Copper(II) Cyclam Complexes with N‐­Propionic Acid Pendant Arms

Abstract

Four cyclam (1,4,8,11‐tetraazacyclotetradecane) ligands with different numbers of N‐substituted propionic acid groups lead to pentacoordinate copper(II) complexes that adopt trans‐I configurations (4+1 geometry), that is, the complexes have a d italicx 2–italicy 2 ground state with significant rhombic distortion. From the structural data (X‐ray diffraction analysis and electron paramagnetic resonance, UV/Vis and IR spectroscopy), as the number of secondary amine groups of the macrocyclic ring substituted with propionic acid groups increases, the distortion from square pyramidal to trigonal bipyramidal increases, and this is expected to lead to relatively low complex stabilities. This is confirmed by in vitro studies with superoxide dismutase (SOD) and human serum challenge experiments as well as by biodistribution data with the 64Cu‐labelled complexes. The 64Cu‐labelled complexes with cyclam monopropionic and dipropionic acid show high in vitro and in vivo stabilities, and the latter provides a comparable biodistribution profile to that of 64Cu–TETA (TETA = 1,4,8,11‐tetraazacyclotetradecane‐1,4,8,11‐tetraacetic acid).

Improved Conjugation, 64-Cu Radiolabeling, in Vivo Stability, and Imaging Using Nonprotected Bifunctional Macrocyclic Ligands: Bis(Phosphinate) Cyclam (BPC) Chelators

“…This modification leads to less stable complexes as it was shown by comparison of behavior of, e.g., copper(II) complexes with TETA and TE2A (Chart 1) derivatives 64−67 or with cyclam derivatives with an increasing number of Npropionate pendant arms. 68 Therefore, the expected problem . The results denoted with asterisks were adopted from our previous study.…”

“…Beside utilization of fully protected ring amines, the macrocycle secondary amines can be converted to tertiary ones by an alkylation. This modification leads to less stable complexes as it was shown by comparison of behavior of, e.g., copper­(II) complexes with TETA and TE2A (Chart ) derivatives − or with cyclam derivatives with an increasing number of N -propionate pendant arms . Therefore, the expected problem with secondary ring amine groups should be solved in a different way.…”

New copper(II) cyclam complexes with aminocarboxylate co-ligands: Synthesis, characterization, and in vitro antiproliferative and antibacterial studies

“…Different ways of coordination of macrocycle and its derivatives for different metal cations allows their application as antitumor, antiviral, antibacterial, antifungal or antimalarial agents. [8][9][10][11][12] The goal of the article was to define structure of the mixed Cu(II) complexes with cyclam and amino acids, glycine and alanine, as additional ligand, to screen the in vitro cytotoxicity of the compounds compared to the effect of commonly used drug, cis-platin against human tumor cell lines. Aqueous solution Cu(ClO4)2•6H2O (111 mg, 0.30 mmol in 5 mL H2O) was added in suspension of cyclam (61 mg, 0.30 mmol) in acetonitrile (10 mL).…”