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The molecular mechanisms of arsenic toxicity are not fully elucidated. The Italian project SEpiAs aims at developing and validating the assay to detect stress biomarkers in individuals living in areas characterized by either natural or industrial arsenic contamination.

Treatment of unsubstituted and substituted phthalonitrile (1a–d) with appropriate equivalents of sodium methoxide and ammonia afforded the corresponding 1,3-diiminoisoindolines (2a–d), which were converted to cobalt(III)-containing penta-dentate "helmet"-type phthalogens (3a–d) by the reaction with CoCl2·6H2O as templating agent in the inert solvent 1,2,4-trichlorobenzene. The identities of 2a–d and 3a–d were established by elemental analysis, infrared spectroscopy (IR), nuclear magnetic resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). A computational study was performed to determine the most stable tautomeric form of 2a–c in the gas phase. The solid-state structures of 2b and 2c were determined by single crystal X-ray diffraction (SC-XRD) studies to confirm their existence in the stereoisomeric anti-form, which is aligned with quantum chemical computations. SC-XRD studies of 3a and 3b revealed a slightly distorted octahedral geometry around the CoIII ions which are coordinated by five N-donor atoms and one extra co-ligand, resulting in a coordination environment of CoN5Cl (3a) and CoN5O (3b), respectively. The thermal stabilities of 2a–d and 3a–d were investigated by thermogravimetric analysis (TGA) in the temperature range of 40–500 °C and 40–800 °C, respectively, revealing that 3a–d were converted to the parent cobalt(II)-containing phthalocyanines (4a–d), which was verified independently by furnace heating experiments. Moreover, the electrochemical behavior of 3a was studied exemplarily for the phthalogens by cyclic voltammetry and square wave voltammetry. This study showed that 4a (CoPc) is formed irreversibly by reducing 3a electrochemically. [ABSTRACT FROM AUTHOR]

Electroorganic synthesis has become an exciting tool for the asymmetric conversion of pro-chiral compounds. Herein, we introduced a wireless methodology based on bipolar electrochemistry in synergy with the enantioselective capabilities of inherently chiral oligomers to induce an umpolung chirality transfer. This was exemplified by the electro-conversion of a racemic mixture of lansoprazole to an enantio -enriched solution of a single antipode.

Developing chemiresistive devices for the wireless detection of complex analytes has gained considerable interest. In particular, the enantioselective recognition of chiral molecules is still a challenge. Here, we design a hybrid chemiresistive device for the wireless enantioselective discrimination of chiral analytes by combining the enantiorecognition capabilities of an inherently chiral oligomer, that is, oligo-(3,3'-dibenzothiophene) (BT 2 T 4 ) and the insulating/conducting transition of polypyrrole (Ppy). The device is obtained by modifying each extremity of an interdigitated electrode (IDE) with Ppy on the interdigitated area and oligo-BT 2 T 4 on the connection pads. Due to the asymmetric electroactivity triggered by bipolar electrochemistry, the wireless enantioselective discrimination of both enantiomers of tryptophan and DOPA was achieved. A difference in the onset resistance values was obtained for both enantiomers due to a favorable or unfavorable diastereomeric interaction between the inherently chiral oligomer and the antipode of the chiral molecule. Interestingly, such a device showed a wide quantification range, from μM to mM levels. This work opens up new alternatives to designing advanced wireless devices in enantiorecognition., (© 2024 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

