Switching on the Fluorescence Emission of Polypyridine Ligands by Simultaneous Zinc(II) Binding and Protonation.

The synthesis and characterization of the two new open-chain ligands 1,15-bis-[6-(2,2'-bipyridyl)]-2,5,8,11,14-pentaaza-octadecane (L1) and 1,15-bis-[2-(1,10-phenanthroline)-9-methyl]-2,5,8,11,14-pentaazaoctadecane (L2), both featuring a tetraethylenpentaamine chain linking via methylene bridges the 6 and 2 positions of two identical 2,2'-bipyridyl (bpy) and 9-methyl-1,10-phenanthroline (9-methyl-phen) moieties respectively, are reported. Their protonation and binding ability for Cu , Zn , Cd and Pb have been studied by coupling potentiometric titrations with UV-vis absorption and fluorescence emission measurements in water. L1 and L2 afford stable mono- and dinuclear complexes, in which the metal ion is bound by a single bpy or 9-methyl-phen unit and the amine groups on the aliphatic chain.

Sensing, Transport and Other Potential Biomedical Applications of Pseudopeptides.

Pseudopeptides are privileged synthetic molecules built from the designed combination of peptide-like and abiotic artificial moieties. Consequently, they are benefited from the advantages of both families of chemical structures: modular synthesis, chemical and functional diversity, tailored three-dimensional structure, usually high stability in biological media and low non-specific toxicity. Accordingly, in the last years, these compounds have been used for different biomedical applications, ranging from bio-sensing, ion transport, the molecular recognition of biologically relevant species, drug delivery or gene transfection.

Supramolecular protection from the enzymatic tyrosine phosphorylation in a polypeptide.

Here we report two new artificial pseudopeptidic cages that bind the EYE peptide epitope in pure water at physiological pH (as studied by fluorescence and NMR spectroscopies). The supramolecular complexation of the Tyr residues efficiently precludes their subsequent PTK-catalysed phosphorylation. Our results show a supramolecular modulation of the PTK activity by competitive substrate caging.

Stereoselective recognition of the Ac-Glu-Tyr-OH dipeptide by pseudopeptidic cages.

Pseudopeptidic molecular cages are appealing receptors since they can display different polar and non-polar interaction sites in a modular framework and a controlled disposition. Inspired by previous host-guest knowledge, two pseudopeptidic molecular cages based on serine and threonine (CySer and CyThr, respectively) were designed and synthesized as hosts for the binding of the four possible stereoisomers of the Ac-Glu-Tyr-OH dipeptide, a target sequence of tyrosine kinases. The careful NMR titration experiments in aqueous acetonitrile allowed the determination of the binding constants and reflected a difference in the stability of the corresponding diastereomeric host-guest complexes.

Copper(ii) complexes of macrocyclic and open-chain pseudopeptidic ligands: synthesis, characterization and interaction with dicarboxylates.

Mono- and dinuclear Cu(ii) complexes were prepared with pseudopeptidic open chain and macrocyclic ligands, respectively. They were characterized by UV-vis spectroscopy, EPR, HRMS and X-ray diffraction. The Cu(ii) cation is coordinated by two amines and two deprotonated amides, in a slightly distorted square planar coordination geometry.

Chiral imidazolium receptors for citrate and malate: the importance of the preorganization.

A family of simple receptors formed by two or three cationic imidazolium arms attached to a central aromatic linkage and displaying different conformational flexibility has been synthesized from the enantiopure (1S,2S)-2-(1-H-imidazol-1-yl)-cyclohexanol. The crystal structures of the corresponding bromides of two of the hosts showed remarkable differences. The tripodal receptor with a trimethylated central benzene ring (1a) showed a cone-type conformation defining an inner anion-binding site, while the bipodal molecule with the central meta-phenylene spacer (m-2a) displayed an extended conformation.

Pseudopeptidic cages as receptors for N-protected dipeptides.

The molecular recognition of short peptides is a challenge in supramolecular chemistry, and the use of peptide-like cage receptors represents a promising approach. Here we report the synthesis and characterization of a diverse family of pseudopeptidic macrobicycles, as well as their binding abilities toward N-protected dipeptides using a combination of different techniques (NMR, ESI-MS, and fluorescence spectroscopy). The cage hosts were assayed for dipeptide binding using competition ESI-MS experiments as high-throughput screening to obtain general trends for the recognition phenomena.

Direct arylation of oligonaphthalenes using PIFA/BF3·Et2O: from double arylation to larger oligoarene products.

Direct dehydrogenative coupling between the linear ter- and quaternaphthalenes and substituted benzenes was achieved under the Kita conditions using the hypervalent PIFA/BF3 reagent. Products resulting from either the double arylation of the naphthalenic substrate or the formal dimerizative arylation have been prepared. For example, in the latter mode, ternaphthalene was converted into a series of linear octiarenes (counting the capping Ar).

Direct assembly of polyarenes via C-C coupling Using PIFA/BF3·Et2O.

Direct oxidative Kita-type coupling between naphthalene and substituted benzenes was found to proceed via four-component coupling, leading to a linear tetraarene with a binaphthalene core. The methodology was extendable to the coupling of unfunctionalized 1,1'-binaphthalene with mesitylene to give a linear hexaarene product in a remarkably chemoselective manner in 87% yield. The method represents an attractive alternative to the traditional syntheses of related oligonaphthalene products via a sequence of metal-catalyzed cross-coupling steps.

Binding of H+ and Zn(II) ions with a new fluorescent macrocyclic phenanthrolinophane.

