Roberto Pontellini

A Macrocyclic Ligand as Receptor and ZnII‐Complex Receptor for Anions in Water: Binding Properties and Crystal Structures

Binding properties of 24,29-dimethyl-6,7,15,16-tetraoxotetracyclo[19.5.5.0(5,8).0(14,17)]-1,4,9,13,18,21,24,29-octaazaenatriaconta-Δ(5,8),Δ(14,17)-diene ligand L towards Zn(II) and anions, such as the halide series and inorganic oxoanions (phosphate (Pi), sulfate, pyrophosphate (PPi), and others), were investigated in aqueous solution; in addition, the Zn(II)/L system was tested as a metal-ion-based receptor for the halide series. Ligand L is a cryptand receptor incorporating two squaramide functions in an over-structured chain that connects two opposite nitrogen atoms of the Me(2)[12]aneN(4) polyaza macrocyclic base. It binds Zn(II) to form mononuclear species in which the metal ion, coordinated by the Me(2)[12]aneN(4) moiety, lodges inside the three-dimensional cavity. Zn(II)-containing species are able to bind chloride and fluoride at the physiologically important pH value of 7.4; the anion is coordinated to the metal center but the squaramide units play the key role in stabilizing the anion through a hydrogen-bonding network; two crystal structures reported here clearly show this aspect. Free L is able to bind fluoride, chloride, bromide, sulfate, Pi, and PPi in aqueous solution. The halides are bound at acidic pH, whereas the oxoanions are bound in a wide range of pH values ranging from acidic to basic. The cryptand cavity, abundant in hydrogen-bonding sites at all pH values, allows excellent selectivity towards Pi to be achieved mainly at physiological pH 7.4. By joining amine and squaramide moieties and using this preorganized topology, it was possible, with preservation of the solubility of the receptor, to achieve a very wide pH range in which oxoanions can be bound. The good selectivity towards Pi allows its discrimination in a manner not easily obtainable with nonmetallic systems in aqueous environment.

CRYPTAND LIGANDS FOR SELECTIVE LITHIUM COORDINATION

Abstract The binding properties, in aqueous solution, toward lithium ion of aza- and azaoxo- macrocycles with cage and cylindrical molecular topology are reviewed. The synthetic procedures and the acid–basic behavior are reported. Most of these compounds are able to selectively encapsulate the small lithium ion in aqueous solution. NMR spectroscopy, mainly 13C and 7Li, has been used to study the encapsulation equilibria. Few crystal structures of lithium complexes, indicating the lithium ion encapsulation have been reported.

Efficient fluorescent sensors based on 2,5-diphenyl[1,3,4]oxadiazole: a case of specific response to Zn(II) at physiological pH.

The coordination properties and photochemical responses of three fluorescent polyamine macrocycles, 9,12,15,24,25-pentaaza-26-oxatetracyclo[21.2.1.0(2,7).0(17,22)]hexaicosa-2,4,6,17,19,21,23,25(1)-octaene (L1), 9,12,15,18,27,28-hexaaza-29-oxatetracyclo[24.2.1.0(2,7).0(20,25)]enneicosa-2,4,6,20,22,24,26,28(1)-octaene (L2), and 9,12,15,18,21,30,31-heptaaza-32-oxatetracyclo[27.2.1.0(2,7).0(23,28)]diatriconta-2,4,6,23,25,27,29,31(1)-octaene (L3), toward Cu(II), Zn(II), Cd(II), and Pb(II) are reported. Each ligand contains the 2,5-diphenyl[1,3,4]oxadiazole (PPD) moiety inserted in a polyamine macrocycle skeleton. The stability constants were determined by means of potentiometric measurements in aqueous solution. L1 forms mononuclear complexes only with Cu(II). L2 and L3 form stable mononuclear species with all of the metals, while L3 is able to form dinuclear Cu(II) species. The fluorescence of all ligands was totally quenched by the presence of Cu(II). L2 behaves as an OFF-ON sensor for Zn(II) under physiological conditions, even in the presence of interfering species such as Cd(II) and Pb(II). This ligand combines selective binding of Zn(II) with a highly specific fluorescent response to Zn(II) due to the chelating enhancement of fluorescence (CHEF) effect. The interaction of Zn(II), Cd(II), and Pb(II) with L3 does not produce an appreciable enhancement of fluorescence at the same pH. The different behavior is attributed to the cavity size of the macrocycle and to the number of amine functions. L2 possesses the best arrangement of these two characteristics, allowing a full participation of all of the amine functions in metal coordination, as shown by the crystal structures of [CuL2(ClO(4))](ClO(4))·H(2)O and [ZnL2Br]Br·H(2)O species; this prevents the PET effect and supplies the higher CHEF effect. The interaction between L2 and Zn(II) can also be observed with the naked eye as an intense sky blue emission.

