Effect of alkali metal ions on dissociation kinetics of Cu(II) complexes of DOTP-like macrocyclic
                                              ligands

           Romana Michalicová, Přemysl Lubal, Luís M.P. LIMA, Rita DELGADO, Petr HERMANN

Cyclen based tetraaza-macrocyclic ligands are well known for their ability to bind ion Cu(II)
leading to formation of complexes with high thermodynamic stability and kinetic inertness which are
required for their in vivo applications and in medicine [1–3]. Some copper(II) complexes are ideal
for using in clinical diagnosis because of their radioisotopic prorerties (positron emission
tomography - PET, ^64Cu with half-life 12.8 h) or in radio-immunotherapy (^67 Cu with half-life 62
h) [4]. In addition, the sodium and potassium ions play an important role in biology, e.g.
concentration gradient of sodium/potassium ions is important in living organism for many cell
functions, and their presence in the solution can affect the kinetic inertness of copper(II)
complexes.


                                 R = H

                                 R = CH[2]-CH[2]-OH

                                 R = CH[2]-P(O)(OH)[2]

                                                      H[6]do3p

                                                      H[6]do3p1ol

                                                      H[8]dotp


In this work, the acid-assisted dissociation kinetics of Cu(II) complexes with DOTP-like ligands
(e.g. H[6]do3p, H[6]do3p1ol, H[8]dotp [1,2]) was studied by means of molecular absorption
spectroscopy in presence of Li^+ , Na^+ and K^+ salts employed as supporting electrolyte. It was
found out that these ions significantly influence the rate of dissociation of copper(II) complex in
K^+; Na^+; Li^+ order and the parameters of chemical model describing this reaction correlate with
their ionic size [5, 6]. This effect was not observed for analogous H[4]dota ligand. This
phenomenon is important for interpretation of reaction mechanism of copper(II) complex dissociation
and it can be explained by formation of weak complexes between the phosphonate group and the alkali
metal ions, analogously as described for lanthanide(III) complexes of DOTP [6].


[1] Lima, L. M. P.; Esteves, C. V.; Delgado, R.; Hermann, P.; Kotek, J.; Ševčíková, R.; Lubal, P.
Eur. J. Inorg. Chem. 2012, 2533 – 2547.

[2] Lima, L. M. P.; Delgado, R.; Hermann, P.; Ševčík, R.; Lubal, P.; Carvalho, H. F.; Martins, A.
F.; Tóth, É.; Geraldes, C. F. G. C. Eur. J. Inorg. Chem. 2012, 2548 – 2559.

[3] Ševčík, R.; Vaněk, J.; Lubal, P.; Kotková, Z.; Kotek, J.; Hermann, P. Polyhedron 2014, 67, 449
– 455.

[4] Shokeen, M.; Anderson, J. A. Acc. Chem. Res. 2009, 42, 832 – 841.

[5] Marcus, I. Chem. Rev. 1988, 88, 1475 – 1498.

[6] Ren, J.; Sherry, A. D. Inorg. Chim. Acta 1996, 246, 331 – 341.