Ebselen analogues with dual human neutrophil elastase (HNE) inhibitory and antiradical activity.

Human neutrophil elastase (HNE) plays an essential role in host defense against bacteria but is also involved in several respiratory diseases. Recent reports suggest that compounds exhibiting a combination of HNE inhibitory activity with antiradical properties may be therapeutically beneficial for the treatment of respiratory diseases involving inflammation and oxidative stress. We report here the synthesis and biological evaluation of novel ebselen analogues exhibiting HNE inhibitory and antiradical activities. HNE inhibition was evaluated in an enzymatic system using human HNE, whereas antiradical activity was evaluated in a cell-based assay system using phorbol 12-myristate 13-acetate (PMA)-stimulated murine bone marrow leukocytes as the source of reactive oxygen species (ROS). HNE inhibition was due to the N-CO group targeting Ser195-OH at position 2 of the scaffold, while antiradical activity was due to the presence of the selenium atom. The most active compounds 4d, 4f, and 4j exhibited a good balance between anti-HNE (IC50 = 0.9-1.4 µM) and antiradical activity (IC50 = 0.05-0.7 µM). Additionally, the solid-state structure of 4d was determined and compared to that of the similar compound N-propionyl-1,2-benzisoselenazol-3(2H)-one.

Highly stable CsPbBr3 perovskite phases from new lead ß-diketonate glyme adducts.

Lead is one of the key metals of the all-inorganic lead halide perovskites. This work tailors novel architectures of lead's coordination sphere using a ß-diketone (H-hfa = 1,1,1,5,5,5-hexafluoro-2,4-pentanedione) and a glyme (monoglyme, diglyme, triglyme, or tetraglyme) ligand. The coordination chemistry and thermal behaviour of these "Pb(hfa)2·glyme" adducts have been analysed through FT-IR spectroscopy, 1H and 13C NMR analyses, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Single-crystal X-ray diffraction studies provide evidence of the formation of a monomeric Pb(hfa)2·monoglyme structure. In order to validate the potentiality of these "Pb(hfa)2·glyme" precursors for the fabrication of Pb-based halide perovskites, a facile, one-step and low-temperature solution approach has been applied to prepare CsPbBr3 microcrystals with a process carried out in air under atmospheric pressure. Pure stoichiometric CsPbBr3 powders, obtained using Cs(hfa) and Br2 as cesium and bromide sources, respectively, show excellent stability under atmospheric conditions. Better results are obtained in terms of yield and stability from the diglyme and tetraglyme lead adducts. Field emission scanning electron microscopy (FE-SEM) indicates a good uniform morphology of cubic grains, while the structure and the 1 : 1 : 3 stoichiometry of Cs : Pb : Br are confirmed by X-ray diffraction (XRD) and energy dispersive X-ray analysis (EDX), respectively. Tauc plots derived from absorption spectroscopy point to optical energy band-gaps (Eg) in the 2.21-2.27 eV range, in agreement with literature data. The present research elucidates the potential of these novel "Pb(hfa)2·glyme" adducts as promising lead precursors for CsPbBr3 perovskite synthesis, paving the way for their implementation in various technological applications.

Selective Trimmed Average: A Resilient Federated Learning Algorithm With Deterministic Guarantees on the Optimality Approximation.

The federated learning (FL) paradigm aims to distribute the computational burden of the training process among several computation units, usually called agents or workers, while preserving private local training datasets. This is generally achieved by resorting to a server-worker architecture where agents iteratively update local models and communicate local parameters to a server that aggregates and returns them to the agents. However, the presence of adversarial agents, which may intentionally exchange malicious parameters or may have corrupted local datasets, can jeopardize the FL process. Therefore, we propose selective trimmed average (SETA), which is a resilient algorithm to cope with the undesirable effects of a number of misbehaving agents in the global model. SETA is based on properly filtering and combining the exchanged parameters. We mathematically prove that the proposed algorithm is resilient against data and local model poisoning attacks. Most resilient methods presented so far in the literature assume that a trusted server is in hand. In contrast, our algorithm works both in server-worker and shared memory architectures, where the latter excludes the necessity of a trusted server. The theoretical findings are corroborated through numerical results on MNIST dataset and on multiclass weather dataset (MWD).

Pyrene-Containing Polyamines as Fluorescent Receptors for Recognition of PFOA in Aqueous Media.