Multi-use NBD-based tetra-amino macrocycle: fluorescent probe for metals and anions and live cell marker.

Ligand L (4-(7-nitrobenzo[1,2,5]oxadiazole-4-yl)-1,7-dimethyl-1,4,7,10-tetra-azacyclododecane) is a versatile fluorescent sensor useful for Cu(II), Zn(II) and Cd(II) metal detection, as a building block of fluorescent metallo-receptor for halide detection, and as an organelle marker inside live cells. Ligand L undergoes a chelation-enhanced fluorescence (CHEF) effect upon metal coordination in acetonitrile solution. In all three complexes investigated the metal cation is coordinatively unsaturated; thus, it can bind secondary ligands as anionic species. The crystal structure of [ZnLCl](ClO(4)) is discussed. Cu(II) and Zn(II) complexes are quenched upon halide interaction, whereas the [CdL](2+) species behaves as an OFF-ON sensor for halide anions in acetonitrile solution. The mechanism of the fluorescence response in the presence of the anion depends on the nature of the metal ion employed and has been studied by spectroscopic methods, such as NMR spectroscopy, UV/Vis and fluorescence techniques and by computational methods. Subcellular localization experiments performed on HeLa cells show that L mainly localizes in spot-like structures in a polarized portion of the cytosol that is occupied by the Golgi apparatus to give a green fluorescence signal.

Ambivalence of nucleophilic attack on central and terminal allyl carbon atoms of [(η3-allyl)ML2]+ (M Pd or Pt) complexes

The coordinated allyl group of complexes [(η3-allyl)ML2]+ (M  Pd or Pt) is shown experimentally to undergo nucleophilic attack on either central (Cc) or terminal (Ct) allyl carbon atoms. A new theoretical discussion is presented, showing that the feasibility of attack at the Cc atom is not as low as previously thought.

New family of polyamine macrocycles containing 2,5-diphenyl[1,3,4]oxadiazole as a signaling unit. Synthesis, acid-base and spectrophotometric properties.

Synthesis and acid-base properties for three fluorescent polyamine macrocycles 9,12,15,24,25-pentaaza-26-oxatetracyclo[21.2.1.0(2,7).0(17,22)]hexaicosa-2,4,6,17,19,21,23,25(1)-octaene (L1), 9,12,15,18,27,28-hexaaza-29-oxatetracyclo[24.2.1.0(2,7).0(20,25)]enneicosa-2,4,6,20,22,24,26,28(1)-octaene (L2) and 9,12,15,18,21,30,31-heptaaza-32-oxatetracyclo[27.2.1.0(2,7).0(23,28)]diatriconta-2,4,6,23,25,27,29,31(1)-octaene (L3) are reported. Each ligand contains the 2,5-diphenyl[1,3,4]oxadiazole (PPD) unit incorporated in the polyamine macrocycle. The protonation constants of L1-L3 were determined by means of potentiometric measurements in 0.15 mol dm(-3) NaCl aqueous solution at 298.1 K. All the ligands are highly fluorescent in aqueous solution under acidic conditions (pH < 2) and their emission drastically decreases when the pH is increased. At pH > 8, a total quenching of fluorescence is observable in all the ligands. The fluorescence is given by the PPD unit, while the behavior as a function of pH can be rationalized on the basis of photoinduced intramolecular electron transfer (PET) from the HOMO of the donor macrocycle nitrogen atoms to the excited fluorophore unit. The insertion of PPD in a polyamine skeleton strongly improves the fluorescence quantum yield of this class of ligands with respect to those already known.