The new macrocyclic ligand 1,9(4,7)-diphenanthroline-3,7,11,15-tetraazacyclohexadecaphane (L) was synthesized by a 2 : 2 reaction of 1,10-phenanthroline-4,7-dialdehyde with 1,3-diaminopropane, followed by reduction with NaBH(4). L contains two phenanthroline groups linked together by two 1,3-diaminopropane chains in such a way that the heteroaromatic nitrogen atoms point outside the ligand cavity. The ligand structure defines two pairs of identical compartments displaying a specific ability in the binding of protons (1,3-diaminopropane) and metal ions (phenanthroline).

A highly pH-sensitive Zn(II) chemosensor.

Proton and Cu(II), Zn(II), Cd(II) and Pb(II) binding by ligand H(2)L, containing two bis(aminoethyl)amine (dien) units connected by a 2',7'-dichlorofluorescein (DCF) unit has been analyzed by means of potentiometric, UV-vis and fluorescence emission measurements. Considering proton binding, the ligand in its fully deprotonated form, L(2-), binds up to four acidic protons in the alkaline pH region. These protonation steps occur on the amine groups, whereas protonation of DCF takes place only below pH 4.

Exploring the binding ability of phenanthroline-based polyammonium receptors for anions: hints for design of selective chemosensors for nucleotides.

The synthesis of receptor 2,6,10,14,18-pentaaza[20]-21,34-phenanthrolinophane (L1), containing a pentaamine chain linking the 2,9 positions of a phenanthroline unit, is reported. The protonation features of L1 and of receptor 2,6,10,14,18,22-hexaaza[23]-24,37-phenanthrolinophane (L2) have been studied by means of potentiometric, (1)H NMR, and spectrofluorimetric measurements; this study points out that the fluorescent emission of both receptors depends on the protonation state of the polyamine chain. In fact, the receptors are emissive only at neutral or acidic pH values, where all the aliphatic amine groups are protonated.

Polyamine receptors containing dipyridine or phenanthroline units: clues for the design of fluorescent chemosensors for metal ions.

The synthesis of the macrocyclic receptor L1, which contains a tetraamine chain linking the 6,6'-positions of a 2,2'-dipyridine moiety, is reported. Its basicity properties and complexation features toward Cu(II), Zn(II), Cd(II) and Pb(II) have been studied in aqueous solutions by means of potentiometric, UV/Vis spectroscopy and fluorescence emission measurements and compared with those of ligand L2, in which a 1,10-phenanthroline moiety replaces the dipyridine unit of L1. In metal coordination, L1 shows a marked selectivity toward Cd(II) over Zn(II) and Pb(II).

Cu(ii) complexation with an acridine-containing macrocycle. Assembly of water cluster chains within the cavity of tetranuclear metallomacrocycles.

The synthesis and characterisation of a new macrocyclic compound (L), composed of a pentamine chain linking the 2,7 positions of an acridine moiety, is reported. Cu(ii) complexation was studied by means of potentiometric, UV-vis and EPR measurements in aqueous solutions. This study reveals that the ligand forms a stable tetranuclear complex with an overall [Cu(4)L(2)(OH)(4)](4+) stoichiometry in aqueous solution.

Total syntheses of casuarine and its 6-O-alpha-glucoside: complementary inhibition towards glycoside hydrolases of the GH31 and GH37 families.

Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6-O-alpha-glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao-Fleming oxidation and selective alpha-glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes. The structural determination of the complexes of NtMGAM with 1 and of Tre37A with 2 revealed interesting similarities in the catalytic sites of these two enzymes which belong to different families and clans.

A dizinc complex for selective fluorescence sensing of uridine and uridine-containing dinucleotides.

A dizinc complex with a polyamine macrocycle is able to selectively bind and sense uridine (U) as well as the uridine-containing ribodinucleotides U(3'-5')pU and U(3'-5')pA, thanks to an exciplex emission arising from a pi-stacked complex involving the dipyridine unit and Zn(II)-bound uridine moieties.

ATP recognition and sensing with a phenanthroline-containing polyammonium receptor.

A new polyammonium receptor is able to selectively recognise and sense ATP among triphosphate nucleotides, thanks to ATP-induced quantitative quenching of its fluorescence emission.

Encapsulation of metal cations and anions within the cavity of bis(1,4,7-triazacyclononane) receptors.

The synthesis and characterisation of a new bis([9]aneN3) ligand (L4) containing two [9]aneN3 macrocyclic moieties separated by a 2,6-dimethylenepyridine unit is reported. A potentiometric and 1H NMR study in aqueous solution reveals that ligand protonation occurs on the secondary amine groups and does not involve the pyridine nitrogen. The coordination properties toward Cu(II), Zn(II), Cd(II) and Pb(II) were studied by means of potentiometric and UV spectrophotometric measurements.

Coordination chemistry of N-aminopropyl pendant arm derivatives of mixed N/S-, and N/S/O-donor macrocycles, and construction of selective fluorimetric chemosensors for heavy metal ions.

The coordination chemistry of the N-aminopropyl pendant arm derivatives (L1c-4c) of the mixed donor macrocyclic ligands [12]aneNS2O, [12]aneNS3, [12]aneN2SO, and [15]aneNS2O2(L1a-4a) towards Cu(II), Zn(II), Cd(II), Hg(II), and Pb(II) in aqueous solution has been investigated. The protonation and stability constants with the aforementioned metal ions were determined potentiometrically and compared, where possible, with those of the unfunctionalised macrocycles. The measured values show that Hg(II) and Cu(II) in water have the highest affinity for all ligands considered, with the N-aminopropyl pendant arm weakly coordinating the metal centres.