Heat shock proteins and metal ions – Reaction or interaction?

Heat shock proteins (HSPs) are part of the cell’s molecular chaperone system responsible for the proper folding (or refolding) of proteins. They are expressed in cells of a wide variety of organisms, from bacteria and fungi to humans. While some HSPs require metal ions for proper functioning, others are expressed as a response of the organism to either essential or toxic metal ions. Their presence can influence the occurrence of cellular processes, even those as significant as programmed cell death. The development of research methods and structural modeling has enabled increasingly accurate recognition of new HSP functions, including their role in maintaining metal ion homeostasis. Current investigations on the expression of HSPs in response to heavy metal ions include not only the direct effect of these ions on the cell but also analysis of reactive oxygen species (ROS) and the increased production of HSPs with increasing ROS concentration. This minireview contains information about the direct and indirect interactions of heat shock proteins with metal ions, both those of biological importance and heavy metals

General Aspects of Metal Ions as Signaling Agents in Health and Disease

This review focuses on the current knowledge on the involvement of metal ions in signaling processes within the cell, in both physiological and pathological conditions. The first section is devoted to the recent discoveries on magnesium and calcium-dependent signal transduction—the most recognized signaling agents among metals. The following sections then describe signaling pathways where zinc, copper, and iron play a key role. There are many systems in which changes in intra- and extra-cellular zinc and copper concentrations have been linked to important downstream events, especially in nervous signal transduction. Iron signaling is mostly related with its homeostasis. However, it is also involved in a recently discovered type of programmed cell death, ferroptosis. The important differences in metal ion signaling, and its disease-leading alterations, are also discussed

A Comparative Study on Nickel Binding to Hpn-like Polypeptides from Two Helicobacter pylori Strains

Combined potentiometric titration and isothermal titration calorimetry (ITC) methods were used to study the interactions of nickel(II) ions with the N-terminal fragments and histidine-rich fragments of Hpn-like protein from two Helicobacter pylori strains (11637 and 26695). The ITC measurements were performed at various temperatures and buffers in order to extract proton-independent reaction enthalpies of nickel binding to each of the studied protein fragments. We bring up the problem of ITC results of nickel binding to the Hpn-like protein being not always compatible with those from potentiometry and MS regarding the stoichiometry and affinity. The roles of the ATCUN motif and multiple His and Gln residues in Ni(II) binding are discussed. The results provided the possibility to compare the Ni(II) binding properties between N-terminal and histidine-rich part of Hpn-like protein and between N-terminal parts of two Hpn-like strains, which differ mainly in the number of glutamine residues

Coordination Diversity in Mono- and Oligonuclear Copper(II) Complexes of Pyridine-2-Hydroxamic and Pyridine-2,6-Dihydroxamic Acids

Solution and solid state studies on Cu­(II) complexes of pyridine-2-hydroxamic acid (<b>HPicHA</b>) and pyridine-2,6-dihydroxamic acid (<b>H</b>_<b>2</b><b>PyDHA</b>) were carried out. The use of methanol/water solvent allowed us to investigate the Cu­(II)–<b>HPicHA</b> equilibria under homogeneous conditions between pH 1 and 11. In agreement with ESI-MS indication, the potentiometric data fitted very well with the model usually reported for copper­(II) complexes of α-aminohydroxamate complexes ([CuL]⁺, [Cu₅(LH_–1)₄]²⁺, [CuL₂], [CuL₂H_–1]⁻), however with much higher stability of the 12-MC-4 species. A series of copper­(II) complexes has been isolated in the solid state and characterized by a variety of spectroscopic methods, X-ray structure analysis, and magnetic susceptibility measurements. The ligands show the tendency to form bi- and trinuclear species with copper­(II) ions due to the {(N,N′); (O,O′)} bis-(bidentate) chelating-and-bridging mode involving (O,O′)-hydroxamate chelate formation combined with (N,N′) chelating with participation of the pyridine and hydroxamic nitrogen atoms, so that the hydroxamate groups play a μ₂-(N,O)-bridging role. Molecular and crystal structures of three synthesized complexes [Cu₃(<b>PicHA</b>-H)₂(dipy)₂]­(ClO₄)₂·4/3DMSO·2/3H₂O (<b>1</b>), [Cu₂(<b>PyDHA</b>)­(dipy)₂(ClO₄)₂]·DMF·H₂O (<b>4</b>), and [Cu₃(<b>PyDHA</b>-2H)­(tmeda)₃]­(ClO₄)₂ (<b>5</b>) (dipy, 2,2′-dipyridyl; tmeda, N,N,N′,N′-tetramethyl-1,2-diaminoethane) have been determined by single crystal X-ray analysis. In <b>1</b>, two trans-situated doubly deprotonated hydroxamic ligands play a {(O,O′)­(N,N′)}–(bis)­bidentate-bridging function forming bridges between the medial, Cu(2) (CuN₄), and the terminal, Cu(1) and Cu(3) (CuN₂O₂), copper­(II) ions; the chelating dipy ligands are coordinated to the latter. In <b>4</b>, the ligand is coordinated in a classical (O,O′)-hydroxamate chelating mode with the help of two separate hydroxamic groups while the central tridentate donor compartment remains vacant. In <b>5</b>, the hydroxamate ligand is coordinated by the {(O,O′);(N,N′,N″);(O″,O‴)}-tridentate-(bis)­bidentate mode, bridging three copper­(II) ions, while the chelating tmeda ligands are coordinated to all three copper­(II) ions. Magnetic susceptibility measurements (1.7–300 K) of powdered samples of the trinuclear complexes <b>1</b> and <b>5</b> revealed strong antiferromagnetic coupling between the copper­(II) ions mediated by the hydroxamate bridges

