Binding of Acetylated Lysine by Using a Water Soluble Aryl Extended Calix[4]pyrrole.

Post-translational modifications of lysine in histones, as methylation and acetylation, have well established functions in epigenetics and are emerging as important actors in broader biological regulation. Currently, the detection of acetylated lysine (Kac) in water solution as free amino acid or protein residue remains challenging. Acetylated lysine is a neutral amino acid, and the lack of ion-dipole interactions causes the decrease in binding affinity displayed by synthetic molecular receptors with respect to the other lysine modifications. Here, we report molecular modeling calculations and 1H NMR experiments to investigate the binding properties of two different calix[4]pyrrole receptors towards Kac. Computational analyses reveal that tetra-aryl-extended calix[4]pyrrole (1) preferentially binds the cis-Kac conformer over the trans one due to steric considerations and more favorable interactions. Experimental 1H NMR titration experiments confirm the formation of a 1 : 1 complex between receptor 1 and cis-Kac, with a Ka exceeding 103 M-1. Conversely, the super-aryl-extended calix[4]pyrrole 2 is less efficient in binding Kac, due to unfavorable solvation/desolvation effects, as proven by 1H NMR experiments. Moreover, receptor 1 showed a higher affinity for Kac over other lysine modifications, such as methylated lysines.

3D electron diffraction analysis of a novel, mechanochemically synthesized supramolecular organic framework based on tetrakis-4-(4-pyridyl)phenylmethane.

Tetrakis-4-(4-pyridyl)phenylmethane (TPPM) is a tetrahedral rigid molecule that crystallizes forming a dynamically responsive supramolecular organic framework (SOF). When exposed to different stimuli, this supramolecular network can reversibly switch from an empty to a filled solvated solid phase. This article describes a novel expanded form of a TPPM-based SOF that has been mechanochemically synthesized and whose crystal structure has been determined by 3D electron diffraction analysis using a novel electron diffractometer.

Stimuli-Responsive, Dynamic Supramolecular Organic Frameworks.

Supramolecular organic frameworks (SOFs) are a class of three-dimensional, potentially porous materials obtained by the self-assembly of organic building blocks held together by weak interactions such as hydrogen bonds, halogen bonds, π⋅⋅⋅π stacking and dispersion forces. SOFs are being extensively studied for their potential applications in gas storage and separation, catalysis, guest encapsulation and sensing. The supramolecular forces that guide their self-assembly endow them with an attractive combination of crystallinity and flexibility, providing intelligent dynamic materials that can respond to external stimuli in a reversible way. The present review article will focus on SOFs showing dynamic behaviour when exposed to different stimuli, highlighting fundamental aspects such as the combination of tectons and supramolecular interactions involved in the framework formation, structure-property relationship and their potential applications.

Two-photon microscopy as a visual tool for polymer compatibilization monitoring: the PE-EVOH case.

In this study, we present two-photon microscopy (2PM) as an original technique to investigate the compatibilization between PE-HEMA and EVOH at the sub-micrometer level, both on the surface and in the bulk. 2PM is a nonlinear fluorescence imaging technique commonly exploited for thick biological tissue analysis. Here, we use 2PM to visualize polymer blending through 3D images of the obtained films. Compatibilization was performed in solution, upon functionalization of PE-HEMA with 1.4% molar of ODIN, a fluorescent molecule able to form multiple hydrogen bonds with EVOH and to act as a fluorescent probe. Different blends were synthesized, and the obtained films were analyzed by 2PM. For all compositions, it was demonstrated that ODIN is evenly distributed both on the surface and in the bulk. 2PM analysis of the thermally reprocessed specimen revealed that repeated reprocessing allows the reformation of ODIN dimers as the most stable H-bonding array in the solid state, partially reversing the compatibilization.

Selective and Reversible Solvent Uptake in Tetra-4-(4-pyridyl)phenylmethane-based Supramolecular Organic Frameworks.

The dynamic behavior of supramolecular organic frameworks (SOFs) based on the rigid tetra-4-(4-pyridyl)phenylmethane (TPPM) organic tecton has been elucidated through 3D electron diffraction, X-ray powder diffraction and differential scanning calorimetry (DSC) analysis. The SOF undergoes a reversible single-crystal-to-single-crystal transformation when exposed to vapours of selected organic solvents, moving from a closed structure with isolated small voids to an expanded structure with solvated channels along the b axis. The observed selectivity is dictated by the fitting of the guest in the expanded SOF, following the degree of packing coefficient. The effect of solvent uptake on TPPM solid-state fluorescence was investigated, evidencing a significant variation in the emission profile only in the presence of chloroform.

