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

The reaction between 2-hydroxybenzaldehyde (1a), isocyanides 2, and ammonium formate, in the conditions of the Ugi four-component condensation, affords 2-alkylamino- and 2-arylamino-3-[(2-hydroxybenzylidene)amino]benzofurans 3a-c. Analogously by employing 5-bromo-2-hydroxybenzaldehyde (1b) as the carbonyl compound, 2-alkylamino- and 2-arylamino-5-bromo-3-[(5-bromo-2-hydroxybenzylidene)amino]benzofurans 3d-f are obtained

The structural characterization of idrapril, (1S,2R)-cis-2-[hydroxyaminocarbonylmethyl(N-methyl)aminocarbonyl]cyclohexanecarboxylic acid (4), a novel ACE inhibitor and its related benzyloxy derivative (3) has been carried out by NMR studies. The crystal structure of 3 has been determined by X-ray diffraction. The NMR spectra indicate the presence of two cis and trans isomers with respect to the amide bond at room temperature, with rotational barriers of 70 kJ mol–1. The preferred conformation of these compounds is the trans rotamer with the carboxylic moiety in the equatorial orientation.Conformational studies in aqueous solution have been reported for idrapril as a function of pH and the equilibrium constant has been determined. The results suggest the presence of intramolecular hydrogen bonds, as is confirmed by molecular mechanics calculations.

The two theophylline derivatives 7-isobutyl-1,3-dimethylxanthine (1) and 7-butyl-1,3-dimethylxanthine (2) show antibronchospastic properties, the first one having a higher pharmacological activity together with a stronger solubility in aqueous solutions. Crystal structures, determined for both compounds, exhibit similar features at the molecular level, but a different crystal packing, i.e. compound 2 has a closer arrangement. Melting points and enthalpic data of the two compounds are in agreement with this closer arrangement of compound 2. NMR measurements show a remarkable mobility of the alkyl side chain of 2 and its very low solubility in aqueous solution. Systematic conformational searches, using the software package provided by Biosym Technologies, were carried out starting from the X-ray crystal structures with the atomic charges calculated with the AM1 routine. Results from these calculations, performed with the CFF91 force field in DISCOVER, underline the high conformational freedom of the side chain of compound 2. The collected results may be useful to understand the different pharmacological activity between compounds 1 and 2.

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].

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

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 autologous and allogeneic mixed lymphocyte reactions of 15 young and 15 aged human adults were compared. Both autologous and allogeneic mixed lymphocyte reactions were significantly reduced in the aged group. T cells from aged adults displayed a reduced proliferative response to non-T cells of either aged or young adults. T cells from young adults also showed a reduced proliferative response to non-T cells from aged adults. Sera from aged adults, showing depression of autologous and allogeneic mixed lymphocyte reaction, did not exert any inhibitory effect on the autologous and allogeneic mixed reaction of lymphocytes from young donors. These data suggest that depression of mixed lymphocyte reaction in aged humans probably reflects intrinsic abnormalities of both responder T cells and stimulatory non-T cells.

Multinuclear n.m.r. and thermodynamic studies in aqueous solution indicate that the cage-like azamacrobicycle 5,12,17-trimethyl-1,5,9,12,17-penta-azabicyclo[7.5.5]nonadecane (L) is able to selectively encapsulate the lithium ion, forming a stable 1 : 1 complex (log k= 3.1, ΔH°=–2.1kJ mol–1, ΔS°= 52.3 J mol–1 K–1); the crystal structures of the complex [LiL][BPh4] and of the monoprotonated salt [HL][Cl]·3H2O have been determined.

Equilibrium data on the interaction of DTMA [(DTMA = DOTA tetrakis(methylammide)] with Gd3+ in aqueous solution, properties of the complexes formed in the pH range 0.6–11.8, water proton relaxation rate enhancement, and the crystal structure analysis of the [Gd(DTMA)H2O]3+ complex are reported. In the crystal structure the metal ion is bound to the nitrogen atoms of the tetraazamacrocyclic moiety, to the amidic oxygen atoms, and to an oxygen atom of a water molecule. The nine donors are located at the vertices of a distorted square antiprism, which is capped by the coordinated water oxygen atom in the axial position. In solution [Gd(DTMA)]3+ is not very stable [logKML = 12.8(1)] and gives rise to the formation of [Gd(DTMA)OH]2+ [pKa = 7.9(1)] and [Gd(HDTMA)]4+ [logK(ML+H) = 3.4(1)]. The proton solvent relaxivity of aqueous complex solutions assumes a constant value in the pH range 3–8, increasing at higher and lower pH. For pH > 3 the data are in good agreement with a previous study on the same compound. For pH < 3 a new interpretation is presented, based on the formation of [Gd(HDTMA)]4+ and the release of Gd3+.

