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The reduction with Vitride® of the cis and trans isomers of octahydro-2a,4a,6a,8a-tetraazacyclopenten[fg]acenaphthylene 1,2-diones (5 and 6) and octahydro-2a,4a,6a,8a-tetraazacyclopenten[fg]acenaphthylene 3,4-diones (7 and 8) led to the cis 9 and the so far unknown trans 10 isomers of decahydro-2a,4a,6a,8a-tetraazacyclopent[fg]acenaphthylene. The stereochemistry of 9 and 10 was determined by comparison of the NMR coupling constants of the proton signals of the ethinic bridge. The results were confirmed by the solid state structure of the trans isomer (10) determined by single crystal X-ray diffraction. Given that the trans bis-aminal species 2 and 4 can undergo rearrangement, i.e. stereoisomerization into the corresponding cis ones (1 and 3, respectively), the conformational behaviour of species 1–4 was investigated by means of both molecular mechanics (MM) and quantum chemical (QC) approaches. The theoretical study was completed by including diamides 5–8 and the final products 9 and 10.

The human tachykinin NK-2 (hNK-2) receptor is considered a promising target for relevant pathologies at the respiratory, gastrointestinal and genitourinary level. With the aim of reducing the complexity of existing peptide antagonists, two series of hNK-2 receptor antagonists were designed, with the support of modelling, and synthesized. The X-ray structure determination of two compounds, each belonging to one of the two series, allowed the experimental validation of the initial rationale. In addition, it has been found that the two series share a β-turn structure, a key feature for binding the hNK-2 receptor.

A novel nickel beta-diketonate adduct, Ni(tta)2.tmeda, has been synthesized using 2-thenoyltrifluoroacetone as the beta-diketonate and N,N,N,'N'-tetramethylethylendiamine as the Lewis base. It has been characterized by elemental analyses, IR, 1H NMR, 13C NMR spectroscopy and single-crystal X-ray diffraction studies. Physical and thermal properties of Ni(tta)2.tmeda precursor have been also extensively investigated. Its efficacy as a metal-organic chemical vapour deposition (MOCVD) precursor for the growth of nickel oxide films has been fully tested by applying it to the deposition of NiO films on quartz substrate. NiO thin films have been characterized by X-ray diffraction (XRD), scanning electron microscopy and UV spectroscopy.

The aim of the paper was to estimate the degrees of freedom, i.e. the flexibility, of four compounds (1‐4) belonging to the tertiary aromatic o-substituted oxo(thio) amide family in the perspective to exploit them as scaffolds for generating chemical libraries. A combined experimental and theoretical structural study was undertaken. Solid state X-ray structures of all the molecules are presented. Thermochemical data for 3 and 4, i.e. DHfus, DSfus and Tfus, were discussed on the basis of the solid state results. A survey of the 3D solid state key features retrieved in the Cambridge Crystallographic Database for molecular fragments featuring CaO(S) grouping directly bound to a phenyl ring is presented. Results from a molecular modelling approach (both force field and ab-initio based) applied to ad-hoc simplified molecules were discussed both from a geometrical and energetic point of view. q 2005 Elsevier B.V. All rights reserved.

The presence of intramolecular CH...π aromatic bonds in organic molecules has been analyzed by means of CSD searches. In particular, molecules containing aromatic and methyl groups have been examined as a function of the length of the chain separating the interacting groups. The type of bonds in the chain and its geometry have also been taken into account. The maximum number of CH...π interactions have been found for five-membered chains joining the aromatic and methyl moieties. In addition, this interaction seems favored when the chain contains two sp 2 hybridized atoms. The interactions involving polypeptides have been carefully examined. Interest has focused on compounds containing both aromatic and methylic residues, i.e., a combination of phenylalanine (phe), tyrosine (tyr), and tryptophan (trp) with alanine (ala), valine (val), leucine (leu), and isoleucine (ile). The maximum number of CH...π interactions have been found when five atoms constituted the chain, i.e., in the sequences phe–ala and ala–phe.