Selective NMR detection of N-methylated amines using cavitand-decorated silica nanoparticles as receptors.

We report a strategy for the realization of NMR chemosensors based on the spontaneous self-assembly of lower rim pyridinium-functionalized tetraphopshonate cavitands on commercial silica nanoparticles. These nanohybrids enable the selective detection of physiologically relevant N-methylated amines, with a limit of detection of 31 µM, via STD-based NMR experiments, achieving for the first time fine structural selectivity in nanoparticle-assisted NMR chemosensing.

Cavitand Decorated Silica as a Selective Preconcentrator for BTEX Sensing in Air.

The monitoring of benzene and other carcinogenic aromatic volatile compounds at the ppb level requires boosting both the selectivity and sensitivity of the corresponding sensors. A workable solution is the introduction in the devices of preconcentrator units containing molecular receptors. In particular, quinoxaline cavitands (QxCav) resulted in very efficient preconcentrator materials for the BTEX in air to the point that they have been successfully implemented in a commercial sensor. In this work, we report a highly efficient quinoxaline-based preconcentrator material, in which the intrinsic adsorption capacity of the QxCav has been maximized. The new material consists of silica particles covalently coated with a suitable functionalized QxCav derivative (QxCav@SiO2). In this way, all the cavities are exposed to the analyte flux, boosting the performance of the resulting preconcentration cartridge well above that of the pure QxCav. It is noteworthy that the preconcentrator adsorption capacity is independent of the relative humidity of the incoming air.

Tuning the conformational flexibility of quinoxaline cavitands for complexation at the gas-solid interface.

The selectivity and efficiency of benzene and toluene uptake at the gas-solid interface by quinoxaline cavitands is strongly enhanced by partial rigidification of the receptor cavity and immobilization of the cavitand onto silica gel particles.

Encapsulation of Trimethine Cyanine in Cucurbit[8]uril: Solution versus Solid-State Inclusion Behavior.

Inclusion of polymethine cyanine dyes in the cavity of macrocyclic receptors is an effective strategy to alter their absorption and emission behavior in aqueous solution. In this paper, the effect of the host-guest interaction between cucurbit[8]uril (CB[8]) and a model trimethine indocyanine (Cy3) on dye spectral properties and aggregation in water is investigated. Solution studies, performed by a combination of spectroscopic and calorimetric techniques, indicate that the addition of CB[8] disrupts Cy3 aggregates, leading to the formation of a 1 : 1 host-guest complex with an association constant of 1.5×106  M-1 . At concentrations suitable for NMR experiments, the slow formation of a supramolecular polymer was observed, followed by precipitation. Single crystals X-ray structure elucidation confirmed the formation of a polymer with 1 : 1 stoichiometry in the solid state.

Reusable Cavitand-Based Electrospun Membranes for the Removal of Polycyclic Aromatic Hydrocarbons from Water.

The removal of toxic and carcinogenic polycyclic aromatic hydrocarbons (PAHs) from water is one of the most intractable environmental problems nowadays, because of their resistance to remediation. This work introduces a highly efficient, regenerable membrane for the removal of PAHs from water, featuring excellent filter performance and pH-driven release, thanks to the integration of a cavitand receptor in electrospun polyacrylonitrile (PAN) fibers. The role of the cavitand receptor is to act as molecular gripper for the uptake/release of PAHs. To this purpose, the deep cavity cavitand BenzoQxCav is designed and synthetized and its molecular structure is elucidated via X-Ray diffraction. The removal efficiency of the new adsorbent material toward the 16 priority PAHs is demonstrated via GC-MS analyses at ng L-1 concentration. A removal efficiency in the 32%, to 99% range is obtained. The regeneration of the membrane is performed by exploiting the pH-driven conformational switching of the cavitand between the vase form, where the PAHs uptake takes place, to the kite one, where the PAHs release occurs. The absorbance and regeneration capability of the membrane are successfully tested in four uptake/release cycles and the morphological stability.

Fabrication of a sensitive colorimetric nanosensor for determination of cysteine in human serum and urine samples based on magnetic-sulfur, nitrogen graphene quantum dots as a selective platform and Au nanoparticles.

