Franco Ugozzoli

The molecular origin of the selective recognition of ephedrine over pseudoephedrine by an achiral phosphonate cavitand receptor was revealed by the crystal structure of the respective complexes.

Ring-closing metathesis (RCM) catalyzed by a second-generation Grubbs catalyst has been used to synthesize resorc[4]arenes 2b-5b starting from undecenyl resorc[4]arene 1b fixed in the cone conformation. X-ray diffraction analysis of the major metathesis product, 3b (50% yield), revealed a cavity-shaped architecture resembling a basket, endowed with a large intramolecular space (∼10 Å) and a strong propensity to self-assemble as a supramolecular trio of heterochiral dimers. This prompted us to investigate the aggregation propensity of basket 3b in THF/water solution by UV-visible spectroscopy. The cavitation Gibbs free-energy change (ΔΔGcav = 4.78 kcal mol(-1)) associated with the self-assembly of macrocycle 3b was calculated as a measure of the solvophobic interactions involved in the process.

Selective uptake of the methamphetamine and amphetamine precursors safrole and benzyl methyl ketone (BMK) in air was obtained exploiting the molecular recognition properties of the quinoxaline-bridged cavitand (QxCav). The interactions responsible for the observed complexation were studied elucidating the molecular structures of the inclusion compounds with the analytes. Then, solid-phase microextraction (SPME) analyses were carried out on fibres coated with QxCav to test the receptor prowess towards the drug precursors uptake from air. Both safrole and BMK, concentration of which in the vapour phase is in the low microgram per cubic metre regime, are collected and pre-concentrated by the QxCav–SPME fibre, then thermally desorbed and identified via GC–MS.

Tetramerization of (E)-2,4-dimethoxycinnamic acid ω-undecenyl ester with ethereal BF₃ gave three stereoisomers 1a, 1b, and 1c, which were assigned as the chair, cone, and 1,2-alternate conformations, respectively. The chair conformation of 1a was confirmed by X-ray diffraction analysis, which also showed a peculiar self-assembly behavior in the crystal lattice, forming intercalated hydrophilic and hydrophobic layers (6–7 Å thickness) as a consequence of strong CH–π interactions. Undecenyl resorc[4]arene 1a, which featured the simplest pattern of substituents, was submitted to olefin metathesis using the second-generation Grubbs complex as the catalyst. Depending on the reaction conditions, different products were isolated: a bicyclic alkene 2a (46%), a linear dimer 3a (5%), and a cross-linked homopolymer P1a (44%).

The 1,3-distal cone-calix[4]arene dialdehyde 1 undergoes Cannizzaro disproportionation in the presence of strong base, but its 1,2-vicinal regioisomer 3 and the analogous monoaldehyde 2 are unreactive under the same conditions. The high intramolecular reactivity of the 1,3-distal regioisomer 1 is measured and discussed in terms of Effective Molarity (EM).

Guest-switchable crystals: A solid-state guest exchange of the tetraphosphonate cavitand Tiiii[H,CH₃,Ph] as host promotes single-crystal-to-single-crystal transformations (see graphic). The strong preference for methanol over water is observed in all three phases (gas, liquid, solid), thus demonstrating the fundamental role played by the preorganized cavity through synergistic H-bonds and CH⋅⋅⋅π interactions.

Three novel dimeric capsules formed by a tetraphosphonate cavitand with barium, calcium and zinc salts have been synthesized and structurally characterized. The role of cation dimensions and of coordinated water molecules in determining different architectures is also described.