Adsorption of Heavy Metal Ions on Alginate-Based Magnetic Nanocomposite Adsorbent Beads.

Graphene oxide and its magnetic nanoparticle-based composites are a well-known tool to remove heavy metals from wastewater. Unfortunately, one of the major issues in handling such small particles consists of their difficult removal from treated wastewater (even when their magnetic properties are exploited), due to their very small diameter. One possible way to overcome this problem is to embed them in a macroscopic biopolymer matrix, such as alginate or chitosan beads. In this way, the adsorbent becomes easier to handle and can be used to build, for example, a packed column, as in a traditional industrial adsorber. In this work, the removal performances of two different embedded magnetic nanocomposite adsorbents (MNAs) are discussed. The first type of MNA is based on ferrite magnetic nanoparticles (MNPs) generated by coprecipitation using iron(II/III) salts and ammonium hydroxide, while the second is based on a 2D material composed of MNP-decorated graphene oxide. Both MNAs were embedded in cross-linked alginate beads and used to treat artificial water contaminated with chromium(III), nickel(II), and copper(II) in different concentrations. The yield of removal and differences between MNAs and non-embedded magnetic nanomaterials are also discussed. From the results, it was found that the time to reach the adsorption equilibrium is higher when compared to that of the nanomaterials only, due to the lower surface/volume ratio of the beads, but the adsorption capacity is higher, due to the additional interaction with alginate.

Chemical and Mechanical Characterization of Unprecedented Transparent Epoxy-Nanomica Composites-New Model Insights for Mechanical Properties.

Two nanomicas of similar composition, containing muscovite and quartz, but with different particle size distributions, have been used to prepare transparent epoxy nanocomposites. Their homogeneous dispersion, due to the nano-size, was achieved even without being organically modified, and no aggregation of the nanoparticles was observed, thus maximizing the specific interface between matrix and nanofiller. No exfoliation or intercalation has been observed by XRD, despite the significant dispersion of the filler in the matrix which produced nanocomposites with a loss in transparency in the visible domain of less than 10% in the presence of 1% wt and 3% wt of mica fillers. The presence of micas does not affect the thermal behavior of the nanocomposites, which remains similar to that of the neat epoxy resin. The mechanical characterization of the epoxy resin composites revealed an increased Young's modulus, whereas tensile strength was reduced. A peridynamics-based representative volume element approach has been implemented to estimate the effective Young's modulus of the nanomodified materials. The results obtained through this homogenization procedure have been used as input for the analysis of the nanocomposite fracture toughness, which has been carried out by a classical continuum mechanics-peridynamics coupling approach. Comparison with the experimental data confirms the capability of the peridynamics-based strategies to properly model the effective Young's modulus and fracture toughness of epoxy-resin nanocomposites. Finally, the new mica-based composites exhibit high values of volume resistivity, thus being excellent candidates as insulating materials.

Novel Silver Complexes Based on Phosphanes and Ester Derivatives of Bis(pyrazol-1-yl)acetate Ligands Targeting TrxR: New Promising Chemotherapeutic Tools Relevant to SCLC Management.

Bis(pyrazol-1-yl)acetic acid (HC(pz)2COOH) and bis(3,5-dimethyl-pyrazol-1-yl)acetic acid (HC(pzMe2)2COOH) were converted into the methyl ester derivatives 1 (LOMe) and 2 (L2OMe), respectively, and were used for the preparation of silver(I) complexes 3-5. The Ag(I) complexes were prepared by the reaction of AgNO3 and 1,3,5-triaza-7-phosphaadamantane (PTA) or triphenylphosphine (PPh3) with LOMe and L2OMe in methanol solution. All Ag(I) complexes showed a significant in vitro antitumor activity, proving to be more effective than the reference drug cisplatin in the in-house human cancer cell line panel containing examples of different solid tumors. Compounds were particularly effective against the highly aggressive and intrinsically resistant human small-cell lung carcinoma (SCLC) cells, either in 2D and 3D cancer cell models. Mechanistic studies revealed their ability to accumulate into cancer cells and to selectively target Thioredoxin (TrxR), thus leading to redox homeostasis unbalance and ultimately inducing cancer cell death through apoptosis.

