Heterobimetallic coordination polymers incorporating [M(CN)(2)](-) (M = Cu,Ag) and [Ag(2)(CN)(3)](-) units: increasing structural dimensionality via M-M' and M...NC interactions

A series of new heterometallic coordination polymers has been prepared from the reaction of metal-ligand cations and KAg(CN)(2) units. Many of these contain silver-silver (argentophilic) interactions, analogous to gold-gold interactions, which serve to increase supramolecular structural dimensionality. Compared to [Au(CN)(2)](-) analogues, these polymers display new trends specific to [Ag(CN)(2)](-), including the formation of [Ag(2)(CN)(3)](-) and the presence of Ag...N interactions. [Cu(en)(2)][Ag(2)(CN)(3)][Ag(CN)(2)] (1, en = ethylenediamine) forms 1-D chains of alternating [Ag(CN)(2)](-) and [Ag(2)(CN)(3)](-) units via argentophilic interactions of 3.102(1) A. These chains are connected into a 2-D array by strong cyano(N)-Ag interactions of 2.572(3) A. [Cu(dien)Ag(CN)(2)](2)[Ag(2)(CN)(3)][Ag(CN)(2)] (2, dien = diethylenetriamine) forms a 1-D chain of alternating [Cu(dien)](2+) and [Ag(CN)(2)](-) ions with the Cu(II) atoms connected in an apical/equatorial fashion. These chains are cross-linked by [Ag(2)(CN)(3)](-) units via argentophilic interactions of 3.1718(8) A and held weakly in a 3-D array by argentophilic interactions of 3.2889(5) A between the [Ag(CN)(2)](-) in the 2-D array and the remaining free [Ag(CN)(2)](-). [Ni(en)][Ni(CN)(4)].2.5H(2)O (4) was identified as a byproduct in the reaction to prepare the previously reported [Ni(en)(2)Ag(2)(CN)(3)][Ag(CN)(2)] (3). In [Ni(tren)Ag(CN)(2)][Ag(CN)(2)] (5, tren = tris(2-aminoethyl)amine), [Ni(tren)](2+) cations are linked in a cis fashion by [Ag(CN)(2)](-) anions to form a 1-D chain similar to the [Au(CN)(2)](-) analogue. [Cu(en)Cu(CN)(2)Ag(CN)(2)] (6) is a trimetallic polymer consisting of interpenetrating (6,3) nets stabilized by d(10)-d(10) interactions between Cu(I)-Ag(I) (3.1000(4) A). Weak antiferromagnetic coupling has been observed in 2, and a slightly stronger exchange has been observed in 6. The Ni(II) complexes, 4 and 5, display weak antiferromagnetic interactions as indicated by their relatively larger D values compared to that of 3. Magnetic measurements on isostructural [Ni(tren)M(CN)(2)][M(CN)(2)] (M = Ag, Au) show that Ag(I) is a more efficient mediator of magnetic exchange as compared to Au(I). The formation of [Ni(CN)(4)](2)(-), [Ag(2)(CN)(3)](-), and [Cu(CN)(2)](-) are all attributed to secondary reactions of the dissociation products of the labile KAg(CN)(2).     

Anticancer Potential of Diiron Vinyliminium Complexes

Invited for the cover of this issue is the group of Fabio Marchetti at the Università di Pisa and Paul J. Dyson at Ecole Polytechnique Fédérale de Lausanne (EPFL). Read the full text of the article at 10.1002/chem.201902885 .     

Bis-conjugation of Bioactive Molecules to Cisplatin-like Complexes through (2,2′-Bipyridine)-4,4′-Dicarboxylic Acid with Optimal Cytotoxicity Profile Provided by the Combination Ethacrynic Acid/Flurbiprofen

A facile route to Pt^II complexes doubly functionalized with bioactive molecules through a bipyridine-type ligand is described. Initially, ligands L ^EE (containing two ethacrynic acid units), L ^EF (ethacrynic acid+flurbiprofen) and L ^EB (ethacrynic acid+biotin) were obtained in moderate to good yields from 2,2′-bipyridine-4,4′-dicarboxylic acid. Subsequent reaction of the ligands with [PtCl₂(DMSO)₂] afforded complexes [PtCl₂( L ^EE )] ( 2 ), [PtCl₂( L ^EF )] ( 3 ) and [PtCl₂( L ^EB )] ( 4 ) in high yields. All compounds were fully characterized by analytical and spectroscopic methods. Complexes 2 – 4 are highly stable in water/DMSO solution at 37 °C after 72 h, whereas progressive release of the bioactive fragments was detected in a cell culture medium. The compounds were assessed for their in vitro antiproliferative activity towards tumorigenic A2780, A2780cisR and Y79 cells and non-tumourigenic HEK293 cells. In particular, the combination of ethacrynic acid and flurbiprofen in 3 overcomes cisplatin-based resistance and provides strong cancer cell selectivity. Enzyme inhibition assays on human GST P1 and human COX-2 and cross-experiments with complex 1 , analogous to 2 – 4 but lacking bio-groups, revealed a clear synergy between the Pt^II frame and the bioactive organic components.     

