Emanuela Berni

Expanding the registry of aromatic amide foldamers: folding, photochemistry and assembly using diaza-anthracene units.

The synthesis of various 1,8-diaza-4,5-dialkoxy-2,7-anthracene dicarboxylic acid derivatives and their incorporation into cyclic and helically folded aromatic oligoamides are reported. The ability of the diaza-anthracene monomers to undergo photoaddition or head-to-tail photodimerization was investigated in the solid state and in solution. Quantitative conversion of a monomer diester to the corresponding head-to-tail photodimer could be achieved in the solid state without protection from oxygen. The formation of an emissive excimer between two diaza-anthracene units appended at the end of a helically folded oligomer was demonstrated. Intramolecular photodimerization was not observed in this compound, possibly due to the low thermal stability of the head-to-head photoadduct. A cyclic oligoamide composed of two diaza-anthracene and two pyridine units was shown to adopt a flat conformation and to form columnar stacks in the solid state. Longer, noncyclic oligoamides composed of one or two diaza-anthracene units were shown to adopt helical conformations that exist preferentially as double helical dimers.

A thermodynamic and spectrophotometric study of anion binding with a multifunctional dipyridine-based macrobicyclic receptor

Abstract Synthesis and characterisation of a new macrobicycle containing two dipyridine units (L) is reported. Protonated forms of L are efficient receptors for inorganic phosphate and nucleotide anions. The binding properties of L toward these substrates have been investigated in aqueous solution by means of potentiometric, microcalorimetric and 1H NMR measurements. Only 1:1 receptor–anion complexes have been found in solution. The stability of the adducts with inorganic phosphates anions is higher than that found for the nucleotides complexes. The complexation reactions are endothermic, and promoted by invariably favourable entropic contributions, indicating that these pairing processes are mostly determined by the desolvation of the interacting species that occurs upon charge neutralisation.

Binding of nucleobases to a dizinc macrocyclic complex. Supramolecular assembling of dinuclear clusters through N-H···O and C-H···O hydrogen bonding

The interaction of cytosine (CyH), thymine (TH) and uracil (UH) with the dinuclear Zn(II) complexes of ligand 1,4,7,16,19,22hexaza-10,13,25,28-tetraoxacyclotriacontane (L) has been studied by means of potentiometric titrations (0.1 mol dm −3 NMe4NO3, 298.1 K), and 1 H NMR measurements. The equilibrium constants for the formation of the ternary complexes with the nucleobases indicate that the [Zn2L] 4 + complex displays similar binding features towards thymine and uracil. The dizinc complex forms stable 1:1 and 1:2 complexes with both deprotonated thymine and uracil at neutral or slightly alkaline pH values. The constants for the addition of first and second substrate molecules are almost equal indicating that each nucleobase is coordinated, almost independently, by one metal ion of [Zn2L] 4 + . This feature is confirmed by the crystal structures of [Zn2LT2] 2 + and [Zn2LU2] 2 + . In the [Zn2LA2] 2 + (A − =T − ,U − ) complexes the two metal ions have almost the same coordination environment and each Zn(II) is coordinated to three nitrogens of the macrocycle and to a deprotonated nitrogen of the nucleobases. In the crystal packing the dinuclear clusters give rise to a supramolecular architecture based on infinite pillars of [Zn2LA2] 2 + (A − =T − , U − ) assembled via hydrogen bonding. Cytosine forms only 1:1 adducts with the dizinc complex and the stability constants values suggest that the deprotonated nucleobase bridges the two metal ions.

Supramolecular Assembling of Dizinc Macrocyclic Complexes with Thymine and Uracil — The Role of Intra- and Intermolecular Hydrogen Bonding

A binuclear ZnII complex with an oxa-aza macrocyclic ligand can bind two deprotonated thymine or uracil moieties, giving versatile building blocks for the assembly of supramolecolar structures, by hydrogen bond pairing of the nucleobases.