A Porous Gelatin Methacrylate-Based Material for 3D Cell-Laden Constructs.

3D constructs are fundamental in tissue engineering and cancer modeling, generating a demand for tailored materials creating a suitable cell culture microenvironment and amenable to be bioprinted. Gelatin methacrylate (GelMA) is a well-known functionalized natural polymer with good printability and binding motifs allowing cell adhesion; however, its tight micropores induce encapsulated cells to retain a non-physiological spherical shape. To overcome this problem, blended GelMa is here blended with Pluronic F-127 (PLU) to modify the hydrogel internal porosity by inducing the formation of larger mesoscale pores. The change in porosity also leads to increased swelling and a slight decrease in Young's modulus. All blends form stable hydrogels both when cast in annular molds and bioprinted in complex structures. Embedded cells maintain high viability, and while Neuroblastoma cancer cells typically aggregate inside the mesoscale pores, Mesenchymal Stem Cells stretch in all three dimensions, forming cell-cell and cell-ECM interactions. The results of this work prove that the combination of tailored porous materials with bioprinting techniques enables to control both the micro and macro architecture of cell-laden constructs, a fundamental aspect for the development of clinically relevant in vitro constructs.

Cyclo- and Polyphosphazenes for Biomedical Applications.

Cyclic and polyphosphazenes are extremely interesting and versatile substrates characterized by the presence of -P=N- repeating units. The chlorine atoms on the P atoms in the starting materials can be easily substituted with a variety of organic substituents, thus giving rise to a huge number of new materials for industrial applications. Their properties can be designed considering the number of repetitive units and the nature of the substituent groups, opening up to a number of peculiar properties, including the ability to give rise to supramolecular arrangements. We focused our attention on the extensive scientific literature concerning their biomedical applications: as antimicrobial agents in drug delivery, as immunoadjuvants in tissue engineering, in innovative anticancer therapies, and treatments for cardiovascular diseases. The promising perspectives for their biomedical use rise from the opportunity to combine the benefits of the inorganic backbone and the wide variety of organic side groups that can lead to the formation of nanoparticles, polymersomes, or scaffolds for cell proliferation. In this review, some aspects of the preparation of phosphazene-based systems and their characterization, together with some of the most relevant chemical strategies to obtain biomaterials, have been described.

Activation of Vegetable Oils by Reaction with Maleic Anhydride as a Renewable Source in Chemical Processes: New Experimental and Computational NMR Evidence.

Vegetable oils are bio-based and sustainable starting materials that can be used to develop chemicals for industrial processes. In this study, the functionalization of three vegetable oils (grape, hemp, and linseed) with maleic anhydride was carried out either by conventional heating or microwave activation to obtain products that, after further reactions, can enhance the water dispersion of oils for industrial applications. To identify the most abundant derivatives formed, trans-3-octene, methyl oleate, and ethyl linoleate were reacted as reference systems. A detailed NMR study, supported by computational evidence, allowed for the identification of the species formed in the reaction of trans-3-octene with maleic anhydride. The signals in the 1H NMR spectra of the alkenyl succinic anhydride (ASA) moieties bound to the organic chains were clearly identified. The reactions achieved by conventional heating were carried out for 5 h at 200 °C, resulting in similar or lower amounts of ASA units/g of oil with respect to the reactions performed by microwave activation, which, however, induced a higher viscosity of the samples.

Ruthenium Complexes Bearing α-Diimine Ligands and Their Catalytic Applications in N-Alkylation of Amines, α-Alkylation of Ketones, and ß-Alkylation of Secondary Alcohols.

New Ru(II) complexes encompassing α-diimine ligands were synthesized by reacting ruthenium precursors with α-diimine hydrazones. The new ligands and Ru(II) complexes were analyzed by analytical and various spectroscopic methods. The molecular structures of L1 and complexes 1, 3, and 4 were determined by single-crystal XRD studies. The results reveal a distorted octahedral geometry around the Ru(II) ion for all complexes. Moreover, the new ruthenium complexes show efficient catalytic activity toward the C-N and C-C coupling reaction involving alcohols. Particularly, complex 3 demonstrates effective conversion in N-alkylation of aromatic amines, α-alkylation of ketones, and ß-alkylation of alcohols.