The Copper(II)‐Catalyzed Oxidation of Glutathione

The kinetics and mechanisms of the copper(II)‐catalyzed GSH (glutathione) oxidation are examined in the light of its biological importance and in the use of blood and/or saliva samples for GSH monitoring. The rates of the free thiol consumption were measured spectrophotometrically by reaction with DTNB (5,5′‐dithiobis‐(2‐nitrobenzoic acid)), showing that GSH is not auto‐oxidized by oxygen in the absence of a catalyst. In the presence of Cu²⁺, reactions with two timescales were observed. The first step (short timescale) involves the fast formation of a copper–glutathione complex by the cysteine thiol. The second step (longer timescale) is the overall oxidation of GSH to GSSG (glutathione disulfide) catalyzed by copper(II). When the initial concentrations of GSH are at least threefold in excess of Cu²⁺, the rate law is deduced to be ?d[thiol]/dt=k[copper–glutathione complex][O₂]^0.5[H₂O₂]^?0.5. The 0.5^th reaction order with respect to O₂ reveals a pre‐equilibrium prior to the rate‐determining step of the GSSG formation. In contrast to [Cu²⁺] and [O₂], the rate of the reactions decreases with increasing concentrations of GSH. This inverse relationship is proposed to be a result of the competing formation of an inactive form of the copper–glutathione complex (binding to glutamic and/or glycine moieties).     

Strong cellulose nanofibre–nanosilica composites with controllable pore structure

Flexible nanocellulose composites with silica nanoparticle loading from 5 to 77 wt% and tunable pore size were made and characterised. The pore structure of the new composites can be controlled (100–1000 nm to 10–60 nm) by adjusting the silica nanoparticle content. Composites were prepared by first complexing nanoparticles with a cationic dimethylaminoethyl methacrylate polyacrylamide, followed by retaining this complex in a nanocellulose fibre network. High retention of nanoparticles resulted. The structural changes and pore size distribution of the composites were characterised through scanning electron microscopy (SEM) and mercury porosimetry analysis, respectively. The heavily loaded composites formed packed bed structures of nanoparticles. Film thickness was approximately constant for composites with low loading, indicating that nanoparticles filled gaps created by nanocellulose fibres without altering their structure. Film thickness increased drastically for high loading because of the new packed bed structure. Unexpectedly, within the investigated loading range, the level of the tensile index on nanocellulose mass basis remained constant, showing that the silica nanoparticles did not significantly interfere with the bonding between the cellulose nanofibres. This hierarchically engineered material remains flexible at all loadings, and its unique packing enables use in applications requiring nanocellulose composites with controlled pore structure and high surface area.     

A comparison of the197Au Mössbauer spectra of MAu (M=K,Rb, Cs) with (2, 2, 2-crypt M) Au

Gold-197 Mössbauer spectroscopy has been used to investigate the MAu system (M=K, Kb, Cs). Of the 11 alloys RbAu and CsAu give Mössbauer spectra consistent with cubic gold environments, while (2,2,2-crypt M) Au, (M=K, Pb, Cs) all have cubic gold environments. Comparison of the isomer shifts for the crypted and uncrypted salts leads to the conclusion that in RbAu and CsAu considerable electron density is removed from the gold 5d orbitals.     

Impact of protein denaturants and stabilizers on water structure

It is of great interest to determine how solutes such as urea, sugars, guanidinium salts, and trimethylamine N-oxide affect the stability, solubility, and solvation of globular proteins. A key hypothesis in this field states that solutes affect protein stability indirectly by making or breaking water structure. We used a new technique, pressure perturbation calorimetry, to measure the temperature dependence of a solute's partial compressibility. Using fundamental thermodynamic relations, we converted these data to the pressure dependence of the partial heat capacity to examine the impact of protein stabilizing and denaturing solutes on water structure by applying the classic two-state mixture model for water. Contrary to widely held expectations, we found no correlation between a solute's impact on water structure and its effect on protein stability. Our results indicate that efforts to explain solute effects should focus on other hypotheses, including those based on preferential interaction and excluded volume.