Ruthenium(II) Polypyridyl Complexes with Benzoxazole Derivatives and Non-Innocent Ligands as Effective Antioxidants in Human Neuroblasts.

Ruthenium(II) polypyridyl complexes continue to raise increasing interest for the encouraging results in several biomedical areas. Considering their vast chemical-physical repertoire, in particular the possibility to switch from the sensitization of reactive oxygen species (ROS) to ROS-scavenging abilities by tuning the nature of their ligands, it is therefore surprising that their potential as antioxidants has not been largely investigated so far. Herein, we explored the antioxidant behaviour of the novel ruthenium compound [Ru(dbpy)(2,3-DAN)Cl]PF6 (Ru1), featuring a benzoxazole derivative (dpby=2,6-bis(4-methyl-2-benzoxazolyl)pyridine) and the non-innocent 2,3-diamminonaftalene (2,3-DAN) ligand, along with the reference tpy-containing analogue [Ru(tpy)(2,3-DAN)Cl]PF6 (Ru2) (tpy=2,2':6',2''-terpyridine). Following the synthesis and the electrochemical characterization, chemical antioxidant assays highlighted the beneficial role of dpby for the ROS-scavenging properties of Ru1. These data have been corroborated by the highest protective effect of Ru1 against the oxidative stress induced in SH-SY5Y human neuroblastoma, which exerts pro-survival and anti-inflammatory actions. The results herein reported highlight the potential of Ru1 as pharmacological tool in neurodegenerative diseases and specially prove that the antioxidant properties of such compounds are likely the result of a non-trivial synergetic action involving the bioactive ligands in their chemical architectures.

Development of a flow system for decentralized electrochemical analysis of heavy metals using screen-printed electrodes: the importance of sensor stability.

Year after year, the need for decentralized tools to tackle the monitoring of heavy metal levels in the environment gradually increases. In this context, suitable electrochemical methodologies are widely established and particularly attractive for the production of low-cost miniaturized field-deployable analytical platforms. This work focused on the development of an automatable portable system based on square-wave anodic stripping voltammetry (SWASV) for the on-line detection of heavy metals. The surface of the sensors is appropriately modified and coupled with a fluidic system equipped with an ad-hoc designed flow cell. A custom software tool was introduced to handle the remote-controlled potentiostat and automate the various steps of the procedure, including stirring operations, cleaning phases, SWASV measurements, and data collection. After studying technical and analytical challenges, the final system developed was applied to the simultaneous detection of Cd(II), Pb(II), and Cu(II) in solution, achieving sub-ppb detection limits. Additionally, the practical applicability of the method was successfully applied to river water samples collected from the Loire basin in France.

Characterization of a Ruthenium(II) Complex in Singlet Oxygen-Mediated Photoelectrochemical Sensing.

A water-soluble ruthenium(II) complex (L), capable of producing singlet oxygen (1O2) when irradiated with visible light, was used to modify the surface of an indium-tin oxide (ITO) electrode decorated with a nanostructured layer of TiO2 (TiO2/ITO). Singlet oxygen triggers the appearance of a cathodic photocurrent when the electrode is illuminated and biased at a proper reduction potential value. The L/TiO2/ITO electrode was first characterized with cyclic voltammetry, impedance spectroscopy, NMR, and Raman spectroscopy. The rate constant of singlet oxygen production was evaluated by spectrophotometric measurements. Taking advantage of the oxidative process initiated by 1O2, the analysis of phenolic compounds was accomplished. Particularly, the 1O2-driven oxidation of hydroquinone (HQ) produced quinone moieties, which could be reduced back at the electrode surface, biased at -0.3 V vs Ag/AgCl. Such a light-actuated redox cycle produced a photocurrent dependent on the concentration of HQ in solution, exhibiting a limit of detection (LOD) of 0.3 µmol dm-3. The L/TiO2/ITO platform was also evaluated for the analysis of p-aminophenol, a commonly used reagent in affinity sensing based on alkaline phosphatase.

Practical tips and new trends in electrochemical biosensing of cancer-related extracellular vesicles.

To tackle cancer and provide prompt diagnoses and prognoses, the constantly evolving biosensing field is continuously on the lookout for novel markers that can be non-invasively analysed. Extracellular vesicles (EVs) may represent a promising biomarker that also works as a source of biomarkers. The augmented cellular activity of cancerous cells leads to the production of higher numbers of EVs, which can give direct information on the disease due to the presence of general and cancer-specific surface-tethered molecules. Moreover, the intravesicular space is enriched with other molecules that can considerably help in the early detection of neoplasia. Even though EV-targeted research has indubitably received broad attention lately, there still is a wide lack of practical and effective quantitative procedures due to difficulties in pre-analytical and analytical phases. This review aims at providing an exhaustive outline of the recent progress in EV detection using electrochemical and photoelectrochemical biosensors, with a focus on handling approaches and trends in the selection of bioreceptors and molecular targets related to EVs that might guide researchers that are approaching such an unstandardised field.