The [Co(hfac)2·CH3OCH2CH2OCH3] adduct was synthesised and investigated by X-ray crystal structure, mass spectra, TG-DTG thermal measurements and infrared transmittance spectroscopy. X-Ray single crystal data provide evidence of a slightly distorted octahedral cobalt cation, coordinated with four oxygen atoms of two hfac anions and two oxygens of the monoglyme molecule. Deposition experiments, in a low-pressure horizontal hot-wall reactor, on optically transparent SiO2 substrates, using the title complex, resulted in CoO films. XRD measurements show that CoO consists of cubic, highly oriented, crystals. The surface atomic composition of the films was investigated by XPS. No fluorine contamination was detected.

The novel [Co(C5F6HO2)2·2H2O·CH3(OCH2CH2)4OCH3] low-melting adduct has been synthesized and characterized. Very mild heating results in the anhydrous Co(hfac)2tetraglyme liquid and thermal stable complex that evaporates intact. This adduct has proven to be a well-suited precursor for MOCVD of cobalt oxide films.

The synthesis and characterization of the new tetraazamacrocycle L, bearing two 1,1'-bis(2-phenol) groups as side-arms, is reported. The basicity behavior and the binding properties of L toward alkali metal ions were determined by means of potentiometric measurements in ethanol/water 50:50 (v/v) solution (298.1+/-0.1 K, I=0.15 mol dm(-3)). The anionic H(-1)L(-) species can be obtained in strong alkaline solution, indicating that not all of the acidic protons of L can be removed under the experimental conditions used. This species behaves as a tetraprotic base (log K(1)=11.22, log K(2)=9.45, log K(3)=7.07, log K(4)=5.08), and binds alkali metal ions to form neutral [MH(-1)L] complexes with the following stability constants: log K(Li)=3.92, log K(Na)=3.54, log K(K)=3.29, log K(Cs)=3.53. The arrangement of the acidic protons in the H(-1)L(-) species depends on the polarity of the solvents used, and at least one proton switches from the amine moiety to the aromatic part upon decreasing the polarity of the solvent. In this way two different binding areas, modulated by the polarity of solvents, are possible in L. One area is preferred by alkali metal ions in polar solvents, the second one is preferred in solvents with low polarity. Thus, the metal ion can switch from one location to the other in the ligand, modulated by the polarity of the environment. A strong hydrogen-bonding network should preorganize the ligand for coordination, as confirmed by MD simulations. The crystal structure of the [Na(H(-1)L)].CH(3)CN complex (space group P2(1)/c, a=12.805(1), b=20.205(3), c=14.170(2) A, beta=100.77(1) degrees, V=3601.6(8) A(3), Z=4, R=0.0430, wR2=0.1181), obtained using CH(2)Cl(2)/CH(3)CN as mixed solvent, supports this last aspect and shows one of the proposed binding areas.

Four novel Cd(C5F6HO2)2·polyether adducts were prepared through simple procedures with stoichiometric quantities of cadmium oxide, hexafluoroacetylacetone C5F6H2O2, and different polyethers. The products were characterized by elemental analysis, X-ray single-crystal analysis, mass spectra, NMR spectra, thermal measurements, and infrared transmittance spectroscopy. X-ray single-crystal data of the Cd(C5F6HO2)2·polyether adducts showed that all the oxygen atoms of the polyether molecules coordinate the cadmium cation. Very mild heating (44−74 °C) resulted in thermal stable, liquid compounds which, in turn, can be easily evaporated. Gas-phase deposition experiments, in a low-pressure horizontal hot-wall reactor, on SiO2 substrates, resulted in CdO films. XRD measurements provided evidence that they consist of cubic, (100)-oriented, crystals. UV−vis spectra showed that the transmittance of as-deposited films in the visible region is about 90%.

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 ability to obtain highly oriented, transparent, and conducting thin films of CdO, onto silica substrates, is demonstrated by using a novel, low-melting, MOCVD precursor. The observed film properties are interpreted on the basis of nonstoichiometric composition of CdO.

