Giuseppe Gattuso

Flavonoid Composition of Citrus Juices

In the early nineties the presence of flavonoids in Citrus juices began to attract the attention of a number of researchers, as a result of their biological and physiological importance. This short review will explore two different aspects. The first part will focus on analytical techniques for the characterization of juices from different Citrus fruits regarding their flavonoid content (even if present in only trace amounts), concentrating on the most widely used methods (LC-MS and LC-MS-MS). The second part analyzes data reported in the literature regarding the composition of Citrus juices. The main components that have been detected so far are flavanone-O-glycosides and flavone-O- or -C-glycosides. The presence of such derivatives in various hand-squeezed and industrial juices is discussed, with special emphasis on their correlation to different species.

Self-Assembly Dynamics of Modular Homoditopic Bis-calix[5]arenes and Long-Chain α,ω-Alkanediyldiammonium Components

Homoditopic building blocks 1, featuring two pi-rich cone-like calix[5]arene moieties connected at their narrow rims by a rigid o-, m-, or p-xylyl spacer in a centrosymmetric divergent arrangement, show a remarkable tendency to spontaneously and reversibly self-assemble with the complementary homoditopic alpha,omega-alkanediyldiammonium dipicrate guest salts C8-C12 x 2Pic through iterative intermolecular inclusion events, forming supramolecular assemblies whose composition and dynamics strongly depend upon the length of the connector, the geometry of the spacer, as well as the concentration and/or molar ratios between the two components. (1)H NMR spectroscopy and ESI-MS studies of 1/C(n) x 2Pic modular homoditopic pairs support the formation of discrete (bis)-endo-cavity assemblies with the shorter C8 and C9 connectors, and/or (poly)capsular assemblies with the longer C10-C12 components under appropriate concentrations and molar ratios (50 mM equimolar solutions). (1)H NMR titration experiments and diffusion NMR studies provide clear evidence for the self-assembly dynamics of the complementary pairs here investigated.

Anion-assisted supramolecular polymerization: from achiral AB-type monomers to chiral assemblies.

Control over the self-assembly process of monomeric species by functional group modulation is highly desirable in the context of supramolecular polymer design. These materials, unlike covalently linked polymers, consist of monomeric arrays held together by reversible and highly directional noncovalent bonds. Owing to the dynamic and reversible nature of noncovalent interactions, supramolecular polymers display unique topologies and unconventional properties (such as stimuli responsiveness and self-healing) and are thus becoming cutting-edge species in modern materials science. Multiple hydrogen bonds, metal–ligand coordination, and p–p stacking are, by far, the most common weak forces used for engineering supramolecular polymers. Recently, however, oligomeric and polymeric architectures based on host–guest inclusion complexes have started to become more and more popular. Within this research frame, we have recently described a pH-responsive aminododecyloxy-calix[5]arene derivative (C5-NH2) that, upon exposure to a variety of acids, selfassembles into linear oligomers. Protonation activates the two latent self-complementary binding sites of this heteroditopic monomer precursor (i.e. a preorganized cone-shaped p-rich calix[5]arene cavity and a linear alkylamine pendant chain) and, according to a well-established host–guest recognition pattern, which involves a concerted set of weak interactions (NH···O, CH–p, cation–p), supramolecular oligomer formation readily occurs. However, because of the intrinsically saline nature of the monomers used, the growth of these supramolecular assemblies was found to be aniondependent. More specifically, the looser the ion-pairing interactions between the ammonium monomer and its counterion, the higher the degree of polymerization observed. Although ion-pairing effects have been analyzed extensively in relation to simple one-to-one host–guest systems, to the best of our knowledge they have not yet been examined in the context of supramolecular polymers derived from charged monomers. Elegant examples of polymeric species derived from crown ethers, cryptands, cyclodextrins, cucurbiturils, calixarenes, 16] and resorcinarenes have been described, but in none of these instances—neither ABtype (self-complementary heteroditopic) 12a,b, 13a, 17a] nor AA/BB-type (complementary homoditopic) 15, 17b] systems—has the role of the counterion in the growth of the polymer or the tuning of the supramolecular properties been addressed. Drawing on our earlier investigations on the simultaneous complexation of cations and anions 18] and on the design of heteroditopic and heterotetratopic receptors in an attempt to override the drawback of ion-pairing effects in AB-type salt monomers, we have now incorporated an ancillary anion-binding site (namely a ureido moiety) into calix[5]arene C5-NH2 with the aim of facilitating salt dissociation and ultimately making polymer formation more efficient. In this communication we demonstrate that the addition of this anion-binding site to the monomer scaffold is beneficial to the supramolecular polymerization process and, most importantly, we show that modulation of the properties [*] Dr. C. Capici, Dr. G. Gattuso, Dr. A. Notti, Prof. M. F. Parisi Dipartimento di Chimica Organica e Biologica Universit di Messina Viale F. Stagno d’Alcontres 31, 98166 Messina (Italy) E-mail: ggattuso@unime.it mparisi@unime.it

