Chirality Sensing of Cryptochiral Guests with Prism[n]arenes.

Optical chirality sensing has gained significant attention in recent years. Within this field, the quest for stereodynamic chiroptical probes capable of detecting cryptochiral guests presents a formidable challenge. Macrocycles exhibiting planar chirality have emerged as promising candidates for amplifying the chirality of cryptochiral guests. In this study, we demonstrate that the formation of host-guest complexes between cryptochiral molecules and planar chiral prismarenes triggers electronic circular dichroism (ECD) signals via host-guest complexation-induced chirality amplification. The absolute configuration of the most stable chiral macrocyclic host-guest complex has been established by resorting to both exciton model and DFT computations. Furthermore, we demonstrated that this supramolecular chirality sensing system can be employed to determine the enantiomeric composition of scalemic mixtures by measuring the ECD bands intensity. The information described here opens the way for the use of prismarenes as stereodynamic probes for sensing of cryptochiral guests.

The Resorcinarene Hexameric Capsule as a Supramolecular Photoacid to Trigger Olefin Hydroarylation in Confined Space.

The self-assembled resorcinarene capsule C6 shows remarkable photoacidity upon light irradiation, which is here exploited to catalyze olefin hydroarylation reactions in confined space. An experimental pKa* value range of -3.3--2.8 was estimated for the photo-excited hexameric capsule C6*, and consequently an increase in acidity of 8.8 log units was observed with respect to its ground state (pKa=5.5-6.0). This makes the hexameric capsule the first example of a self-assembled supramolecular photoacid. The photoacid C6* can catalyze hydroarylation reaction of olefins with aromatic substrates inside its cavity, while no reaction occurred between them in the absence of irradiation and/or capsule. DFT calculations corroborated a mechanism in which the photoacidity of C6* plays a crucial role in the protonation step of the aromatic substrate. A further proton transfer to olefin with a concomitant C-C bond formation and a final deprotonation step lead to product releasing.

Insights into the Friedel-Crafts Benzoylation of N-Methylpyrrole inside the Confined Space of the Self-Assembled Resorcinarene Capsule.

Friedel-Crafts benzoylation of N-methylpyrrole 2 can run inside the confined space of the hexameric resorcinarene capsule C. The bridged water molecules at the corner of C act as H-bonding donor groups to polarize the C-Cl bond of benzoyl chlorides 3a-f. Confinement effects on the regiochemistry of the FC benzoylation of N-methylpyrrole are observed. The nature of the para-substituents of 3a-f and their ability to establish H-bonds with the water molecules of C work synergistically with the steric constrictions imposed by the capsule to drive the regiochemistry of products 4a-f. QM investigations indicate that inside the cavity of C, the FC benzoylation of 2 has a bimolecular concerted SN2 mechanism, appropriately, above-plane nucleophilic vinylic substitution (SNVπ)─supported by H-bonding interactions between water molecules and both the leaving Cl atom and the carbonyl group.

Hexahexyloxycalix[6]arene, a Conformationally Adaptive Host for the Complexation of Linear and Branched Alkylammonium Guests.

Hexahexyloxycalix[6]arene 2b leads to the endo-cavity complexation of linear and branched alkylammonium guests showing a conformational adaptive behavior in CDCl3 solution. Linear n-pentylammonium guest 6a+ induces the cone conformation of 2b at the expense of the 1,2,3-alternate, which is the most abundant conformer of 2b in the absence of a guest. In a different way, branched alkylammonium guests, such as tert-butylammonium 6b+ and isopropylammonium 6c+, select the 1,2,3-alternate as the favored 2b conformation (6b+/6c+⊂2b1,2,3-alt), but other complexes in which 2b adopts different conformations, namely, 6b+/6c+⊂2bcone, 6b+/6c+⊂2bpaco, and 6b+/6c+⊂2b1,2-alt, have also been revealed. Binding constant values determined via NMR experiments indicated that the 1,2,3-alternate was the best-fitting 2b conformation for the complexation of branched alkylammonium guests, followed by cone > paco > 1,2-alt. Our NCI and NBO calculations suggest that the H-bonding interactions (+N-H···O) between the ammonium group of the guest and the oxygen atoms of calixarene 2b are the main determinants of the stability order of the four complexes. These interactions are weakened by increasing the guest steric encumbrance, thus leading to a lower binding affinity. Two stabilizing H-bonds are possible with the 1,2,3-alt- and cone-2b conformations, whereas only one H-bond is possible with the other paco- and 1,2-alt-2b stereoisomers.

