Synthesis and crystallographic, spectroscopic and computational characterization of 3,3',4,4'-substituted biphenyls: effects of OR substituents on the intra-ring torsion angle.

Presented here are the synthesis, characterization and study (using single crystal X-ray diffraction, Raman scattering, quantum mechanics calculations) of the structures of a series of biphenyls substituted in positions 3, 3', 4 and 4' with a variety of R (R = methyl, acetyl, hexyl) groups connected to the biphenyl core through oxygen atoms. The molecular conformation, particularly the torsion angle between aromatic rings has been extensively studied both in the solid as well as in the liquid state. The results show that the compounds appearing as rigorously planar in the solid present instead a twisted conformation in the melt. The solid versus melt issue strongly suggests that the reasons for planarity are to be found in the packing restraints. A `rule of thumb' is suggested for the design of biphenyls with different molecular conformations, based on the selection of the OR substituent.

Exchange couplings and quantum phases in two dissimilar arrays of similar copper dinuclear units.

To investigate the magnetic properties and the spin entanglement of dinuclear arrays, we prepared compounds [{Cu(pAB)(phen)H2O}2·NO3·pABH·2H2O], 1, and [Cu2(pAB)2(phen)2pz]n, 2 (pABH = p-aminobenzoic acid, phen = 1,10-phenanthroline and pz = pyrazine). The structure of 1 is known and we report here that of 2. They contain similar dinuclear units of CuII ions with 1/2-spins S1 and S2 bridged by pairs of pAB molecules, with similar intradinuclear exchange and fine interactions , but different 3D crystal arrays with weak interdinuclear exchange J', stronger in 2 than in 1. To investigate the magnetic properties and the spin entanglement produced by J', we collected the powder spectra of 1 and 2 at 9.4 GHz and T between 5 and 298 K, and at 34.4 GHz and T = 298 K and single-crystal spectra at room T and 34.4 GHz as a function of magnetic field (B0) orientation in three crystal planes, calculating intradinuclear magnetic parameters J(1)0 = (-75 ± 1) cm-1, J(2)0 = (-78 ± 2) cm-1, |D(1)| = (0.142 ± 0.006) cm-1, |D(2)| = (0.141 ± 0.006) cm-1 and E(1) ∼ E(2) ∼ 0. Single crystal data indicate a quantum entangled phase in 2 around the crossing between two fine structure EPR absorption peaks within the spin triplet. This phase also shows up in powder samples of 2 as a U-peak collecting the signals of the entangled microcrystals, a feature that allows estimating |J'|. Transitions between the two quantum phases are observed in single crystals of 2 changing the orientation of B0. We estimate interdinuclear exchange couplings |J'(1)| < 0.003 cm-1 and |J'(2)| = (0.013 ± 0.005) cm-1, in 1 and 2, respectively. Our analysis indicates that the standard approximation of a spin Hamiltonian with S = 1 for the dinuclear spectra is valid only when the interdinuclear coupling is large enough, as for compound 2 (|J'(2)/J(2)0| ∼ 1.7 × 10-4). When J' is negligible as in 1, the real spin Hamiltonian with two spins 1/2 has to be used. Broken-symmetry DFT predicts correctly the nature and magnitude of the antiferromagnetic exchange coupling in 1 and 2 and ferromagnetic interdinuclear coupling for compound 2.

Br...Br and van der Waals interactions along a homologous series: crystal packing of 1,2-dibromo-4,5-dialkoxybenzenes.

The crystalline structures of four homologues of the 1,2-dibromo-4,5-dialkoxybenzene series [Br2C6H2(OCnH2n + 1)2 for n = 2, 12, 14 and 18] have been solved by means of single-crystal crystallography. Comparison along the series, including the previously reported n = 10 and n = 16 derivatives, shows a clear metric trend (b and c essentially fixed along the series and a growing linearly with n), in spite of some subtle differences in space groups and/or packing modes. A uniform packing pattern for the aliphatic chains has been found for the n = 12 to 18 homologues, which slightly differs from that of the n = 10 derivative. The crystalline structures of all the higher homologues (n = 10-18) seem to arise from van der Waals interchain interactions and, to a lesser extent, type II Br...Br interactions. The dominant role of interchain interactions provides direct structural support for the usual interpretation of melting point trends like that found along this series. Atoms in Molecules (AIM) analysis allows a comparison of the relative magnitude of the interchain and Br...Br interactions, an analysis validated by the measured melting enthalpies.

