ic401206u_si_001.pdf (1.04 MB)
X‑ray Absorption Spectroscopy Proves the Trigonal-Planar Sulfur-Only Coordination of Copper(I) with High-Affinity Tripodal Pseudopeptides
journal contribution
posted on 2013-09-03, 00:00 authored by Anne-Solène Jullien, Christelle Gateau, Isabelle Kieffer, Denis Testemale, Pascale DelangleA series
of tripodal ligands L derived from nitrilotriacetic acid
(NTA) and extended by three converging metal-binding cysteine chains
were previously found to bind selectively copper(I) both in vitro
and in vivo. The ligands L1 (ester)
and L2 (amide) were demonstrated
to form copper(I) species with very high affinities, close to that
reported for the metal-sequestering metallothioneins (MTs; log KCu‑MT ≈ 19). Here, an in-depth
study by Cu K-edge X-ray absorption spectroscopy (XAS) was performed
to completely characterize the copper(I) coordination sphere in the
complexes, previously evidenced by other physicochemical analyses.
The X-ray absorption near-edge structure (XANES) spectra shed light
on the equilibrium between a mononuclear complex and a cluster for
both L1 (ester) and L2 (amide). The exclusive symmetric CuS3 geometry adopted in the mononuclear complexes (Cu–S
≈ 2.23 Å) was clearly demonstrated by extended X-ray absorption
fine structure (EXAFS) analyses. The EXAFS analyses also proved that
the clusters are organized on a symmetric CuS3 core (Cu–S
≈ 2.26 Å) and interact with three nearby copper atoms
(Cu---Cu ≈ 2.7 Å), consistent with the Cu6S9-type clusters previously characterized by pulsed gradient
spin echo NMR spectroscopy. XAS data obtained for other architectures
based on the NTA template (L3 acid, L4 without a functionalized
carbonyl group, etc.) demonstrated the formation of polymetallic species
only, which evidence the necessity of the proximal ester or amide
group to stabilize the CuS3 mononuclear species. Finally,
XAS was demonstrated to be a powerful method to quantify the equilibrium
between the two copper(I) environments evidenced with L1 and L2 at different copper concentrations and to determine the equilibrium
constants between these two complexes.