The globally widespread perfluorooctanoic acid (PFOA) is a concerning environmental contaminant, with a possible toxic long-term effects on the environment and human health The development of sensible, rapid, and low-cost detection systems is a current change in modern environmental chemistry. In this context, two triamine-based chemosensors, L1 and L2, containing a fluorescent pyrene unit, and their Zn(II) complexes are proposed as fluorescent probes for the detection of PFOA in aqueous media. Binding studies carried out by means of fluorescence and NMR titrations highlight that protonated forms of the receptors can interact with the carboxylate group of PFOA, thanks to salt bridge formation with the ammonium groups of the aliphatic chain. This interaction induces a decrease in the fluorescence emission of pyrene at neutral and slightly acidic pH values. Similarly, emission quenching has also been observed upon coordination of PFOA by the Zn(II) complexes of the receptors. These results evidence that simple polyamine-based molecular receptors can be employed for the optical recognition of harmful pollutant molecules, such as PFOA, in aqueous media.

Design, Synthesis and Pharmacological Evaluation of New Quinoline-Based Panx-1 Channel Blockers.

Pannexins are an interesting new target in medicinal chemistry, as they are involved in many pathologies such as epilepsy, ischemic stroke, cancer and Parkinson's disease, as well as in neuropathic pain. They are a family of membrane channel proteins consisting of three members, Panx-1, Panx-2 and Panx-3, and are expressed in vertebrates. In the present study, as a continuation of our research in this field, we report the design, synthesis and pharmacological evaluation of new quinoline-based Panx-1 blockers. The most relevant compounds 6f and 6g show an IC50 = 3 and 1.5 µM, respectively, and are selective Panx-1 blockers. Finally, chemical stability, molecular modelling and X-ray crystallography studies have been performed providing useful information for the realization of the project.

Different Topologies of Hg(II)-Bispidine 1D Coordination Polymers: Dynamic Behavior in Solvent Adsorption and Exchange Processes.

One-dimensional (1D) coordination polymers (CPs) featuring three different topologies, comprising zig-zag, ribbon-like and poly-[n]-catenane structures, were obtained by reaction of Hg(II) ions with a novel bispidine ligand L3, and structurally characterized by SC- and P-XRD methods. The CPs obtained in the form of microcrystalline powders were tested for their ability to undergo solvent adsorption and exchange by P-XRD and 1 H NMR spectroscopy. The extent of their dynamic behavior was then correlated to their structural features, highlighting the role of interchain interactions established among their constituting linear arrays. Zig-zag CPs proved to be resilient to external chemical stimuli, while they differently respond to thermal treatments, depending on the solvent originally included within the CP. In the case of polycatenated structures, we observed transformations where the original topology was maintained upon guest exchange, but also cases where it changed to zig-zag, even under solid/vapor conditions (i. e., no complete dissolution of the CP). Given the presence of linear interconnected 1D channels, 3 ⋅ ClBz-polycatenanePwd is also able to trap volatile guests such as n-hexane when exposed to its vapors.

Cellulose for the Production of Air-Filtering Systems: A Critical Review.

The control of airborne contaminants is of great interest in improving air quality, which has deteriorated more and more in recent years due to strong industrial growth. In the last decades, cellulose has been largely proposed as suitable feedstock to build up eco-friendly materials for a wide range of applications. Herein, the issue regarding the use of cellulose to develop air-filtering systems is addressed. The review covers different cellulose-based solutions, ranging from aerogels and foams to membranes and films, and to composites, considering either particulate filtration (PM10, PM2.5, and PM0.3) or gas and water permeation. The proposed solutions were evaluated on the bases of their quality factor (QF), whose high value (at least of 0.01 Pa-1 referred to commercial HEPA (high-efficiency particulate air) filters) guarantees the best compromise between high filtration efficiency (>99%) and low pressure drop (<1 kPa/g). To face this aspect, we first analyzed the different morphological aspects which can improve the final filtration performance, outlining the importance on using nanofibers not only to increase surface area and to modulate porosity in final solutions, but also as reinforcement of filters made of different materials. Besides the description of technological approaches to improve the mechanical filtration, selected examples show the importance of the chemical interaction, promoted by the introduction of active functional groups on cellulose (nano)fibers backbone, to improve filtration efficiency without reducing filter porosity.

Tuneable solvent adsorption and exchange by 1D bispidine-based Mn(II) coordination polymers via ligand design.

