Evolution of Zn^II–Macrocyclic Polyamines to Biological Probes and Supramolecular Assembly

Catalytic Hydrolysis of Phosphate Monoester by Supramolecular Phosphatases Formed from a Monoalkylated Dizinc(II) Complex, Cyclic Diimide Units, and Copper(II) in Two-Phase Solvent System

“…Supramolecular strategies are useful for the construction of three-dimensional and well-defined structures that can be useful in molecular recognition, molecular sensing, molecular storage, electronic devices, and catalytic reactions. − In this context, we previously reported on the formation of a supramolecular complex 8 by the 2:2:2 assembly of dimeric zinc­(II) (Zn 2+ -cyclen) complexes containing a 2,2′-bipyridyl (bpy) linker 1 (Zn 2 L 1 ), a dianion of barbital (Bar 2– ) and its analogues ( 4 ), and a copper ion (Cu 2+ ) via 2:2 complexes of 1 with 4 (cyclen = 1,4,7,10-tetraazacyclododecane). , It was discovered that 8 possesses a Cu 2 (μ-OH) 2 core that is analogous to the active sites (Fe–Zn or Zn–Zn) of naturally occurring dinuclear metalloenzymes such as AP. In addition, these supramolecular complexes were found to accelerate the hydrolysis of MNP at a neutral pH in single-phase aqueous solution and in a two-phase solvent system (CHCl 3 /50 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES)).…”

Design, Synthesis, and Biological Applications of Boron-Containing Polyamine and Sugar Derivatives

“…It is well established that macrocyclic polyamine ligands such as 1,4,7-triazacyclononane ( [9]aneN 3 ) 1, 1,4,7,10-tetraazacyclododecane ( [12]aneN 4 , cyclen) 2, and 1,4,7,10,13-pentaazacyclopentadecane ([15]aneN 5 ) 3 are able to form more stable complexes 4-6 with metal ions such as Cu 2+ , Ni 2+ , and Zn 2+ in aqueous solution (Figure 1) than metal complexes of linear polyamine types [16,17]. In addition, metal ions in these complexes, especially the Zn 2+ ion in Zn 2+ -cyclen complex (5), possess strong Lewis acidity and the deprotonated Zn 2+ -bound H 2 O (HO − ) functions as a nucleophile and a base in aqueous solution at neutral pH [18][19][20][21][22][23].…”

“…It was assumed that these boron-containing macrocyclic polyamine monomers 44-49 (L 6 -L 12 ) and their Zn 2+ complexes 50-52 (ZnL 6 -ZnL 12 ) would be efficiently transferred into cancer cells and that thermal neutron irradiation would induce effective DNA damage in cancer cells due the 10 B atoms being located in close proximity to DNA molecules (Figure 17). We also expected that the interaction of homoand heterodimer of macrocyclic polyamines 53-62 (L 13 -L 22 ) and their corresponding monozinc(II) complexes 63-68 (ZnL 13 -ZnL 21 ) and dizinc(II) complexes 69-78 (Zn 2 L 13 -Zn 2 L 22 ) with DNA would be stronger than that of monomeric polyamines, resulting in efficient DNA damage upon thermal neutron irradiation (Figure 18). These mono-and dimeric macrocyclic polyamines were first prepared with boron in a natural abundance ratio ( 10 B/ 11 B = 19.9/80.1) to evaluate their cytotoxicity and intracellular uptake in several cancer cell lines, and some of the promising compounds were synthesized in the corresponding 10 B-enriched forms for the BNCT experiments.…”

Design, Synthesis, and Biological Evaluation of Boron-Containing Macrocyclic Polyamines and Their Zinc(II) Complexes for Boron Neutron Capture Therapy

“…It is also well known that macrocyclic polyamines form stable complexes with intracellular metal ions such as Zn 2+ , Cu 2+ , and Ni 2+ in aqueous solutions at physiological pH (Scheme ), − and these complexes are much more stable than Zn 2+ complexes of linear polyamines such as spermidine 3 and spermine 4 . In addition, it was reported that the cytotoxicity of macrocyclic polyamines is reduced by the complexation with Zn 2+ .…”