Coordination Diversity in Mono- and Oligonuclear Copper(II) Complexes of Pyridine-2-Hydroxamic and Pyridine-2,6-Dihydroxamic Acids

Solution and solid state studies on Cu­(II) complexes of pyridine-2-hydroxamic acid (<b>HPicHA</b>) and pyridine-2,6-dihydroxamic acid (<b>H</b>_<b>2</b><b>PyDHA</b>) were carried out. The use of methanol/water solvent allowed us to investigate the Cu­(II)–<b>HPicHA</b> equilibria under homogeneous conditions between pH 1 and 11. In agreement with ESI-MS indication, the potentiometric data fitted very well with the model usually reported for copper­(II) complexes of α-aminohydroxamate complexes ([CuL]⁺, [Cu₅(LH_–1)₄]²⁺, [CuL₂], [CuL₂H_–1]⁻), however with much higher stability of the 12-MC-4 species. A series of copper­(II) complexes has been isolated in the solid state and characterized by a variety of spectroscopic methods, X-ray structure analysis, and magnetic susceptibility measurements. The ligands show the tendency to form bi- and trinuclear species with copper­(II) ions due to the {(N,N′); (O,O′)} bis-(bidentate) chelating-and-bridging mode involving (O,O′)-hydroxamate chelate formation combined with (N,N′) chelating with participation of the pyridine and hydroxamic nitrogen atoms, so that the hydroxamate groups play a μ₂-(N,O)-bridging role. Molecular and crystal structures of three synthesized complexes [Cu₃(<b>PicHA</b>-H)₂(dipy)₂]­(ClO₄)₂·4/3DMSO·2/3H₂O (<b>1</b>), [Cu₂(<b>PyDHA</b>)­(dipy)₂(ClO₄)₂]·DMF·H₂O (<b>4</b>), and [Cu₃(<b>PyDHA</b>-2H)­(tmeda)₃]­(ClO₄)₂ (<b>5</b>) (dipy, 2,2′-dipyridyl; tmeda, N,N,N′,N′-tetramethyl-1,2-diaminoethane) have been determined by single crystal X-ray analysis. In <b>1</b>, two trans-situated doubly deprotonated hydroxamic ligands play a {(O,O′)­(N,N′)}–(bis)­bidentate-bridging function forming bridges between the medial, Cu(2) (CuN₄), and the terminal, Cu(1) and Cu(3) (CuN₂O₂), copper­(II) ions; the chelating dipy ligands are coordinated to the latter. In <b>4</b>, the ligand is coordinated in a classical (O,O′)-hydroxamate chelating mode with the help of two separate hydroxamic groups while the central tridentate donor compartment remains vacant. In <b>5</b>, the hydroxamate ligand is coordinated by the {(O,O′);(N,N′,N″);(O″,O‴)}-tridentate-(bis)­bidentate mode, bridging three copper­(II) ions, while the chelating tmeda ligands are coordinated to all three copper­(II) ions. Magnetic susceptibility measurements (1.7–300 K) of powdered samples of the trinuclear complexes <b>1</b> and <b>5</b> revealed strong antiferromagnetic coupling between the copper­(II) ions mediated by the hydroxamate bridges