Progesterone and ß-hCG Determination Using an Electrochemical Combo-Strip for Pregnancy Monitoring.

The development of analytical devices that can allow an easy, rapid and cost-effective measurement of multiple markers, such as progesterone and ß-hCG, could have a role in decreasing the burden associated with pregnancy-related complications, such as ectopic pregnancies. Indeed, ectopic pregnancies are a significant contributor to maternal morbidity and mortality in both high-income and low-income countries. In this work, an effective and highly performing electrochemical strip for a combo determination of progesterone and ß-hCG was developed. Two immunosensing approaches were optimized for the determination of these two hormones on the same strip. The immunosensors were realized using cost-effective disposable electrode arrays and reagent-saving procedures. Each working electrode of the array was modified with both the IgG anti-ß-hCG and anti-progesterone, respectively. By adding the specific reagents, progesterone or ß-hCG can then be determined. Fast quantitative detection was achieved, with the analysis duration being around 1 h. Sensitivity and selectivity were assessed with a limit of detection of 1.5 × 10-2 ng/mL and 2.45 IU/L for progesterone and ß-hCG, respectively. The proposed electrochemical combo-strip offers great promise for rapid, simple, cost-effective, and on-site analysis of these hormones and, thus, for the development of a point-of-care diagnostic tool for early detection of pregnancy-related complications.

Nitroimidazole-Based Ruthenium(II) Complexes: Playing with Structural Parameters to Design Photostable and Light-Responsive Antibacterial Agents.

5-Nitroimidazole (5NIMH), chosen as a molecular model of nitroimidazole derivatives, which represent a broad-spectrum class of antimicrobials, was incorporated into the ruthenium complexes [Ru(tpy)(phen)(5NIM)]PF6 (1) and [Ru(tpy)(dmp)(5NIM)]PF6 (2) (tpy = terpyridine, phen = phenanthroline, dmp = 2,9-dimethyl-1,10-phenanthroline). Besides the uncommon metal coordination of 5-nitroimidazole in its imidazolate form (5NIM), the different architectures of the spectator ligands (phen and dmp) were exploited to tune the "mode of action" of the resulting complexes, passing from a photostable compound where the redox properties of 5NIMH are preserved (1) to one suitable for the nitroimidazole phototriggered release (2) and whose antibacterial activity against B. subtilis, chosen as cellular model, is effectively improved upon light exposure. This study may provide a fundamental knowledge on the use of Ru(II)-polypyridyl complexes to incorporate and/or photorelease biologically relevant nitroimidazole derivatives in the design of a novel class of antimicrobials.

Electrochemical sensors based on sewage sludge-derived biochar for the analysis of anthocyanins in berry fruits.

The reutilization of waste and the reduction of the general environmental impact of every production are fundamental goals that must be achieved in the framework of a circular economy. Recycled carbon-rich materials may represent a promising alternative to other less-sustainable carbonaceous materials used in the production of electrochemical sensing platforms. Herein, we propose an innovative carbon paste electrode (CPE) composed of biochar derived from biological sludge obtained from municipal and industrial wastewater treatment plants. The physicochemical properties of the biochar after a chemical treatment with an acidic solution obtained from industrial by-products were investigated. The electrode surface characterization was carried out by analyzing common redox probes and multiple phenols bearing varying numbers of -OH and -OCH3 groups in their structure. Furthermore, the CPE was also tested on the evaluation of the phenolic fingerprints of Vaccinium myrtillus, Vaccinium uliginosum subsp. gaultherioides, and Fragaria × ananassa. Standard anthocyanin mixtures and extracts of the aforementioned fruits were analyzed to provide a phenolic characterization of real samples. The obtained results show that the sewage sludge-derived biochar can be a promising material for the development of electroanalytical sensors.

Highly Charged Ru(II) Polypyridyl Complexes as Photosensitizer Agents in Photodynamic Therapy of Epithelial Ovarian Cancer Cells.

Ovarian cancer recurrence is frequent and associated with chemoresistance, leading to extremely poor prognosis. Herein, we explored the potential anti-cancer effect of a series of highly charged Ru(II)-polypyridyl complexes as photosensitizers in photodynamic therapy (PDT), which were able to efficiently sensitize the formation of singlet oxygen upon irradiation (Ru12+ and Ru22+) and to produce reactive oxygen species (ROS) in their corresponding dinuclear metal complexes with the Fenton active Cu(II) ion/s ([CuRu1]4+ and [Cu2Ru2]6+). Their cytotoxic and anti-tumor effects were evaluated on human ovarian cancer A2780 cells both in the absence or presence of photoirradiation, respectively. All the compounds tested were well tolerated under dark conditions, whereas they switched to exert anti-tumor activity following photoirradiation. The specific effect was mediated by the onset of programed cell death, but only in the case of Ru12+ and Ru22+ was preceded by the loss of mitochondrial membrane potential soon after photoactivation and ROS production, thus supporting the occurrence of apoptosis via type II photochemical reactions. Thus, Ru(II)-polypyridyl-based photosensitizers represent challenging tools to be further investigated in the identification of new therapeutic approaches to overcome the innate chemoresistance to platinum derivatives of some ovarian epithelial cancers and to find innovative drugs for recurrent ovarian cancer.