Exploring the Antitumor Potential of Copper Complexes Based on Ester Derivatives of Bis(pyrazol-1-yl)acetate Ligands.

Bis(pyrazol-1-yl)acetic acid (HC(pz)2COOH) and bis(3,5-dimethyl-pyrazol-1-yl)acetic acid (HC(pzMe2)2COOH) were converted into the methyl ester derivatives 1 (LOMe) and 2 (L2OMe), respectively, and were used for the preparation of Cu(I) and Cu(II) complexes 3-10. The copper(II) complexes were prepared by the reaction of CuCl2·2H2O or CuBr2 with ligands 1 and 2 in methanol solution. The copper(I) complexes were prepared by the reaction of Cu[(CH3CN)4]PF6 and 1,3,5-triaza-7-phosphaadamantane (PTA) or triphenylphosphine with LOMe and L2OMe in acetonitrile solution. Synchrotron radiation-based complementary techniques (XPS, NEXAFS, and XAS) were used to investigate the electronic and molecular structures of the complexes and the local structure around copper ions in selected Cu(I) and Cu(II) coordination compounds. All Cu(I) and Cu(II) complexes showed a significant in vitro antitumor activity, proving to be more effective than the reference drug cisplatin in a panel of human cancer cell lines, and were able to overcome cisplatin resistance. Noticeably, Cu complexes appeared much more effective than cisplatin in 3D spheroid cultures. Mechanistic studies revealed that the antitumor potential did not correlate with cellular accumulation but was consistent with intracellular targeting of PDI, ER stress, and paraptotic cell death induction.

Dinuclear gold(I) Complexes with Bidentate NHC Ligands as Precursors for Alkynyl Complexes via Mechanochemistry.

The use of alkynyl gold(I) complexes covers different research fields, such as bioinorganic chemistry, catalysis, and material science, considering the luminescent properties of the complexes. Regarding this last application, we report here the synthesis of three novel dinuclear gold(I) complexes of the general formula [(diNHC)(Au-C≡CPh)2]: two Au-C≡CPh units are connected by a bridging di(N-heterocyclic carbene) ligand, which should favor the establishment of semi-supported aurophilic interactions. The complexes can be easily synthesized through mechanochemistry upon reacting the pristine dibromido complexes [(diNHC)(AuBr)2] with phenylacetylene and KOH. Interestingly, we were also able to isolate the monosubstituted complex [(diNHC)(Au-C≡CPh)(AuBr)]. The gold(I) species were fully characterized by multinuclear NMR spectroscopy and mass spectrometry. The emission properties were also evaluated, and the salient data are comparable to those of analogous compounds reported in the literature.

Cu(I) and Cu(II) Complexes Based on Lonidamine-Conjugated Ligands Designed to Promote Synergistic Antitumor Effects.

Bis(pyrazol-1-yl)- and bis(3,5-dimethylpyrazol-1-yl)-acetates were conjugated with the 2-hydroxyethylester and 2-aminoethylamide derivatives of the antineoplastic drug lonidamine to prepare Cu(I) and Cu(II) complexes that might act through synergistic mechanisms of action due to the presence of lonidamine and copper in the same chemical entity. Synchrotron radiation-based complementary techniques [X-ray photorlectron spectroscopy and near-edge X-ray absorption fine structure (NEXAFS)] were used to characterize the electronic and molecular structures of the complexes and the local structure around the copper ion (XAFS) in selected complexes. All complexes showed significant antitumor activity, proving to be more effective than the reference drug cisplatin in a panel of human tumor cell lines, and were able to overcome oxaliplatin and multidrug resistance. Noticeably, these Cu complexes appeared much more effective than cisplatin against 3D spheroids of pancreatic PSN-1 cancer cells; among these, PPh3-containing Cu(I) complex 15 appeared to be the most promising derivative. Mechanistic studies revealed that 15 induced cancer cell death by means of an apoptosis-alternative cell death.

Novel Magnetic Inorganic Composites: Synthesis and Characterization.