Two polyaminophenolic fluorescent chemosensors for H+ and Zn(II). Spectroscopic behaviour of free ligands and of their dinuclear Zn(II) complexes

The UV-Vis and fluorescence optical properties of the two polyamino-phenolic ligands 3,3′-bis[N,N-bis(2-aminoethyl)aminomethyl]-2,2′-dihydroxybiphenyl (L1) and 2,6-bis{[bis(2-aminoethyl)amino]methyl}phenol (L2) were investigated in aqueous solution at different pH values as well as in the presence of Zn(II) metal ion. Both ligands show two diethylenetriamine units separated by the 1,1′-bis(2-phenol) (BPH) or the phenol (PH) for L1 and L2, respectively. Both ligands are fluorescence-emitting systems in all fields of pH examined, with L1 showing a higher fluorescence emission than L2. In particular, the emission of fluorescence mainly depends on the protonation state of the phenolic functions and thus on pH. The highest emitting species is H3L3+ for both systems, where the BPH is monodeprotonated (in L1) and the PH is in the phenolate form (in L2). On the contrary, when BPH and PH are in their neutral form both ligands show the lowest fluorescence, since H-bonds occurring between the phenol and the closest tertiary amine functions decrease fluorescence. The Zn(II)-dinuclear species are also fluorescent in the pH range where they exist; the highest emitting species being [Zn2(H−2L1)]2+ and [Zn2(H−1L2)]3+ which are present in a wide range of pH including the physiological one. Fluorescence experiments carried out at physiological pH highlighted that, in the case of L1, the presence of Zn(II) ion in solution produces a simultaneous change in λem with a drop in fluorescence due to the formation of the [Zn2(H−2L1)]2+ species, while, in the case of L2, it gives rise to a strong CHEF effect (a twenty-fold enhancement was observed) due to the formation of the [Zn2(H−1L2)]3+ species. These results, supported by potentiometric, 1H and 13C NMR experiments, are of value for the design of new efficient fluorescent chemosensors for both H+ and Zn(II) ions.

New ligand bearing preorganized binding side-arms interacting with ammonium cations: Synthesis, conformational studies and crystal structureElectronic supplementary information (ESI) available: molecular modeling studies. See http://www.rsc.org/suppdata/nj/b3/b306778e/

The synthesis and characterization of the new tetraazamacrocycle 4-(N),10-(N)-bis[2-(3-hydroxy-2-oxo-2H-pyridin-1-yl)acetamido]-1,7-dimethyl-1,4,7,10-tetraazacyclododecane (L) is reported. L shows two 3-(hydroxy)-1-(carbonylmethylen)-2(1H)-pyridinone moieties as side-arms of a tetra-aza-macrocyclic base. The key coupling of side-arms was studied and the most significant results were obtained by activating the 3-(benzyloxy)-1-(carboxymethyl)-2(1H)-pyridinone as pentafluorophenol ester. The acid–base properties of L and its capability to interact with simple ammonium cations were investigated by potentiometric measurements in aqueous solution (298.1 ± 0.1 K, I = 0.15 mol dm−3). Protonated species of L can bind NH4+ or primary ammonium cations such as MeNH3+ discriminating them from secondary or tertiary ammonium cations such as Me2NH2+ or Me3NH+ which are not bound in aqueous solution. 1 H and 13C NMR spectra showed the existence in solution of two conformers on the NMR time scale due to the rotational restriction of the two N–CO groups. The activation parameters were determined by dynamic variable-temperature NMR analysis.Molecular dynamics calculations gave results in agreement with the experimental data for both conformation and ammonium-binding studies, underlining that the transformation of the two secondary amines of the macrocyclic base to amide functions, forces the side-arms to remain fixed in position, almost face to face and thus to be preorganized to interact with other species. The crystal structure of the [HL]Cl·8H2O species shows the high number of preorganized hydrogen bond sites capable, in this case, of interacting directly with five H2O molecules.