In recent years, transductors of chiral information based on conducting polymers have gained considerable attention. In particular, inherently chiral materials, which allow differentiation between the antipodes of a chiral analyte in terms of energetic variations, are highly desired. In this work, we successfully synthesized a novel inherently chiral oligomer based on an indole-benzothiophene core, namely, 2-([2,2'-bithiophen]-5-yl)-3-(2-([2,2'-bithiophen]-5-yl)benzo[b]thiophen-3-yl)-N-methylindole (BTIndT 4 ). The electrochemical characterization evidences a stabilization of electrogenerated radical cations due to the presence of the indole group, which guides the oligomerization, producing well-ordered polymeric matrices. Furthermore, the in situ electrochemical conductance analysis demonstrates a simultaneous intrachain and interchain transfer of charge carriers. Finally, the highly efficient enantiorecognition capabilities of the antipodes of the oligo-BTIndT 4 films toward the enantiomers of tryptophan and 3,4-dihydroxyphenylalanine (DOPA), as model chiral analytes, were demonstrated., (© 2024 The Author(s). Chirality published by Wiley Periodicals LLC.)

Chirality is a fundamental and ubiquitous property of nature involved in multiple fields of science. In particular, the possible resolution of the enantiomeric forms of a molecule is crucial in the pharmaceutical, food, and agrochemical industries. The search for efficient, broad-spectrum, and yet simple methods for obtaining enantiomerically pure substances is a current challenge. Enantioselective resolution methods rely on an asymmetric environment that allows the two antipodes of a chiral molecule to be distinguished. In addition to enantiomeric separation techniques, such as chromatography and electrophoresis, new promising approaches involving out-of-the-scheme synergistic effects between chiral selectors (CS) and external stimuli are emerging. This Trends article discusses different enantioselective mechanisms triggered by unconventional physicochemical stimuli for the design of avant-garde approaches that could offer novel perspectives in the field of chiral resolution., (© 2024. The Author(s).)

Among inherently chiral selectors of axial stereogenicity, usually resulting in very good enantiodiscrimination performances, the biindole-based family has the additional advantage of very easy functionalization of the two nitrogen atoms with a variety of substituents with desirable properties. Aiming to evaluate the possibility of exploiting such feature to enhance the enantiodiscrimination ability of the archetype structure, a series of three inherently chiral monomers were designed and synthesized, characterised by a 2,2'-biindole atropisomeric core conjugated to bithiophene wings enabling fast and regular electrooligomerization, and functionalised at the nitrogen atoms with an ethyl, a methoxyethyl, or a hydroxyethyl substituent. Nitrogen alkylation was also exploited to obtain for the first time the chemical resolution of the biindole selectors without employing chiral HPLC. The enantiodiscrimination ability of the selector series was comparatively evaluated in proof-of-concept chiral voltammetry experiments with a "benchmark" chiral ferrocenyl probe as well as with chiral non-steroidal anti-inflammatory drugs naproxen and ketoprofen. The large enantiomer potential differences for all probes increased in the ethyl < methoxyethyl ≪ hydroxyethyl sequence of selector substituents, supporting our assumption on the beneficial role of an additional coordination element. The powerful hydroxyethyl selector was also applied to ketoprofen in a commercial drug matrix., (© 2024 Wiley‐VCH GmbH.)

An environmentally friendly and sustainable approach was adopted to produce a molecularly imprinted polymer (MIP) via electropolymerization, with remarkable electrochemical sensing properties, tested in tyrosine (tyr) detection. The 2,2'-bis(2,2'-bithiophene-5-yl)-3,3'-bithianaphtene (BT 2 -T 4 ) was chosen as functional monomer and MIP electrosynthesis was carried out via cyclic voltammetry on low-volume (20 μL) screen-printed carbon electrodes (C-SPE) in ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ((BMIM) TFSI). An easy and rapid washing treatment allowed us to obtain the resulting MIP film, directly used for tyr electrochemical detection, carried out amperometrically. The sensor showed a linear response in the concentration range of 15-200 μM, with LOD of 1.04 µM, LOQ of 3.17 μM and good performance in selectivity, stability, and reproducibility. Tyrosine amperometric detection was also carried out in human plasma, resulting in a satisfactory recovery estimation. The work represents the first use of BT 2 -T 4 as a functional monomer for the production of a molecularly imprinted polymer, with a green approach afforded by using a few microliters of a room temperature ionic liquid as an alternative to common organic solvents on screen-printed carbon electrodes, resulting in a valuable system that meets the green chemistry guidelines, which is today an essential criterion in both research and application field.