Molecular Dynamics (MD) simulations were performed on several species (anion, zwitterion, and neutral metal complexes) of two phenolic aza cages (L1 and L2) in aqueous solution. The anionic species of the smaller L1 ligand appears to be able to selectively encapsulate Li+, while the other alkaline metal ions tested (Na+ and K+) are too large to be encapsulated. The larger cage L2 does not show any selectivity; the anion binds all the alkaline metal ions. The two aza cages L1 and L2 were synthesized. Both basicity and alkali metal complex formation were studied in aqueous solution at 25 °C in 0.15 mol dm−3 Me4NCl, using potentiometric, UV/Vis- and NMR-spectroscopic techniques. Both cages behave as triprotic bases in the pH range investigated; logK1 = 12.15(6), logK2 = 7.39(5), logK3 = 1.4(1) for L1 and logK1 = 11.76(5), logK2 = 8.24(5), logK3 = 2.9(2) for L2. The last proton cannot be removed because both compounds are strongly basic under the experimental conditions studied. Proton localization was studied by UV/Vis and NMR spectroscopy, both in water and nonaqueous solutions. The crystal structures of [HL1](ClO4) and [NaL2](ClO4) were determined by X-ray analysis. The crystals of [HL1](ClO4) are triclinic, space group P(1¯); cell parameters are a = 10.3628(8), b = 11.938(1), c = 12.201(4) A, α = 117.53(1), β = 101.25(1), γ = 102.774°. The crystals of [NaL2](ClO4) are monoclinic, space group P21/n; cell parameters are a = 10.6154(7), b = 17.0418(9), c = 14.9452(9) A, β = 95.634(6)°.

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 .

7-Substituted 1,4,7,10-tetraazacyclododecane-1-carbaldehydes have been prepared through the ring opening of orthoamide protected intermediates which, in turn, were obtained by reaction of mono N-substituted 1,4,7,10-tetraazacyclododecane derivatives with dimethylformamide diethyl acetal. Orthoamide ring opening occurs under mild reaction conditions and is highly regiospecific. A number of mono- and bi-dimensional NMR experiments have been performed to assign unambiguously the structure of the opened compounds. The regiochemistry of such compounds has also been confirmed by elucidation of the solid-state structure of 7-triphenylmethyl-1,4,7,10-tetraazacyclododecane-1-carbaldehyde by X-ray crystallography. The crystal structure of 7-triphenylmethyloctahydro-5H,9bH-2a,4a,7,9a-tetraazacycloocta[cd]pentalene has also been determined.

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.

The transformation of acetylene into vinylidene, as promoted by the metal fragment [(pp3)Co]+ [pp3 = P(CH2CH2PPh2)3], is unimolecular and features the hydride–acetylide species as an intermediate. The paper describes a detailed ab initio study of the reaction, in particular with regard to the step involving 1,3-H shift. The best computational results are obtained by mimicking the pp3 ligand with actual ethylenic chains rather than with single PH3 molecules. The keypoints along the two-step reaction path (π-acetylene, hydride–acetylide, and vinylidene complexes, as well as intermediate transition states) have been optimized for CoI and RhI derivatives at the MP2 level. For the fragment [(pp3)Co]+, the barrier associated with transformation of the hydride–acetylide intermediate to vinylidene (20.6 kcal/mol) is easier to surmount compared to that for reversion to the reactants (28.6 kcal/mol). The situation is reversed for the analogous RhI system, with the initial π-acetylene adduct being slightly more stable. Although higher in energy, the hydride–acetylide species is the experimentally detected product of the reaction of acetylene with the fragment [(pp3)Rh]+. The salient chemical aspects of the 1,3-H shift are discussed in terms of perturbation theory arguments. Parallel EHMO calculations, which have provided a relatively good consistency with the ab initio results, allow the proposal of an orbital rationale for the mode of migration of the hydride ligand along the substantially linear Co–Cα–Cβ grouping.

The structure of the disodium salt of the [Eu(C 22 H 26 -N 3 O 11 )(H 2 O)] 2- complex anion is isomorphous with that of the corresponding gadolinium(III) compound. The EU III atom is nine-coordinate with the donor atoms disposed at the vertices of a tricapped trigonal prism, the cap positions being occupied by two N atoms of the ligand and the O atom of the ligated water molecule.

The aryltetralins 7a and 7b and the keto-lactone 8 are synthesised by cyclisation and deprotection of the conjugate addition products 4a and 4b; the structure of 7b was unambiguously confirmed by an X-ray structural analysis.