The addition of magnetic particles to inorganic matrices can produce new composites exhibiting intriguing properties for practical applications. It has been previously reported that the addition of magnetite to concrete improves its mechanical properties and durability in terms of water and chloride ions absorption. Here we describe the preparation of novel magnetic geopolymers based on two different matrices (G1 without inert aggregates and G2 with inert quartz aggregates) containing commercial SrFe12O19 particles with two weight concentrations, 6% and 11%. The composites' characterization, including chemical, structural, morphological, and mechanical determinations together with magnetic and electrical measurements, was carried out. The magnetic study revealed that, on average, the SrFe12O19 magnetic particles can be relatively well dispersed in the inorganic matrix. A substantial increase in the composite samples' remanent magnetization was obtained by embedding in the geopolymer SrFe12O19 anisotropic particles at a high concentration under the action of an external magnetic field during the solidification process. The new composites exhibit good mechanical properties (as compressive strength), higher than those reported for high weight concretes bearing a similar content of magnetite. The impedance measurements indicate that the electrical resistance is mainly controlled by the matrix's chemical composition and can be used to evaluate the geopolymerization degree.

Synthesis and Biological Studies on Dinuclear Gold(I) Complexes with Di-(N-Heterocyclic Carbene) Ligands Functionalized with Carbohydrates.

The design of novel metal complexes with N-heterocyclic carbene (NHC) ligands that display biological activity is an active research field in organometallic chemistry. One of the possible approaches consists of the use of NHC ligands functionalized with a carbohydrate moiety. Two novel Au(I)-Au(I) dinuclear complexes were synthesized; they present a neutral structure with one bridging diNHC ligand, having one or both heterocyclic rings decorated with a carbohydrate functionality. With the symmetric diNHC ligand, the dicationic dinuclear complex bearing two bridging diNHC ligands was also synthesized. The study was completed by analyzing the antiproliferative properties of these complexes, which were compared to the activity displayed by similar mononuclear Au(I) complexes and by the analogous bimetallic Au(I)-Au(I) complex not functionalized with carbohydrates.

Synthesis, Characterization and Biological Activity of Novel Cu(II) Complexes of 6-Methyl-2-Oxo-1,2-Dihydroquinoline-3-Carbaldehyde-4n-Substituted Thiosemicarbazones.

Three new 6-methyl-2-oxo-1,2-dihydroquinoline-3-carbaldehyde-thiosemicarbazones-N-4-substituted pro-ligands and their Cu(II) complexes (1, -NH2; 2, -NHMe; 3, -NHEt) have been prepared and characterized. In both the X-ray structures of 1 and 3, two crystallographically independent complex molecules were found that differ either in the nature of weakly metal-binding species (water in 1a and nitrate in 1b) or in the co-ligand (water in 3a and methanol in 3b). Electron Paramagnetic Resonance (EPR) measurements carried out on complexes 1 and 3 confirmed the presence of such different species in the solution. The electrochemical behavior of the pro-ligands and of the complexes was investigated, as well as their biological activity. Complexes 2 and 3 exhibited a high cytotoxicity against human tumor cells and 3D spheroids derived from solid tumors, related to the high cellular uptake. Complexes 2 and 3 also showed a high selectivity towards cancerous cell lines with respect to non-cancerous cell lines and were able to circumvent cisplatin resistance. Via the Transmission Electron Microscopy (TEM) imaging technique, preliminary insights into the biological activity of copper complexes were obtained.

Pentafluorophenyl Platinum(II) Complexes of PTA and its N-Allyl and N-Benzyl Derivatives: Synthesis, Characterization and Biological Activity.

From the well-known 1,3,5-triaza-phosphaadamantane (PTA, 1a), the novel N-allyl and N-benzyl tetrafuoroborate salts 1-allyl-1-azonia-3,5-diaza-7-phosphaadamantane (APTA(BF4), 1b) and 1-benzyl-1-azonia-3,5-diaza-7-phosphaadamantane (BzPTA(BF4), 1c) were obtained. These phosphines were then allowed to react with (Pt(µ-Cl)(C6F5)(tht))2 (tht = tetrahydrothiophene) affording the water soluble Pt(II) complexes trans-(PtCl(C6F5)(PTA)2) (2a) and its bis-cationic congeners trans-(PtCl(C6F5)(APTA)2)(BF4)2 (2b) and trans-(PtCl(C6F5)(BzPTA)2)(BF4)2 (2c). The compounds were fully characterized by multinuclear NMR, ESI-MS, elemental analysis and (for 2a) also by single crystal X-ray diffraction, which proved the trans configuration of the phosphine ligands. Furthermore, in order to evaluate the cytotoxic activities of all complexes the normal human dermal fibroblast (NHDF) cell culture were used. The antineoplastic activity of the investigated compounds was checked against the human lung carcinoma (A549), epithelioid cervix carcinoma (HeLa) and breast adenocarcinoma (MCF-7) cell cultures. Interactions between the complexes and human serum albumin (HSA) using fluorescence spectroscopy and circular dichroism spectroscopy (CD) were also investigated.

