Roberta Pinalli

Supramolecular sensing with phosphonate cavitands.

Molecular recognition is a recurrent theme in chemical sensing because of the importance of selectivity for sensor performances. The popularity of molecular recognition in chemical sensing has resulted from the progress made in mastering weak interactions, which has enabled the design of synthetic receptors according to the analyte to be detected. However, the availability of a large pool of modular synthetic receptors so far has not had a significant impact on sensors used in the real world. This technological gap has emerged because of the difficulties in transferring the intrinsic molecular recognition properties of a given receptor from solution to interfaces and in finding high fidelity transduction modes for the recognition event. This Account focuses on the ways to overcome these two bottlenecks, and we recount our recent efforts to produce highly selective supramolecular sensors using phosphonate cavitands as receptors. Through two examples, we present an overview of the different operating strategies that are implemented depending on whether the interface is vapor-solid or liquid-solid. First we describe the selective detection of short chain aliphatic alcohols in the vapor phase. In this example, we solved a key issue common to all sensors for organic vapors: the dissection of the specific interaction (between cavitand and the alcohol) from ubiquitous nonspecific dispersion interactions (between the analytes and interferents in the solid layer). We removed responses resulting from the nonspecific interactions of the analytes with interferents by directly connecting the recognition event at the interface to the transduction mechanism (photoinduced charge transfer). The second example addresses the specific detection of sarcosine in urine. Recent research has suggested that sarcosine can serve as reliable biomarker of the aggressive forms of prostate cancer. Tetraphosphonate cavitands can complex N-methyl ammonium salts with impressive selectivity in solution, and we used this property as a starting point. The sensor implementation requires that we first graft the cavitand onto silicon and gold surfaces as monolayers. The exclusive recognition of sarcosine by these supramolecular sensors originates from their operation in aqueous environments, where synergistic multiple interactions with the phosphonate cavitand are possible only for N-methyl ammonium derivatives. We couple that selectivity with detection modes that probe the strength of the complexation either directly (microcantilever) or via exchange with molecules that have comparable affinity for the cavity (fluorescence dye displacement).

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).

Cavitand-functionalized porous silicon as an active surface for organophosphorus vapor detection.

This paper reports on the preparation of a porous silicon-based material covalently functionalized with cavitand receptors suited for the detection of organophosphorus vapors. Two different isomeric cavitands, both containing one acid group at the upper rim, specifically designed for covalent anchoring on silicon, were grafted on H-terminated porous silicon (PSi) by thermal hydrosilylation. The covalently functionalized surfaces and their complexation properties were characterized by combining different analytical techniques, namely X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and mass spectroscopy analysis coupled with thermal desorption experiments. Complexation experiments were performed by exposing both active surfaces and a control surface consisting of PSi functionalized with a structurally similar but inactive methylene-bridged cavitand (MeCav) to dimethyl methylphosphonate (DMMP) vapors. Comparison between active and inactive surfaces demonstrated the recognition properties of the new surfaces. Finally, the nature of the involved interactions, the energetic differences between active and inactive surfaces toward DMMP complexation, and the comparison with a true nerve gas agent (sarin) were studied by DFT modeling. The results revealed the successful grafting reaction, the specific host-guest interactions of the PSi-bonded receptors, and the reversibility of the guest complexation.

Cavitands as superior sorbents for benzene detection at trace level

We present an innovative dynamic headspace-based approach to sampling of BTX using molecular receptors. For this purpose methylene-bridged (MeCav) and quinoxaline-bridged (QxCav) cavitands were silylated at the lower rim and grafted onto silica gel. In the case of QxCav, the resulting sorbent material selectively retains BTX at ppb levels in the adsorption phase and delivers a benzene-enriched fraction in the desorption phase. Under the same conditions, commercial sorbents like Carbotrap 100® and Tenax TA® proved to be unselective both in the uptake and in the release steps. The molecular origins of the observed selectivity were traced by theoretical calculations in the presence of multiple electrostatic and CH–π interactions, possible only in the case of QxCav–aromatic analyte complexes.