The synthesis of the flexible ligand 2,6-bis-{(bis-(2-aminoethyl)amino(methyl}anisole (L) is reported. The basicity behaviour in aqueous solution was studied by potentiometry (25°C, I = 0.15 mol dm−3, Me4NCl). L behaves as pentaprotic base (logK1 = 10.31(2), logK2 = 9.65(2), logK3 = 9.16(2), logK4 = 8.39(2), logK5 = 2.14(2)). The stability constants for Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes were determined by potentiometry and all of these metalions were found to form both mono and binuclear species: logKML = 9.39(3) for Co(II); 14.5(1) for Ni(II); 17.57(7) for Cu(II); 10.62(2) for Zn(II) and 9.83(3) for Cd(II). LogKM2L = 15.19(3) for Co(II); 19.57(5) for Ni(II); 28.44(3) for Cu(II); 16.77(6) for Zn(II) and 14.62(3) for Cd(II). The crystals of [Cu4L2(N3)6](ClO4)2·H2O are triclinic, space group P-1 a = 13.770(6), b = 14.043(2), c = 16.800(3) A, α = 105.700(1), β = 102.790(3), γ = 103.660(3)°, Z = 2. L behaves as ditopic ligand and the crystal lattice consists of branched chains of Cu...

The synthesis and characterization of the macrobicycle 4,10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.5]-heptadecane (L) is reported. The proton-transfer properties of L in aqueous solution have been, investigated by potentiometry (25 °C, I= 0.15 mol dm–3) and NMR spectroscopy (1H and 13C). L behaves as a fairly strong base in the first protonation step (log K1= 11.55), and as a moderate base in the second step (log K2= 6.94). 1H and 13C resonances have been assigned for both [HL]+and [H2L]2+ species. NMR experiments also indicate the stepwise protonation sites. Crystals of [H2L]-[ClO4]2 are orthorhombic, space group Pca21 with a= 13.130(1), b= 16.185(4), c= 20.320(6)A, and Z= 8; final R value of 0.086 (Rw= 0.079) for 2383 unique observed reflections with I > 3σ(I). Two independent [H2L]2+ cations are present in the unit cell; they differ from each other in the conformation of the hydrocarbon chain connecting the two unmethylated nitrogen atoms. In both cases the overall cage conformation is due to the presence of two internal hydrogen bonds, connecting the two bridgehead nitrogens and the two methylated nitrogens.

A variety of studies have shown that group identification (a sense of belonging to one’s social group, coupled with a sense of commonality with the group’s members) is linked to high levels of satisfaction with life (SWL). The aim of the present study was to support and extend this literature by: (1) investigating the link between group identification and SWL with a large cross-cultural community sample; (2) examining whether the relationship is moderated by nationality; and (3) considering whether SWL is enhanced by possessing multiple group identifications simultaneously. Utilizing data from Wave 1 of the Health in Groups project, 3829 participants from both Scotland and Italy completed a questionnaire assessing their identification with their family, their local community, and a group of their choice, as well as their level of SWL. Higher identification with each group predicted higher SWL. Nationality was a marginal moderator of the relationship between family identification and SWL, with the relationship being stronger for Italian participants than for Scottish participants. There was also an additive effect of group identification, with a positive relationship between the number of groups with which participants identified and their SWL. These effects were obtained even after controlling for gender, age, employment status, nationality, and extent of contact with each group. The implications for healthcare professionals and their patients are discussed.

In preceding works, which have dealt with the synthesis and characterisation of a series of macrobicyclic compounds with five donor atoms, the unusually high basicity constants of these polyaminic cage-like molecules have been ascribed to the inclusion of the proton inside the macrobicyclic cavity which results in a very efficient hydrogen-bond network. The present paper, based on previously reported X-ray crystal structures regarding five-atoms bridging units and on molecular modelling studies shows that the disposition of the five donor atoms in the monoprotonated species is related to the protonation site. Precisely, if the protonation occurs on a bridge-head nitrogen the resulting geometry of the donors is a trigonal bipyramid, whereas it is square pyramidal when the proton is bound to a nitrogen belonging to a macrobicyclic chain. For what concerns the geometrical array of the donor atoms in the free amines, the favoured array seems to be the trigonal bipyramidal.

Single crystals of the copper(II) chain of formula [Cu(bpym) (N32]n (bpym = 2,2′-bipyrimidine) were prepared and characterized by X-ray diffraction methods. The structure consists of neutral chains of copper (II) ions bridged by a single azide group exhibiting the asymmetric end-to-end coordination mode. A terminally bound azide ligand and a didentate bpym group complete the square pyramidal geometry of the metal atom. The intrachain copper-copper separation is 5.063(1)A. The magnetic behaviour was investigated in the temperature range 2.0–290 K. The susceptibility curve exhibits a maximum at .9 K showing the occurrence of a weak intrachain antiferromagnetic coupling. Analysis of the magnetic data using the Heisenberg uniform linear chain model ( H ^ = − J ∑ S ^ i ⋅ S ^ i + 1 ) leads to J = −3.8cm−1 and g = 2.12. The value of magnetic coupling of this compound is compared with that observed in the parent double end-to-end azido-bridged dinuclear copper(II) complexes.