The three-component cocrystal 1,3,5-trifluoro-2,4,6-triiodobenzene-pyridine N-oxide-water (1/2/1) built up by halogen bonds, hydrogen bonds and π-π interactions.

The title three-component cocrystal, C6F3I3·2C5H5NO·H2O, has been prepared as a strong candidate for multiple I...O interactions. Its crystal structure is compared with its 1:1 close relative, C6F3I3·C5H5NO [Aakeröy et al. (2014a). CrystEngComm, 16, 28-31]. The 1,3,5-trifluoro-2,4,6-triiodobenzene and water species both have crystallographic twofold axial symmetry. The main synthon in both structures is the π-π stacking of benzene rings, complemented by a number of O-H...O, C-F...π and, fundamentally, C-I...O interactions. As expected, the latter are among the strongest and more directional interactions of the sort reported in the literature, confirming that pyridine N-oxide is an eager acceptor. On the other hand, the structure presents only two of these contacts per 1,3,5-trifluoro-2,4,6-triiodobenzene molecule instead of the expected three. Possible reasons for this limitation are analyzed.

Structure and magnetism of a binuclear Cu(II) pyrophosphate: transition to a 3D magnetic behaviour studied by single crystal EPR.

A binuclear Cu(II) compound [Cu2(bpa)2(P2O7)(H2O)2]·2.5H2O, 1, (bpa = 2,2'-bipyridylamine), with pairs of Cu(II) ions bridged by one pyrophosphate tetra-anion, was synthesized and crystallized. Its triclinic structure was determined by single-crystal X-ray diffraction. Electron paramagnetic resonance (EPR) spectra of single crystal samples of 1 were recorded for a fixed orientation of the magnetic field (B0) as a function of temperature (T) between 4.7 and 293 K, and at T = 4.7, 50 and 293 K, as a function of the orientation of B0. Below ∼8 K, the spectra are assigned to two types of mononuclear crystal defects hyperfine-coupled to one copper and two nitrogen nuclei. The g-matrices and hyperfine couplings at these T provide information about the structures of these defects. Above 10 K, the spectrum is dominated by the response of the bulk binuclear Cu(II) material, showing hyperfine interactions with two copper nuclei, collapsing to a single peak above 18 K when the units are magnetically connected, and the magnetic behaviour becomes 3D. We attribute the results above 10 K to the interplay of an AFM intrabinuclear exchange interaction J0 = -28(3) cm(-1) (defined as Hex = -J0S1·S2), and three orders of magnitude weaker exchange coupling with average magnitude |J1| ≥ 0.022 cm(-1) between Cu(II) ions in neighbouring binuclear units. The interplays between structure, exchange couplings, magnetic dimension and spin dynamics in the binuclear compound are discussed. A previously unreported situation, where the structure of the spectra arising from the anisotropic spin-spin interaction term (D) within the binuclear unit is averaged out, but the forbidden half field transition is not, is observed and explained.

Pyrophosphate-bridged Cu(II) chain magnet: {[Na3Cu(P2O7)(NO3)].3H2O}n.

