A water-responsive calix[4]resorcinarene system: self-assembly and fluorescence modulation.

This study explores how water content modulates the self-assembly and fluorescence behavior of two novel calix[4]resorcinarene macrocycles. These macrocycles transition from large, flattened structures in pure THF to large giant vesicles (500-5000 nm) coexisting with small micelles (3.4-3.

7-Amino-[1,2,4]triazolo[1,5-a][1,3,5]triazines as CK1δ inhibitors: Exploring substitutions at the 2 and 5-positions.

CK1δ is a serine-threonine kinase involved in several pathological conditions including neuroinflammation and neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. Specifically, it seems that an inhibition of CK1δ could have a neuroprotective effect in these conditions. Here, a series of [1,2,4]triazolo[1,5-a][1,3,5]triazines were developed as ATP-competitive CK1δ inhibitors.

The effect of water in THF/water mixtures on CMC, aggregation sizes, and fluorescence quenching of a new calix[4]resorcinarene macrocycle.

This study explores how water content modulates the self-assembly and fluorescence behavior of a novel calixarene, C1. C1 forms large, flattened structures in pure THF, but water addition triggers a transition to smaller, unimodal clusters. A critical micellar concentration (CMC) is identified, decreasing with increasing water content.

Celebrating Maurizio Prato's Passion, Talent and Imagination.

This Editorial introduces a Special Collection of papers dedicated to Maurizio Prato, featuring prominent examples of his team's efforts to integrate complex frontier research with pioneering achievements in the field of carbon nanostructures and molecular nanoscience.

Gaucher Disease: A Glance from a Medicinal Chemistry Perspective.

Rare diseases are particular pathological conditions affecting a limited number of people and few drugs are known to be effective as therapeutic treatment. Gaucher disease, caused by a deficiency of the lysosomal enzyme glucocerebrosidase, belongs to this class of disorders, and it is considered the most common among the Lysosomal Storage Diseases. The two main therapeutic approaches are the Enzyme Replacement Therapy (ERT) and the Substrate Reduction Therapy (SRT).

Pyrazolo-triazolo-pyrimidine Scaffold as a Molecular Passepartout for the Pan-Recognition of Human Adenosine Receptors.

Adenosine receptors are largely distributed in our organism and are promising therapeutic targets for the treatment of many pathologies. In this perspective, investigating the structural features of the ligands leading to affinity and/or selectivity is of great interest. In this work, we have focused on a small series of pyrazolo-triazolo-pyrimidine antagonists substituted in positions 2, 5, and N8, where bulky acyl moieties at the N5 position and small alkyl groups at the N8 position are associated with affinity and selectivity at the A adenosine receptor even if a good affinity toward the A adenosine receptor has also been observed.

[1,2,4]Triazolo[1,5-c]pyrimidines as Tools to Investigate A Adenosine Receptors in Cancer Cell Lines.

The A adenosine receptor is an interesting target whose role in cancer is controversial. In this work, a structural investigation at the 2-position of the [1,2,4]triazolo[1,5-c]pyrimidine nucleus was performed, finding new potent and selective A adenosine receptor antagonists such as the ethyl 2-(4-methoxyphenyl)-5-(methylamino)-[1,2,4]triazolo[1,5-c]pyrimidine-8-carboxylate (20, DZ123) that showed a K value of 0.47 nM and an exceptional selectivity profile over the other adenosine receptor subtypes.

Functionalization of filled radioactive multi-walled carbon nanocapsules by arylation reaction for delivery of radio-therapy.

Functionalized multi-walled carbon nanotubes (MWCNTs) containing radioactive salts are proposed as a potential system for radioactivity delivery. MWCNTs are loaded with isotopically enriched 152-samarium chloride (SmCl), the ends of the MWCNTs are sealed by high temperature treatment, and the encapsulated Sm is neutron activated to radioactive Sm. The external walls of the radioactive nanocapsules are functionalized through arylation reaction, to introduce hydrophilic chains and increase the water dispersibility of CNTs.

Nanocellulose/Fullerene Hybrid Films Assembled at the Air/Water Interface as Promising Functional Materials for Photo-electrocatalysis.

Cellulose nanomaterials have been widely investigated in the last decade, unveiling attractive properties for emerging applications. The ability of sulfated cellulose nanocrystals (CNCs) to guide the supramolecular organization of amphiphilic fullerene derivatives at the air/water interface has been recently highlighted. Here, we further investigated the assembly of Langmuir hybrid films that are based on the electrostatic interaction between cationic fulleropyrrolidines deposited at the air/water interface and anionic CNCs dispersed in the subphase, assessing the influence of additional negatively charged species that are dissolved in the water phase.