A Novel 3D Scaffold for Cell Growth to Asses Electroporation Efficacy.

Tumor electroporation (EP) refers to the permeabilization of the cell membrane by means of short electric pulses thus allowing the potentiation of chemotherapeutic drugs. Standard plate adhesion 2D cell cultures can simulate the in vivo environment only partially due to lack of cell-cell interaction and extracellular matrix (ECM). In this study, we assessed a novel 3D scaffold for cell cultures based on hyaluronic acid and ionic-complementary self-assembling peptides (SAPs), by studying the growth patterns of two different breast carcinoma cell lines (HCC1569 and MDA-MB231). This 3D scaffold modulates cell shape and induces extracellular matrix deposit around cells. In the MDA-MB 231 cell line, it allows three-dimensional growth of structures known as spheroids, while in HCC1569 it achieves a cell organization similar to that observed in vivo. Interestingly, we were able to visualize the electroporation effect on the cells seeded in the new scaffold by means of standard propidium iodide assay and fluorescence microscopy. Thanks to the presence of cell-cell and cell-ECM interactions, the new 3D scaffold may represent a more reliable support for EP studies than 2D cancer cell cultures and may be used to test new EP-delivered drugs and novel EP protocols.

Correction: New light on an old debate: does the RCN-PtCl2 bond include any back-donation? RCN ← PtCl2 backbonding vs. the IR νC[triple bond, length as m-dash]N blue-shift dichotomy in organonitriles-platinum(ii) complexes. A thorough density functional theory - energy decomposition analysis study.

Correction for 'New light on an old debate: does the RCN-PtCl2 bond include any back-donation? RCN ← PtCl2 backbonding vs. the IR νC[triple bond, length as m-dash]N blue-shift dichotomy in organonitriles-platinum(ii) complexes. A thorough density functional theory - energy decomposition analysis study' by Girolamo Casella et al., Dalton Trans., 2019, DOI: 10.1039/c9dt02440a.

New light on an old debate: does the RCN-PtCl2 bond include any back-donation? RCN←PtCl2 backbonding vs. the IR νC[triple bond, length as m-dash]N blue-shift dichotomy in organonitriles-platinum(ii) complexes. A thorough density functional theory - energy decomposition analysis study.

For a series of organonitrile [RCN (R = Me, CF3, Ph, CH3Ph, CF3Ph)] ligands, the nature of the N-Pt bond in the related cis-/trans-(RCN)2PtCl2 complexes has been computationally investigated by Density Functional Theory. A fragment based bond analysis has been performed in the canonical Kohn-Sham molecular orbitals framework, and it has been ultimately assessed that this bond is characterized both by N→Pt σ and by N←Pt π contributions. Voronoi Deformation Density charges further confirms the occurrence of N←Pt π interactions. Moreover, the Energy Decomposition Analysis-Natural Orbital for Chemical Valence (EDA-NOCV) method shows that the strength of the N←Pt π interaction is not negligible by contributing to about 30-40% of the total orbital interaction. Finally, the well-known νC[triple bond, length as m-dash]N blue-shift occurring upon coordination to PtII, has been thoroughly investigated by exploiting the EDA-NOCV and by evaluating νC[triple bond, length as m-dash]N and force constants. The origin of the νC[triple bond, length as m-dash]N blue-shift in these systems has been discussed on the basis of the CN bond polarization. N←Pt π backbonding causes only a systematic decrease of the observed νC[triple bond, length as m-dash]N blue-shift when compared to the one calculated for RCN-X (X = H+, alkaline, Lewis acids) herein reported (X = purely σ acceptors).