The Origin of Selectivity in the Complexation of N-Methyl Amino Acids by Tetraphosphonate Cavitands

We report on the eligibility of tetraphosphonate resorcinarene cavitands for the molecular recognition of amino acids. We determined the crystal structure of 13 complexes of the tetraphosphonate cavitand Tiiii[H, CH3, CH3] with amino acids. (1)H NMR and (31)P NMR experiments and ITC analysis were performed to probe the binding between cavitand Tiiii[C3H7, CH3, C2H5] or the water-soluble counterpart Tiiii[C3H6Py(+)Cl(-), CH3, C2H5] and a selection of representative amino acids. The reported studies and results allowed us (i) to highlight the noncovalent interactions involved in the binding event in each case; (ii) to investigate the ability of tetraphosphonate cavitand receptors to discriminate between the different amino acids; (iii) to calculate the Ka values of the different complexes formed and evaluate the thermodynamic parameters of the complexation process, dissecting the entropic and enthalpic contributions; and (iv) to determine the solvent influence on the complexation selectivity. By moving from methanol to water, the complexation changed from entropy driven to entropy opposed, leading to a drop of almost three orders in the magnitude of the Ka. However, this reduction in binding affinity is associated with a dramatic increase in selectivity, since in aqueous solutions only N-methylated amino acids are effectively recognized. The thermodynamic profile of the binding does not change in PBS solution. The pivotal role played by cation-π interactions is demonstrated by the linear correlation found between the log Ka in methanol solution and the depth of (+)N-CH3 cavity inclusion in the molecular structures. These findings are relevant for the potential use of phosphonate cavitands as synthetic receptors for the detection of epigenetic modifications of histones in physiological media.

Cavitand-based solid-phase microextraction coating for the selective detection of nitroaromatic explosives in air and soil.

A selective cavitand-based solid-phase microextraction coating was synthesized for the determination of nitroaromatic explosives and explosive taggants at trace levels in air and soil. A quinoxaline cavitand functionalized with a carboxylic group at the upper rim was used to enhance selectivity toward analytes containing nitro groups. The fibers were characterized in terms of film thickness, morphology, thermal stability, and pH resistance. An average coating thickness of 50 (±4) μm, a thermal stability until 400 °C, and an excellent fiber-to-fiber and batch to batch repeatability with RSD lower than 4% were obtained. The capabilities of the developed coating for the selective sampling of nitroaromatic explosives were proved achieving LOD values in the low ppbv and ng kg(-1) range, respectively, for air and soil samples.

Triptycene-Roofed Quinoxaline Cavitands for the Supramolecular Detection of BTEX in Air

Two novel triptycene quinoxaline cavitands (DiTriptyQxCav and MonoTriptyQxCav) have been designed, synthesized, and applied in the supramolecular detection of benzene, toluene, ethylbenzene, and xylenes (BTEX) in air. The complexation properties of the two cavitands towards aromatics in the solid state are strengthened by the presence of the triptycene moieties at the upper rim of the tetraquinoxaline walls, promoting the confinement of the aromatic hydrocarbons within the cavity. The two cavitands were used as fiber coatings for solid-phase microextraction (SPME) BTEX monitoring in air. The best performances in terms of enrichment factors, selectivity, and LOD (limit of detection) values were obtained by using the DiTriptyQxCav coating. The corresponding SPME fiber was successfully tested under real urban monitoring conditions, outperforming the commercial divinylbenzene-Carboxen-polydimethylsiloxane (DVB-CAR-PDMS) fiber in BTEX adsorption.

Resorcinarene-based cavitands as building blocks for crystal engineering

Since their first appearance in the chemistry scene thirty years ago, resorcinarene-based cavitands have been recognized to be a highly versatile class of compounds. Endowed with a rigid cavity of molecular dimensions, which can be decorated at the upper and lower rims with a variety of functional groups, they are efficient molecular receptors for chemical sensing, as well as tunable building blocks in the formation of covalent and supramolecular architectures. In this paper, we highlight and discuss “classic” and recent results concerning their chemistry, applications and crystal structure.

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.

Reliability of the TTC approach: learning from inclusion of pesticide active substances in the supporting database.

Data on pesticide active substances were used to assess the reliability of the Threshold of Toxicological Concern (TTC) approach. Pesticides were chosen as a robust test because of their potential for toxicity. 328 pesticide substances were classified on the basis of their chemical structure, according to the generic scheme proposed by the European Food Safety Authority. 43 carbamates and organophosphates were allocated to the group for neurotoxicity alerts, and 279 substances to Cramer structural Class III. For Class III, the 5th percentile value as calculated from the cumulative distribution curve of the no-observed-effect levels (0.20 mg/kg bw per day), was slightly higher than that determined by Munro (0.15 mg/kg bw per day) from his original database. The difference is explained by the inclusion of carbamates and organophosphates in Munros Class III. Consideration of the acceptable daily intakes and their underlying toxicity data showed that the TTC approach is conservative for 96.2% of the substances. Overall, this analysis gives added support to the utility of the generic scheme of application of the TTC approach for hazard assessment of substances for which few or no experimental toxicity data are available. A convenient alternative to the Cramer decision tree is proposed.