An unprecedented palladium-arsenic catalytic cycle for nitriles hydration

An unprecedented palladium/arsenic-based catalytic cycle for the hydration of nitriles to the corresponding amides is here described. It occurs in exceptionally mild conditions such as neutral pH and moderate temperature (60°C). The versatility of this new catalytic cycle was tested on various nitriles from aliphatic to aromatic. Also, the effect of ring substitution with electron withdrawing and electron donating groups was investigated in the cases of aromatic nitriles, as well as the effect of potentially interferent functional groups such as hydroxy group or pyridinic nitrogen. Furthermore, a pilot study on the potential suitability of this approach for its scale-up is presented, revealing that the catalytic cycle could be potentially and quickly scaled up

AS101: An overview on a leading tellurium-based prodrug

Inorganic chemistry holds a central role in the management of several diseases both from the diagnostic as well as from the therapeutic point of view. Various platinum drugs are approved at the global or local level for cancer treatment while other transition metals are used for different therapeutic applications or diagnosis. However, even semimetals i.e., the elements which lie on the diagonal connecting boron to polonium are being used in medicine where some compounds with therapeutic properties have been approved by the Food and drugs Administration (FDA) and the European Medicinal Agency (EMA). In the last decades growing attention has been devoted towards tellurium for the preparation of pharmacologically active agents. In this context, Ammonium trichloro(dioxoethylene-O,O′)tellurate (AS101) emerged as a reference tellurium-based compound. This Te(IV) compound is well tolerated in animal models and its peculiar reactivity towards thiol residues of enzymes such as cysteine proteases is at the heart of its pharmacological effects. Actually, AS101 entered several clinical trials due to its good tolerability. In this mini-review the main chemical and biological aspects of this promising metalloid-based drug are briefly summarized and the outcomes as well as future perspectives for the design of improved Te-based compounds are discussed

Metallo therapeutics for COVID-19. Exploiting metal-based compounds for the discovery of new antiviral drugs

Introduction: The COVID-19 pandemic poses an unprecedented challenge for the rapid discovery of drugs against this life-threatening disease. Owing to the peculiar features of the metal centers that are currently used in medicinal chemistry, metallodrugs might offer an excellent opportunity to achieve this goal. Areas covered: Two main strategies for developing metal-based drugs against the SARS-CoV-2 are herein illustrated. Firstly, a few clinically approved metallodrugs could be evaluated in patients according to a ‘drug repurposing’ approach. To this respect, the gold drug auranofin seems a promising candidate, but some other clinically established metal compounds are worthy of a careful evaluation as well. On the other hand, libraries of inorganic compounds, featuring a large chemical diversity, should be screened to identify the most effective molecules. This second strategy might be assisted by a pathway-driven discovery approach arising from a preliminary knowledge of the mode of action, exploitable to inhibit the functional activities of the key viral proteins. Also, attention must be paid to selectivity and toxicity issues. Expert opinion: The medicinal inorganic chemistry community may offer a valuable contribution against COVID-19. The screening of metallodrugs’ libraries can expand the explored ‘chemical space’ and increase the chance of finding effective anti-COVID agents

A simulation code to assist designing space missions of the Airwatch type

The design of an Airwatch type space mission can greatly benefit from a flexible simulation code for establishing the values of the main parameters of the experiment. We present here a code written for this purpose. The cosmic ray primary spectrum at very high energies, the atmosphere modelling, the fluorescence yield, the photon propagation and the detector response are taken into account in order to optimize the fundamental design parameters of the experiment, namely orbit height, field of view, mirror radius, number of pixels of the focal plane, threshold of photo-detection. The optimization criterion will be to maximize counting rates versus mission cost, which imposes limits both on weight and power consumption. Preliminary results on signals with changing energy and zenith angle of incident particles are shown