Possible Synthetic Approaches for Heterobimetallic Complexes by Using nNHC/tzNHC Heteroditopic Carbene Ligands.

The synthesis of heterobimetallic complexes remains a synthetic challenge in the field of organometallic chemistry. A possible approach in this regard might be the use of a bidentate heteroditopic bis(carbene) ligand that combines an imidazol-2-ylidene (nNHC) with a 1,2,3-triazol-5-ylidene (tzNHC) connected by an organic spacer. The optimized strategy to heterobimetallic complexes with this type of ligand involves a 3-step procedure: (i) Coordination of the nNHC, functionalized with a 1,2,3-triazole ring, to a metal center; (ii) formation of the triazolium ring by alkylation of the triazole N-3; (iii) deprotonation of the tzNHC precursor and coordination of the second metal center. Following this procedure, a novel Au(I)-Ag(I) dinuclear complex was isolated and its properties were compared to the analogous homobimetallic Ag(I)-Ag(I) and Au(I)-Au(I) complexes. The study was completed by the determination of the molecular structures of some synthetic intermediates.

Cell-seeded 3D scaffolds as in vitro models for electroporation.

Electroporation of cells is usually studied using cell suspensions or monolayer cultures. 3D scaffolds for cell culture have been recently designed in order to reproduce in vitro the complex and multifactorial environment experimented in vivo by cells. In fact, it is well known that 2D cell cultures are not able to simulate the complex interactions between the cells and their extracellular matrix (ECM). Recently, some examples of 3D models, like spheroids, have been investigated also in the electroporation field. Spheroids have been proposed in electrochemotherapy (ECT) studies to mimic tumor in vivo conditions: they are easy-to-handle 3D models but their sensitivity to electric field pulses depends from their diameter and, more interestingly, despite being relevant for intercellular junctions, they are not so much so for cell-ECM interactions. In this work, we propose a 3D macroscopic myxoid matrix for cell culture that would mimic the in vivo environment of myxoid stroma tumors. The myxoid stroma consists of abundant basic substances with large amounts of glycosaminoglycans (hyaluronic acid) and proteoglycans, poor collagen fibers and no elastin content. In the proposed approach, tumor cells seeded on 3D scaffolds mimic of myxoid stroma can establish both cell-cell and cell-ECM 3D interactions. The MCF7 cells (human breast adenocarcinoma cell line) were seeded in complete culture medium. Cell cultures were incubated at 37 °C for either 24 h, 3 days or 7 day. Some samples were used to assess cell vitality using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) test and others for electroporation tests and for histopathological analysis. The electroporation has been verified by the fluorescent dye Propidium cellular uptake. The proposed myxoid stroma scaffold induces cell proliferation and shows fibrous structures produced by cells, the concentration of which increases with culture time. The proposed matrix will be used for further investigations as a new scaffold for cell culture. Tumor cells grown into these new scaffolds will be used to evaluate electroporation including the stroma effect.

Effect of Tissue Inhomogeneity in Soft Tissue Sarcomas: From Real Cases to Numerical and Experimental Models.

Electrochemotherapy is an established treatment option for patients with superficially metastatic tumors, mainly malignant melanoma and breast cancer. Based on preliminary experiences, electrochemotherapy has the potential to be translated in the treatment of larger and deeper neoplasms, such as soft tissue sarcomas. However, soft tissue sarcomas are characterized by tissue inhomogeneity and, consequently, by variable electrical characteristic of tumor tissue. The inhomogeneity in conductivity represents the cause of local variations in the electric field intensity. Crucially, this fact may hamper the achievement of the electroporation threshold during the electrochemotherapy procedure. In order to evaluate the effect of tissue inhomogeneity on the electric field distribution, we first performed ex vivo analysis of some clinical cases to quantify the inhomogeneity area. Subsequently, we performed some simulations where the electric field intensity was evaluated by means of finite element analysis. The results of the simulation models are finally compared to an experimental model based on potato and tissue mimic materials. Tissue mimic materials are materials where the conductivity can be suitably designed. The coupling of computation and experimental results could be helpful to show the effect of the inhomogeneity in terms of variation in electric field distribution and characteristics.