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Pannexins are an interesting new target in medicinal chemistry, as they are involved in many pathologies such as epilepsy, ischemic stroke, cancer and Parkinson’s disease, as well as in neuropathic pain. They are a family of membrane channel proteins consisting of three members, Panx-1, Panx-2 and Panx-3, and are expressed in vertebrates. In the present study, as a continuation of our research in this field, we report the design, synthesis and pharmacological evaluation of new quinoline-based Panx-1 blockers. The most relevant compounds 6f and 6g show an IC50 = 3 and 1.5 µM, respectively, and are selective Panx-1 blockers. Finally, chemical stability, molecular modelling and X-ray crystallography studies have been performed providing useful information for the realization of the project.

Very few sodium complexes are available as precursors for the syntheses of sodium-based nanostructured materials. Herein, the diglyme, triglyme, and tetraglyme (CH3O(CH2CH2O)nCH3, n = 2–4) adducts of sodium hexafluoroacetylacetonate were synthesized in a single-step reaction and characterized by IR spectroscopy, 1H, and 13C NMR. Single-crystal X-ray diffraction studies provide evidence of the formation of the ionic oligomeric structure [Na4(hfa)6]2−•2[Na(diglyme2]+ when the diglyme is coordinated, while a mononuclear seven-coordinated complex Na(hfa)•tetraglyme is formed with the tetraglyme. Reaction with the monoglyme (CH3OCH2CH2OCH3) does not occur, and the unadducted polymeric structure [Na(hfa)]n forms, while the triglyme gives rise to a liquid adduct, Na(hfa)•triglyme•H2O. Thermal analysis data reveal great potentialities for their applications as precursors in metalorganic chemical vapor deposition (MOCVD) and sol-gel processes. As a proof-of-concept, the Na(hfa)•tetraglyme adduct was successfully applied to both the low-pressure MOCVD and the sol-gel/spin-coating synthesis of NaF films.

The metoprolol free base has been characterized in the solid state by X-ray diffaction (both single-crystal and variable-temperature powder diffraction) and differential scanning calorimetry. These studies are supplemented by mol­ecular modelling and Hirshfeld surface analysis. Structural relationships with the strictly related betaxolol are discussed., Metoprolol {systematic name: (RS)-1-iso­propyl­amino-3-[4-(2-meth­oxy­eth­yl)phen­oxy]propan-2-ol}, C15H25NO3, is a cardioselective β1-adrenergic blocking agent that shares part of its mol­ecular skeleton with a large number of other β-blockers. Results from its solid-state characterization by single-crystal and variable-temperature powder X-ray diffraction and differential scanning calorimetry are presented. Its mol­ecular and crystal arrangements have been further investigated by mol­ecular modelling, by a Cambridge Structural Database (CSD) survey and by Hirshfeld surface analysis. In the crystal, the side arm bearing the isopropyl group, which is common to other β-blockers, adopts an all-trans conformation, which is the most stable arrangement from modelling data. The crystal packing of metoprolol is dominated by an O—H⋯N/N⋯H—O pair of hydrogen bonds (as also confirmed by a Hirshfeld surface analysis), which gives rise to chains containing alternating R and S metoprolol mol­ecules extending along the b axis, supplemented by a weaker O⋯H—N/N—H⋯O pair of inter­actions. In addition, within the same stack of mol­ecules, a C—H⋯O contact, partially oriented along the b and c axes, links homochiral mol­ecules. Amongst the solid-state structures of mol­ecules structurally related to metoprolol deposited in the CSD, the β-blocker drug betaxolol shows the closest analogy in terms of three-dimensional arrangement and inter­actions. Notwithstanding their close similarity, the crystal lattices of the two drugs respond differently on increasing temperature: metoprolol expands anisotropically, while for betaxolol, an isotropic thermal expansion is observed.

The ibuprofen alkaline-earth compounds Ibuprofen-Mg and Ibuprofen-Ca were investigated by using combined solid state and solution studies. The molecular and crystal structures of the calcium (Ca_Ibu_Hy, a 1D-coordination polymer based on ibuprofen) and magnesium (Mg_Ibu_Hy_RT and Mg_Ibu_Hy_LT) ibuprofen dihydrate salts have been analyzed in depth by using X-ray diffraction (both single crystal and powder) and in-silico tools. Differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), variable temperature X-ray diffraction experiments were carried out to study the stability of the solid forms under different temperature conditions. The Mg_Ibu_Hy_LT → Mg_Ibu_Hy_RT transition, which occurs between 250 and 300 K, is fully reversible and consists of a mild rearrangement of the crystal structure. Upon raising the temperature, dehydration of the Mg_Ibu_Hy_RT phase occurs, which leads to a completely amorphous phase at T > 340 K. As a consequence, the RT phase of the MgII compound is stable in a quite narrow temperature range. The calcium salt, in turn, gives a partially crystalline anhydrous phase with rising temperature. The coordination behavior of ibuprofen towards MgII, CaII and SrII in a water–ethanol mixture has been studied by means of potentiometric titrations. Based on the almost identical formation constants for CaII- and MgII-Ibuprofen complexes and on the well-known great affinity of MgII-for water molecules, we speculated the formation of solvent-shared ion pairs in the latter case, where the MgII-carboxylate interaction is of the outer-sphere type.

Dexketoprofen [(2S)-2-(3-benzoylphenyl)propanoic acid], C16H14O3, is the S-enantiomer of ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, antipyretic and anti-inflammatory properties, and finds applications for the short-term treatment of mild to moderate pain. A new crystalline phase of dexketoprofen is reported. Its solid-state structure was determined by single-crystal X-ray diffraction (SCXRD). The molecular structure of the two independent molecules found in the asymmetric unit of this new phase (DXKP-β) were compared to those of the already known crystal form of dexketoprofen (DXKP-α) and with the S-enantiomer of the racemic compound. The three different conformers of dexketoprofen found in DXKP-α and DXKP-β were then investigated by computational methods. The optimized structures are very close to the corresponding starting geometries and do not differ significantly in energy. The crystal packing of DXKP-β was studied by means of Hirshfeld surface (HS) analysis; interaction energies were also calculated. A comparison with DXKP-α shows close similarities between the two crystal forms, i.e. in both cases, molecules assemble through the catemer O—H...O synthon of the carboxylic acid stabilized by additional C—H...O contacts and, accordingly, the interaction energies, as well as the contributions to the HS area, are very similar. Finally, the thermal behaviour of the two polymorphs of dexketoprofen was assessed by means of XRD (both from single crystal and microcrystalline powder) and differential scanning calorimetry (DSC); both crystal forms are stable under the experimental conditions adopted (air, 300–350 K for DXKP-α and 300–340 K DXKP-β) and no solid–solid phase transition occurs between the two crystal forms in the investigated temperature range (from 100 K up to ca 350 K).

