Modelling Binuclear Metallobiosites: Insights from Pyrazole‐Supported Biomimetic and Bioinspired Complexes

Abstract

The development of a new route to α‐aminoboronates using an iridium‐catalyzed allylic amination on boronated substrates is described. Unlike the boronate group, the trifluoroborato substituent was found to govern the regioselectivity exclusively in favor of branched products. The transformation of an allylic substitution product into an α‐aminoboronic ester in an efficient way validated the implementation of this approach.

Improved Synthesis and Detailed Characterization of a Hybrid Pyrazole‐TACN Dinucleating Ligand

“…[23,24] Several complexes are known in which pyrazole-TACN hybrid scaffolds support two nickel, copper, or zinc ions with metal separations of 3.5-4.5 Å, leading to their investigation as models for dinuclear metallobiosites. [25][26][27][28][29][30][31][32] In addition to studies focusing on hydrolytic reactivity resembling that mediated by urease, [28,33] phosphoesterases, [26,34,35] and metallo-β-lactamases, [35] these complexes have also been applied in emulating functional and structural aspects of Type 3 (T3) dinuclear copper active sites, such as those found in hemocyanin, tyrosinase, and catechol oxidase. [25,36,37] Very recently, we have used pyrazole-TACN hybrid scaffolds to fully characterize and determine the crystal structures of two dinuclear copper(II)-peroxo complexes, which can be regarded as models for early stages of the O 2 binding to reduced T3 centers.…”

Metallo - Bioactive Compounds as Potential Novel Anticancer Therapy

“…The cytotoxic effect of standard drugs and metal complexes in the ranges of concentrations used against human HEPG-2 cell lineare shown in Figures 6-8. Moreover, Gaetke and Chow had reported that, metal has been suggested to facilitate oxidated tissue injury through a free-radical mediated pathway analogous to the Fenton reaction [66]. By applying the ESR-trapping technique, evidence for metal -mediated hydroxyl radical formation in vivo has been obtained [48].…”

“…Chemotherapeutic activity of the complexes may be attributed to the central metal atom which was explained by Tweedy's chelation theory [63,64]. Also, the positive charge of the metal increases the acidity of coordinated ligand that bears protons, leading to stronger hydrogen bonds he biological activity [65,66]. Moreover, Gaetke and Chow had reported that, metal has been suggested to facilitate oxidated tissue injury through a free-radical mediated pathway analogous to the Fenton reaction [66].…”

“…Also, the positive charge of the metal increases the acidity of coordinated ligand that bears protons, leading to stronger hydrogen bonds he biological activity [65,66]. Moreover, Gaetke and Chow had reported that, metal has been suggested to facilitate oxidated tissue injury through a free-radical mediated pathway analogous to the Fenton reaction [66]. By applying the ESR-trapping technique mediated hydroxyl radical formation in vivo has been obtained [48] type reaction as follows:…”

“…Also, the Cu(II) complex (2) shows the highest potency of inhibition at 500 µg/ml against HEPG-2 cell line, compared with the standard drug [51].Cytotoxicity results indicated that the tested complexes (2) and ( with IC 50 value of 0.95 µg/ml, followed by copper complex cytotoxicity of the copper complexes This can be explained as Cu(II) nature of the metal ion has effect on the biological behavior, due to alter binding ability of DNA binding, so testing of different complexes is very interesting from this point of view. Chemotherapeutic activity of the complexes was explained by Tweedy's chelation theory increases the acidity of coordinated ligand that bears protons, leading to stronger hydrogen bonds which enhance the biological activity [65,66]. metal has been suggested to facilitate oxidated tissue injury through a free pathway analogous to the Fenton reaction evidence for metal -mediated hydroxyl radical formation produced through a Fenton-type reaction as follows:…”