Homo- and Heteronuclear Group 12 Metallothionein Type B Cluster Analogs: Synthesis, Structure, ¹H NMR and ESI-MS

Abstract

Metallothioneins (MTs) are a ubiquitous class of small cysteine-rich metal-binding proteins involved in metal homeostasis and detoxification with highly versatile metal binding properties. Despite the long-standing association of MT with M 3 S 3 and M 4 S 5 metal clusters, synthetic complexes with these core architectures are exceptionally rare. Here, we demonstrate an approach to synthesizing and characterizing aggregates of group 12 metal ions with monocyclic M 3 S 3 cores in acetonitrile solution without the protection of a protein. Multidentate monothiol ligand N,N-bis(2-pyridylmethyl)-2-aminoethanethiol (L1H) provided [Cd 3 (L1) 3 ](ClO 4 ) 3 (1), the first structurally characterized nonproteinaceous aggregate with a metallothionein-like monocyclic Cd 3 S 3 core. In addition, [Zn 3 (L1) 3 ](ClO 4 ) 3 •4CH 3 CN (2•4CH 3 CN) was characterized by X-ray crystallography. The complex cations of 1 and 2 had comparable structures despite being nonisomorphic. Variable temperature and concentration 1 H NMR were used to investigate aggregation equilibria of 1, 2, and a precipitate with composition "Hg(L1)(ClO 4 )" (3). Cryogenic 1 H NMR studies of 3 revealed a J( 199 Hg 1 H) coupling constant pattern consistent with an aggregate possessing a cyclic core. ESI-MS was used for gas-phase characterization of 1−3, as well as mixed-metal [M 2 M′(L1) 3 (ClO 4 ) 2 ] + ions prepared in situ by pairwise acetonitrile solution combinations of the group 12 complexes of L1. Access to synthetic variants of metallothionein-like group 12 aggregates provides an additional approach to understanding their behavior.

Aggregation behavior of group 12 complexes of a tripodal mixed NS(thiolato) donor ligand

“…Finally, the metallothionein-like trinuclear complexes [CdL] 3 (ClO 4 ) 3 and [ZnL] 3 (ClO 4 ) 3 Á4 CH 3 CN were recently reported, the first structurally characterized aggregates of group 12 metal ions with monocyclic M 3 S 3 cores in the absence of a protein. 9 These complexes had predominantly trigonal bipyramidal metal coordination geometry (t 4 0.85). 53 The rich variety of ligand coordination modes and aggregation states potentially available to complexes of L À emphasizes the importance of complementing crystallographic characterization of low solubility compounds with additional studies to help clarify speciation when potentially pertinent.…”

“…Correlations between solid-state structures and solution-state spectroscopy are rarely definitive for group 12 metal ion complexes due to intramolecular reorganization, intermolecular exchange and variable oligomerization. 9,57,58 However, spectral changes with temperature and concentration were informative.…”

“…Despite the concurrence of histidine and cysteine in the active sites of proteins associated with stable group 12 metal ions, coordination studies of these metal ions with chelating ligands containing a combination of aromatic amine and alkylthiolate (N A x S y − ) donors have been rare. A search of the Cambridge Crystallographic Database 7 reveals two Cd 2+ complexes 8,9 and one Hg 2+ complex 10 incorporating chelating N A x S y − ligands. Interestingly, a study inspired by the metal-promiscuity of metallothionein used a N A x S y − ligand to provide the first crystallographically characterized complexes containing both Zn 2+ and Hg 2+ bound to the same ligand.…”

“…x S y À ) donors have been rare. A search of the Cambridge Crystallographic Database 7 reveals two Cd 2+ complexes 8,9 and one Hg 2+ complex 10…”

Crystal structure and Hirshfeld surface analysis of cyclo-tetrabromido-1κ2 Br,3κ2 Br-tetrakis(μ2-2-{[(pyridin-2-yl)methyl]amino}ethane-1-thiolato-κ3 N,S:S)tetramercury(II)

“…For many years, we and others have been interested in the structures of group 12 coordination compounds including an aminoethanethiolate moiety (Hu et al, 2020;Hallinger et al, 2017;Akhtar et al, 2015;Bharara et al, 2006a,b;Fleischer et al, 2006;Viehweg et al, 2010;Brand & Vahrenkamp, 1995;Avdeef et al, 1992;Tuntulani et al, 1992;Kaptein et al, 1987). Single-crystal X-ray diffraction is critical to the characterization of group 12 aminoethanethiolate complexes since the nuclearity of complexes with 1:1 metal-to-ligand ratio can vary with the identity of ancillary ligands and counter-ions (Brennan et al, 2022;Lai et al, 2013;Brand & Vahrenkamp, 1995) and complexes with novel ring structures have been produced (Ritz et al, 2019;Viehweg et al, 2010).…”