Calix[5]arene-based heteroditopic receptor for 2-phenylethylamine hydrochloride.

Novel (1,2-3,5)-calix[5]arene-bis-crown-3 and (1,3)-calix[5]arene-crown-3 derivatives, bearing one or three ureido moieties at the lower rim, respectively, have been synthesized and investigated as heteroditopic receptors for inorganic and organic salts. Tris-ureido-calix[5]arene-crown-3 10, in particular, efficiently binds 2-phenylethylamine hydrochloride (PEA.HCl) as a spatially separated ion pair.

Hybrid Calixarene/Inorganic Salt/Diiodoperfluorocarbon Supramolecular Assemblies

1,3-Bis(α-picolyloxy)-p-tert-butylcalix[4]crown-5 in the cone conformation (2), 1,8-diiodoperfluorooctane or 1,6-diiodoperfluorohexane, and potassium iodide ternary mixtures undergo in solution self-sorting and afford crystalline “supramolecular salts”. These hybrid materials consist of supercation [K+ ⊂ 2] and superanion [I–(CF2) n –I…I− …I–(CF2) n –I…I− …] (n = 6,8) components. In the supercations the potassium ion is embedded in the ionophoric pocket created by the heteroatoms present at the lower rim. In the superanions the iodide ions form infinite fluorous polyanionic chains as a result of a self-assembly process which relies on halogen bonding. Both cation encapsulation and anion-perfluorocarbon halogen bonding were detected in solution by 1H and 19F NMR, and in the gas phase by ESI MS.

Threading the Calix[5]arene Annulus

Among the fast-expanding collection of molecular systems available for nanoscale applications, mechanically interlocked molecules, such as rotaxanes and catenanes, have already moved towards becoming technological realities. Rotaxanes (and their pseudorotaxane precursors), in particular, have been constructed by using the most diverse macrocyclic receptors as wheel components. Crown ethers, cyclodextrins, cyclic amides, and more recently cucurbiturils have all been threaded onto suitable complementary linear axle components. Calix[n]arenes, on the other hand, have received much less attention as building blocks for the construction of interlocked supermolecules, despite their tunable size, their versatility of derivatization (both at the wide and narrow rims), and their ready availability. The only notable exceptions are the findings of Arduini, Pochini, and co-workers, who have extensively investigated pseudorotaxanes and rotaxanes based on heterotopic calix[6]arene receptors adorned with ureido groups and viologen-derived linear components. Leaving aside calix[4]arenes, the cavity of which is too small to be threaded by a linear guest, the slightly larger calix[5]arenes are the next potential candidates for pseudorotaxane formation. Although calix[5]arenes have previously been shown to efficiently perform a number of tasks, which range from the complexation of alkyl(di)ammonium ions and ion pairs to the self-assembly of supramolecular polymers, to the best of our knowledge, no studies have so far been carried out to evaluate whether or not a linear thread can interpenetrate the calix[5]arene annulus. Herein we describe the first examples of [2]pseudorotaxanes derived from a calix[5]arene and linear secondary alkylammonium ions and we show that the ease of formation of these species is predominantly determined by salt ion-pairing effects, whereas the time course of the threading/dethreading process depends on the length of the cation alkylammonium chains. Very recently we have reported the solid-state structure of a calix[5]arene/n-butylammonium endo-cavity complex. Inspection of this structure revealed that the spatial arrangement of the oxygen atoms around the nitrogen atom of the included guest is reminiscent of the oxygen array present in crown ether/secondary ammonium ion complexes. Even though the cavity size of a calix[5]arene (at its narrow rim) appears to be slightly smaller than that found in the solidstate structure of the dibenzo[24]crown-8 encircling the dibutylammonium ion (ca. 5 vs. 6 , respectively), calix[5]arenes were judged to be sufficiently flexible to allow for the inclusion of secondary alkylammonium cations. After a preliminary screening, penta-tert-butylpentakis(tert-butoxycarbonylmethoxy)calix[5]arene (1) was selected as the prototype wheel component, whereas di-n-butylammonium (2·H) and di-n-hexylammonium (3·H) were chosen as axle components. The axle components were all tested as chloride, picrate (Pic ), and hexafluorophosphate salts to evaluate the influence of ion pairing on the pseudorotaxane assembly process.