Protonation and coordination properties towards Zn(II), Cd(II) and Hg(II) of a phenanthroline-containing macrocycle with an ethylamino pendant arm

Protonation and Zn(II), Cd(II) and Hg(II) coordination with the ligand 5-aminoethyl-2,5,8-triaza-[9]-10,23-phenanthrolinophane (L2), which contains an aminoethyl pendant attached to a phenanthroline-containing macrocycle, have been investigated by means of potentiometric, 1H NMR and spectrofluorimetric titrations in aqueous solutions. The coordination properties of L2 are compared with those of the ligand 2,5,8-triaza-[9]-10,23-phenanthrolinophane (L1). Ligand protonation occurs on the aliphatic amine groups and does not involve directly the heteroaromatic nitrogens. The fluorescence emission properties of L2 are controlled by the protonation state of the benzylic nitrogens: when not protonated, their lone pairs are available for an electron transfer process to the excited phenanthroline, quenching the emission. As a consequence, the ligand is emissive only in the highly charged [H3L2]3+ and [H4L2]4+ species, where the benzylic nitrogens are protonated. Considering metal complexation, both [ML1]2+ and [ML2]2+ complexes (M = Zn(II) and Cd(II)) are not emissive, since the benzylic nitrogens are weakly involved in metal coordination, and, once again, they are available for quenching the fluorescence emission. Protonation of the L2 complexes to give [MHL2]3+ species, instead, leads to a recovery of the fluorescence emission. Complex protonation, in fact, occurs on the ethylamino group and gives a marked change of the coordination sphere of the metals, with a stronger involvement in metal coordination of the benzylic nitrogens; consequently, their lone pairs are not available for the process of emission quenching.

Protonated macrocyclic Zn(II) complexes as polyfunctional receptors for ATP

Zn(II) coordination by the phenanthroline-containing macrocycle 2,6,10,14-tetraaza[15](2,9)cyclo(1,10)phenanthrolinophane (L4) has been studied by means of potentiometric measurements in aqueous solution. Its coordination properties have been compared with those of other phenanthroline- or dipyridine-containing open-chain (L1, L2) or cyclic (L3) ligands. ATP binding to the Zn(II) complexes with L1–L4 has been examined by means of potentiometric and 1H and 31P NMR measurements in aqueous solution. In the ATP adducts with the [ZnL]2+ complexes, the nucleotide interacts with the metal via the terminal Pγ phosphate group; the equilibrium constants for the addition of ATP to the complexes depend on the number and arrangement of the nitrogen donors coordinated to the metal ion. Protonation of the [ZnL]2+ complexes gives [ZnHxL](x + 2)+ species, which contain two binding sites for the phosphate chain of ATP; while the Pγ phosphate group gives a coordination bond with the metal, the Pβ one interacts via P–O−⋯H–N+ salt bridges with the ammonium functions of the complex. In consequence, protonated complexes are better ATP receptors than the simple [ZnL]2+ species and even than the protonated forms [HxL]x+ of the ligands, due to the synergetic action of the metal ion and of ammonium functions in ATP binding.

Proton and Cu(II) binding to tren-based tris-macrocycles. Affinity towards nucleic acids and nuclease activity

Proton binding by the two tren-based tris-macrocycles L1 and L2, composed, respectively, by three 1,4,7,10-tetrazacyclododecane ([12]aneN4) and three 1-oxa-4,7,10-triazacyclododecane ([12]aneN3O) macrocyclic moieties appended to a “tren” unit (tren = tris(2-aminoethyl)amine), has been analyzed by means of potentiometric and 1H and 13C NMR measurements in aqueous solutions. This study reveals that the ligands form highly charged polyammonium cations at neutral pH, containing six acidic protons equally distributed among the three macrocyclic units. A potentiometric and UV-vis spectrophotometric study shows that both ligands can form stable trinuclear Cu(II) complexes in a wide pH range. In the polynuclear complexes each metal is coordinated to a single macrocyclic unit. While the Cu(II) complexes with L1 do not show any tendency to form hydroxylated complexes, the mono-, di- and trinuclear L2 complexes give stable hydroxo-complexes, present in aqueous solutions from slightly acidic to alkaline pH values. Melting point studies indicate that the new tris-macrocyles and their Cu(II) complexes lead to stronger stabilization of double-stranded nucleic acids than those observed earlier with analogous ditopic macrocyclic ligands, again with preference for RNA-type polymers compared to DNA. The copper complexes promote cleavage of plasmid DNA and of bis-p-nitrophenyl phosphate (BNPP). Particular rate enhancements for BNPP with some complexes are attributed to the simultaneous action of three metal ions and partially to the formation of hydroxo complexes at neutral pH.