The Cd(C5F6HO2)2·2H2O complex was investigated by X-ray crystallography, mass spectroscopy, 1H NMR spectroscopy, TG−DTG thermal measurements, and infrared transmittance spectroscopy. X-ray single-crystal data show that the cadmium ion is chelated by the oxygens of the hfa anion ligand and bound to the oxygens of two cis-disposed water molecules. Deposition experiments, in a low-pressure horizontal hot-wall reactor, on optically transparent SiO2 substrates using the above complex result in CdO films. XRD measurements provide evidence that these complexes consist of highly oriented cubic crystals. UV−vis spectra show that the transmittance of as-deposited films in the visible region is about 70%. The surface structure of the CdO films was investigated by XPS. Resistivity measurements of the CdO films suggest TCO properties.

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.

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.

A new H-bonded supramolecular assembly of the diamine-diol family has been obtained from (1R,2R)-1,2-diaminocyclohexane (DAC) and (S)-1-phenyl-1,2-ethanediol (PED). The structure was characterized by single-crystal X-ray analysis and showed the typical architecture of DAC based assemblies, consisting of a three-stranded helicate coiling around a H-bonded core, with a predictable helicity sense determined by the configuration of DAC. The new assembly, while reconfirming the unique role of DAC as a powerful assembler of supramolecular structures, demonstrated that the C2 symmetry of diol partners employed so far is not essential for assembling helicates, although chirality is. In the case of the adduct between (1R,2R)-1,2-diaminocyclohexane and (2R,3R)-2,3-butanediol, molecular recognition and self-assembly have been shown to take place even in the absence of solvent, in the gas phase, where long crystals were formed by spontaneous organized aggregation of diamine-diol units. A thorough analysis of the results from the present and previous investigations has lead to a deeper understanding of the key features of the diamine-diol molecular code and of the requirements for recognition and assembly.Key words: supramolecular, hydrogen bonding, molecular recognition, self-assembly, diamines, diols.

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.

Three novel Zn(hfa)2·2H2O·polyether adducts have been prepared through simple procedures with stoichiometric quantities of zinc hydroxide, Hhfa, and polyether. The products have been characterized by elemental analysis, X-ray single-crystal analysis, fast atom bombardment mass spectra, 1H and 19F NMR spectra, thermogravimetric (TG)−differential TG−differential scanning calorimetry (DSC) thermal measurements, and infrared transmittance spectroscopy. An attempt to obtain water-free adduct was unsuccessful even using excess polyethers. X-ray single-crystal data of the Zn(hfa)2·2H2O·diglyme adduct show that the polyether does not coordinate to the metal center. Nevertheless, metrical data are indicative of bridging interactions involving the oxygen of one coordinated H2O molecule and the three oxygens of the diglyme. Very mild heating (37−51 °C) results in liquid compounds that, in turn, can easily be evaporated. Preliminary gas-phase Fourier transform-IR measurements in vacuo suggest that the anhydrous Zn(hf...

The crystal structures of the azamacrocycle 1,7–bis(2–hydroxy-5–nitrobenzyl)-4,10–dimethyl-1, 4,7,10–tetraazadodecane (L) (zwitterionic form) (L-0.5CH3OH-3.5H2O) and the monocharged derivative (HL+) (HL-Br-2C2H5OH) are reported. The crystals of L-0.5CH3 OH-3.5H2O are rhombohedral (hexagonal axes), space group R3, a = b = 42.472(7), c = 9.415(9) A, Z = 18, R = 0,034, whereas the crystals of HL-Br-2C2H5OH are monoclinic, space group C2/c, a = 20.418(5), b = 13.814 (4), c = 11.785(3) A, β = 99.00(2)°, Z = 4, R = 0.067. The differences in their conformation are discussed. Molecular mechanics calculations were carried out and indicate that the energy difference between the two species is very small. The stepwise enthalpies of protonation in solution were determined by direct microcalorimetry: ΔH° = −23.8(4) kJ mol−1 for H−1L− + H+ = L; ΔH°≅O for reactions L + H+ = HL+ and HL+ + H+ = H2L2+. The addition of the third proton is also athermic and fully entropy-controlled.