Chiral resolution plays a crucial role in the field of drug development, especially for a better understanding of biochemical processes. In such a context, classic separation methods have been used for decades due to their versatility and easy scale-up. Among the many attempts proposed for enantioselective separation, electroassisted methods are presented as an interesting alternative. Herein, we present the use of wirelessly activated hollow tubular systems for the effective, simple, and tunable separation of racemic and enantioenriched mixtures. These double-layered tubular objects consist of an external polypyrrole chassis, a polymer with good electromechanical properties, functionalized in its inner part with an inherently chiral oligomer. The synergy between the electromechanical pumping process of the outer layer and the enantioselective affinity of the inner part induces the system to behave as a miniaturized chiral column. These hybrid objects are able to separate racemic and enantioenriched solutions of chiral model analytes into the corresponding enantiomers in high enantiomeric purity. Finally, these electromechanical systems can resolve mixtures formed by chiral probes with completely uncorrelated molecular structures injected simultaneously into the single antipodes.

Treatment of unsubstituted and substituted phthalonitrile (1a-d) with appropriate equivalents of sodium methoxide and ammonia afforded the corresponding 1,3-diiminoisoindolines (2a-d), which were converted to cobalt(III)-containing penta-dentate "helmet"-type phthalogens (3a-d) by the reaction with CoCl 2 ·6H 2 O as templating agent in the inert solvent 1,2,4-trichlorobenzene. The identities of 2a-d and 3a-d were established by elemental analysis, infrared spectroscopy (IR), nuclear magnetic resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). A computational study was performed to determine the most stable tautomeric form of 2a-c in the gas phase. The solid-state structures of 2b and 2c were determined by single crystal X-ray diffraction (SC-XRD) studies to confirm their existence in the stereoisomeric anti -form, which is aligned with quantum chemical computations. SC-XRD studies of 3a and 3b revealed a slightly distorted octahedral geometry around the Co III ions which are coordinated by five N-donor atoms and one extra co-ligand, resulting in a coordination environment of CoN 5 Cl (3a) and CoN 5 O (3b), respectively. The thermal stabilities of 2a-d and 3a-d were investigated by thermogravimetric analysis (TGA) in the temperature range of 40-500 °C and 40-800 °C, respectively, revealing that 3a-d were converted to the parent cobalt(II)-containing phthalocyanines (4a-d), which was verified independently by furnace heating experiments. Moreover, the electrochemical behavior of 3a was studied exemplarily for the phthalogens by cyclic voltammetry and square wave voltammetry. This study showed that 4a (CoPc) is formed irreversibly by reducing 3a electrochemically.

Chirality plays a crucial role in different research fields, ranging from fundamental physico-chemistry to applied aspects in materials science and medicine. In this context, enantioselective loading and pumping of chiral analytes for analysis, separation, and cargo delivery applications is an interesting scientific challenge. Herein, we introduce artificial chiral soft electromechanical pumps based on a bi-layer film built up by electrodepositing polypyrrole and an inherently chiral conducting oligomer at its internal surface. The enantioselective device can be driven by bipolar electrochemistry to act as a pump, allowing the selective loading and separation of different chiral analytes injected as pure enantiomers and in racemic form (i.e., doxorubicin, a chemotherapy drug, limonene, carvone, and a chiral ferrocene). The synergy between wireless electromechanical actuation and inherent enantiodiscrimination features makes these actuators excellent candidates for the controlled handling of chiral molecules in the frame of potential applications ranging from analysis to drug delivery., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