A novel colorimetric nanosensor is reported for the selective and sensitive determination of cysteine using magnetic-sulfur, nitrogen graphene quantum dots (Fe3O4/S, N-GQDs), and gold nanoparticles (Au NPs). Thus, S, N-GQDs was firstly immobilized on Fe3O4 nanoparticles through its magnetization in the presence of Fe3+ in the alkali solution. The prepared Fe3O4/S, N-GQDs were dispersed in cysteine solution resulting in its quick adsorption on the surface of the Fe3O4/S, N-GQDs through hydrogen bonding interaction. Then, Au NPs solution was added to this mixture that after a short time, the color of Au NPs changed from red to blue, the intensity of surface plasmon resonance peak of Au NPs at 530 nm decreased, and a new peak at a higher wavelength of 680 nm appeared. The effective parameters on cysteine quantification were optimized via response surface methodology using the central composite design. Under optimum conditions, the absorbance ratio (A680/A530) has a linear proportionality with cysteine concentration in the range of 0.04-1.20 µmol L-1 with a limit of detection of 0.009 µmol L-1. The fabrication of the reported nanosensor is simple, fast, and is capable of efficient quantification of ultra traces of cysteine in human serum and urine real samples.

Mechanically-Driven Vase-Kite Conformational Switch in Cavitand Cross-Linked Polyurethanes.

The eligibility of tetraquinoxaline cavitands (QxCav) as molecular grippers relies on their unique conformational mobility between a closed (vase) and an open (kite) form, triggered in solution by conventional stimuli like pH, temperature and ion concentration. In the present paper, the mechanochemical conformational switching of ad hoc functionalized QxCav covalently embedded in an elastomeric polydimethylsiloxane and in a more rigid polyurethane matrix is investigated. The rigid polymer matrix is more effective in converting mechanical force into a conformational switch at the molecular level, provided that all four quinoxaline wings are covalently connected to the polymer.

Solvent-responsive cavitand lanthanum complex.

Stimuli-responsive supramolecular assemblies are dynamic systems that can reversibly switch between different states upon external stimuli. In this context, metal coordination offers a reliable strategy for the preparation of stimuli responsive supramolecular architectures. Herein we report the preparation of a solvent-responsive cavitand-lanthanum coordination complex. A tetra-phosphonate cavitand has been functionalized with four hydroxyl moieties at the upper rim to form a pre-organized octadentate ligand capable of binding lanthanum salts. Exploiting the orthogonal recognition sites, two different complex architectures are formed in acetonitrile and acetone, respectively. The complexes have been characterized in solution by NMR spectroscopy, ITC experiments, while at the solid state, the single crystal structure of the acetonitrile derivative has been determined. Furthermore, as observed by DOSY-NMR spectroscopy, small quantities of acetone in acetonitrile are sufficient to trigger assembly interconversion.

Host-guest supra-molecular inter-actions between a resorcinarene-based cavitand bearing a -COOH moiety and acetic acid.

The cavitand 5,11,17,23-tetra-methyl-4,24:6,10:12,16:18,22-tetra-kis-(methyl-enedi-oxy)resorcin[4]arene functionalized at the upper rim with a carb-oxy-lic acid group, CavCOOH-in, of chemical formula C37H32O10, was synthesized in order to study its supra-molecular inter-actions with acetic acid in the solid state. Crystals suitable for X-ray diffraction analysis were obtained by slow evaporation of a di-chloro-methane-acetone solution of CavCOOH-in, to which glacial acetic acid had been added. The resulting compound, C37H32O10·2C2H4O2 (1) crystallizes in the space group P and its asymmetric unit consists of one mol-ecule of cavitand and two mol-ecules of acetic acid, one of which is encapsulated inside the aromatic cavity and disordered over two positions with a refined occupancy ratio of 0.344 (4):0.656 (4). The guest inter-acts with the host primarily through its methyl group, which (in both orientations) forms C-H⋯π inter-actions with the benzene rings of the cavitand. The crystal structure of 1 is dominated by O-H⋯O and C-H⋯O hydrogen bonding due to the presence of acetic acid and of the carb-oxy-lic group functionalizing the upper rim. Further stabilization is provided by offset π-π stacking inter-actions between the aromatic walls of adjacent cavitands [inter-centroid distance = 3.573 (1) Å].

Fluorinated Tetraphosphonate Cavitands.

Two synthetic protocols for the introduction of fluorine atoms into resorcinarene-based cavitands, at the lower and upper rim, respectively, are reported. Cavitand 1, bearing four fluorocarbon tails, and cavitand 2, which presents a fluorine atom on the para position of a diester phosphonate phenyl substituent, were synthesized and their complexation abilities toward the model guest sarcosine methyl ester hydrochloride were evaluated via NMR titration experiments. The effect of complexation on the 19F NMR resonance of the probe is evident only in the case of cavitand 2, where the inset of the cation-dipole and H-bonding interactions between the P=O bridges and the guest is reflected in a sizable downfield shift of the fluorine probe.