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.

The compound [2-(1-diethylaminopropyl)] 1-hydroxy-1,1′-bicyclohexyl-2-carboxylate 1 is a muscarinic antagonist characterized by the presence of three chiral atoms and eight possible stereoisomers. The binding affinities to the five cloned m1–m5 muscarinic receptors of the stereoisomers of 1 were previously investigated and proved to be related to the chirality of the molecules. The eight isomers are prepared through the synthesis of their racemates followed by chemical resolution as (+) and (−) tartrate or (+) and (−) dibenzoyltartrate salts. The isomers with cis-configuration of OH and COOH substituents of the cyclohexane are also obtained by coupling optically active (1S, 2S) or (1R,2R)-1-hydroxy-[1,1′-bicyclohexyl]-2-carboxylic acid with (S)- or (R)-1-diethylamino-2-propanol. Chiral GC and HPLC methods are used to determine their optical purity. The absolute configurations of the four cis- and four trans-isomers are established by stereospecific synthesis and X-ray crystallographic data. Chirality 9:713–721, 1997. © 1997 Wiley-Liss, Inc.

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 enantiomers of 1-methyl-3-(10H-phenothiazine-10-ylmethyl)-1-azoniabicyclo[2,2,2]octane iodide (1) were prepared by chiral chromatographic resolution of the precursor mequitazine (2). The (+)-(S)-enantiomer 1b is 10-fold more potent than (−)-(R)-enantiomer 1a as a histamine antagonist, while the two enantiomers show the same antimuscarinic activity in vitro. The absolute configuration of the more active dextrorotatory isomer has been determined by X-ray analysis. Conformational analysis and molecular modeling suggest that the (+)-(S)-enantiomer can adopt a conformation similar to that attributed to the receptor binding conformers of classical antihistamines. © 1994 Wiley-Liss, Inc.

A dinuclear Ni(II)–Zn(II) complex of 2-bis-(aminoethyl)-aminomethylphenol ( L ) was prepared by mixing the homo-dinuclear complexes of Ni(II) and Zn(II). The mixed hetero-dinuclear complex was characterized by X-ray analysis. Crystal data for the compound [NiZn(H -1 L ) 2 (H 2 O) 2 ][ClO 4 ] 2 revealed that it is monoclinic; space group P2 1 /n with a =20.137(2) A, b =9.480(1) A, c =15.934(1) A, β=100.45(1)°, V =2991.3(5) A 3 , Z =4, R =0.094.

The interaction of Pb2+ with the macrocyclic amines 1,4,7,10,13,16-hexaazacyclooctadecane (L1), 1,4,7,10,13,16,19-heptaazacyclohenicosane (L2), 1,4,7,10,13,16,19,22-octaazacyclotetracosane (L3), 1,4,7,10,13,16,19,22,25-nonaazacycloheptacosane (L4), 1,4,7,10,13,16,19,22,25,28-decaazacyclotriacontane (L5), 1,4,7,10,13,16,19,22,25,28,31-undecaazacyclotritriacontane (L6) and 1,4,7,10,13,16,19,22,25,28,31,34-dodecaazacyclohexatriacontane (L7) belonging to the [3k]aneNg series and with their related open-chain, terminally methylated polyamines 1,14-bis(methylamino)-3,6,9,12-tetraazatetra-decane (L8), 1,17-bis(methylamino)-3,6,9,12,15-pentaazaheptadecane (L9), 1,20-bis(methylamino)-3,6,9,12,15,18-hexaazaicosane (L10) and 1,23-bis(methylamino)-3,6,9,12,15,18,21-heptaazatricosane (L11) has been studied by potentiometry at 298.1 K in 0.15 mol dm–3 NaClO4. The cyclic amines L1 and L2 form only mononuclear complexes, while L3–L5 can form both mono- and bi-nuclear species. The largest amines of this series L6 and L7 form bi- and tri-nuclear lead(II) complexes. Of the open-chain ligands, L8 forms only mononuclear complexes, while L9–L11 form both mono- and bi-nuclear species. The crystal structure of the solid compound [Pb2L5][ClO4]4 has been solved by X-ray diffraction analysis [space group P21/n, Z= 2, a= 9.052(9), b= 11.400(9), c= 18.689(8)A, β= 94.42(6)°, R= 0.082 and R′= 0.068]. It shows that both Pb2+ ions are tightly co-ordinated to four nitrogens of the macrocycle (Pb–N ranging from 2.27 to 2.71 A). A fifth nitrogen and three oxygens of two perchlorate anions are weakly interacting at much larger distances (Pb–N 3.04; Pb–O 2.98, 3.38, 3.41 A). The complex cation is situated around a crystallographic symmetry centre. The arrangement of the eight atoms around the lead ion is rather asymmetric leaving a zone free from co-ordinated donor atoms which is believed to be occupied by a lone pair of electrons.