A family of inherently chiral electroactive selectors based on the 2,2'-biindole atropisomeric scaffold, of easy synthesis and modulable functional properties, is studied in cascade in two enantioselection contexts. They are at first investigated as probes in enantioselective HPLC, studying molecular structure and temperature effects, and achieving very efficient semipreparative enantioseparation. The enantiomers thus obtained, of remarkable chiroptical features (optical rotation as well as circular dichroism), are successfully applied as selectors in chiral voltammetry in different media for discrimination of the enantiomers of chiral electroactive probes, either by conversion into enantiopure electroactive electrode surfaces by electrooligomerization on glassy carbon substrate (the two monomers with shorter alkyl chains), or as chiral additive in achiral ionic liquid (the monomer with longest alkyl chains). Discrimination is conveniently and reproducibly achieved in terms of significant potential differences for the two enantiomers, specularly inverting either probe or selector configuration. In one case successful discrimination is also observed with the two probe enantiomers concurrently present, either as racemate or with enantiomeric excesses, neatly accounted for by the peak current ratios., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Configurationally stable 5-aza[6]helicene ( 1 ) was envisaged as a promising scaffold for non-conventional ionic liquids (IL)s. It was prepared, purified, and separated into enantiomers by preparative HPLC on a chiral stationary phase. Enantiomerically pure quaternary salts of 1 with appropriate counterions were prepared and fully characterized. N -octyl-5-aza[6]helicenium bis triflimidate ( 2 ) was tested in very small quantities as a selector in achiral IL media to perform preliminary electrochemical enantiodifferentiation experiments on the antipodes of two different chiral probes. The new organic salt exhibited outstanding enantioselection performance with respect to these probes, thus opening the way to applications in the enantioselective electroanalysis of relevant bioactive molecules.

Enantioselective electroanalysis, which aims to discriminate the enantiomers of electroactive chiral probes in terms of potential difference, is a very attractive goal. To achieve this, its implementation is being studied for various "inherently chiral" selectors, either at the electrode surface or in the medium, yielding outstanding performance. In this context, the new inherently chiral monomer Naph 2 T 4 is introduced, based on a biaromatic atropisomeric core, which is advantageously obtainable in enantiopure form without HPLC separation steps by a synthetic route hinging on enantiopure 2,2'-dibromo-1,1'-binaphthalenes. The antipodes of the new inherently chiral monomer can be easily electrooligomerized, yielding inherently chiral electrode surfaces that perform well in both cyclic voltammetry (CV) enantiodiscrimination tests with pharmaceutically interesting molecules and in magnetoelectrochemistry experiments.

Chiral oligothiophene monomers with C 2 symmetry, based on 3,3'-bithiophene atropisomeric cores with high racemization barriers, have recently been shown to provide excellent chiral starting materials with high electroactivity for the easy preparation of enantiopure electroactive films endowed with powerful chirality manifestations. We now introduce an inherently chiral monomer based on a 2,2'-biindole core, as the prototype of a new inherently chiral monomer family, whose properties could be modulable through functionalization of the pyrrolic N atoms. By fast, regular electrooligomerization the new monomer yields inherently chiral films with high, reversible electroactivity and, above all, impressive enantioselectivity towards very different chiral probes, some of pharmaceutical interest, as general-scope electrode surfaces. Such results, while opening the way to a new, attractive inherently chiral selector class, nicely confirm the general validity of the inherent chirality strategy for chiral electrochemistry. Furthermore, the enantioselectivity of the new selectors not only holds with electroactive chiral probes, but also with circularly polarized light components as well as electron spins, resulting in good chiroptical and spin filter performances, which suggests fascinating correlations between the three contexts.

