Antiproliferative Homoleptic and Heteroleptic Phosphino Silver(I) Complexes: Effect of Ligand Combination on Their Biological Mechanism of Action

A series of neutral mixed-ligand [HB(pz)₃]Ag(PR₃) silver(I) complexes (PR₃ = tertiary phosphine, [HB(pz)₃]⁻ = tris(pyrazolyl)borate anion), and the corresponding homoleptic [Ag(PR₃)₄]BF₄ compounds have been synthesized and fully characterized. Silver compounds were screened for their antiproliferative activities against a wide panel of human cancer cells derived from solid tumors and endowed with different platinum drug sensitivity. Mixed-ligand complexes were generally more effective than the corresponding homoleptic derivatives, but the most active compounds were [HB(pz)₃]Ag(PPh₃) (5) and [Ag(PPh₃)₄]BF₄ (10), both comprising the lipophilic PPh₃ phosphine ligand. Detailed mechanistic studies revealed that both homoleptic and heteroleptic silver complexes strongly and selectively inhibit the selenoenzyme thioredoxin reductase both as isolated enzyme and in human ovarian cancer cells (half inhibition concentration values in the nanomolar range) causing the disruption of cellular thiol-redox homeostasis, and leading to apoptotic cell death. Moreover, for heteroleptic Ag(I) derivatives, an additional ability to damage nuclear DNA has been detected. These results confirm the importance of the type of silver ion coordinating ligands in affecting the biological behavior of the overall corresponding silver complexes, besides in terms of hydrophilic–lipophilic balance, also in terms of biological mechanism of action, such as interaction with DNA and/or thioredoxin reductase.     

Fast Cyclization of a Proline‐Derived Self‐Immolative Spacer Improves the Efficacy of Carbamate Prodrugs

Self‐immolative (SI) spacers are sophisticated chemical constructs designed for molecular delivery or material degradation. We describe herein a (S)‐2‐(aminomethyl)pyrrolidine SI spacer that is able to release different types of anticancer drugs (possessing either a phenolic or secondary and tertiary hydroxyl groups) through a fast cyclization mechanism involving carbamate cleavage. The high efficiency of drug release obtained with this spacer was found to be beneficial for the in vitro cytotoxic activity of protease‐sensitive prodrugs, compared with a commonly used spacer of the same class. These findings expand the repertoire of degradation machineries and are instrumental for the future development of highly efficient delivery platforms.     

Minimization of Carrier Losses for Efficient Perovskite Solar Cells through Structural Modification of Triphenylamine Derivatives

Three hole transport materials (HTMs) based on a substituted triphenylamine moiety have been synthesized and successfully employed in triple‐cation mixed‐halide PSCs, reaching efficiencies of 19.4 %. The efficiencies, comparable to those obtained using spiro‐OMeTAD, point them out as promising candidates for easily attainable and cost‐effective alternatives for PSCs, given their facile synthesis from commercially available materials. Interestingly, although all these HTMs show similar chemical and physical properties, they provide different carrier recombination kinetics. Our results demonstrate that is feasible through the molecular design of the HTM to minimize carrier losses and, thus, increase the solar cell efficiencies.     

Study of the Complexation of Pb(II) with meso‐2,3‐ Dimercaptosuccinic Acid (DMSA) and 2,3‐Dimercapto‐1‐propanesulfonic acid (DMPS) Using a Bismuth‐Bulk Rotating Disk Electrode

For the first time, the suitability of bismuth bulk rotating disk electrode (BiB‐RDE) for the study of metal complexation has been tested. Cyclic (CV) and differential pulse (DPV) voltammetry have been used to study the complexation of Pb(II) with two of the most effective chelating agents for the treatment of Pb(II) poisoning (meso‐2,3‐dimercaptosuccinic acid, DMSA, and 2,3‐dimercapto‐1‐propanesulfonic acid, DMPS). Multivariate curve resolution has been applied to voltammetric data to obtain the stoichiometries and stability constants of the complexes formed. In both systems, the ML₂ complex was predominant, with log β₂ values of 10.13 and 8.80 for DMSA‐Pb(II) and DMPS‐Pb(II), respectively.     

Atmospheric pressure gas chromatography coupled to quadrupole‐time of flight mass spectrometry as a tool for identification of volatile migrants from autoadhesive labels used for direct food contact

Pressure‐sensitive adhesives (PSA) are used to manufacture labels that are applied directly on the food. These adhesives could contain not only intentionally added compounds (IAS) to the adhesive formula but also non‐intentionally added substances (NIAS), due to the impurities from the raw materials used, decomposition of the initial components or from chemical interactions between them. These compounds could migrate to the food and contaminate it. In this study, gas chromatography coupled with mass spectrometry (GC‐MS/Q) and atmospheric pressure gas chromatography coupled to a quadrupole hyphenated to a time of flight mass spectrometer (APGC‐MS/Q‐TOF) have been used for identification of unknown compounds and NIAS coming from a PSA. Seven compounds were identified by GC‐MS/Q, and other eight compounds remained initially unknown. The structure of these eight new compounds was elucidated by working with the spectra obtained by APGC‐MS/Q‐TOF. Finally, two different migration studies were carried out. The first one with Tenax as solid food simulant in contact with the paper label containing the adhesive and the second one with isooctane filled in a natural pork intestine where the label containing the adhesive was applied on the external side. The results are shown and discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