The anisotropic lattice expansion is a different variation of one crystallographic axis respect the other ones. In a temperature dependent X-Ray Powder Diffraction experiment, the anisotropic lattice expansion can be visualized as a significant shift of a set of peaks while others practically did not move. As a consequence, the anisotropic expansion could lead wrong conclusions on the purity and/or composition of a crystalline phase. We observed anisotropic lattice expansion for metoprolol succinate salt ( metoprolol = (±)-1-isopropylamino-3-[4- (2-methoxy-ethyl)-phenoxy]-propan-2-ol) salt. For the related and structural close, metoprolol tartrate salt no such behavior was found. [1] Moreover also the metoprolol free base is subject to anisotropic expansion while the related betaxolol, with similar solid state arrangement and very small structural difference, expands isotropically. [2] In this work, we show that semiempirical HF-3c method [3] is able to reproduce the experimental observations at a reasonable computational cost within the standard error in reproducing crystal structures. [4] Our protocol could help to shed some light on the anisotropic lattice expansion in organic crystals and to rationalize the factor responsible for the phenomenon. [1] P. Paoli, P. Rossi, E. Macedi, A. Ienco, L. Chelazzi, G. L. Bartolucci, B. Bruni Cryst. Growth Des. 2016, 16, 789. [2] P. Rossi, P. Paoli, L. Chelazzi, L. Conti, A. Bencini Acta Cryst. 2019, C75, 87. [3] R. Sure, S. Grimme J. Comput. Chem. 2013, 34, 1672. [4] M. Cutini, B. Civalleri, M. Corno, R. Orlando, J. G. Brandenburg, L. Maschio, P. Ugliengo J. Chem. Theory Comput. 2016, 12, 3340.

We synthesized and characterized the ligand N,N'-bis[(2,2'-dihydroxybiphen-3-yl)methyl]-N,N'-dimethylethylenediamine (L), which contains two biphenol moieties linked as side arms to an N,N'-dimethylethylenediamine scaffold. The ligand is highly soluble in a 50/50 (v/v) water/ethanol mixture and, in its deprotonated form H-2L(2-), is able to coordinate transition-metal ions such as Ni(II), Zn(II), Cu(II), Cd(II), and Pd(II). The crystal structures of [Ni(H-2L)·2n-BuOH], [Ni(H-2L)·2MeOH], [Cd(H-2L)·2DMF], [Cu(H-2L)(DMF)], and [Pd(H-2L)(DMF)] were also determined and described. Potentiometric titrations were carried out in a mixed solvent with Zn(II), Cu(II), and Ni(II) metal ions to determine the acid-base and stability constants. L was highly fluorescent in the visible range (400 nm). Moreover, its emission intensity increased upon the addition of Zn(II) or Cd(II) ions in an ethanol/water solution and behaved as a chemosensor for the presence of these ions in the solution.

The discovery of cisplatin (cis-Pt(NH3)2Cl2) as an antineoplastic agent has focussed attention on the rational design of metal complexes that can be potentially used in cancer chemotherapy. Today, the pharmaceutical industry invests more than $1 billion each year in the development of new metal-based drugs to improve biological activities, in terms of cellular selectivity, therapeutic efficiency and minimization of side effects. Chemotherapies based on transition metals play a key role in cancer treatment, and among them platinum and palladium are the most fruitful. This article reviews the main recent advances in the design and synthesis of platinum- and palladium-based drugs, their structural features and biological studies of them. The rationale for the choice of the ligand, related to leaving groups, the geometry of the complex and the oxidation state of the metal ion, is discussed. An overview of the main biological techniques and approaches for testing the interaction of these molecules with the biological environment, mainly DNA, to validate the effect is also provided.

We report the synthesis of novel heterobimetallic precursors of the formula [RE(hfa)4]-[Na·tetraglyme]+ [RE = Y, Gd; Hhfa = 1,1,1,5,5,5-hexafluoro-2,4-pentanedione; tetraglyme = 2,5,8,11,14-pentaoxapentadecane], which can be efficiently used as a single source for the metal-organic chemical vapor deposition of NaREF4 films.

The properties of two Cu(II) and Co(II) complexes with two maltol derivative ligands [ L1 = N,N′-bis[(3-hydroxy-4-pyron-2-yl)methyl]-N,N′-dimethylethylendiamine (Malten) and L2 = 4,10-bis[(3-hydroxy-4-pyron-2-yl)methyl]-1,7-dimethyl-1,4,7,10-tetraazacyclododecane (Maltonis)] as binders for lanthanide cations [Eu(III) and Dy(III)], were investigated by means of single crystal X-ray diffraction and by UV–Vis experiments. [M(II)(H -2 L)] species [Cu(H -2 L1 )] and [Co(H -2 L2 )] are able to stabilize one hard metal ion such as Eu(III) and Dy(III), giving rise to the formation of hetero-trinuclear complexes of {Ln(III)[M(II)(H -2 L)] 2 } 3+ general formula. The crystal structures of all the studied hetero-trinuclear species highlight that such systems are formed thanks to the synergy between the different stereochemical requirement of the transition metal (Cu(II) or Co(II)) and the different donor atoms set of the ligands. The suitable transition metal ion preorganizes the maltol units in the [M(II)(H -2 L)] complexes for the binding of the hard Ln(III) metal, otherwise difficult to bind in water.

Ligand L (2,6-bis{[7-(7-nitrobenzo[1,2,5]oxadiazole-4-yl)-3,10-dimethyl-1,4,7,10-tetraazacyclododeca-1-yl]methyl}phenol) is a fluorescent sensor that is useful for detecting Cu(II), Zn(II), and Cd(II). Some of the complexes formed are able to sense the presence of halides in solution. L passes through the cellular membrane, becoming fluorescent inside cells. The H(-1)L- species is able to form dinuclear complexes with [M(2)H(-1)L]3+ stoichiometry with Cu(II), Zn(II), and Cd(II) ions, experiencing a CHEF effect upon metal coordination in an acetonitrile/water 95:5 (v/v) solution. In all three of the complexes investigated, the metal cations are coordinatively unsaturated and can therefore bind secondary ligands as anionic species. The crystal structure of [Cd(2)(H(-1)L)Cl(2)](ClO(4))·4H(2)O is discussed. The Zn(II) complex behaves as an OFF-ON sensor for fluoride and chloride anions.