Biochemical sensing with macrocyclic receptors.

Preventive healthcare asks for the development of cheap, precise and non-invasive sensor devices for the early detection of diseases and continuous population screening. The actual techniques used for diagnosis, e.g. MRI and PET, or for biochemical marker sensing, e.g. immunoassays, are not suitable for continuous monitoring since they are expensive and prone to false positive responses. Synthetic supramolecular receptors offer new opportunities for the creation of specific, selective and cheap sensor devices for biological sensing of specific target molecules in complex mixtures of organic substances. The fundamental challenges faced in developing such devices are the precise transfer of the molecular recognition events at the solid-liquid interface and its transduction into a readable signal. In this review we present the progress made so far in turning synthetic macrocyclic hosts, namely cyclodextrins, calixarenes, cucurbiturils and cavitands, into effective biochemical sensors and the strategies utilized to solve the above mentioned issues. The performances of the developed sensing devices based on these receptors in detecting specific biological molecules, drugs and proteins are critically discussed.

Environmental Gas Sensing with Cavitands.

Environmental gas sensing needs stringent sensor requirements in terms of sensitivity, selectivity and ruggedness. One of the major issues to be addressed is combining in a single device the conflicting requirements of molecular-level selectivity and low-ppb sensitivity. The exploitation of synthetic molecular receptors as sensing materials is particularly attractive to address the selectivity issue, to single out the desired analytes in the presence of overwhelming amounts of interferents. This minireview summarizes the strategies in environmental gas and vapor sensing using molecular receptors as selective hosts for specific analytes, with the main focus on cavitands. In particular, we highlight the use of these macrocycles as selective preconcentrator units to be integrated into portable devices for environmental monitoring. Depending on the class of analytes to be detected, the molecular recognition properties of cavitands can be manipulated through the proper choice of the bridging groups at the upper rim, and their transducer integration can be implemented through the manifold functionalization options at the lower rim.

Self-Assembly of TbPc2 Single-Molecule Magnets on Surface through Multiple Hydrogen Bonding.

The complexation between 2-ureido-4[1H]-pyrimidinone (UPy) and 2,7-diamido-1,8-naphthyridine (NaPy) is used to promote the mild chemisorption of a UPy-functionalized terbium(III) double decker system on a silicon surface. The adopted strategy allows the single-molecule magnet behavior of the system to be maintained unaltered on the surface.

In Search of the Ultimate Benzene Sensor: The EtQxBox Solution.

In this work we report a comprehensive study leading to the fabrication of a prototype sensor for environmental benzene monitoring. The required high selectivity and ppb-level sensitivity are obtained by coupling a silicon-integrated concentration unit containing the specifically designed EtQxBox cavitand to a miniaturized PID detector. In the resulting stand-alone sensor, the EtQxBox receptor acts at the same time as highly sensitive preconcentrator for BTEX and GC-like separation phase, allowing for the selective desorption of benzene over TEX. The binding energies of the complexes between EtQxBox and BTX are calculated through molecular mechanics calculations. The examination of the corresponding crystal structures confirms the trend determined by computational studies, with the number of C-H···N and CH···π interactions increasing from 6 to 9 along the series from benzene to o-xylene. The analytical performances of EtQxBox are experimentally tested via SPME, using the cavitand as fiber coating for BTEX monitoring in air. The cavitand EFs are noticeably higher than those obtained by using the commercial CAR-DVB-PDMS. The LOD and LOQ are calculated in the ng/m3 range, outperforming the commercial available systems in BTEX adsorption. The desired selective desorption of benzene is achieved by applying a smart temperature program on the EtQxBox mesh, which starts releasing benzene at lower temperatures than TEX, as predicted by the calculated binding energies. The sensor performances are experimentally validated and ppbv level sensitivity toward the carcinogenic target aromatic benzene was demonstrated, as required for environmental benzene exposure monitoring in industrial applications and outdoor environment.

Formation of TbPc2 Single-Molecule Magnets' Covalent 1D Structures via Acyclic Diene Metathesis.

We present here a reaction scheme to connect TbPc2 single-molecule magnets into 1D architectures using acyclic diene metathesis. To investigate the impact of the bonding through aliphatic chains on the magnetic properties of TbPc2, we isolate and characterize the dimeric species obtained as one of the products of the reaction. Remarkably, the magnetic properties are only slightly modified after the formation of the bond between molecules, enlightening the great potential of this reaction scheme.