Ultra-sensitive solid-phase Microextraction-Gas Chromatography-Mass spectrometry determination of polycyclic aromatic hydrocarbons in snow samples using a deep cavity BenzoQxCavitand.

A very sensitive and selective solid-phase microextraction-gas chromatography-mass spectrometry method based on the use of a deep cavity BenzoQxCavitand as innovative coating was developed and validated for the simultaneous determination of the 16 US-EPA priority pollutants polycyclic aromatic hydrocarbons (PAHs) in snow samples at ultra-trace levels. The presence of a 8.3 Å deep hydrophobic cavity allowed the engulfment of all the 16 PAHs, providing enhanced selectivity also in presence of interfering aromatic pollutants at high concentration levels. Validation proved the reliability of the method for the determination of the investigated compounds achieving detection limits in the 0.03-0.30 ng/L range, good precision, with relative standard deviations <18% and recovery rates in the 90.8(±2.1)%-109.6(±1.0)%. The detection of low-molecular weight PAHs in snow samples from Antarctica and Alps confirms the widespread occurrence of these compounds, thus assessing the impact of anthropogenic activities onto the environment.

Probing lysine mono-methylation in histone H3 tail peptides with an abiotic receptor coupled to a non-plasmonic resonator.

Binder and effector molecules that allow studying and manipulating epigenetic processes are of biological relevance and pose severe technical challenges. We report the first example of a synthetic receptor able to recognize mono-methylated lysines in a histone H3 tail peptide, which has relevant functions in epigenetic regulation. Recognition is robust and specific regardless of the position and the number of mono-methylated lysines along the polypeptide chain. The peptide is first captured in solution by a tetraphosphonate cavitand (Tiiii) that selectively binds its Lys-NMe+ moieties. Separation from solution and detection of the peptide-Tiiii complexes is then enabled in one single step by an all dielectric SiO2-TiO2 core-shell resonator (T-rex), which captures the complex and operates fully reproducible signal transduction by non-plasmonic surface enhanced Raman scattering (SERS) without degrading the complex. The realized abiotic probe is able to distinguish multiple mono-methylated peptides from the single mono-methylated ones.

Conformationally blocked quinoxaline cavitand as solid-phase microextraction coating for the selective detection of BTEX in air.

A tetraquinoxaline cavitand functionalized with methylenoxy bridges at the upper rim is proposed as selective solid-phase microextraction (SPME) coating for the determination of BTEX at trace levels in air. The SPME fibers were characterized in terms of film thickness, morphology, thermal stability and extraction capabilities. An average coating thickness of 35 (±4) µm, a thermal stability up to 350 °C and a good fiber-to-fiber and batch-to-batch repeatability with RSD lower than 15% were obtained. Excellent enrichment factors ranging from 360-700 × 10(3) were obtained for the investigated compounds. Finally, method validation proved the capabilities of the developed coating for the selective sampling of BTEX, achieving LOD values in the 0.4-1.2 ng m(-3) range.

A fluorescent probe for ecstasy.

A nanostructure formed by the insertion in silica nanoparticles of a pyrene-derivatized cavitand, which is able to specifically recognize ecstasy in water, is presented. The absence of effects from interferents and an efficient electron transfer process occurring after complexation of ecstasy, makes this system an efficient fluorescent probe for this popular drug.

Multifunctional magnetic nanoparticles for enhanced intracellular drug transport.

In this paper we report the synthesis and characterization of biocompatible multi-functional magnetic nanoparticles (MNPs) able to enhance the intracellular transport of N-methylated drugs. The Fe3O4 magnetic core was first functionalized with a mixed monolayer consisting of two different phosphonic acids having terminal acetylenic and amino groups, which provide an active platform for further functionalization with organic molecules. Then, a tetraphosphonate cavitand receptor (Tiiii) bearing an azide moiety and the N-hydroxysuccinimide (NHS) activated forms of poly(ethylene glycol) (PEG), folic acid (FA) and carboxy-X-rhodamine (Rhod) were covalently anchored on alkyne and amine moieties respectively, through 1,3-dipolar cycloaddition and EDC/NHS coupling reactions. The obtained MNPs are biocompatible and possess magnetic, luminescence and recognition properties which make them suitable for multimodal theranostic applications. In particular, combined confocal microscopy and cytotoxicity experiments showed that these multi-functional MNPs are able to recognize a specific drug "in situ" and promote its cellular internalization, thus enhancing its efficiency.

Probing cavitand-organosilane hybrid bilayers via sum-frequency vibrational spectroscopy.

Quinoxaline cavitands (QxCav) are transferred by Langmuir-Schaefer method on self-assembled monolayers (SAMs) of octadecyltrichlorosilane (OTS) and N,N-dimethyl-N-octadecyl-3-aminopropyltrimethoxysilyl chloride (DMOAP) on fused silica substrates. The molecular architectures of both the hydrophobic SAMs templates and the hybrid cavitand-organosilanes bilayers at the solid-air interface are investigated and correlated by sum-frequency vibrational spectroscopy. The results show that QxCav are always in the closed vase configuration and orient with their principal axis normal to the substrates. The role of the alkyl chains density in the SAM templates on the QxCav transfer ratio is pointed out.