International audience; A giant-size polyamine macrocycle L, composed of four 1,4,8,11-tetraazacyclotetradecane (cyclam) units linked by 1,3-dimethylenbenzyl spacers, strongly interacts in aqueous solution with four pH indicators (bromocresol purple (H2BCP), phenol red (H2PR), phenolphthalein (H2PP) and fluorescein (H2F)) in their anionic forms. Besides 1 : 1 complexes, L also forms assemblies with an unusual 1 : 2 receptor to dye stoichiometry, thanks to its large dimensions, which allow for the simultaneous interaction of the receptor protonated forms with two anionic dyes. The formation of the assemblies markedly affects the pKa values of the phenol groups of the dyes, which change colour upon complexation in well-defined pH ranges. This property can be effectively exploited for optical detection of anions. The L-H2BCP 1 : 2 assembly is able to selectively detect the triphosphate anion at slightly acidic pH values, thanks to the release, upon triphosphate coordination, of the dye from the ensemble, with a consequent colour change of the solution from purple-violet (complexed BCP2− dye) to yellow (free BCP2−). No effect is caused by other inorganic anions. The L-H2BCP 1 : 2 assembly represents a rare case of an optical chemosensor for the triphosphate anion.

The ligational properties of the ligand 2-[bis-(2-aminoethyl)-aminomethyl]phenol (L) towards Co(II) ion were studied by means of potentiometric measurements in aqueous solution (298.1 ± 0.1 K, I = 0.15 mol dm−3). L forms a stable mononuclear [CoH−1L]+ (log K = 13.42), a hydroxylated mononuclear [CoH−1LOH] and a dinuclear [(CoH−1L)2]2+ species in which the ligand/metal ratio is 2:2. The Co(II) species is prone to bind dioxygen forming a μ-peroxo-μ-hydroxo [(CoH−1L)2(μOH)(μO2)]+ dinuclear species. The stability constants of μ-peroxo-μ-hydroxo dinuclear and μ-peroxo-mono-hydroxo species were analyzed in a series of open-chain polyamine and polyamino phenol ligands pointing out the role played by the ligand on the stability and the reversibility of the bound dioxygen. DFT calculations were carried out to predict the structure of the oxygenated Co(II)–dinuclear species for L and the related LI amino-phenol ligand. The crystal structure of the Co(III) species, derived from the oxydation of the Co(II)–oxygenated one, was also reported.

The synthesis and characterization of the new ligand 2,9-bis[N,N-bis(2-aminoethyl)aminomethyl]-1,10-phenanthroline (L) are reported. L contains two diethylenetriamine units connected on the central nitrogen atom by a 1,10-phenanthroline group forming a symmetrical branched ligand. The basicity and binding properties of L toward Cu(II) and Zn(II) in aqueous solution were determined by means of potentiometric, UV-vis, fluorescence, and 1H and 13C NMR techniques. L behaves as pentaprotic base under the experimental conditions used; from HL+ to H4L4+ species it is the secondary amine functions that are protonated while in the H5L5+ species also the phenanthroline is involved in protonation. L does not show fluorescence properties in the range of pH (0-14) investigated. It forms both mono- and dinuclear stable species where the phenanthroline is directly involved with both nitrogens in the coordination of the first metal which is coordinated in a pentacoordination environment also by one dien unit. The other dien unit undergoes easy protonation in the mononuclear complex while it binds the second metal in the dinuclear species. For this reason, L, in providing two different binding areas for metal coordination, behaves as an unsymmetrical compartmental ligand; one area is formed by one dien unit and by the phenanthroline, and the other by the remaining dien unit. This produces unsymmetrical metal complexes both for the mono- and dinuclear species; however, the role of the binding areas is fast exchanging in aqueous solution, at least on the NMR time scale. Solution studies and the three crystal structures of the [Zn(H2L)]4+, [[Cu(H2L)](ClO4)]3+, and [[Cu2LCl2](ClO4)]+ species highlight the unsymmetrical compartmental behavior of L as well as the host properties of the complexes in adding exogenous ligands such as hydroxide, pherchlorate, and chloride anions.

The synthesis and characterization of the new polyamino-phenolic ligand 3,3'-bis[N,N-bis(2-aminoethyl)aminomethyl]-2,2'-dihydroxybiphenyl (L) are reported. L contains two diethylenetriamine units linked by a 1,1'-bis(2-phenol) group (BPH) on the central nitrogen atom which allows two separate binding amino subunits in a noncyclic ligand. The basicity and binding properties of L toward Cu(II) and Zn(II) were determined by means of potentiometric measurements in aqueous solution (298.1 +/- 0.1 K, I = 0.15 mol dm-3). L behaves as a pentaprotic base and as a monoprotic acid under the experimental conditions used, yielding the H5L5+ or H-1L- species, respectively. L forms both mono- and dinuclear species with both metal ions investigated; the dinuclear species are largely prevalent in aqueous solution with a L/M(II) molar ratio of 1:2 at pH higher than 7. L shows different behavior in Cu(II) and Zn(II) binding, affecting the dinuclear species formed and the distance between the two coordinated metal ions, which is greater in the Zn(II) than in the Cu(II) dinuclear species. This difference can be attributed to the different degree of protonation of BPH which influences the angle between the phenyl rings in the two systems. In this way, it is possible to modulate the M(II)-M(II) distance by the choice M(II) and to space the two M(II) farther away than was possible with the previously synthesized ligands. L does not saturate the coordination sphere of the coordinated M(II) ions in the dinuclear species, and thus, these latter species are prone to add guests. 1H and 13C NMR experiments carried out in aqueous solution, as well as the crystal structures of the dinuclear Cu(II) and Zn(II) species formed in aqueous solution, aided in elucidating the involvement of L and BPH in Zn(II) and Cu(II) stabilization.

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.

Reactivity of [Pd(CH3)(CO)(PriDAB)]+[B{3,5-(CF3)2C6H3}4]- (1), where PriDAB = 1,4-diisopropyl-1,4-diaza-1,3-butadiene, toward alkynes and carbon monoxide was investigated. While the reaction of 1 with phenylacetylene produced stereoregular homopolymer, a stoichiometric insertion of 1-phenyl-1-propyne and 2-butyne into the Pd−acyl bond yielded the palladacycles 2 and 3; subsequent reaction with CO resulted in the formation of novel complexes 4 and 5, which represent the first experimental evidence of a key intermediate in alkyne cyclocarbonylation processes.

Three different 3,5-trans disubstituted piperidine derivatives, namely 1 (3R,5R)-1-benzyl-piperidine-3,5-diol, 2 (3R,5R)-1-benzyl-1-oxy-piperidine-3,5-diol and 3 (3R,5R)-1-benzyl-3,5-difluoro-piperidine 1-oxide were studied by using both experimental and theoretical methods. Solid state X-ray structures of all the molecules are presented. Structural differences and analogies in the piperidine rings are discussed in terms of intramolecular H-bond and non-bonded repulsions. In addition, the H-bonding pattern in each crystal packing is discussed in view of the hydroxy groups orientation. The geometrical parameters from ab initio calculations performed on simplified models of the studied molecules, in the gas phase, were also discussed. Finally, in all cases, attention was paid to the energetics of the experimentally isolated conformational isomer and to that obtained as the results of the ring and/or nitrogen inversion.