Macrocyclic ligands bearing two 3-(Hydroxy)-2-pyridinone moieties as side-arms. Conformational studies, synthesis, crystal structure, and alkali and alkaline earth complex formation

The synthesis and characterization of the new tetraazamacrocycle 4(N),10(N)-bis[2-(3-hydroxy-2-oxo-2H-pyridin-1-yl)ethyl]-1,7-dimethyl-1,4,7,10-tetraazacyclododecane (L1) is reported. L1 shows two 3-(hydroxy)-1-(carbonylmethylen)-2(1H)-pyridinone (HPO) moieties linked to the macrocyclic base 4,7-dimethyl-1,4,7,10-tetrazacyclododecane, as side-arms. The acid–base and coordination properties towards alkali, alkaline earth ions of L1 together with those of the structurally similar ligand 4-(N),10-(N)-bis[2-(3-hydroxy-2-oxo-2H-pyridin-1-yl)acetamido]-1,7-dimethyl-1,4,7,10-tetraazacyclododecane (L2) are reported. L2 binds all the metal ions investigated forming stable mono-nuclear complexes, while L1 binds only some alkaline earth ions with stability constants lower than those of L2. Both compounds show selectivity towards the Mg(II) ion with respect to the alkaline earth series. The binding area is formed by the four converging oxygen atoms of the two HPO groups. L2 appears to be a more efficient ligand in the coordination of hard metal ions because the two HPO binding groups are forced by the macrocyclic skeleton to stay on the same part of the macrocyclic ring, while this conformation is unfavourable for L1. These data are supported by molecular dynamics (MD) simulations performed on both ligands and by the crystal structure of the [H2L1](ClO4)2 species which shows the two side-arms displaced opposite to the macrocyclic ring. The effects of pH and metal ion coordination on the UV-Vis absorption and fluorescence emission properties of both ligands were investigated, highlighting that the optical properties changes in acid–base reactions as well as in the coordination of metal ions.

Heavy metal ion complexes with a simple phenolic ligand. Solid state and solution studies

Abstract The coordination properties of the ligand 2-[bis-(aminoethyl)-aminomethyl]-phenol (L) toward Cd(II) and Pb(II) are reported. The studies were carried out using potentiometric measurements (298.1 K, I=0.15 mol dm−3), UV–Vis absorption and 1H, 13C, 113Cd NMR spectra both in aqueous and non-aqueous solution. By potentiometric measurements performed in aqueous solution, L was found to form only mononuclear species with both the ions investigated; [MH−1L]+ is the main species formed. A dinuclear species with stoichiometry [M2(H−1L)2](ClO4)2 was almost quantitatively isolated in solid state from an aqueous solution in the pH range in which the [MH−1L]+ mononuclear species are present. This behavior is ascribed mainly to the low solubility of the dinuclear complex formed. L does not fulfill the coordination requirement of the ion in the mononuclear species and to saturate it, each metal ion binds the phenolate oxygen of another mononuclear species. The dinuclear species were characterized in organic solution by NMR and ESI mass spectroscopy. The results are confirmed by the crystal structure of [Cd2(H−1L)2](ClO4)2, which displays the two Cd(II) ions close to each other and bridged by two phenolic oxygens each belonging to a H−1L− species.