Functionalization of PEGylated Fe3O4 magnetic nanoparticles with tetraphosphonate cavitand for biomedical application.

In this contribution, Fe3O4 magnetic nanoparticles (MNPs) have been functionalized with a tetraphosphonate cavitand receptor (Tiiii), capable of complexing N-monomethylated species with high selectivity, and polyethylene glycol (PEG) via click-chemistry. The grafting process is based on MNP pre-functionalization with a bifunctional phosphonic linker, 10-undecynylphosphonic acid, anchored on an iron surface through the phosphonic group. The Tiiii cavitand and the PEG modified with azide moieties have then been bonded to the resulting alkyne-functionalized MNPs through a "click" reaction. Each reaction step has been monitored by using X-ray photoelectron and FTIR spectroscopies. PEG and Tiiii functionalized MNPs have been able to load N-methyl ammonium salts such as the antitumor drug procarbazine hydrochloride and the neurotransmitter epinephrine hydrochloride and release them as free bases. In addition, the introduction of PEG moieties promoted biocompatibility of functionalized MNPs, thus allowing their use in biological environments.

Self-assembly and anion encapsulation properties of cavitand-based coordination cages.

Two novel classes of cavitand-based coordination cages 7a--j and 8a--d have been synthesized via self-assembly procedures. The main factors controlling cage self-assembly (CSA) have been identified in (i) a P--M--P angle close to 90 degrees between the chelating ligand and the metal precursor, (ii) Pd and Pt as metal centers, (iii) a weakly coordinated counterion, and (iv) preorganization of the tetradentate cavitand ligand. Calorimetric measurements and dynamic (1)H and (19)F NMR experiments indicated that CSA is entropy driven. The temperature range of the equilibrium cage-oligomers is determined by the level of preorganization of the cavitand component. The crystal structure of cage 7d revealed the presence of a single triflate anion encapsulated. Guest competition experiments revealed that the encapsulation preference of cages 7b,d follows the order BF(4)(-) > CF(3)SO(3)(-) >> PF(6)(-) at 300 K. ES-MS experiments coupled to molecular modeling provided a rationale for the observed encapsulation selectivities. The basic selectivity pattern, which follows the solvation enthalpy of the guests, is altered by size and shape of the cavity, allowing the entrance of an ancillary solvent molecule only in the case of BF(4)(-).

Diastereoselective formation of host-guest complexes between a series of phosphate-bridged cavitands and alkyl- and arylammonium ions studied by liquid secondary-ion mass spectrometry.

The reactions occurring between a new class of cavitands that carry up to four dioxaphosphocin binding units and alkyl- and arylammonium ions was investigated by liquid secondary-ion mass spectrometry (LSIMS). As the cavitands existed as distinct diastereomers with different spatial orientation of their binding groups, these geometrical differences proved to have a dramatic influence on their chemical properties, including their ability to form host-guest complexes. In practice, only the cavitands that carry at least three P=O groups oriented toward the inside of the cavity were demonstrated to be strong ligands toward organic ammonium ions, whereas those with only two converging binding groups (either adjacent or opposite in the cavitand structure) still formed host-guest complexes, but they were much weaker. Adjacent binding sites proved to be more effective in interacting with organic ammonium ions than those lying in opposite positions. The isomers with no converging P=O groups did not act as molecular receptors. Even the isomer with one group oriented toward the inside of the cavity did not form host-guest complexes, as the absence of synergistic hydrogen bonding made the interaction from inside the cavity energetically equivalent (or even less favorable) to the outside binding. The presence in the cavitand structure of substituents with an electron-donating character proved to increase the proton affinity of the P=O binding groups and, consequently, their binding energy. The strong proton affinity of the cavitands led to the formation of stable host-guest complexes, as confirmed by the collisionally activated dissociation experiments. Effects of steric hindrance were weak, at least for the cavitands with three converging P=O groups. This confirmed that the cavity has a wide and readily accessible opening. The relative complexation constants were measured for the various guests, yielding scales of relative affinity toward each cavitand. These relative constants may represent thermodynamic values referred to the matrix used in LSIMS experiments, namely 3-nitrobenzyl alcohol (NBA), provided that kinetically controlled selvedge processes are negligible. Absolute complexation constants could not be obtained on account of the unknown pH and the protonation constant in the NBA matrix.

Supramolecular Sensors for the Detection of Alcohols.

Cooperativity between different noncovalent host-guest interactions is the key for the successful generation of selective supramolecular sensors. A new class of cavitands capable of synergistic CH small middle dot small middle dot small middle dotpi interactions and hydrogen bonding has been designed and exploited for the detection of alcohol vapors using mass transducers (see schematic representation).