The effect of the catalyst structure on the stereoselectivity of CO/vinyl arene copolymerization has been studied with the aim of developing catalytic systems able to improve the yields while maintaining the high degree of copolymer isotacticity previously obtained using achiral nitrogen ligands. Aryl α-diimine ligands having extended aromatic rings (Ar)2DABMe2, with Ar = 1-C10H7 (e), 1-C14H9 (f), 9-C14H9 (g), have been synthesized, and α-diimine coordination to cationic methylpalladium complexes has been investigated in solution, by means of NMR spectroscopy, and in the solid state for [Pd(Me)(NCMe)((9-C14H9) 2DABMe2)][PF6] (2g). The performance of these catalysts in CO/vinyl arene copolymerization, under mild conditions, was analyzed in terms of productivity and degree of stereoregularity of the resulting polyketones. In comparison with previous results, a remarkable enhancement in the yield of isotactic copolymer was observed using the new achiral 9-anthryl α-diimine ligand g, confirming that the ortho disubstitution and the extended aromatic rings play key roles in obtaining good stereoselectivity and good productivity. To perform a structural analysis of the first steps of the CO/p-methylstyrene copolymerization, complex [Pd(Me)(CO)((9-C14H9)2DABMe2)] [BAr′4] (3g) was used as a starting point: NMR investigation reveals the stereoselective formation of the olefin/CO/olefin insertion product (6g), which prevalently exists in solution in only one diastereoisomeric form, thus justifying the observed high polymer isotacticity.

The coordination properties of the ligand 2,6-bis-[[bis-(2-aminoethyl)-amino]methyl]-phenol (L) toward the zinc ion were determined by means of potentiometric measurements in aqueous solution (298.1 +/- 0.1 K, I = 0.15 mol dm(-3)). L forms mono- and dinuclear complexes with zinc; the stable dinuclear complexes are practically the only existing species using L/Zn(II), molar ratio of 1:2. In these species, each dien subunit binds one zinc ion, while the phenolate moiety bound to both ions allows the two metal centers to be in close proximity with an incomplete coordination environment. The role of this metal-metal distance in binding secondary ligands was investigated for the dinuclear systems 2Zn/L and 2Cu/L by potentiometric (298.1 +/- 0.1 K, I = 0.15 mol dm(-3)) and NMR experiments in aqueous and methanol solution with a series of small guests having nitrogen donor atoms. The coordination sphere of the two metals was completed by adding 1 equiv of only those guests, which showed at least two contiguous donor atoms or two lone pairs on the same atom, to exactly fit the metal-metal distance without modifying the metal cluster. To do this, the imidazole molecule which shows the highest addition constants to the [M(2)H(-1)L](3+) species probably forms a mu-1,1-amino. These results are in agreement with the two crystal structures reported herein [Zn(2)(H(-1)L)(CH(3)CH(2)CH(2)CH(2)O)](ClO(4))(2) (space group P2(1)nb, a = 11.483(5), b = 14.166(5), c = 18.279(5) A, V = 2973(19) A(3), Z = 4, R = = 0.0701, wR2 = 0.1611) and [Zn(2)(H(-1)L)N(3)](ClO(4))(2) (space group C 2/c, a = 14.460(3), b = 12.814(3), c = 14.875(3) A, beta = 105.35(2) degrees, V = 2658(10) A(3), Z = 4, R = 0.0783, wR2 = 0.1806). In fact, these structures display a butanolate or azide guest linked to both Zn(II) ions of the dinuclear complex, resulting in a mu-1,1-oxo and mu-1,1-azido bridge, respectively.

Gd(III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid bearing two and four hydroxymethyl moieties on the cyclen ring were prepared to be studied as low toxicity MRI contrast agents. The key intermediates in the syntheses of the two ligands are the corresponding bis and tetrasubstituted cyclen derivatives. Bis(hydroxymetyl)cyclen was obtained according the so-called ‘crab-like’ cyclization procedure. Photoelectron transfer-induced tetramerization of (R)-2-(benzyloxymethyl)-N-(benzyl)aziridine stereoselectively led to homochiral tetra(hydroxymethyl)cyclen. The X-ray crystal structure of the latter compound unambiguously proved the alike stereochemical configuration of the four stereogenic carbon atoms in the cyclen ring. Carboxymethylation of the cyclen derivatives followed by complexation with either GdCl3 or Gd(OAc)3 afforded the target complexes.

An investigation into the structure of the N-t-butyloxycarbonyl-N′-cyclohexyl-5,5-dimethyl-hydantoin (1) is presented. The structural characterisation was carried out by means of X-ray diffraction analysis: most part of the atoms lie on a crystallographic mirror plane and a lot of intra-molecular C–H⋯O interactions is present. Attention was paid to the side arms conformation and to the intra-molecular C–H⋯O contacts, which were examined by means of a comparison with appropriate solid state structures retrieved from the Cambridge Structural and ab initio calculations.

The synthesis and characterization of two new polyazamacrocycles, 1,4,7,10-tetraaza[12](2,6)phenolphane (L1) and 1,4,7,10,13-pentaaza[15](2,6)phenolphane (L2), are reported. Both ligands incorporate the 2,6-phenolic unit within the cyclic framework. The basicity behavior and the ligational properties of L1 and L2 toward Ni(II), Zn(II), and Cu(II) were determined by means of potentiometric measurements in aqueous solution (298.1 +/- 0.1 K, I = 0.15 mol dm-3). UV spectra were used to understand the role of the phenolic function in the stabilization of the cations. L1 and L2 behave as pentaprotic bases under the experimental conditions used. The UV spectra showed that the deprotonation of the phenolic function occurs at low pH values for both ligands, giving rise to the simultaneous presence of positive and (one) negative charges on the macrocycle. While L1 forms only mononuclear complexes, L2 can also form binuclear species with all the metal ions investigated. In the mononuclear species of both ligands, one nitrogen atom close to the phenol remains unbound. The UV spectra revealed that the phenol, bridging the two metal ions in phenolate form, plays an important role in the stabilization of the binuclear complexes of L2. The coordination sphere of the two metals is completed by adding a secondary ligand such as water molecules or OH-, in any case preferring substrates able to bridge the two close metal ions. These results are confirmed by the crystal structure of [Ni2(C16H28ON5)(H2O)2Cl2]Cl.H2O.CH3OH (space group P21/a, a = 14.821(5) A, b = 10.270(4) A, c = 17.663(6) A, beta = 108.87(3) degrees, V = 2544(2) A3, Z = 4, R1 = 0.0973, wR2 = 0.2136). This structure displays a Ni(II) binuclear complex of L2 in which the phenolic oxygen and a chlorine ion bridge the two close Ni(II) ions.