Hydride Migration from a Triangular Face to a Tetrahedral Cavity in Tetranuclear Iron Carbonyl Clusters upon Coordination of [AuPPh3]+ Fragments

Metal hydrides are of fundamental importance in chemistry, both as solid‐state materials and molecular compounds. The first low‐valent molecular metal cluster containing an interstitial four‐coordinate hydride in a tetrahedral site is decribed, which undergoes hydride migration from the surface to the tetrahedral cavity of the cluster upon coordination of a [AuPPh₃]⁺ fragment. The [HFe₄(CO)₁₂(AuPPh₃)₂]^? mono‐anion, which contains a surface μ₃‐H, was obtained from the reaction of [HFe₄(CO)₁₂]^3? with two equivalents of [Au(PPh₃)Cl]. This is, in turn, transformed into the neutral [HFe₄(CO)₁₂(AuPPh₃)₃] upon addition of a third [AuPPh₃]⁺ fragment, with concomitant migration of the unique hydride from the surface of the cluster to its tetrahedral cavity. All of these species have been fully characterized in solution by means of IR and multinuclear NMR spectroscopy, and in the solid state by single‐crystal X‐ray diffractometry.     

Cavitand‐Grafted Silicon Microcantilevers as a Universal Probe for Illicit and Designer Drugs in Water

The direct, clean, and unbiased transduction of molecular recognition into a readable and reproducible response is the biggest challenge associated to the use of synthetic receptors in sensing. All possible solutions demand the mastering of molecular recognition at the solid–liquid interface as prerequisite. The socially relevant issue of screening amine‐based illicit and designer drugs is addressed by nanomechanical recognition at the silicon–water interface. The methylamino moieties of different drugs are all first recognized by a single cavitand receptor through a synergistic set of weak interactions. The peculiar recognition ability of the cavitand is then transferred with high fidelity and robustness on silicon microcantilevers and harnessed to realize a nanomechanical device for label‐free detection of these drugs in water.     

Development of CN Coupling Using Mechanochemistry: Catalytic Coupling of Arylsulfonamides and Carbodiimides

Reported herein is the mechanochemical synthesis of sulfonyl guanidines, a family of molecules which are relevant as pharmaceuticals and herbicides, by direct coupling of sulfonamides and aromatic or aliphatic carbodiimides. Attempts to conduct the coupling in solution have either failed or given very low conversions, thus demonstrating mechanochemistry as the necessary component for the discovery of this synthetic strategy.     

Out‐of‐Water Constitutional Self‐Organization of Chitosan–Cinnamaldehyde Dynagels

An investigation of the constitutional adaptive gelation process of chitosan/cinnamaldehyde ( C / Cy ) dynagels is reported. These gels generate timely variant macroscopic organization across extended scales. In the first stage, imine‐bond formation takes place “in‐water” and generates low‐ordered hydrogels. The progressive formation of imine bonds further induces “ out‐of‐water” increased reactivity within interdigitated hydrophobic self‐assembled layers of Cy , with a protecting environmental effect against hydrolysis and that leads to the stabilization of the imine bonds. The hydrophobic swelling due to Cy layers at the interfaces reaches a critical step when lamellar self‐organized hybrids are generated (24 hours). This induces an important restructuration of the hydrogels on the micrometric scale, thus resulting in the formation of highly ordered microporous xerogel morphologies of high potential interest for chemical separations, drug delivery, and sensors.     

Cathepsin‐B Induced Controlled Release from Peptide‐Capped Mesoporous Silica Nanoparticles

New capped silica mesoporous nanoparticles for intracellular controlled cargo release within cathepsin B expressing cells are described. Nanometric mesoporous MCM‐41 supports loaded with safranin O ( S1‐P ) or doxorubicin ( S2‐P ) containing a molecular gate based on a cathepsin B target peptidic sequence were synthesized. Solids were designed to show “zero delivery” and to display cargo release in the presence of cathepsin B enzyme, which selectively hydrolyzed in vitro the capping peptide sequence. Controlled delivery in HeLa, MEFs WT, and MEFs lacking cathepsin B cell lines were also tested. Release of safranin O and doxorubicin in these cells took place when cathepsin B was active or present. Cells treated with S2‐P showed a fall in cell viability due to nanoparticles internalization, cathepsin B hydrolysis of the capping peptide, and cytotoxic agent delivery, proving the possible use of these nanodevices as new therapeutic tools for cancer treatment.