and kinetic stability of their transition metal ion complexes that has opened them several fields of application. One of the most interesting features of this type of ligands when compared to those based on the cyclen (1,4,7,10-tetraazacyclododecane) skeleton is the selectivity towards some metal ions. Lately the spotlight has been mainly on the possible medical uses of metal complexes of these ligands and much effort is still placed on the synthesis of new and more efficient compounds.
One of our on-going interests is the study of cyclam derivatives with acetic and methylphosphonic acid pendant arms for the coordination of metal ions. The presence of N-methylphosphonate pendant arms increases the overall basicity of the ligands and could also increase the thermodynamic and kinetic stability of their metal ion complexes, when compared with acetate arms. The well-known tetraacetic acid derivative of cyclam, H₄teta, has been extensively studied but the same is not true for its tetramethylphosphonic acid counterpart, H₈tetp. There are some reports of cyclam derivatives containing more than one type of pendant arms, but none containing both acetate and phosphonate arms. Aditionally, examples of studied cyclam derivatives with less than four donor pendant arms are limited to just a few ligands containing one or two arms.
Therefore we decided to study the effect of the removal of one of the acetate pendant arms of teta and of its replacement by a phosphonate arm, namely on the thermodynamic stability of the metal complexes formed and on the possible selectivity of the new ligands towards some metal ions. In this work we present the synthesis and study of two new ligands, the triacetic-methylphosphonic acid and the triacetic acid derivatives of cyclam, respectively H₅te3a1p and H₃te3a. The acid-base behaviour of the new ligands and the properties of their complexes with significant divalent transition and trivalent lanthanide metal ions were studied using potentiometric, spectroscopic and structural techniques, and the results obtained are rationalised by comparison with those available for the related ligands H₄teta and H₈tetp.