The structures of three β-lactam penem antibiotics—i.e. the sodium[5R-[5α,6α(R*)]]-6-(1-hydroxyethyl)-7-oxo-3-[[(1-pyrrolidinylthioxomethyl)thio]methyl]-4-thia-1-azabicyclo[3.2.0] hept-2-ene-2-carboxylate (compound 1), the [5R-[3(S*),5α,6α(R*)]]-3-[[2-(aminocarbonyl)-1-pyrrolidinyl] methyl]-6-(1-hydroxyethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (compound 2), and the [5R-[5α,6α(R*)]]-3-[[(2-amino-2-oxoethyl) methylamino]methyl]-6-(1-hydroxyethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (compound 3)—have been determined by X-ray analyses. In the crystal lattice two conformational isomers of 1 are present, which differ from each other in the spatial arrangement of the dithiocarbamate chain. Compounds 2 and 3 are in zwitterionic form, being the hydrogen of the carboxylic acid moved to the amino nitrogen of the chain at C2. This hydrogen atom, in both molecules, forms intramolecular hydrogen bonds with an oxygen atom of the carboxylate moiety and with the oxygen atom of the amido group of the side chain. The 3D structures of 1, 2, and 3 have been compared with those of previously reported β-lactam penem antibiotics. Particularly, the Woodward parameter and the Cohen distance, which are considered important in determining the antibiotic activity, have been discussed. Least-squares minimizations (RMS) of the distances between nuclei of selected pairs of atoms defining the pharmacological pattern have been performed, comparing five common antibiotics (imipenem, ritipenem, cephaloridine, amoxycillin, and benzylpenicillin) with our compounds. Finally, molecular dynamics calculations have been carried out on the three penem antibiotics at different temperatures. The conformational behavior of the hydroxyethyl chain, the carboxylate group, and the chain at C2 is discussed by considering the variation of some selected dihedral angles.

Crown ether complex formed by the dibenzo-18-crown-6 (DB18C6) macrocycle with ammonium and potassium hexafluorophosphate have been prepared and their crystal structures have been determined by single crystal X-ray analyses. The ammonium compound consists of a 2:1 mixture of NH4 (DB18C6)PF6 and free DB18C6 ligand (compound 1). Crystals are monoclinic, space group P21/c with a=12.638(2), b=13.118(4), c=20.927(9) A , β=106.21(2)°, V=3331(2) A 3 and Z=4 (R=0.0457) . The ammonium cation interacts with the six oxygen atoms of the crown ether and with two fluorine atoms of a PF6− anion. The potassium derivative (compound 2) consists of K(DB18C6)PF6 units. Crystals are monoclinic, space group P2/c, with a=15.744(8), b=7.945(3), c=37.59(2) A , β=94.27(4)° , V=4689(4) A 3 and Z=8 (R=0.0786) . The potassium atoms of the three independent complexes are linked to the six oxygen atoms of the DB18C6 ligand and to fluorine atoms of two PF6− anions. Molecular mechanics calculations were performed on the uncomplexed DB18C6 molecule by using the MM2 force field.

The syntheses of the ligand BOPTA, (4-carboxy-5,8,1 l-tris(carboxymethyl)-l-pheny1-2-oxa-5,8,1 l-triazatridecan13-oic acid; benic acid) and its Gd(III), La(III), and Lu(1U) complexes are reported. Protonation constants for BOPTA have been determined by potentiometry, and the microscopic protonation sequence has been investigated by 'H NMR. The results obtained together with the value of the Gd-BOPTA2- stability constant (log KML = 22.59) show that the complexing properties of the ligand, in comparison with DTPA, are little affected by the presence of the benzyloxymethyl residue in the structure. The solid state structure of Gd-BOPTA disodium salt [C22H2&01 I (H~O)Gd]Na2~/2H20 was determined in a single-crystal X-ray diffraction study. The structure consists of [C22H2a3011(H20)Gdl2- anions, sodium cations, and water molecules; the space group is Pi (Z = 2), with a = 9.083(6) A, b = 9.469(2) A, c = 16.698(6) A, a = 102.22(3)", = 92.48(4)', y = 102.26(3)", V = 1366(1) A3, and d = 1.84 g/mL. The gadolinium ion adopts a nine-coordinate geometry, which is best described as a distorted tricapped trigonal prism. Eight coordinating sites are occupied by the ligand (three nitrogen atoms and five carboxylate oxygens), and the ninth site is occupied by the oxygen atom of a water molecule. Relaxation studies have shown that in solution also Gd-BOPTA2- has one water molecule directly coordinated to the metal ion. 139La NMR studies on the La-BOPTA2- complex have further supported the view that such complexes maintain in solution the same kind of coordination as found in the solid state for Gd-BOPTA disodium salt. I3C NMR spectra of the diamagnetic La- and Lu-BOPTA2- complexes at various temperatures are consistent with the presence of two couples of isomers interconverting through a dynamic process. Such a process has previously been reported for the parent Ln-DTPA2- complexes.

A. Introduction 51 B. Macrocycles and macrobicycles able to incorporate several metal ions 52 C. Bis(macrocycles) 71 D. Bridged macrocyclic metal complexes 73 Acknowledgements 83 References 83

The synthesis of two novel DOTA-like ligands (5a,b) containing a polyhydroxy(benzyloxy)propionamide substituent and their Gd(III) complexes (6a,b) is reported. Debenzylation by hydrogenolysis of the latter complexes in the presence of Pd/C leads to the corresponding derivatives (7a,b) with a primary alcoholic function. Water proton relaxation rates of aqueous solutions of 6a,b and 7a,b strongly suggest that these complexes contain only one water molecule in their inner coordination sphere, as was previously found for the parent DOTA complex

The new ligand L-OH, containing two diethylenetriamine subunits linked by 2,6-dimethylphenol, forms stable binuclear metal complexes in aqueous solution, in which the coordination environment of the metal ions is unsaturated. The phenolate unit forces the two metal ions to remain close to each other, and the binuclear species then adds a secondary ligand that bridges the two metal centers. This is illustrated by two crystal structures of Cu(II) and Ni(II) binuclear complexes.