Guest-induced capsular assembly of calix[5]arenes

Abstract Novel dimeric capsules are generated from the non-covalent assembly of cone calix[5]arenes and alkyldiammonium ions [H 3 N-(CH 2 ) n -NH 3 ] 2+ featuring an appropriate length of the spacer joining the two charged end groups. 1 H NMR spectroscopy and electrospray ionisation mass spectrometry provide evidence that in the capsule a single ditopic guest holds together a pair of calix[5]arene units, which are oriented rim-to-rim to form a closed cavity encapsulating the shape-complementary dication.

Ion-pair separation via selective inclusion/segregation processes

Segregation of iodide ions—via trifurcated halogen bonding to diiodoperfluoroalkanes—within fluorous layers consisting of 1D networks, provides the driving force for the isolation, in the solid state, of the first alkylammonium–calix[5]arene 1 : 1 endo-cavity complex.

Selective Amine Recognition Driven by Host–Guest Proton Transfer and Salt Bridge Formation

The stepwise synthesis of ionizable p-tert-butylcalix[5]arenes 1a·H and 1b·H, featuring a fixed cone cavity endowed with a carboxyl moiety at the narrow rim, is described. Single-crystal X-ray analyses have shown that in the solid state 1a·H and 1b·H adopt a cone-out conformation with the carboxylic OH group pointing in, toward the bottom of the aromatic cavity, as a result of a three- or two-center hydrogen-bonding pattern between the carboxyl group and the phenolic oxygen atom(s). The affinity of amines for calix[5]arene derivatives 1a·H and 1b·H was probed by (1)H NMR spectroscopy and single-crystal X-ray diffraction studies. These carboxylcalix[5]arenes are shown to selectively recognize linear primary amines--over branched, secondary, and tertiary amines--by a two-step process involving a proton transfer from the carboxyl to the amino group to provide the corresponding alkylammonium ion, followed by binding of the latter inside the cavity of the ionized calixarene. Proton transfer occurs only with linear primary amines, that is, when the best size and shape fit between host and substrate is achieved, while the other amines remain in their noncompeting unprotonated form. The role of the solvent in the ionization/complexation process is discussed. Structural studies on the n-BuNH(2) complexes with 1a·H and 1b·H provide evidence that binding of the in situ formed n-BuNH(3)(+) substrate to the cavity of the ionized macrocycle is ultimately secured, in the case of 1a·H, by the formation of an unprecedented salt-bridge interaction.

Sequence, Stoichiometry, and Dimensionality Control in Porphyrin/Bis‐calix[4]arene Self‐Assemblies in Aqueous Solution

The use of a water-soluble octacationic bis-calix[4]arene with divergent cavities (BC(4)) as a templating agent for the assembly of a tetraanionic porphyrin (CuTPPS) has allowed the noncovalent synthesis of 2D or 3D multiporphyrin assemblies. Self-assembly of CuTPPS and BC(4) molecules proceeded under hierarchical control in a stepwise fashion to yield discrete and isolable supramolecular nanostructures containing up to 33 molecular elements (i.e., the CuTPPS/BC(4) 17:16 assembly, obtained in less than three hours). The formation of these species could be conveniently monitored by means of UV/Vis spectroscopy by following the absorbance of the Soret band at 412 nm. In particular, the attainment of the pivotal CuTPPS/BC(4) 5:4 species with a cruciform structure, as the key fork-point intermediate for the subsequent formation of the higher 2D and 3D assemblies, has been demonstrated by light-scattering studies and by an unequivocal synthesis of mixed-porphyrin/calixarene 5:4 species involving the use of two different types of metallated porphyrins, namely CuTPPS and MnTPPS. The remarkable stability of these assemblies permits a stepwise synthesis that makes it possible to choose the desired porphyrin sequence.