Distribution in the brain and possible neuroprotective effects of intranasally delivered multi-walled carbon nanotubes.

Carbon nanotubes (CNTs) are currently under active investigation for their use in several biomedical applications, especially in neurological diseases and nervous system injury due to their electrochemical properties. Nowadays, no CNT-based therapeutic products for internal use appear to be close to the market, due to the still limited knowledge on their fate after delivery to living organisms and, in particular, on their toxicological profile. The purpose of the present work was to address the distribution in the brain parenchyma of two intranasally delivered MWCNTs (MWCNTs 1 and a-MWCNTs 2), different from each other, the first being non electroconductive while the second results in being electroconductive.

Nanomaterial synthesis, an enabler of amyloidosis inhibition against human diseases.

Amyloid diseases are global epidemics with no cure currently available. In the past decade, the use of engineered nanomaterials as inhibitors or probes against the pathogenic aggregation of amyloid peptides and proteins has emerged as a new frontier in nanomedicine. In this Minireview, we summarize for the first time the pivotal role of chemical synthesis in enabling the development of this multidisciplinary field.

Thiolated Graphene Oxide Nanoribbons as Templates for Anchoring Gold Nanoparticles: Two-Dimensional Nanostructures for SERS.

Graphene oxide nanoribbons (GONRs), obtained from the oxidative unzipping of carbon nanotubes, have been investigated as building blocks towards reaching active platforms in surface-enhanced Raman scattering (SERS). The complete development of carbon nanomaterials is strongly related to the exploitation of their chemical versatility, so this work is focused on the positive effect that a specific chemical functionalization provides to the SERS effect when gold nanoparticles are used. The covalent derivatization of GONRs with terminal thiol groups boosts their interaction with different types of gold nanoparticles (namely, 'naked' or citrate-stabilized), and the resulting two-dimensional aggregates show an intense enhancement of the Raman scattering from the carbon nanostructures because of their two-dimensional extended aggregation pattern.

Neutron Activated Sm Sealed in Carbon Nanocapsules for Imaging and Tumor Radiotherapy.

Radiation therapy along with chemotherapy and surgery remain the main cancer treatments. Radiotherapy can be applied to patients externally (external beam radiotherapy) or internally (brachytherapy and radioisotope therapy). Previously, nanoencapsulation of radioactive crystals within carbon nanotubes, followed by end-closing, resulted in the formation of nanocapsules that allowed ultrasensitive imaging in healthy mice.

Covalent Decoration of Cortical Membranes with Graphene Oxide as a Substrate for Dental Pulp Stem Cells.

(1) Background: The aim of this study was to optimize, through a cheap and facile protocol, the covalent functionalization of graphene oxide (GO)-decorated cortical membrane (Lamina) in order to promote the adhesion, the growth and the osteogenic differentiation of DPSCs (Dental Pulp Stem Cells); (2) Methods: GO-coated Laminas were fully characterized by Scannsion Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) analyses. In vitro analyses of viability, membrane integrity and calcium phosphate deposition were performed; (3) Results: The GO-decorated Laminas demonstrated an increase in the roughness of Laminas, a reduction in toxicity and did not affect membrane integrity of DPSCs; and (4) Conclusions: The GO covalent functionalization of Laminas was effective and relatively easy to obtain. The homogeneous GO coating obtained favored the proliferation rate of DPSCs and the deposition of calcium phosphate.

A tool box to ascertain the nature of doping and photoresponse in single-walled carbon nanotubes.

The effect of doping on the electronic properties in bulk single-walled carbon nanotube (SWCNT) samples is studied for the first time using a new in situ Raman spectroelectrochemical method, and further verified by DFT calculations and photoresponse. We use p-/n-doped SWCNTs prepared by diazonium reactions as a versatile chemical strategy to control the SWCNT behavior. The measured and calculated data testify an acceptor effect of 4-aminobenzenesulfonic acid (p-doping), and a donor effect (n-doping) in the case of benzyl alcohol.

The idebenone metabolite QS10 restores electron transfer in complex I and coenzyme Q defects.

Idebenone is a hydrophilic short-chain coenzyme (Co) Q analogue, which has been used as a potential bypass of defective complex I in both Leber Hereditary Optic Neuropathy and OPA1-dependent Dominant Optic Atrophy. Based on its potential antioxidant effects, it has also been tested in degenerative disorders such as Friedreich's ataxia, Huntington's and Alzheimer's diseases. Idebenone is rapidly modified but the biological effects of its metabolites have been characterized only partially.