The synthesis and characterization of the new macrobicyclic cage 4,10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.4]hexadecane L is reported. Its basicity behaviour in aqueous solution has been investigated by potentiometric (25 °C, I= 0.15 mol dm–3) and NMR (1H and 13C) techniques. It behaves as a very strong base (proton sponge) in the first protonation step, and as a moderate base in the second step (log K2= 7.8). 1H–1H and 1H–13C two-dimensional NMR experiments permitted the unequivocal assignment of all 1H proton and 13C resonances of both species HL+ and H2L2+. Furthermore NMR experiments indicate that the first protonation involves the bridgehead nitrogens. Crystals of [HL][ClO4] are orthorhombic, space group P21cn, with a= 9.044(2), b= 12.573(2), c= 16.126(3)A, and Z= 4; final R value of 0.089 (Rw= 0.086) for 1267 unique observed reflections with I > 3σ(I). X-Ray analysis shows that protonation occurs on the bridgehead nitrogen N(2) and an overall macrocyclic conformation with the all nitrogen atoms in the endoconfiguration. The short H(2)⋯(4)[1.69(1)A] and N(2)⋯ N(4)[2.75(1)A] distances indicate a strong hydrogen bond. H(2) further interacts with the other two tertiary nitrogens: H(2)⋯ N(1)[2.53(1)A] and H(2)⋯ N(3)[2.46(1)A]. This arrangement makes the monoprotonated species very stable from the thermodynamic point of view and explains the high basicity of L. Crystals of [H3L][ClO4]3 are tetragonal, space group P43212, with a= 8.498(2), b= 8.498(2), c= 32.855(8)A, and Z= 4; final R value of 0.083 (Rw= 0.093) for 1076 unique observed reflections with I > 3σ(I). The X-ray analysis shows an overall macrocyclic conformation with two nitrogen atoms in the endoconfiguration and two in exo configuration.

The title compound 2 is found to undergo thermal isomerization into the quinoxaline derivative 3, as shown by a crystal structure determination of the latter; a mechanistic rationale for this unusual rearrangement is suggested.

The synthesis and characterization of the small, new benzyl aza-cage 4-benzyl-10,15-dimethyl-1,4,7,10,15-pentaazabicyclo[5.5.5]heptadecane (L) are reported. The basicity constants have been determined in aqueous solution by potentiometry (25 °C, [NaCl] 0.15 mol dm–3). L behaves as a biprotic base: log K1= 11.8, log K2= 8.3. The crystal structure of the monoprotonated salt [HL][BPh4] has been determined by single-crystal X-ray analysis. The compound crystallizes in an orthorhombic unit cell (space group Pc21n, Z= 4) with lattice constants a= 11.400(4), b= 16.893(3), c= 20.537(6)A. Least-squares refinement converged at R= 0.078 (Rw= 0.056) for 1290 unique reflections with I > 3σ(I). The structure of [HL]+ shows the five nitrogens atoms in an endo configuration, indicating that the proton is inside the cage cavity. The cage L encapsulate Li+ and the complex formation equilibrium for [LiL]+ has been investigated by potentiometry [log K= 3.0(1)] and 7Li NMR techniques.