Following the Problem Organisation: A Design Strategy for Engineering Emergence

To support the development of self-organising systems, we explain and rationalise the following architectural strategy: directly mapping the solution decomposition on the problem organisation and only relying on the problem abstractions for the design. We illustrate this with an example from swarm robotics

On the Different Mode of Action of Au(I)/Ag(I)-NHC Bis-Anthracenyl Complexes Towards Selected Target Biomolecules

Gold and silver N-heterocyclic carbenes (NHCs) are emerging for therapeutic applications. Multiple techniques are here used to unveil the mechanistic details of the binding to different biosubstrates of bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) silver chloride [Ag(EIA)2]Cl and bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) gold chloride [Au(EIA)2]Cl. As the biosubstrates, we tested natural double-stranded DNA, synthetic RNA polynucleotides (single-poly(A), double-poly(A)poly(U) and triple-stranded poly(A)2poly(U)), DNA G-quadruplex structures (G4s), and bovine serum albumin (BSA) protein. Absorbance and fluorescence titrations, mass spectrometry together with melting and viscometry tests show significant differences in the binding features between silver and gold compounds. [Au(EIA)2]Cl covalently binds BSA. It is here evidenced that the selectivity is high: low affinity and external binding for all polynucleotides and G4s are found. Conversely, in the case of [Ag(EIA)2]Cl, the binding to BSA is weak and relies on electrostatic interactions. [Ag(EIA)2]Cl strongly/selectively interacts only with double strands by a mechanism where intercalation plays the major role, but groove binding is also operative. The absence of an interaction with triplexes indicates the major role played by the geometrical constraints to drive the binding mode

Diruthenium(ii,iii) paddlewheel complexes: effects of bridging and axial ligands on anticancer properties

This article provides an overview of the application of diruthenium(ii,iii) paddlewheel complexes for anticancer purposes. The use of this coordinative construct is indeed attractive because it provides an excellent opportunity to combine the pharmacological properties of the dimetallic ruthenium center with those derived from the specific choice of ligands bearing a carboxylic function capable of coordination towards the Ru-Ru core. Indeed, the combination of carboxylate ligands with specific anticancer properties and the dimetallic center permits the production of new entities endowed with improved biological profiles. Additionally, these systems allow the simultaneous multiple deliveries of a drug to the target site. Nevertheless, in order to obtain the desired effects, it is mandatory to consider some relevant chemico-physical aspects such as the steric hindrance of the ligands or the possibility of their release under specific biological conditions that should be taken into account in the design of effective complexes. Accordingly, through various examples from the literature, the key features of this family of unconventional compounds are summarized here, also providing useful hints for the design of improved diruthenium(ii,iii) paddlewheel complexes

A Graphene Oxide-Angiogenin Theranostic Nanoplatform for the Therapeutic Targeting of Angiogenic Processes: The Effect of Copper-Supplemented Medium

Graphene oxide (GO) nanosheets with different content in the defective carbon species bound to oxygen sp3 were functionalized with the angiogenin (ANG) protein, to create a novel nanomedicine for modulating angiogenic processes in cancer therapies. The GO@ANG nanocomposite was scrutinized utilizing UV-visible and fluorescence spectroscopies. GO exhibits pro- or antiangiogenic effects, mostly attributed to the disturbance of ROS concentration, depending both on the total concentration (i.e., >100 ng/mL) as well as on the number of carbon species oxidized, that is, the C/O ratio. ANG is considered one of the most effective angiogenic factors that plays a vital role in the angiogenic process, often in a synergic role with copper ions. Based on these starting hypotheses, the GO@ANG nanotoxicity was assessed with the MTT colorimetric assay, both in the absence and in the presence of copper ions, by in vitro cellular experiments on human prostatic cancer cells (PC-3 line). Laser confocal microscopy (LSM) cell imaging evidenced an enhanced internationalization of GO@ANG than bare GO nanosheets, as well as significant changes in cell cytoskeleton organization and mitochondrial staining compared to the cell treatments with free ANG