A Cu(II)...Cu(II) pyrophosphate-bridged compound of formula {[Na(3)Cu(P(2)O(7))(NO(3))].3H(2)O}(n) (1) has been characterized. X-ray diffraction measurements show that it crystallizes in the monoclinic space group P2(1)/m, with unit cell dimensions a = 7.2492(5) A, b = 8.2446(6) A, c = 9.9050(7) A, beta = 107.123(1) degrees, and Z = 2. The structure consists of chains of Cu(II) cations at inversion symmetry sites bound to four equatorial oxygen atoms provided by two pyrophosphate anions halved by a symmetry plane and two axial oxygen atoms of nitrate anions. The molar magnetic susceptibility chi(0) of a powdered sample was measured in the temperature range 2 K < T < 273 K, and an isothermal magnetization curve, M(B(0),T), was obtained at T = 30 K, with the magnetic field B(0) between 0 and 5 T. Fitting a spin-chain model to the susceptibility data, we evaluate an antiferromagnetic exchange coupling 2J = -24.3(1) cm(-1) (defined as H(ex) = -2JS(i)S(j)) between Cu(II) neighbors. For any orientation of B(0), single-crystal electron paramagnetic resonance (EPR) spectra obtained at 9.8 and 33.9 GHz at 300 K display a single signal having a g matrix with orthorhombic symmetry, arising from the merger produced by the exchange interaction of the resonances corresponding to the two rotated Cu(II) sites. The g matrices of the individual molecules calculated assuming axial symmetry yielded principal values g(parallel) = 2.367(1) and g(perpendicular) = 2.074(1) at both frequencies, indicating a d(x(2)-y(2)) ground-state orbital for the Cu(II) ions. The angular variation of the EPR line width suggests exchange narrowing in a system with one-dimensional spin dynamics, as expected from the structure and susceptibility data. The results, discussed in terms of the crystal and electronic structures and of the spin dynamics of the compound, are compared with those obtained in other materials.

Synthesis and GABA(A) receptor activity of oxygen-bridged neurosteroid analogs.

Three analogs of neuroactive steroids were prepared (4-6) in which 1,11- or 11,19-oxygen bridges give a constrained conformation. Their 3D structures were obtained by ab initio calculations and in the case of 3alpha-hydroxy-11,19-epoxypregn-4-ene-20-one (4), confirmed by X-ray analysis. Biological activity of the synthetic steroids was assayed in vitro using t-[(3)H]butylbicycloorthobenzoate as radiolabeled ligand for the GABA(A) receptor. The activity of compound 4 was similar to that of allopregnanolone (1). 1alpha,11alpha-Epoxypregnanolone (6) was more active than pregnanolone (2).

Synthesis of 6,19-cyclopregnanes. Constrained analogues of steroid hormones.

A procedure for the synthesis of 6,19-cyclopregnanes is described involving an intramolecular alkylation reaction of Delta(4)-3-keto steroids with a 19-mesylate in the presence of KOH in isopropanol. Three 6,19-cyclopregnanes were prepared (4, 5 ,9); in the rat, 6,19-cycloprogesterone (4) and its 21-hydroxy derivative 5 displaced [3H]-dexamethasone from glucocorticoid receptors, the former compound being more active. Both compounds did not compete with [3H]-aldosterone for kidney mineralocorticoid receptors nor with [3H]-R5020 for uterus progesterone receptors.

Phytotoxic withanolides from Jaborosa rotacea.

Twelve new withanolides were isolated from the aerial part of Jaborosa rotacea: five had a spiranoid delta-lactone (1-5); one contained a 26,12-delta-lactone and a C-12-C-23 bond (6); five corresponded to trechonolide-type withanolides with configuration at C-23 opposite of those previously isolated (7, 8, 10-12); two of these have an additional oxido-bridge between C-21 and C-24; finally a withanolide with a hemiketal ring formed between a 21-hydroxyl and a 12-ketone (13) and the closely related jaborosalactone R were also isolated. New compounds were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS). The structures of the spiranoid withanolide and of the epimer of trechonolide A were confirmed by X-ray diffraction studies. Compounds 4, 5, 6, and 8 showed selective phytotoxicity toward monocotyledoneous and dicotyledoneous species.

Azorellane diterpenes from Azorella cryptantha.

Azorella cryptantha yielded the diterpenes, azorellolide and the dihydroderivative, dihydroazorellolide, together with the known yaretol and 1alpha,10beta,4beta,5alpha-diepoxy-7alpha-germacran-6beta-ol. Both possess a carbon skeleton type that may originate from rearrangement of the mulinane skeleton.