Coordination properties of cyclam (1,4,8,11-tetraazacyclotetradecane) endowed with two methylphosphonic acid pendant arms in the 1,4-positions

Abstract

The title ligand, 1,4,8,11-tetraazacyclotetradecane-1,4-diyl-bis(methylphosphonic acid) (H4te2p1,4, H4L), was prepared by an optimized synthetic approach and its complexing properties towards selected metal ions were studied by means of potentiometry. The ligand forms a very stable complex with copper(II) (log beta(CuL) = 27.21), with a high selectivity over binding of other metal ions (e.g. log beta(ZnL) = 20.16, log beta(NiL) = 21.92). The crystal structures of two intermediates in the ligand synthesis and two forms of the nickel(II) complex (obtained by crystallization at different pH) were determined. From acid solution, the crystals of trans-O,O-[Ni(H3L)]Cl.H2O were isolated. In such complex species, one phosphonate pendant arm is double- and the second arm is monoprotonated. The isolation of such species demonstrates a high kinetic inertness of the complex. The central metal ion is surrounded by four in-plane nitrogen atoms (in the ring configuration III) and two oxygen atoms of pendant moieties in the apical positions of octahedral coordination sphere. From neutral solution, the crystals of (trans-O,O-[Ni(H2L)])3.5H2O were isolated. The molecular structures of the complex units found in this structure are analogous to that found in trans-O,O-[Ni(H3L)]Cl.H2O.

Bifunctional Cyclam‐Based Ligands with Phosphorus Acid Pendant Moieties for Radiocopper Separation: Thermodynamic and Kinetic Studies

“…For complexes of the phosphonate ligand H 4 L2 , the first two protonations of the complexes should take place on phosphonate groups 26. 34, 35 The resulting doubly protonated species are very probably “in‐cage” complexes for all three metal ions (a PO 3 H − group can be firmly bound to central metal ions),26, 30, 35 as almost all corresponding log K h values (5.0–7.6, Table 2) are lower than the analogous ones found for the free ligand (7.46 and 6.25, Table 1). Such a decrease is attributable to the electron‐withdrawing effect of the coordinated metal ion and it indirectly confirms the expected coordination of a phosphonate pendant arm.…”

Establishment of two complementary in vitro assays for radiocopper complexes achieving reliable and comparable evaluation of in vivo stability

“…These macrocyclic chelates possess different in vivo behaviours which result from a kinetic stability dependent resistance against transchelation. 4,9,27,28,[58][59][60] In order to estimate the stability of the radiometal complexes, they were incubated in the presence of human serum and human SOD and the level of complex dissociation was analysed by polyacrylamide gel electrophoresis (PAGE) followed by electronic autoradiography. To quantify the data, we used free [ 64 Cu]CuCl 2 as 100% normalized standard which was treated in the same way as the chelators.…”

Metal Complexes of 4,11‐Dimethyl‐1,4,8,11‐tetraazacyclotetradecane‐1,8‐bis(methylphosphonic acid) – Thermodynamic and Formation/Decomplexation Kinetic Studies

“…[26] The isomeric ligand, 1,4-H 4 te2p (H 4 L 4 , Scheme 1), [31] forms also very stable complexes and is even more selective for copper(II); an analogous isomerism was observed for the complexes. [32] Similarly, the monophosphonic acid cyclam derivative H 2 te1p (Scheme 1) forms a thermodynamically highly stable complex with copper(II) having a cyclam ring in the trans-III conformation and the phosphonic acid group in the apical position; the complex is also kinetically inert. [33] It is known that cyclam derivatives fully substituted on the nitrogen atoms (so, only tertiary amines are present, e.g.…”