Here we report novel bispidine-based coordination polymers (CPs) 2·TCM, 3·TCM, 3·NB, 5·TCM and 5·TCM·NB, of compostition [Mn(Cl)2(L2)2·(TCM)2], [Mn(Cl)2(L3)2·(TCM)5], [Mn(Cl)2(L3)2·(NB)8], [Mn(Cl)2(L5)2·(TCM)4], [Mn(Cl)2(L5)2·(TCM)2·(NB)2], respectively (NB = nitrobenzene; TCM = chloroform). They were obtained starting from novel bispidine ligands L2 (dimethyl 7-isopropyl-3-methyl-9-oxo-2,4-di(pyridin-4-yl)-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarboxylate), L3 (dimethyl 7-(cyclohexylmethyl)-3-methyl-9-oxo-2,4-di(pyridin-4-yl)-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarboxylate) and L5 (dimethyl 7-(4-(dimethylamino)benzyl)-3-methyl-9-oxo-2,4-di(pyridin-4-yl)-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarboxylate), The novel CPs were characterized by single crystal X-ray diffraction (SC-XRD), powder X-ray diffraction (PXRD) and thermal analyses (TGA). We describe their structural and dynamic properties in terms of solvent exchange and adsorption processes, and we outline the general trends observed on the basis of a total of 16 X-ray structures (4 new) and 21 microcrystalline powder phases (10 new), which have been obtained so far for CPs by coordination of ligands L1-L5, having different substitution at the N7 position. This large set of CPs comprises monosolvated, bisolvated and desolvated species, and it shows a good demonstration of how small differences in the functionalization of the organic ligand can have a strong impact on the resulting structural and dynamic properties of this class of 1D CPs.

Combined structural and theoretical investigation on differently substituted bispidine ligands: predicting the properties of their corresponding coordination polymers.

Pyridine-based bispidine ligands L1-L7, which differ in the substituent at the N7 position of the bispidine scaffold, have been studied by single crystal X-ray diffraction and density functional theory (DFT) calculations, also including solid-state algorithms. Qualitative description of the packing interactions and quantitative data on the stability of each ligand in the solid-state have been employed to draw reasonable predictions on the ligand potential for the formation of linear 1D coordination polymers (CPs) with Mn(ii)Cl2 and on their resulting dynamic properties, in terms of adsorption and solvent exchange capabilities. The basic assumption lies in the fact that volume and polarizability of the ligands would similarly affect packing energies in both molecular solids and CP materials. The results here obtained confirm the data previously reported on CPs (those made from L4 are less dynamic than the ones with L1), but they also allow the prediction that CPs made with L2 and L5 should be more dynamic than expected, while CPs with L6 and L7 should not form altogether. This latter prediction was derived from the analysis of the steric and electronic factors of the ligand substituents on the N7 position and it is further substantiated by the obtainment of a 2 : 1 molecular complex, and not a CP, by crystallization of L6 with MnCl2.

Ab initio powder X-ray diffraction structural analysis of bispidine based 1D coordination polymers: insights into their guest responsive behaviour.

The first ab initio synchrotron powder X-ray diffraction (XRD) data structure solution, employing real-space global optimization strategies followed by Rietveld refinement, was obtained for a bispidine based one-dimensional ribbon-like coordination polymer (CP) 1. The structure solution of 1, a non-dynamic phase containing no solvent molecules, is crucial to obtain a more comprehensive view of the dynamic behaviour of a new family of 1D CPs, in terms of solvent adsorption and exchange processes by direct comparison among the structures, solvent-ribbon and inter-ribbon interactions of the CP materials. This work also reports novel bisolvated phases, 1·TCM·oNT, 1·TCM·pCT and 1·TCM·NB, in the form of single crystals and microcrystalline powders and shows that 1 can be thermally activated to regain dynamic selective adsorption features.

Highly Dynamic and Tunable Behavior of 1D Coordination Polymers Based on the Bispidine Ligand.

Ligands L1 and L2 have been designed, synthesized, and used to build for the first time bispidine-based coordination polymers (CPs) in combination with MnII . The novel CPs have been structurally characterized by single-crystal (SC) and powder X-ray diffraction (P-XRD) techniques, showing that they are composed of 1D ribbon-like chains that adopt various arrangements depending on the trapped solvent species. These materials show highly dynamic behavior as they undergo heterogeneous solid/liquid and solid/vapor multiple solvent exchange processes, comprising crystalline-amorphous-crystalline, selective adsorption and SC-to-SC transformations, where major structural reorganization of the 1D ribbons are observed. By tuning inter-ribbon interactions through expansion of the ligand's accessible surface, the dynamic behavior can be effectively modulated.