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.

3,5-Dimethyl-4-nitroisoxazole (1) was found to undergo tandem condensation-cyclization processes with 4-(1-cylopenten-1-yl)- and 4-(1-cyclohexen-1-yl)morpholine in ethanol solution to give, through the intermediates (4) and (7), the N-oxides (5) and (9) respectively. The reactivity of 1 towards 1-diethylamino-propyne in different solvents was also investigated; the structure of the unexpected acycloxime (13), coming from the above reagents in acetonitrile, was determined by an X-ray analysis. Plausible mechanistic pathways for these new reactions are suggested

A new series of 11-[(aminoalkyl) carbonyl] derivatives of 6,11-dihydrobibenzo [c,f] [1,2,5] thiadiazepine 5,5-dioxide (10-39) were synthesized and evaluated for potential antidepressant activity in the apomorphine-induced hypothermia (Apo 16) tests. Effects on reserpine-induced hypothermia and toxicity for the most potent antagonists of Apo 16 hypothermia were also studied. Structure-activity relationships are reported. Anticholinergic effects were evaluated for compound 12, identified as the most potent and least toxic in this series, by assessing physostigmine lethality. Compound 12 was also subjected to X-ray analysis

The synthesis and characterization of the new macrotricycle 10,22,28,32-tetraoxa-1,4,7,13,16,18-hexaazatricyclo[17.5.5.57,13]tetratriacontane L is reported. Its basicity in aqueous solution has been investigated by potentiometric and spectroscopic (1H, 13C NMR) techniques. The basicity constants have been determined (25 °C, I= 0.15 mol dm–3) in two ionic media. Macrotricycle L behaves as a hexaprotic base: log K1= 10.27(3), log K2= 9.52(3), log K3= 7.12(3), log K4= 4.62(3), log K5= 2.80(3), log K6= 2.27(3) in NaClO4 and log K1= 10.09(3), log K2= 9.27(3), log K3= 6.54(3), log K4= 4.88(3), log K5= 3.75(3), log K6= 3.07(3) in NaCl. The constants relative to the equilibrium Cl–+ HnLn+⇌ HnLCl(n–1)+ have been measured: n= 5, log K= 2.48(3); n= 6, log K= 3.59(3). The crystal structure of L has been determined by single-crystal X-ray analysis. The compound crystallizes in a triclinic unit cell (space group P, Z= 2) with lattice constants a= 8.984(5), b= 12.122(2), c= 14.667(3)A, α= 109.52(2), β= 105.47(3), γ= 95.24(3)°. Least-squares refinement converged at R= 0.088 (R′= 0.075) for 3198 unique reflections with I > 4σ(I). The structure shows that the molecule has a skewed cylindrical shape, the bases being formed by the two N2O2 macrocycles with the N(CH2CH2)2 chains constituting the walls. The cylindrane L binds two Li+ ions and the resulting complex has been studied by 7Li NMR spectroscopy. Copper(II) and cadmium(II) complexes with L have been investigated in aqueous solution and their stability constants determined by potentiometric techniques. For both metals the following species have been found: [ML]2+, [MLH]3+, [ML(OH)]+ and [ML(OH)2].

The synthesis and the spectroscopic characterization of a new potential drug for urinary incontinence, adosupine, is described. Adosupine and its potential synthesis impurities were analyzed by a new HPLC method that was developed with a C18 reversed-phase column. The analysis was made under isocratic conditions, with a mobile phase of acetonitrile:water (15:85, v/v). Resolution of all synthesis impurities was allowed. The method was also applied to stability studies of adosupine in solid state and in solution under different conditions. With the conditions used, only one degradation product was shown by HPLC analysis; it was isolated, characterized, and identified as the hydrolysis product of the lactam ring present in the adosupine structure.

The solid state conformation of the title compound was determined. Conformational analysis based on molecular modelling mechanics allowed the calculation of the energy of the most stable conformers and their comparison with X-ray conformation.

