The First Cu(I)‐Peptoid Complex: Enabling Metal Ion Stability and Selectivity via Backbone Helicity

Abstract

Stabilization of Cu(I) is ubiquitous within native copper proteins. Understanding how to stabilize Cu(I) within synthetic biomimetic systems is therefore desired towards biological applications. Peptoids are an important class of peptodomimetics, that can bind metal ions and stabilize them in their high oxidation state. Thus, to date, they were not used for Cu(I) binding. Here we show how the helical peptoid hexamer, having two 2,2'-bipyridine (Bipy) groups that face the same side of the helix, forms the intramolecular air stable Cu(I) complex. Further study of the binding site by rigorous spectroscopic techniques suggests that Cu(I) is tetracoordinated, binding to only three N atoms from the Bipy ligands and to the N-terminus of the peptoid's backbone. A set of control peptoids and experiments indicates that the Cu(I) stability and selectivity are dictated by the intramolecular binding, forced by the helicity of the peptoid, which can be defined as the second coordination sphere of the metal center.

A Peptoid-Chelator Selective to Cu2+ That Can Extract Copper from Metallothionein-2 and Lead to the Production of ROS

“…at 330 nm was plotted against the mole fraction (Figure 2A, inset), and from the intersection point at χ = 0.522, a stoichiometry ratio was determined to be 1.09 [66], supporting the metal-to-peptoid ratio obtained from the UV/Vis titrations. In addition to UV/Vis experiments, the stoichiometric ratio was confirmed by HR-MS techniques: 1 equiv.…”

“…The total molar concentration of a mixture solution containing both Cu 2+ and TB was kept constant at 35 µM, while their mole fractions (χ) were varied, and the UV/Vis spectra of these mixtures were recorded. The absorbance proportional to CuTB complex formation at 330 nm was plotted against the mole fraction (Figure 2A, inset), and from the intersection point at χ = 0.522, a stoichiometry ratio was determined to be 1.09 [66], supporting the metal-to-peptoid ratio obtained from the UV/Vis titrations.…”

“…Bipy and Terpy ligands were chosen because they are bi-and tridentate ligands that can flip between the cis and trans conformations of N-atoms at different pH conditions, as a result of steric disturbance or upon binding to metal ions [65]. In addition, we have recently shown that Bipy ligands within the peptoid-based helical chelator can dissociate into a hypodentatic mode when binding Cu(I) if a more appropriate coordination environment is provided [66]. Therefore, we anticipate, that the relative flexibility of the Bipy-Terpy coordination environment about the metal center will lead to the binding of Cu in an adjustable coordination geometry that will enable high affinity and selectivity, while allowing the redox activity of the Cu-center to catalyze ROS production.…”

Low Potential CO2 Reduction by Inert Fe(II)‐Macrobicyclic Complex: A New Concept of Cavity Assisted CO2 Activation

“…This result reveals that the helicity of the complex along with electron withdrawing effect of O-atom, satisfies our expectation by shifting the redox potential of the metal center toward positive. [9] After having these low potential values of our complex, we have been eventually interested to check whether the complex may reduce CO 2 with the assistance of the 𝜋-cavities. To find out this, we have looked into the electrochemical behavior of the complex toward CO 2 reduction, electrochemical CO 2 RR represents a gradual increment of current in the peak at −1.3 V upon continued purging of CO 2 in [BMC-Fe(II)] solution (Figure 5).…”

“…This result reveals that the helicity of the complex along with electron withdrawing effect of O‐atom, satisfies our expectation by shifting the redox potential of the metal center toward positive. [ 9 ]…”