Impressive spin-related effects are observed in cyclic voltammetry (CV) experiments performed under an applied magnetic field on a non-ferromagnetic electrode modified with a thin electroactive oligothiophene film, either "inherently chiral" or featuring chiral pendants with stereogenic centres. When flipping the magnet's north/south orientation, the CV peaks of two achiral, chemically reversible Fe(iii)/Fe(ii) redox couples in aqueous or organic solution undergo impressive potential shifts (up to nearly 0.5 V depending on protocol conditions), specularly by changing the film's ( R )- or ( S )-configuration. The magnitude of the potential shift decreases upon increasing both the polymer film thickness and the distance between the permanent magnet and the electrode surface. Such unprecedented spin-related redox potential modulation, obtained in the absence of a magnetic electrode acting as a spin injector, provides striking evidence (as well as an attractive evaluation criterion) of the spin selectivity properties of chiral thin films.

Chiral electroanalysis could be regarded as the highest recognition degree in electrochemical sensing, implying the ability to discriminate between specular images of an electroactive molecule, particularly in terms of significant peak potential difference. A groundbreaking strategy was recently proposed, based on the use of "inherently chiral" molecular selectors, with chirality and key functional properties originating from the same structural element. Large differences in peak potentials have been observed for the enantiomers of different chiral molecules, also of applicative interest, using different selectors, all of them based on atropisomeric biheteroaromatic scaffolds of axial stereogenicity. However, helicene systems also provide inherently chiral building blocks with attractive features. In this paper the enantiodiscrimination performances of enantiopure inherently chiral films obtained by electrooxidation of a thiahelicene monomer with helicoidal stereogenicity are presented for the first time. The outstanding potentialities of this novel approach are evaluated towards chiral probes with different chemical nature and bulkiness, in comparison with a representative case of the so far exploited class of inherently chiral selectors with axial stereogenicity. It is also verified that the high enantiodiscrimination ability holds as well for electron spins, as for atropisomeric selectors.

"Inherently chiral" thiophene-based electroactive oligomer films have recently been shown to exhibit outstanding chirality manifestations. One of the most exciting among them is an unprecedented enantioselection ability as electrode surfaces. In fact, in preliminary chiral voltammetry experiments, the new electrodes have been shown to both discriminate the enantiomers of chiral probes (either enantiopure or in a mixture, in terms of large differences in peak potentials) and quantify them (in terms of linear dynamic ranges in peak currents), without the need for preliminary separation steps. Such ability has now been tested on a series of chiral DOPA-related molecules, from phenolic amino acid tyrosine (together with its methyl ester) to catecholic amino acid DOPA (together with its methyl ester), to catecholamine epinephrine (adrenaline). The wide-range enantioselectivity of the new inherently chiral electrode surfaces is fully confirmed, as large peak potential differences are obtained for probe enantiomers of the whole series working in common aqueous buffers. Moreover, interesting modulating effects on enantiodiscrimination can be observed as a function of both molecular structure and pH. Graphical abstract Inherently chiral thiophene-based electrodes at work with pharmaceutically relevant probes.

