Unveiling the reaction mechanism of novel copperN-alkylated tetra-azacyclophanes with outstanding superoxide dismutase activity

Abstract

<p>One of the first theoretical studies of the reaction mechanism of a small superoxide dismutase mimetic reveals the key role played by the metal bound water molecule and the molecular organisation.</p>

Inertness of Superoxide Dismutase Mimics Mn(II) Complexes Based on an Open-Chain Ligand, Bioactivity, and Detection in Intestinal Epithelial Cells

“…The substitution on the secondary amine by a propyl group resulted also in a slight decrease of the association constant with Mn 2+ . A similar effect of N-alkylations on association constants was described by Martínez-Camarena et al [66]: the presence of isopropyl substituents on the secondary amines of a tetra-azacyclophanes ligand was shown to produce a decrease in the stability of the corresponding copper complex. Riley et al reported elsewhere that methyl substituents on cyclic polyamine ligands were not affecting clearly the association constant with Mn 2+ [67], and previous functionalization with peptides showed the same weak effect of tertiarization of the secondary amine in EnPI2 [43].…”

“…This is consistent with results recently published by the group of E. Garcia-Espana. The authors reported an increase in SOD activity upon N-alkylation of tetra-azacyclophanes copper complexes [66]. They ran quantum mechanics/ molecular mechanic molecular dynamic simulations to rationalize this effect.…”

SOD mimics: From the tool box of the chemists to cellular studies

“…Bulky substituents can also favor catalysis by modulating the stability of intermediates of the catalytic cycle (MÀOO). Indeed, isopropyl moieties (Cp9) were shown to preclude hydrogen bonds that stabilize a Cu-peroxo intermediate (with Cp10) [28]. This was in favor of catalysis, as a too stable intermediate would disfavor the release of the product (H 2 O 2 ).…”

Adaptive coordination assemblies based on a flexible tetraazacyclododecane ligand for promoting carbon dioxide fixation

“…1,4,7,10-Tetraazaz-cyclododecane and its derivatives are well-studied macrocyclic ligands to form stable complexes with various metal ions. [103][104][105][106] However, its utilization in coordination-directed self-assembly has been hampered due to its structural flexibility. 21,23 Herein, we report the synthesis of a series of coordination tubes or cages from a 1,4,7,10tetraazaz-cyclododecane-N,N',N'',N'''-tetra-p-methylpyridine ligand (L) and cis-blocking Me 4 enPd units (Scheme 1).…”