International audience; Synthesis, characterisation and proton-sponge behaviour of a new linear constrained tris-macrocycle (L), containing three cyclen (cyclen = 1,4,7,10-tetraazacyclododecane) reinforced macrocycles connected by two 2,6-pyridinediylbis(methylene) linkers, is reported. Protonated forms of L are efficient receptors for inorganic phosphate and nucleotide anions (ATP and ADP). The binding properties of L toward these substrates have been investigated in aqueous solution by means of potentiometric titrations, determining the stability constants of the adducts. The interaction mode was clarified by using 1H and 31P NMR measurements in aqueous solution and by means of molecular modelling calculations carried out on differently protonated species of L as well as on several nucleotide-receptor adducts. The stability of the adducts is mainly due to charge-charge and hydrogen bonding interactions between the polyphosphate chain of nucleotides and the ammonium groups of L.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Two Zn(II)-dinuclear systems were studied as receptors for phosphates; they were obtained by using the two polyamino-phenolic ligands 3,3'-bis[N,N-bis(2-aminoethyl)aminomethyl]-2,2'-dihydroxybiphenyl (L1) and 2,6-bis[N,N-bis(2-aminoethyl)aminomethyl]phenol (L2) in which the difference lies in the spacers between the two dien units, biphenol or phenol in L1 and L2, respectively. The metallo-receptors obtained are able to selectively discriminate phosphate (Pi) from pyrophosphate (PPi) and vice versa in aqueous solution in a wide range of pH (6pH10). The L1 receptor system shows selectivity toward PPi over Pi, and on the contrary the L2 system exhibits opposite selectivity. This different selectivity is ascribed to the different Zn(II)-Zn(II) distances between the two metal centers which, showing a similar coordination requirement and binding phosphate in a bridge disposition, fit in a different way with the different guests. Furthermore, NMR studies supported the model of interaction proposed between guests and receptors, highlighting that they are also able to bind biological phosphates such as G6P and ATP at physiological pH. Fluorescence studies showed that the receptor system based on L1 is able to signal the presence in solution of Pi and PPi at physiological pH; the presence of Pi is detected by a quenching of the emission, that of PPi by an enhancement of it. With the aid of an external colored sensor (PCV), the receptors were then used to produce simple signaling systems for phosphates based on the displacement method; the two chemosensors obtained are able to signal and quantify these anions at physiological pH, preserving the selectivity between phosphate and pyrophosphate and extending it to G6P and ATP.

The density functional theory has been utilized to study a series of model compounds of the first intermediates in CO/p-methylstyrene copolymerization reactions catalyzed by Pd(II) complexes, bearing aryl α-diimine achiral ligands. The results of the computation are correlated with the microstructure of the resulting polyketones ranging from atactic to stereoblock isotactic, depending on the substituents on the aryls.

The synthesis and characterization of the new polytopic ligands 1,14-bis(3,6,9-triaza-15-hydroxybicyclo[9.3.1]pentadeca-11,13,1(15)-trien-6-yl)-3,6,9,12-tetraazatetradecane L1, 1,15-bis(3,6,9-triaza-15-hydroxybicyclo[9.3.1]pentadeca-11,13,1(15)-trien-6-yl)-3,6,10,13-tetraazapentadecane L2, and 1,16-bis(3,6,9-triaza-15-hydroxybicyclo[9.3.1]pentadeca-11,13,1(15)-trien-6-yl)-3,7,10,14-tetraazahexadecane L3, containing two equal amino-phenol macrocycles spaced by several linear tetraamines, are reported. The basicity and coordination behavior toward the Cu(II) ion were potentiometrically determined in aqueous solution at 298.1 K. All the ligands show similar acid-base properties behaving as octaprotic bases in the examined pH range (pH = 2-12). The acid protons of L1-L3 cannot be removed under the experimental conditions used; thus, the main deprotonated species obtainable in aqueous solution are the neutral ligands, having amphionic character as demonstrated by UV-vis experiments. These species are able to form mono-, di-, and trinuclear Cu(II) complexes having stoichiometry [CuL](2+), [Cu(2)L](4+), and [Cu(3)L](6+), respectively, that can lose one or two protons giving rise to [CuH(-1)L](+), [Cu(2)H(-2)L](2+), and [Cu(3)H(-2)L](4+). Depending on the used ligand to metal molar ratio, the mono-, di-, or trinuclear species prevail over the others in solution. Both di- and trinuclear complexes are able to add secondary ligands (such as OH(-)), and in some cases two Cu(II) can cooperate to stabilize them by coordinating the guest in a bridged conformation. The structure of the [Cu(2)L3](4+) cation was resolved by X-ray analysis of the {[Cu(2)L3](ClO(4))(4) x 3 H(2)O}(2) x H(2)O crystalline complex. It shows that each Cu(II) is penta-coordinated by one phenolate oxygen, two amine functions, belonging to one macrocyclic unit, and two amine functions of the spacer; in this species the distance between the two Cu(II) is about 5.3 A.

The Ugi four-component condensation between cycloalkanones, isocyanides, and ammonium formate affords N-substituted 1-formylamino-1-cycloalkanecarboxamides 1 which are dehydrated to give the corresponding isocyanides 2. Compounds 2 are cyclized with arylsulfenyl thiocyanates to 1,3-diazaspiro-2-thiones 4 and 5. A series of 1,3-diazaspiro[4,5]dec-1-en-4-ones 7 is prepared by cyclizing 2c–j with butyllithium. The structures of these compounds are confirmed by means of IR, 1H-NMR, and X-ray analysis.

The cage selectively encapsulates Li + , and the inclusion [LiL] + complex formation equilibrium has been investigated by potentiometry (log K=4.8) and 7 Li NMR techniques. The molecular structure of the complex [LiL] [ClO 4 ] has been determined by single-crystal X-ray analysis. The compound crystallizes in a monoclinic unit cell (space group P2 1 /n) with lattice constants a=15.046 (11) A, b=8.893 (4) A, c=15.305 (8) A, and β=113.58 (4)°, with Z=4. Least-squares refinement converged at R=0.065 for 1385 observed reflections of I>3 σ(I). Li + is wholly enclosed in the cage cavity and adopts a five-coordinate geometry, with a short Li-N mean distance of 2.04 A. The molecular structure of the complex [CuL] [Br 2 ]•3H 2 O has been determined by single-crystal X-ray analysis. The compound crystallises in an orthorhombic unit cell (space group Cmc2 1 ) with lattice constants a=11.629 (1) A, b=13.031 (1) A, and c=14.702 (1) A, with Z=4. Least-squares refinement converged at R=0.068 for 542 observed reflections of I>3 σ (I)

The migratory insertions of cis or trans olefins CH(X)=CH(Me) (X=Ph, Br, or Et) into the metal–acyl bond of the complex [Pd(Me)(CO)( iPr2dab)] + [B{3,5-(CF3)2C6H3}4]- (1) ( iPr2dab=1,4-diisopropyl-1,4-diazabuta-1,3-diene=N,N’-(ethane-1,2-diylidene)bis[1-methylethanamine]) are described (Scheme1). The resulting five-membered palladacycles were characterized by NMR spectroscopy and X-ray analysis. Experimental data reveal some important aspects concerning the regio- and stereochemistry of the insertion process. In particular, the presence of a Ph or Br substituent at the alkene leads to the formationof highly regiospecific products. Moreover, in all cases, the geometry of the substituents in the formed palladacycle was the same as in the starting olefin, as a consequence of a cisaddition of the Pd–acyl fragment to the C=C bond. Reaction with CO and MeOH of the five-membered complex derived from trans b-methylstyrene (=[(1E)-prop-1-enyl]benzene) insertion, yielded the 2,3-substitutedg-keto ester 9 with an (2RS,3SR)-configuration (Scheme 3)