Zn(II) coordination to tren-based tris-macrocycles. Activity of their trinuclear Zn(II) complexes in carboxy- and phosphate-ester hydrolysis

Zn(II) binding by two tren-based tris-macrocycles has been analysed by means of potentiometric measurements in aqueous solutions. Both ligands form stable trinuclear Zn(II) complexes. Deprotonation of Zn(II)-coordinated water molecules gives mono-, di- and tri-hydroxo complexes. The ability of these trinuclear complexes as hydrolytic agents has been tested by using p-nitrophenyl acetate and bis(p-nitrophenyl) phosphate (BNPP) as substrates. BNPP cleavage takes place through a bridging interaction of the substrate with at least two metals and simultaneous nucleophilic attack of a Zn–OH function at phosphorus. A significant increase of the hydrolysis rate with respect to the mononuclear Zn(II) complex with [12]aneN4 is observed.

ApA Cleavage Promoted by Oxa-aza Macrocycles and Their Zn(II) Complexes. The Role of pH and Metal Coordination in the Hydrolytic Mechanism

Abstract The thermodynamic parameters for protonation and Zn(II) complex formation with ligand 1,4,7,16,19,22-hexaza-10,13,25,28-tetraoxacyclotriacontane (L1) have been determined. L1 forms stable dizinc complexes from neutral to alkaline pH. The hydrolytic ability toward adenylyl(3′-5′)adenosine (ApA) of L1 and its dizinc(II) complexes have been analyzed by means of HPLC chromatography. Only partially protonated species of L promote ApA hydrolysis suggesting that the cleavage process is cooperatively promoted by a general base catalysis by neutral amine groups and a general acid catalysis by protonated ammonium functions. Concerning the Zn(II) complexes, the hydrolysis rates increase in the presence of the hydroxo complexes [Zn2L1(OH)]3+ and [Zn2L1(OH)2]2+. This indicates that Zn-OH functions play a crucial role in the hydrolytic process, assisting the deprotonation of the 2′-OH group of ApA, which may act as nucleophile in the cleavage process. Both binuclear L1 complexes are better catalysts than the mononuclear [ZnL2(OH)]+ complex (L2 = 1,4-Dioxa-7,10,13-triazacyclopentadecane), indicating a cooperative role of the two Zn(II) ions in ApA cleavage by [Zn2L1(OH)]3+ and [Zn2L1(OH)2]2+, probably due to a bridging coordination of the phosphate moiety of ApA to the two metal centers.

Basicity and coordination ability of linear hexa-amines in relation to N-(CH2)n-N chain-link lengths. A solution study

Abstract The synthesis of the two new linear hexa-amines, 3,7,10,14-tetraazahexadecane-l,16-diamine (L 1 ) and 5,9,12,16-tetraazaicosane-l,20-diamine (L 2 ) has been reported. Ligand protonation and Cu(II) and Zn(II) coordination have been studied in aqueous solution by means of potentiometric, microcalorimetric (298.1 K, I =0.1 mol dm −3 ) and spectrophotometric (UV–Vis, 1 H and 13 C NMR) measurements. The species present in solution and their stability constants have been determined. L 1 forms mono- and binuclear complexes in aqueous solution with Cu(II). In the [ML 1 ] 2+ complexes, the metal ion is coordinated by five nitrogen atoms, while in the [ML 2 ] 2+ complexes the metal ion is four-coordinate. This different behavior is explained in terms of the different numbers of methylene groups between adjacent nitrogen atoms.