Confused-Prism[5]arene: a Conformationally Adaptive Host by Stereoselective Opening of the 1,4-Bridged Naphthalene Flap.

The confused-prism[5]arene macrocycle (c-PrS[5]Me ) shows conformational adaptive behavior in the presence of ammonium guests. Upon guest inclusion, the 1,4-bridged naphthalene flap reverses its planar chirality from pS to pR (with reference to the pS(pR)4 enantiomer). Stereoselective directional threading is also observed in the presence of directional axles, in which up/down stereoisomers of homochiral (pR)5 -c-PrS[5]Me pseudorotaxanes are formed.

Untargeted metabolomic analysis by ultra-high-resolution mass spectrometry for the profiling of new Italian wine varieties.

The chemical composition of wine samples comprises numerous bioactive compounds responsible for unique flavor and health-promoting properties. Thus, it's important to have a complete overview of the metabolic profile of new wine products in order to obtain peculiar information in terms of their phytochemical composition, quality, and traceability. To achieve this aim, in this work, a mass spectrometry-based phytochemical screening was performed on seven new wine products from Villa D'Agri in the Basilicata region (Italy), i.e., Aglianico Bianco, Plavina, Guisana, Giosana, Malvasia ad acino piccolo, Colata Murro and Santa Sofia. Ultra-high-resolution mass spectrometry data were processed into absorption mode FT-ICR mass spectra, in order to remove artifacts and achieve a higher resolution and lower levels of noise. Accurate mass-to-charge ratio (m/z) values were converted into putative elemental formulas. Therefore, 2D van Krevelen diagrams were used as a tool to obtain molecular formula maps useful to perform a rapid and more comprehensive analysis of the wine sample metabolome. The presence of important metabolite classes, i.e., fatty acid derivatives, amino acids and peptides, carbohydrates and phenolic derivatives, was assessed. Moreover, the comparison of obtained metabolomic maps revealed some differences among profiles, suggesting their employment as metabolic fingerprints. This study shed some light on the metabolic composition of seven new Italian wine varieties, improving their value in terms of related bioactive compound content. Moreover, different metabolomic fingerprints were obtained for each of them, suggesting the use of molecular maps as innovative tool to ascertain their unique metabolic profile.

Carbocation catalysis in confined space: activation of trityl chloride inside the hexameric resorcinarene capsule.

Carbocation catalysis can be performed inside the confined space of the hexameric resorcinarene capsule. The inner cavity of the capsule can host the trityl carbocation, which catalyses the Diels-Alder reaction between dienes and unsaturated aldehydes. Experimental results and in silico calculations show that the hexameric resorcinarene capsule C6 can promote the formation of the trityl carbocation from trityl chloride through the cleavage of the carbon-halogen bond promoted by OH⋯X- hydrogen bonding. Here it is shown that the combination of the nanoconfined space and the latent carbocation catalysis provides a convenient complementary strategy for the typical carbocation catalysis. The latent strategy bypasses the typical pitfalls associated with active carbocations and provides control of the reaction efficiency in terms of reaction rate, conversion, and selectivity.

Molecular Recognition in an Aqueous Medium Using Water-Soluble Prismarene Hosts.

The synthesis of water-soluble prism[n]arenes (n = 5 and 6) bearing anionic carboxylato groups on the rims is described. The binding properties of this novel class of water-soluble hosts are studied by nuclear magnetic resonance and calorimetry. The complexation of singly and doubly charged ammonium guests with the more rigid pentamer is enthalpically driven by secondary interactions, while the thermodynamic fingerprint for the larger hexamer reveals driving forces that strongly depend on the guest charge and/or size.

