Trinuclear Copper(II) Complex Showing High Selectivity for the Hydrolysis of 2‘−5‘ over 3‘−5‘ for UpU and 3‘−5‘ over 2‘−5‘ for ApA Ribonucleotides

Abstract

The cooperative action of multiple Cu(II) nuclear centers is shown to be effective and selective in the hydrolysis of 2'-5' and 3'-5' ribonucleotides. Reported herein is the specific catalysis by two trinuclear Cu(II) complexes of L3A and L3B. Pseudo first-order kinetic studies reveal that the L3A trinuclear Cu(II) complex effects hydrolysis of Up(2'-5')U with a rate constant of 28 x 10(-)(4) min(-)(1) and Up(3'-5')U with a rate constant of 0.5 x 10(-)(4) min(-)(1). The hydrolyses of Ap(3'-5')A and Ap(2'-5')A proceed with rate constants of 24 x 10(-)(4) min(-)(1) and 0.5 x 10(-)(4) min(-)(1) respectively. The L3A trinuclear Cu(II) complex demonstrates high specificity for Up(2'-5')U and Ap(3'-5')A. Similar studies with the more rigid L3B trinuclear Cu(II) complex shows no selectivity and yields lower rate constants for hydrolysis. The selectivity observed with the L3A ligand is attributed to the geometry of the ligand-bound diribonucleotide which ultimately dictates the proximity of the attacking hydroxyl and the phosphoester to a Cu(II) center for activation and subsequent hydrolysis.

Large pKa Shifts of α‐Carbon Acids Induced by Copper(II) Complexes

“…[12,13] This kind of Cu II complexes is known to form chelates with oxygen-containing ligands such as (benzyloxy)acetaldehyde. [13] Therefore, an enolate will be bound in the equatorial position on the metal and hence lie parallel to the host aromatic rings (Scheme 3).…”

Zinc(II) tweezers containing artificial peptides mimicking the active site of phosphotriesterase: The catalyzed hydrolysis of the toxic organophosphate parathion

“…Recently, in order to increase the reactivity of artificial hydrolytic catalysts, several hydrolytic metalloenzyme models containing diand trinuclear zinc(II) complexes have been designed and studied to account for or mimic the function played by the cooperativity of two or three zinc(II) ions, as occurs in several phosphatases and nucleases [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. In these systems, we found that the multinuclear complexes were generally more active than their corresponding mononuclear ones.…”

Dinuclear macrocyclic polyamine zinc(II) complexes: Syntheses, characterization and their interaction with plasmid DNA

“…Most of enzymes that participate in the biochemistry of nucleic acids require divalent metal ion cofactors to promote its activity for the cleavage of phosphodiester bond of DNA [10][11][12][13][14]. Multinuclear metal complexes such as di-or oligonuclear Fe [15], Co [16,17], Cu [18][19][20][21], Zn [22][23][24][25] or heterometal [26,27] complexes have ever been known as hydrolyzing reagents for phosphodiester backbone of DNA in past few years [28][29][30][31][32][33][34][35][36]. Recently the studies have proved that macrocyclic polyamine metal complexes as chemical nucleases are the efficient cleavage agents of DNA [37][38][39][40][41][42].…”