During the last decades, several studies have proposed manganese (Mn) complexes as alternative contrast agents for magnetic resonance imaging (MRI). With the nanotechnology surge in recent years, different types of Mn-based nanoparticles (Nps) have been developed. However, to design effective and safe administration procedures, preliminary studies on target cells, aimed at verifying their full biocompatibility and biodegradability, are mandatory. In this study, MnO containing-Nps encapsulated in a phospholipidic shell (PL-MnO Nps) were tested in cultured cells and flow cytometry; confocal and transmission electron microscopy were combined to understand the Nps uptake mechanism, intracellular distribution and degradation pathways, as well as possible organelle alterations. The results demonstrated that PL-MnO Nps undergo rapid and massive cell internalization, and persist free in the cytoplasm before undergoing lysosomal degradation without being cytotoxic or inducing subcellular damage. Based on the results with this cell model in vitro, PL-MnO Nps thus proved to be suitably biocompatible, and may be envisaged as very promising tools for therapeutic and diagnostic applications, as drug carriers or contrast agent for MRI., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Arsenic and its inorganic compounds are classified as carcinogenic to humans. Exposures to inorganic arsenic (iAs) in drinking water are associated with both carcinogenic and non-carcinogenic effects. The risk assessment of exposures to low-moderate levels of environmental arsenic (As) is a challenging objective for research and public health. The SEpiAs study, funded by the Italian Ministry of Health (CCM), was carried out in four areas with arsenic pollution prevalently of natural origin, Amiata and Viterbo areas, or of industrial origin, Taranto and Gela., Materials and Methods: 271 subjects (132 men) aged 20-44, were randomly sampled stratifying by area, gender and age classes. Individual data on residential history, socio-economic status, environmental and occupational exposures, lifestyle and dietary habits, were collected through interviews using questionnaire. In urine samples of recruited subjects, the concentration of inorganic arsenic (iAs) and methylated species (MMA, DMA) was measured using inductively coupled mass spectrometer (DRCICP- MS), after chromatographic separation (HPLC). Molecular biomarkers and biomarkers of DNA damage, as well as markers of cardiovascular risk were measured The distributions of iAs and iAs+MMA+DMA were described by area and gender, geometric mean (GM), percentiles and standard deviation (SD). The associations between As species and variables collected by questionnaire were evaluated by multiple regression analysis., Results: Results showed a high variability of As species within and among areas. Gela and Taranto samples showed higher iAs concentration compared to Viterbo and Amiata. Subjects with iAs>1,5 μg/L or iAs+MMA+DMA>15 μg/L (thresholds suggested by the Italian Society of Reference Values), are 137 (50,6%) and 68 (25,1%), respectively. A positive association between iAs and use of drinking water emerged in the Viterbo sample, between iAs and occupational exposure in the Gela and Taranto samples. Fish consumption was associated with higher iAs concentration in the whole sample, and particularly in men of the Gela sample. Similar results were observed for iAs+MMA+DMA. Subjects with iAs or iAs+MMA+DMA values higher than the 95th percentile were 15 (6Taranto, 5 Gela, 3Viterbo, 1 Amiata). The relationships between iAs and organic species (methylation efficiency ratios) were different between sex in the four areas. The relevance of polymorphisms AS3MT Met287Thr, GST-T1, GST-M1, OGG1 was confirmed. The analysis of carotid intima-media-thickness showed normal values, but higher among man of Viterbo, Taranto and Gela areas., Conclusions: Results are informative of exposure to inorganic and organic As in large or at least non-negligible quotas of the samples. The SEpiAs results suggest a further deepening on routes of exposure to arsenic species, and support the recommendation to implement primary prevention measures to reduce population exposure.

Multiple Sclerosis (MS) is a chronic disease of the central nervous system, the etiology of which, although not completely known, involves inflammation and autoimmunity. In the present study we aimed at identifying molecular markers of apoptosis, cellular stress and DNA damage in isolated peripheral blood mononuclear cells (PBMCs) of MS patients. The analysis was carried on 19 relapsing-remitting untreated MS patients and 13 healthy individuals. We investigated the emergency-driven synthesis of poly(ADP-ribose) (PAR), the expression level of the constitutive enzyme poly(ADP-ribose) polymerase-1 (PARP-1) and the DNA damage-induced phosphorylation of histone H2AX. PAR accumulation, PARP-1 and phosphorylated H2AX (γH2AX) were detected by immunofluorescence experiments on PBMCs isolated from 19 patients and 13 healthy volunteers. Our results show for the first time a net increased amount in PAR and γH2AX in MS patients compared to healthy individuals. Patients were further subdivided in three groups, according to the neuroimaging (MRI)-based classification of disease phase. Remarkably, we found a positive correlation between the level of γH2AX and MS aggressiveness. In addition, apoptosis in PBMCs was monitored by flow cytometry of both phosphatidylserine exposure (revealed by Annexin V-FITC labeling) and membrane permeability to propidium iodide. Our observations provide the evidence that the number of apoptotic cells was significantly higher in patients compared to healthy individuals, thus suggesting that apoptosis could affect MS lymphocyte function.