Epoxidation of Carbon Nanocapsules: Decoration of Single-Walled Carbon Nanotubes Filled with Metal Halides.

Methyl(trifluoromethyl)dioxirane (TFDO) can be used for the oxyfunctionalization of SWCNTs filled with NaI and LuCl₃ under mild conditions. The chosen metal halides are of interest for theranostics, both for imaging and therapy when in their radioactive form. The applied functionalization methodology does not require metal catalyst, preserves the integrity of the nanotubes during treatment, avoiding the release of the filling material.

Iron-related toxicity of single-walled carbon nanotubes and crocidolite fibres in human mesothelial cells investigated by Synchrotron XRF microscopy.

Carbon nanotubes (CNTs) are promising products in industry and medicine, but there are several human health concerns since their fibrous structure resembles asbestos. The presence of transition metals, mainly iron, in the fibres seems also implicated in the pathogenetic mechanisms. To unravel the role of iron at mesothelial level, we compared the chemical changes induced in MeT-5A cells by the exposure to asbestos (crocidolite) or CNTs at different content of iron impurities (raw-SWCNTs, purified- and highly purified-SWCNTs).

The Glitter of Carbon Nanostructures in Hybrid/Composite Hydrogels for Medicinal Use.

In recent years, we have witnessed to fast developments in the medicinal field of hydrogels containing various forms of integrated nanostructured carbon that adds interesting mechanical, thermal, and electronic properties. Besides key advances in tissue engineering (especially for conductive tissue, such as for the brain and the heart), there has been innovation also in the area of drug delivery on-demand, with engineered hydrogels capable of repeated response to light, thermal, or electric stimuli. This mini-review focusses on the most promising developments as applied to the gelation of protein/ peptide (including self-assembling amino acids and low-molecular-weight gelators), polysaccharide, and/or synthetic polymer components in medicine.

Shuttling as a Strategy to Control the Regiochemistry of Bis-Additions on Fullerene Derivatives.

The reactivity of a fullerene-stoppered rotaxane, a C60 monoadduct, towards a second cycloaddition reaction is explored. The close proximity of the macrocycle to the fullerene sphere is able to allosterically influence the second cycloaddition reaction, giving rise to a selected mixture of bis-adducts.

Kinetics of functionalised carbon nanotube distribution in mouse brain after systemic injection: Spatial to ultra-structural analyses.

Earlier studies proved the success of using chemically functionalised multi-walled carbon nanotubes (f-MWNTs) as nanocarriers to the brain. Little insight into the kinetics of brain distribution of f-MWNTs in vivo has been reported. This study employed a wide range of qualitative and quantitative techniques with the aim of shedding the light on f-MWNT's brain distribution following intravenous injection.

Multipurpose Nature of Rapid Covalent Functionalization on Carbon Nanotubes.

In the vast field of functionalization routes to carbon nanoforms, the fulfillment of such critical requirements as quick and nonharsh methods, good dispersibility, introduction of reactive groups, short reaction time, and low cost can be quite challenging. Traditional thermally induced diazonium chemistry on single-walled carbon nanotubes (SWCNTs) is revisited by using commercial anilines and providing useful insight into the versatility of this approach. Functionalized SWCNTs with multiple controllable features, such as degree (and ratio) of coverage, orthogonalization, doping, and high water dispersibility, are obtained by introducing benzenesulfonic acid and benzylamine moieties.

Effects of Two Fullerene Derivatives on Monocytes and Macrophages.

Two fullerene derivatives (fullerenes 1 and 2), bearing a hydrophilic chain on the pyrrolidinic nitrogen, were developed with the aim to deliver anticancer agents to solid tumors. These two compounds showed a significantly different behaviour on human neoplastic cell lines in vitro in respect to healthy leukocytes. In particular, the pyrrolidinium ring on the fullerene carbon cage brings to a more active compound.

Study of the cytotoxic effects of the new synthetic Isothiocyanate CM9 and its fullerene derivative on human T-leukemia cells.

One important strategy to develop effective anticancer agents is based on natural products. Many active phytochemicals are in human clinical trials and have been used for a long time, alone and in association with conventional anticancer drugs, for the treatment of various types of cancers. A great number of in vitro, in vivo and clinical reports document the multi-target anticancer activities of isothiocyanates and of compounds characterized by a naphthalenetetracarboxylic diimide scaffold.