The synthesis and characterization of the new polyaza-phenolic-macrobicycle 32-hydroxy-1,4,7,10,13,16,19,22-octaazatricyclo-[11.11.7.1(26,30)]-diatriconta-26,28,Delta(30,32)-triene (L) are reported. L incorporates a 2,6-dimethyl-phenolic unit bridging two opposite amine functions of the [24]aneN(8) polyazamacrocyclic base to obtain a large cage. The basicity and binding properties of L toward Cu(II), Zn(II), and Cl(-) were determined by means of potentiometric measurements in aqueous solution (298.1 +/- 0.1 K, I = 0.15 mol dm(-3)). L can add up to six acidic protons, yielding the H(5)L(5+) species or the H(6)L(6+) species, depending on the ionic medium used. The molecular topology of L permits the formation of a highly positive three-dimensional cavity in the polyprotonated species that is able to host the chloride anion. This was detected both using potentiometric data, log K = 41.33 for the reaction L + 6H(+) + Cl(-) = H(6)LCl(5+), and in (35)Cl NMR experiments that showed interactions also with the H(5)L(5+) and H(4)L(4+) species. The anion is probably hosted inside the three-dimensional cavity of L, and stabilized by H-bonding interactions with the ammonium groups, as depicted in the crystal structure of the H(6)L(6+) cation reported. L forms mono- and dinuclear complexes with all the metal ions investigated; the dinuclear species are the only existing species with an L:M(II) molar ratio of 1:2 at pH higher than 6. The phenolate oxygen atom coordinates the two metal ions in a bridged disposition, drawing them inside the macrobicyclic cavity. The two metals were found to be quite isolated by the medium, and were coordinated by all the amine groups of L, as shown by the crystal structure of the dinuclear [Zn(2)H(-1)L](3+) species. This species can bind guests such as hydroxide and phosphate anions. Studies of anion binding in aqueous solution using pyrochatecol violet as the sensing guest revealed that the [Zn(2)H(-1)L](3+) species is able to bind one phosphate at physiological pH.

The synthesis and characterization of new polydentate ligand 2-(N),2'-(N')-bis[2-(3-hydroxy-2-oxo-2H-pyridin-1-yl)acetamido]-1(N'),2(N),2'(N')-trimethyl-2,2'-diaminodiethylamine (L3) is reported. The coordination properties of L3 and of two analogous macrocyclic ligands (L1 and L2) toward Cu(II) and Zn(II) metal ions are reported. All three ligands show the 3-hydroxy-2(1H)-pyridinone (HPO) groups attached as sidearms to a polyaza fragment, which is a macrocyclic framework in the case of L1 and L2 while it is an open chain in the case of L3. The role of the polyaza fragments in preorganizing the two sidearms was investigated. The basicity of L3 and the binding properties of L1-L3 were determined by means of potentiometric measurements in aqueous solution (298.1 +/- 0.1 K, I = 0.15 mol dm(-3)). UV-vis spectra as well 1H and 13C NMR experiments were used to understand the role of the HPO and of the polyaza fragments in the stabilization of the cations. While L1 forms stable mono- and dinuclear complexes, L2 and L3 can form only mononuclear species with each of the metal ions investigated. In the main mononuclear species of L2 and L3, the two HPO moieties stabilize the M(II) in a square planar geometry due to the two oxygen atoms of each HPO. The coordination sphere of the metal is completed by adding a secondary ligand such as water molecules in the case of Cu(II) systems or OH- in the Zn(II) systems. These results are confirmed by the crystal structures of the [CuH(-1)L2]+ and [CuH(-1)L3]+ species reported herein. Two conformations of L1 can be hypothesized in the formation of the dinuclear species, as suggested by NMR experiments on the [ZnH(-2)L1] species, which shows two conformers slowly interchanging on the NMR time scale, one of which was found to be more insoluble.

The basicity behavior and ligational properties of the ligand 2-((bis(aminoethyl)amino)methyl)phenol (L) toward Ni(II), Cu(II), and Zn(II) ions were studied by means of potentiometric measurements in aqueous solution (298.1 +/- 0.1 K, l = 0.15 mol dm-3). The anionic L-H- species can be obtained in strong alkaline solution; this species behaves as tetraprotic base (log K1 = 11.06, log K2 = 9.85, log K3 = 8.46, log K4 = 2.38). L forms mono- and dinuclear complexes in aqueous solution with all the transition metal ions examined; the dinuclear species show a [M2(L-H)2]2+ stoichiometry in which the ligand/metal ratio is 2:2. The studies revealed that two mononuclear [ML-H]+ species self-assemble, giving the dinuclear complexes, which can be easily isolated from the aqueous solution due to their low solubility. This behavior is ascribed to the fact that L does not fulfill the coordination requirement of the ion in the mononuclear species and to the capacity of the phenolic oxygen, as phenolate, to bridge two metal ions. All three dinuclear species were characterized by determining their crystal structures, which showed similar coordination patterns, where all the single metal ions are substantially coordinated by three amine functions and two oxygen atoms of the phenolate moieties. The two metals in the dinuclear complexes are at short distance interacting together as shown by magnetic measurements performed with Ni(II) and Cu(II) complexes, which revealed an antiferromagnetic coupling between the two metal ions. The [Cu2(L-H)2]2+ cation shows a phase transition occurring by the temperature between 100 and 90 K; the characterization of the compounds existing at different temperatures was investigated using X-ray single-crystal diffraction, EPR, and magnetic measurements.

Crown ether complexes formed by sodium hexafluorophosphate with dibenzo-18-crown-6 (DB18C6) and dibenzo-24-crown-8 (DB24C8) were synthesized and their crystal structures determined by single crystal X-ray analyses. The complex with DB18C6 consists of [Na(DB18C6)(H2O)]+ cations, free DB18C6 ligand and PF6− anions (compound 1). The sodium cation interacts with the six oxygen atoms of the crown ether and with the oxygen atom of the water molecule, which forms short contacts also with the free DB18C6 molecule. The compound with DB24C8 (compound 2) consists of [Na(DB24C8)]+ cations and PF6− anions. The sodium atom is linked to the eight oxygen atoms of the DB24C8 macrocycle, whereas the fluorine atoms of the hexafluorophosphate anions do not interact with the sodium atom.

