Stabilization of Cu(i) for binding and calorimetric measurements in aqueous solution

Abstract

Conditions have been developed for the comproportionation reaction of Cu2+ and copper metal to prepare aqueous solutions of Cu+ that are stabilized from disproportionation by MeCN and other Cu+-stabilizing ligands. These solutions were then used in ITC measurements to quantify the thermodynamics of formation of a set of Cu+ complexes (CuI(MeCN)3+, CuIMe6Trien+, CuI(BCA)23−, CuI(BCS)23−), which have stabilities ranging over 15 orders of magnitude, for their use in binding and calorimetric measurements of Cu+ interaction with proteins and other biological macromolecules. These complexes were then used to determine the stability and thermodynamics of formation of a 1 : 1 complex of Cu+ with the biologically important tri-peptide glutathione, GSH. These results identify Me6Trien as an attractive Cu+-stabilizing ligand for calorimetric experiments, and suggest that caution should be used with MeCN to stabilize Cu+ due to its potential for participating in unquantifiable ternary interactions.

Dissecting ITC data of metal ions binding to ligands and proteins

“…Notably, many common experimental buffers and ligands (e.g. Tris and NTA) have been shown to form ternary complexes with a variety of metal ions [46,61,63]. These complexes are particularly worrisome and challenging to account for in situations when the ligand of interest (i.e.…”

“…As such, caution is strongly urged with using reducing agents to prevent metal oxidation. Using thoroughly deoxygenated solutions and placing an ITC in an anaerobic chamber has been effectively used in many labs as a way to prevent these undesirable reactions [41,[44][45][46].…”

Synthesis of Various Water Soluble and Stable Copper Complexes Bearing N‐Heterocyclic Carbene Ligands and Their Activity in DNA Alkylation

“…The crude complex was dissolved in CH 2 Cl 2 and triturated with pentane (16 mg, 70 %). 1 (6). Compound 6 was synthesized according to a published procedure to obtain a brown solid (30 mg, 19 %).…”

“…The obtained precipitate was filtered and washed with pentane to yield 7 as white solid (1.17 g, 64 %). 1…”

“…Copper catalysis is used extensively in chemical biology despite the fact that copper(I) is prone to disproportionation under aqueous conditions [1] and has a proclivity for oxygen activation. [2,3] In organic synthesis, N-heterocyclic carbenes (NHCs) have proven extremely effective in steering reactivity and selectivity in copper-catalyzed reactions, [4,5] while having the additional advantage of reducing the propensity of copper(I) to activate molecular oxygen.…”