Unusual Calixarenes Incorporating Chromene and Benzofuran Moieties Obtained via Propargyl Claisen Rearrangement.

Monopropargyloxy-tripropoxy-calix[4]arene 1 was subjected to a propargyl Claisen rearrangement to give unusual calix[3]arene[1]chromene and homocalix[3]arene[1]benzofuran macrocycles. Quantum mechanical density functional theory calculations indicated that an initial [3,3] sigmatropic reaction affords a highly reactive allene intermediate, stabilized by two main diradical pathways leading to six- and five-membered oxygenated rings. In the presence of a n-butylammonium guest, calix[3]arene[1]chromane 6 forms two stereoisomeric complexes stabilized by +N-H···O and cation···π interactions.

per-Hydroxylated Prism[n]arenes: Supramolecularly Assisted Demethylation of Methoxy-Prism[5]arene.

Methoxy-prism[5]arene PrS[5]Me is demethylated by a supramolecularly assisted reaction. In the presence of a tetramethylammonium cation, PrS[5]Me is demethylated by BBr3 in high yield, while in its absence a 55/40 mixture of PrS[5]OH/PrS[6]OH is formed. The dealkylation of prismarenes, such as PrS[6]R (R = Et, nPr) and c-PrS[5]Me, can be easily obtained in high yields in the presence of BBr3.

Chromogenic Properties of p-Pyridinium- and p-Viologen-Calixarenes and Their Cation-Sensing Abilities.

The synthesis of calix[4]- and -[6]arene derivatives P6(H)22+·(Cl-)2, V4(H)24+·(Cl-)2·(I-)2, and V6(H)24+·(Cl-)2·(I-)2 bearing N-linked pyridinium (P) and viologen (V) units at the upper rim is described here. A rare example of an anionic conformational template is reported for p-pyridiniumcalix[6]arene P6(H)22+, which adopts a 1,3,5-alternate conformation in the presence of chloride anions. Derivatives P6(H)22+·(Cl-)2, V6(H)24+·(Cl-)2·(I-)2, and V4(H)24+·(Cl-)2·(I-)2 show a negative solvatochromism, while their UV-vis acid-base titration evidenced that upon addition of a base, new bands appear at 487, 583, and 686 nm, respectively, due to the formation of betainic monodeprotonated species P6(H)1+, V6(H)13+, and V4(H)13+. These new bands were attributable to the intramolecular charge-transfer (CT) transition from the phenoxide to the pyridinium or viologen moiety and were responsive to the presence of cations. In fact, the band at 487 nm of P6(H)1+ was quenched in the presence of a hard Li+ cation, and the color of its acetonitrile solution was changed from pink to colorless upon addition of LiI. Consequently, this derivative can be considered as a useful host for the recognition and sensing of lithium cations.

An intramolecularly self-templated synthesis of macrocycles: self-filling effects on the formation of prismarenes.

Ethyl- and propyl-prism[6]arenes are obtained in high yields and in short reaction times, independent of the nature and size of the solvent, in the cyclization of 2,6-dialkoxynaphthalene with paraformaldehyde. PrS[6]Et or PrS[6]nPr adopt, both in solution and in the solid state, a folded cuboid-shaped conformation, in which four inward oriented alkyl chains fill the cavity of the macrocycle. On these bases, we proposed that the cyclization of PrS[6]Et or PrS[6]nPr occurs through an intramolecular thermodynamic self-templating effect. In other words, the self-filling of the internal cavity of PrS[6]Et or PrS[6]nPr stabilizes their cuboid structure, driving the equilibrium toward their formation. Molecular recognition studies, both in solution and in the solid state, show that the introduction of guests into the macrocycle cavity forces the cuboid scaffold to open, through an induced-fit mechanism. An analogous conformational change from a closed to an open state occurs during the endo-cavity complexation process of the pentamer, PrS[5]. These results represent a rare example of a thermodynamically controlled cyclization process driven through an intramolecular self-template effect, which could be exploited in the synthesis of novel macrocycles.