Solutions containing Zn(II) and Cu(II) complexes with [15]aneN(3)O(2) rapidly adsorb atmospheric CO(2) to give {[ZnL](3)(mgr;(3)-CO(3))}.(ClO(4))(4) (2) and {[CuL](3)(mgr;(3)-CO(3))}.(ClO(4))(4) (4) complexes. The crystal structures of both complexes have been solved (for 2, space group R3c, a, b = 22.300(5) Å, c = 17.980(8) Å, V = 7743(4) Å(3), Z = 6, R = 0.0666, R(w)(2) = 0.1719; for 4, space group R3c, a, b = 22.292(7) Å, c = 10.096(8) Å, V = 7788(5) Å(3), Z = 6, R = 0.0598, R(w)(2) = 0.1611), and the spectromagnetic behavior of 4 has been studied. In both compounds a carbonate anion triply bridges three metal cations. Each metal is coordinated by one oxygen of the carbonate, three nitrogens, and an oxygen of the macrocycle; the latter donor weakly interacts with the metals. Although the two compounds are isomorphous, they are not isostructural, because the coordination geometries of Zn(II) in 2 and Cu(II) in 4 are different. The mixed complex {[CuZn(2)L(3)](mgr;(3)-CO(3))}.(ClO(4))(4) has been synthesized. X-ray analysis (space group R3c, a, b = 22.323(7) Å, c = 17.989(9) Å, V = 7763(5) Å(3), Z = 6, R = 0.0477, R(w)(2) = 0.1371) and EPR measurements are in accord with amgr;(3)-carbonate bridging one Cu(II) and two Zn(II) ions in {[CuZn(2)L(3)](mgr;(3)-CO(3))}(4+). Both the Zn(II) and Cu(II) cations exhibit the same coordination sphere, almost equal to that found in the trinuclear Zn(II) complex 2. The systems Zn(II)/L and Cu(II)/Lhave been studied by means of potentiometric measurements in 0.15 mol dm(-)(1) NaCl and in 0.1 mol dm(-)(3) NaClO(4) aqueous solutions; the species present in solution and their stability constants have been determined. In both systems [ML](2+) species and hydroxo complexes [M(II)LOH](+) (M = Zn, Cu) are present in solution. In the case of Cu(II), a [CuL(OH)(2)] complex is also found. The process of CO(2) fixation is due to the presence of such hydroxo-species, which can act as nucleophiles toward CO(2). In order to test the nucleophilic ability of the Zn(II) complexes, the kinetics of the promoted hydrolysis of p-nitrophenyl acetate has been studied. The [ZnLOH](+) complex promotes such a reaction, where the Zn(II)-bound OH(-) acts as a nucleophile to the carbonyl carbon. The equilibrium constants for the addition of HCO(3)(-) and CO(3)(2)(-) to the [ZnL](2+) complex have been potentiometrically determined. Only [ML(HCO(3))](+) and [ML(CO(3))] species are found in aqueous solution. A mechanism for the formation of {[ML](3)(mgr;(3)-CO(3))}.(ClO(4))(4) is suggested.

Two new azamacrocycles 1,7-bis(2-hydroxy-5-nitrobenzyl)-4,10-dimethyl-1,4,7,10-etraazadodecane (L1) and 1,13-bis(2-hydroxy-5-nitrobenzyl)-4-10-dimethyl-4,7,10,16-tetramethyl-1,4,7,10,13,16,-hexaazaoctadecane (L2) have been synthesised and characterised. The basicity behaviour has been studied by potentiometry at 298.1 K in 0.15 mol dm 4Me4NCl, by 1H and 13C NMR spectroscopy, as well as by UV-Vis spectroscopy. L1 behaves as a tetraprotic base in the pH range investigated: log K113, log K2 = 10.59(1), log K3 = 7.18(2) and log K4 = 4.86(2). L2 behaves as a hexaprotic base; log K1 = 10.38(2), log K2 = 9.96(2), log K3 = 8.29(2), log K4 = 5.71(2), log K5 = 4.68(3) and log K6 = 2.2(1). The influence on the basicity behaviour of the nitrophenolic side arms is dicussed. In the case of L2, the equilibria with Cu(II) have been studied by a potentiometric technique. Four main species have been found: the binuclear species [Cu2L2]2+ (log K = 28.7(1)), and three protonated species: [CuH2L2]2+, [CuH3L2]3+, [CuH4L2]4+, For the L1/Cu(II) system the precipitation of a solid compound prevents the determination of any stability constants, however the coordination behaviour of L1 toward Cu(II) is observed in the crystal structure of [CuL1]ClO4. Crystals of [CuL1]CO4 are triclinic, space group P1, with a = 8.777(3), b = 10.744(3), c = 15.814(3) A , α = 100.58(2), β = 98.47(2), γ = 101.16(2) 0 , Z = 2, R = 0.070 .

The synthesis and characterization of the new azamacrocycle 4,10,15-trimethyl-1,4,7,10,15-pentaazabicyclo[5.5.5]heptadecane (L) are reported. The stepwise basicity constants have been determined by potentiometry (25C, NaCl 0.15 mol dm[sup [minus]3]). L behaves as biprotic base: log K[sub 1] = 11.8; log K[sub 2] = 10.0. The molecular structure of the monoprotonated salt [HL][BPh[sub 4]] has been determined by single-crystal X-ray analysis. The structure of [HL]+ shows the five nitrogen atoms in endo configuration, indicating that the proton is inside the cage cavity. Geometrical considerations indicate that the proton is bound to the bridgehead nitrogen atom N(2). The cage L selectivity encapsulates Li+, and the equilibrium for the formation of the inclusion complex [LiL]+ has been investigated by potentiometry (log K = 5.5) and [sup 7]Li NMR techniques. The molecular structure of the complex [LiL][BPh[sub 4]] has been determined by single-crystal X-ray analysis. Li+ is wholly enclosed in the cage cavity adopting a regular bipyramidal geometry with the Li-N distances for the 2.01-2.08-[angstrom] range. Cu(II) is also encapsulated by L; the electronic spectra of the complex show essentially the same features in the solid state and in solution and are diagnostic of a five-coordinate trigonal-bipyramidal structure.

The series of polyazaalkanes 1,16-dimethyl-hexaazahexadecane, 1,19-dimethyl-heptaazanonadecane, 1,22-dimethyl-octaazadocosane, 1,25-dimethyl-nonaazapentacosane, and 1,28-dimethyl-decaazaoctacosane have been synthesized and characterized. Their protonation behavior has been studied potentiometrically at 298.15 K in 0.15 mol dm −3 NaClO 4 as well as by 13 C NMR spectroscopy. A protonation pattern that minimizes electrostatic repulsions between polyammonium sites has been found

The interaction of polyprotonated forms of [3k]aneN k (k=7-12) macrocycles with the complexed anions Fe(CN) 6 4- , Co(CN) 6 3- and Pt(CN) 4 2- has been studied by potentiometry in 0.15 mol dm -3 NaClO 4 solution at 298.15 K, and the stability constants of the second-sphere complexes formed have been determined

The formation of Pd 2+ complexes of [18]aneN 6 (1,4,7,10,13,16-hexaazacyclooctadecane), [24]aneN 8 (1,4,7,10, 13,16,19-heptaazacyclobenicosane), and [24]aneN 8 (1,4,7,10,13,16,19,21-octaazacyclotetracosane) in solution has beeen studied by microcalorimetry and 1 H and 13 C NMR.