A microfluidic card-based electrochemical assay for the detection of sulfonamide resistance genes.

Most electroanalytical detection schemes for DNA markers require considerable time and effort from expert personnel to thoroughly follow the analysis and obtain reliable outcomes. This work aims to present an electrochemical assay performed inside a small card-based platform powered by microfluidic manipulation, requiring minimal human intervention and consumables. The assay couples a sample/signal dual amplification and DNA-modified magnetic particles for the detection of DNA amplification products. Particularly, the sul1 and sul4 genes involved in the resistance against sulfonamide antibiotics were analyzed. As recognized by the World Health Organization, antimicrobial resistance threatens global public health by hampering medication efficacy against infections. Consequently, analytical methods for the determination of such genes in environmental and clinical matrices are imperative. Herein, the resistance genes were extracted from E. coli cells and amplified using an enzyme-assisted isothermal amplification at 37 °C. The amplification products were analyzed in an easily-produced, low-cost, card-based set-up implementing a microfluidic system, demanding limited manual work and small sample volumes. The target amplicon was thus captured and isolated using versatile DNA-modified magnetic beads injected into the microchannel and exposed to the various reagents in a continuously controlled microfluidic flow. After the optimization of the efficiency of each phase of the assay, the platform achieved limits of detections of 44.2 pmol L-1 for sul1 and 48.5 pmol L-1 for sul4, and was able to detect down to ≥500-fold diluted amplification products of sul1 extracted from E. coli living cells in around 1 h, thus enabling numerous end-point analyses with a single amplification reaction.

The Role of Peptides in the Design of Electrochemical Biosensors for Clinical Diagnostics.

Peptides represent a promising class of biorecognition elements that can be coupled to electrochemical transducers. The benefits lie mainly in their stability and selectivity toward a target analyte. Furthermore, they can be synthesized rather easily and modified with specific functional groups, thus making them suitable for the development of novel architectures for biosensing platforms, as well as alternative labelling tools. Peptides have also been proposed as antibiofouling agents. Indeed, biofouling caused by the accumulation of biomolecules on electrode surfaces is one of the major issues and challenges to be addressed in the practical application of electrochemical biosensors. In this review, we summarise trends from the last three years in the design and development of electrochemical biosensors using synthetic peptides. The different roles of peptides in the design of electrochemical biosensors are described. The main procedures of selection and synthesis are discussed. Selected applications in clinical diagnostics are also described.

Gold nanoparticles modified graphene platforms for highly sensitive electrochemical detection of vitamin C in infant food and formulae.

An easy and reliable method based on a novel electroanalytical nanostructured sensor has been developed to perform quantification of vitamin C in commercial and fortified cow-milk-based formulae and foods for infants and young children. The work is motivated by the need of a reliable analytical tool to be applied in quality control laboratories for the quantitative assessment of vitamin C where its rapid and cost-effective monitoring is essential. The ad hoc designed sensor, based on disposable screen-printed carbon electrodes modified with Au nanoparticles decorated reduced graphene oxide flakes, exhibits a LOD of 0.088 mg L-1. The low cost, easy sample preparation, fast response and high reproducibility (RSD ≈ 8%) of the proposed method highlight its suitability for usage in quality control laboratories for determining vitamin C in real complex food matrices, envisaging the application of the sensing platform in the determination of other compounds relevant in food chemistry and food manufacturing.

Sustainable Printed Electrochemical Platforms for Greener Analytics.

The development of miniaturized electrochemical platforms holds considerable importance for the in situ analytical monitoring of clinical, environmental, food, and forensic samples. However, it is crucial to pay attention to the sustainability of materials chosen to fabricate these devices, in order to decrease the amount and the impact of waste coming from their production and use. In the framework of a circular economy and an environmental footprint reduction, the electrochemical sensor production technology must discover the potentiality of innovative approaches based on techniques and materials that can satisfy the needs of environmental-friendly and greener analytics. The aim of this review is to describe some of the printing technologies most used for sensor production, including screen-printing, inkjet-printing, and 3D-printing, and the low-impact materials that are recently proposed for these techniques, such as polylactic acid, cellulose, silk proteins, biochar.