Modified Carboxymethylcellulose-Based Scaffolds as New Potential Ecofriendly Superplasticizers with a Retardant Effect for Mortar: From the Synthesis to the Application.

This article is focused on the research and development of new cellulose ether derivatives as innovative superplasticizers for mortar systems. Several synthetic strategies have been pursued to obtain new compounds to study their properties on cementitious systems as new bio-based additives. The new water-soluble admixtures were synthesized using a complex carboxymethylcellulose-based backbone that was first hydrolyzed and then sulfo-ethylated in the presence of sodium vinyl sulphonate. Starting with a complex biopolymer that is widely known as a thickening agent was very challenging. Only by varying the hydrolysis times and temperatures of the reactions was achieved the aimed goal. The obtained derivatives showed different molecular weight (Mw) and anionic charges on their backbones. An improvement in shear stress and dynamic viscosity values of CEM II 42.5R cement was observed with the samples obtained with a longer time of higher temperature hydrolysis and sulfo-ethylation. Investigations into the chemical nature of the pore solution, calorimetric studies and adsorption experiments clearly showed the ability of carboxymethyl cellulose superplasticizer (CMC SP) to interact with cement grains and influence hydration processes within a 48-h time window, causing a delay in hydration reactions in the samples. The fluidity of the cementitious matrices was ascertained through slump test and preliminary studies of mechanical and flexural strength of the hardened mortar formulated with the new ecological additives yielded values in terms of mechanical properties. Finally, the computed tomography (CT) images completed the investigation of the pore network structure of hardened specimens, highlighting their promising structure porosity.

Poly(Ethylene Glycol)/ß-Cyclodextrin Pseudorotaxane Complexes as Sustainable Dispersing and Retarding Materials in a Cement-Based Mortar.

Pseudorotaxane complexes between ß-CD and mPEG derivatives bearing a carboxylic acid function (mPEG-COOH) were synthesized and investigated for their dispersing properties in a cement-based mortar. The formation of mPEG-COOH derivatives and their pseudorotaxanes was investigated by 1D nuclear magnetic resonance, diffusion ordered spectroscopy, and thermogravimetric analysis experiments. Mortar tests clearly indicate that mPEG-COOH@ß-CD-interpenetrated supramolecules show excellent dispersing abilities. In addition, the supramolecular complexes show a retarding effect, analogously to other known ß-CD-based superplasticizers in which the ß-CD is covalently grafted on a polymeric backbone.

Untargeted analysis of pure snail slime and snail slime-induced Au nanoparticles metabolome with MALDI FT-ICR MS.

Chronic wounds result from the failure of the normal wound healing process. Any delay during the tissue repair process could be defined as chronic wound healing, potentially having a highly detrimental impact on human health. To face this problem, in the last years, the use of different technologies alternative to therapeutic agents is gaining more attention. The Helix aspersa snail slime-based products are increasingly being used for skin injury, thanks to their ability to make tissue repair processes faster. To date, a comprehensive overview of pure snail slime metabolome is not available. Besides, Au nanoparticles (AuNPs) technology is spreading rapidly in the medical environment, and the search for AuNPs "green" synthetic routes that involve natural products as precursor agents is demanded, alongside with a deep comprehension of the kind of species that actively take part in synthesis and product stabilization. The aim of this work is to characterize the metabolic profile of a pure snail slime sample, by an untargeted high-resolution mass spectrometry-based analysis. In addition, insights on AuNPs synthesis and stabilization by the main components of pure snail slime used to induce the synthesis were obtained. The untargeted analysis provided a large list of important classes of metabolites, that is, fatty acid derivatives, amino acids and peptides, carbohydrates and polyphenolic compounds that could be appreciated in both samples of slime, with and without AuNPs. Moreover, a direct comparison of the obtained results suggests that mostly nitrogen and sulfur-bearing metabolites take part in the synthesis and stabilization of AuNPs.

Expanding Coefficient: A Parameter To Assess the Stability of Induced-Fit Complexes.

