trans-Methylpyridine cyclen versus cross-bridged trans-methylpyridine cyclen. Synthesis, acid–base and metal complexation studies (metal = Co2+, Cu2+, and Zn2+)

Abstract

The synthesis of the cross-bridged cyclen CRpy(2) {4,10-bis((pyridin-2-yl)methyl)-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane}, a constrained analogue of the previously described trans-methylpyridine cyclen Cpy(2) is reported. The additional ethylene bridge confers to CRpy(2) proton-sponge type behaviour which was explored by NMR and potentiometric studies. Transition metal complexes have been synthesized (by complexation of both ligands with Co(2+), Cu(2+) and Zn(2+)) and characterized in solution and in the solid state. The single crystal X-ray structures of [CoCpy(2)](2+), [CuCpy(2)](2+) and [ZnCpy(2)](2+) complexes were determined. Stability constants of the complexes, including those of the cross-bridged derivative, were determined using potentiometric titration data and the kinetic inertness of the [CuCRpy(2)](2+) complex in an acidic medium (half-life values) was evaluated by spectrophotometry. The pre-organized structure of the cross-bridged ligand imposes an additional strain for the complexation leading to complexes with smaller thermodynamic stability in comparison with the related non-bridged ligand. The electrochemical study involving cyclic voltammetry underlines the importance of the ethylene cross-bridge on the redox properties of the transition metal complexes.

Synthesis and structural studies of two pyridine-armed reinforced cyclen chelators and their transition metal complexes

“…This behavior has been observed for other cross-bridged cyclen ligand analogues with cobalt. [30] [37]…”

“…Structural comparisons with CB-Py 2 Cyclen [30] and PyCyclen [21] [22] (see Figure 1) are also desirable. Unfortunately, although Co 3+ , Cu 2+ , and Zn 2+ complexes with CB-Py 2 Cyclen, the most direct analogue including an ethylene cross-bridge, have been synthesized and characterized, no X-ray crystal structures have been published.…”

“…Ligands discussed within this work; SB-PyCyclam [10] PyMeEBC [12] Me 2 BCyclen, [31] PyCyclen [21] [22] CB-Py 2 Cyclen [30]; alongside SB-PyCyclen and CB-MePyCyclen first described in this study.…”

“…[25] [26] [27] [28] [29] Transition metal complexes of macrocycles of this type are known to be stable to a range of pH’s and temperatures. A cross-bridged cyclen ligand with two pyridyl pendant arms (CB-Py 2 Cyclen, Figure 1) has been reported [30], but its hexadentate nature coordinatively saturates its complexed metal ions, while we wished to leave at least one coordination site available for interaction with oxidant and/or substrate. Our first communications regarding complexes incorporating a single pyridyl labile coordinating group have described reinforced cyclam derivatives with modified steric and electronic properties to cause improved properties as oxidation catalysts, [10] [12] see Figure 1.…”

Intracellular Transport Studies of Picolinate Macrocyclic Copper and Lanthanide Complexes

“…In order to develop copper‐based imaging and therapeutic agents, the cupric cation must be stabilized into a suitable chelating structure, which should be thermodynamically stable and kinetically inert in the biological media to prevent transmetalation. Ideally, the complexation of the ligand should occur in mild conditions, and its kinetics should be fast enough to preserve the activity of the radioisotope …”