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.

The diglyme [CH3O(CH2CH2O)2CH3] adduct of the magnesium bis-hexafluoroacetyl-acetonato [Mg(hfa)2·2H2O·2diglyme] has been synthesized in a single-step reaction. It has been characterized by elemental analyses, IR spectroscopy, and 1H and 13C NMR. Single-crystal X-ray diffraction studies provide evidence of a mononuclear hexa-coordinated complex with an octahedral structure for the Mg(hfa)2·2H2O moiety and diglyme coordinated in the outer sphere (triclinic system, space group= P1; a = 8.952(3) A, b = 9.036(3) A, c = 11.98(1) A, α = 110.44(5)°, β = 108.64(4)°, γ = 97.06(3)°, Z = 1). The “thermal robustness” and mass transport properties of the adduct have been investigated by thermogravimetric analysis and chemical vapor deposition experiments. Thermal analysis data revealed high volatility and good thermal stability with a residue left lower than 1%. The Mg(hfa)2·2H2O·2diglyme has been successfully applied to the low-pressure metal-organic chemical vapor deposition (MOCVD) of MgF2 films. The good quality o...

The nitroderivatives 1a–c were found to react with the title ynamine 2 under mild conditions to give the corresponding fused isoxazoles 3a–c, as proved by an X-ray diffraction of 3a; a plausible mechanistic pattern for these conversions is presented. Treatment of the nitroderivatives 1a–c with the ynamine 2 afforded the new bicyclic isoxazoles 3a–c as proved by an X-ray analysis of 3a.

Carbon dioxide, formic acid, and water molecules are trapped in the crystal lattice of manganese(III) formate (see 1), which was obtained by reducing permanganate with formic acid. Each CO2 guest molecule exhibits four C-H⋅⋅⋅O-C-O interactions with the three-dimensional host framework of Mn(HCOO)3 units. Compound 1 undergoes an antiferromagnetic phase transition at 27 K.

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 synthesis and characterization of the new aza-cage 12,17-dimethyl-1,9,12,17-tetra-azabicyclo-[7.5.5]nonadecane (L) are described. The basicity behaviour in both aqueous and water–DMSO (50 : 50, mol : mol) solutions has been investigated by potentiometric and microcalorimetric (25 °C, 0.15 mol dm–3 NaCl) techniques. L behaves, in aqueous solution, as a fairly strong base (log K1= 12.00; ΔH1⊖=–54.0 kJ mol–1; TΔS1⊖= 14.5 kJ mol–1) in the first protonation step and as a moderate base in the second step (log K2= 7.86 ΔH2⊖=–44.8 kJ mol–1; TΔS2⊖ca. 0). The enthalpic and entropic contributions are discussed in terms of molecular topology and translational entropy. The CuII ion is encapsulated by L, the electronic spectra being diagnostic of a square-planar structure. The molecular structures of the diprotonated salts [H2L][CoCl4] and [H2L1][CoCl4](L1 = 5,12,17-trimethyl-1,5,9,12,17-penta-azabicyclo[7.5.5]nonadecane) have been determined by single-crystal X-ray analysis.Crystals of [H2L][CoCl4] are orthorhombic, space group pbn21, with a= 9.311 (3)A, b= 15.480(2)A, c = 16.636(6)A, and Z= 4. Final R values of 0.043 (Rw= 0.037) for 1 358 observed reflections. X-Ray analysis shows that the protonation occurs on the N–CH3 groups. Each hydrogen atom of the NH+–CH3 interacts with the two bridgehead nitrogen atoms.The compound [H2L1][CoCl4] crystallizes in a monoclinic unit cell (space group P21) with lattice constants a= 8.877(3)A, b= 14.088(8)A, c= 10.122(5)A, β= 105.51 (4)°, and Z= 2. Final R values of 0.064 (Rw= 0.049) for 2 374 observed reflections. In this case the conformation of the diprotonated cage is different and the protonation probably occurs at one of the two methylated nitrogens and at the apical nitrogen atom.

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.