Here we propose a new parameter, the Expanding Coefficient (EC), that can be correlated with the thermodynamic stability of supramolecular complexes governed by weak secondary interactions and obeying the induced-fit model. The EC values show a good linear relationship with the log Kapp of the respective pseudorotaxane complexes investigated. According to Cram's Principle of Preorganization, the EC can be considered an approximate mechanical measure of the host's reorganization energy cost upon adopting the final bound geometry.

Pistacia lentiscus Hydrosol: Untargeted Metabolomic Analysis and Anti-Inflammatory Activity Mediated by NF-κB and the Citrate Pathway.

Pistacia lentiscus shows a long range of biological activities, and it has been used in traditional medicine for treatment of various kinds of diseases. Moreover, related essential oil keeps important health-promoting properties. However, less is known about P. lentiscus hydrosol, a main by-product of essential oil production, usually used for steam distillation itself or discarded. In this work, by using ultra-high-resolution ESI(+)-FT-ICR mass spectrometry, a direct identification of four main classes of metabolites of P. lentiscus hydrosol (i.e., terpenes, amino acids, peptides, and condensed heterocycles) was obtained. Remarkably, P. lentiscus hydrosol exhibited an anti-inflammatory activity by suppressing the secretion of IL-1ß, IL-6, and TNF-α proinflammatory cytokines in lipopolysaccharide- (LPS-) activated primary human monocytes. In LPS-triggered U937 cells, it inhibited NF-κB, a key transcription factor in inflammatory cascade, regulating the expression of both the mitochondrial citrate carrier and the ATP citrate lyase genes. These two main components of the citrate pathway were downregulated by P. lentiscus hydrosol. Therefore, the levels of ROS, NO, and PGE2, the inflammatory mediators downstream the citrate pathway, were reduced. Results shed light on metabolic profile and anti-inflammatory properties of P. lentiscus hydrosol, suggesting its potential as a therapeutic agent.

Biomolecules from snail mucus (Helix aspersa) conjugated gold nanoparticles, exhibiting potential wound healing and anti-inflammatory activity.

In this work, for the first time, snail slime from garden snails "Helix Aspersa Müller", has been used to induce the formation of eco-friendly gold nanoparticles (AuNPs-SS) suitable for biomedical applications. An AuNPs-SS comprehensive investigation was performed and AuNPs with an average particle size of 14 ± 6 nm were observed, stabilized by a slime snail-based organic layer. Indeed, as recognized in high-resolution MALDI-MS analyses, and corroborated by FESEM, UV-Vis, ATR-FTIR, and XPS results, it was possible to assess the main presence of peptides and amino acids as the main components of the slime, that, combined with the AuNPs confers on them interesting properties. More specifically, we tested, in vitro, the AuNPs-SS safety in human keratinocytes and their potential effect on wound healing as well as their anti-inflammatory properties in murine macrophages. Moreover, the AuNPs-SS treatment resulted in a significant increase of the urokinase-type plasminogen activator receptor (uPAR), essential for keratinocyte adhesion, spreading, and migration, together with the reduction of LPS-induced IL1-ß and IL-6 cytokine levels, and completely abrogated the synthesis of inducible nitric oxide synthase (iNOS).

Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters.

A set of 6- to 24-valent clusters was constructed with terminal deoxynojirimycin (DNJ) inhibitory heads through C6 or C9 linkers by way of Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions between mono- or trivalent azido-armed iminosugars and calix[8]arene scaffolds differing in their valency and their rigidity but not in their size. The power of multivalency to upgrade the inhibition potency of the weak DNJ inhibitor (monovalent DNJ Ki being at 322 and 188 µM for C6 or C9 linkers, respectively) was evaluated on the model glycosidase Jack Bean α-mannosidase (JBα-man). Although for the clusters with the shorter C6 linker the rigidity of the scaffold was essential, these parameters had no influence for clusters with C9 chains: all of them showed rather good relative affinity enhancements per inhibitory epitopes between 70 and 160 highlighting the sound combination of the calix[8]arene core and the long alkyl arms. Preliminary docking studies were performed to get insights into the preferred binding modes.