Coordination Diversity in Mono- and Oligonuclear Copper(II) Complexes of Pyridine-2-Hydroxamic and Pyridine-2,6-Dihydroxamic Acids

Solution and solid state studies on Cu­(II) complexes of pyridine-2-hydroxamic acid (<b>HPicHA</b>) and pyridine-2,6-dihydroxamic acid (<b>H</b>_<b>2</b><b>PyDHA</b>) were carried out. The use of methanol/water solvent allowed us to investigate the Cu­(II)–<b>HPicHA</b> equilibria under homogeneous conditions between pH 1 and 11. In agreement with ESI-MS indication, the potentiometric data fitted very well with the model usually reported for copper­(II) complexes of α-aminohydroxamate complexes ([CuL]⁺, [Cu₅(LH_–1)₄]²⁺, [CuL₂], [CuL₂H_–1]⁻), however with much higher stability of the 12-MC-4 species. A series of copper­(II) complexes has been isolated in the solid state and characterized by a variety of spectroscopic methods, X-ray structure analysis, and magnetic susceptibility measurements. The ligands show the tendency to form bi- and trinuclear species with copper­(II) ions due to the {(N,N′); (O,O′)} bis-(bidentate) chelating-and-bridging mode involving (O,O′)-hydroxamate chelate formation combined with (N,N′) chelating with participation of the pyridine and hydroxamic nitrogen atoms, so that the hydroxamate groups play a μ₂-(N,O)-bridging role. Molecular and crystal structures of three synthesized complexes [Cu₃(<b>PicHA</b>-H)₂(dipy)₂]­(ClO₄)₂·4/3DMSO·2/3H₂O (<b>1</b>), [Cu₂(<b>PyDHA</b>)­(dipy)₂(ClO₄)₂]·DMF·H₂O (<b>4</b>), and [Cu₃(<b>PyDHA</b>-2H)­(tmeda)₃]­(ClO₄)₂ (<b>5</b>) (dipy, 2,2′-dipyridyl; tmeda, N,N,N′,N′-tetramethyl-1,2-diaminoethane) have been determined by single crystal X-ray analysis. In <b>1</b>, two trans-situated doubly deprotonated hydroxamic ligands play a {(O,O′)­(N,N′)}–(bis)­bidentate-bridging function forming bridges between the medial, Cu(2) (CuN₄), and the terminal, Cu(1) and Cu(3) (CuN₂O₂), copper­(II) ions; the chelating dipy ligands are coordinated to the latter. In <b>4</b>, the ligand is coordinated in a classical (O,O′)-hydroxamate chelating mode with the help of two separate hydroxamic groups while the central tridentate donor compartment remains vacant. In <b>5</b>, the hydroxamate ligand is coordinated by the {(O,O′);(N,N′,N″);(O″,O‴)}-tridentate-(bis)­bidentate mode, bridging three copper­(II) ions, while the chelating tmeda ligands are coordinated to all three copper­(II) ions. Magnetic susceptibility measurements (1.7–300 K) of powdered samples of the trinuclear complexes <b>1</b> and <b>5</b> revealed strong antiferromagnetic coupling between the copper­(II) ions mediated by the hydroxamate bridges

Novel pyrazolate-based copper(II) [2 x 2] grid complexes: Synthesis, structure and properties

5-Acetyl-substituted pyrazole-3-carboxylic acid (H2L) forms [2 x 2] grid-like tetranuclear Cu(II) complexes with four five-coordinated copper(II) ions bridged by pyrazolate groups. Despite a significant dissociation of [Cu4L4(H2O)(4)]center dot 4H(2)O (1) in aqueous solution(1), it was possible to substitute the coordinated water molecules by pyridine ligands or azide anions. The resulting tetranuclear complexes [Cu4L4Py4]center dot 2H(2)O (2) and Na-4[Cu4L4(N-3)(4)]center dot 7MeOH (3) were isolated and studied by X-ray diffraction analysis. In 2 and 3 the azide anions or pyridine molecules complete the distorted square-pyramidal coordination of each copper(II) center. Magnetic susceptibilities of the obtained compounds have been measured by SQUID techniques. Simulation of the data using a Heisenberg spin Hamiltonian approach showed that the bridges between the metals mediate weak intramolecular antiferromagnetic coupling (J in the range -13.3 to -17.1 cm (1)) and lead to a singlet ground state in all cases. (C) 2012 Elsevier B.V. All rights reserved