Charles J. Simmons

Crystal structure and electronic properties of dibromo- and dichloro-tetrakis[µ3-bis(2-pyridyl)amido]tricopper(II) hydrate

The crystal structures of [Cu3(bipyam–H)4Cl2]·H2O (1) and [Cu3(bipyam–H)4Br2]·H2O (2) where bipyam–H = bis(2-pyridyl)amide, have been determined by X-ray analysis, in the orthorhrombic space group Pnn2: (1), a= 14.092(3), b= 12.895(3), (c)= 11.190(2)A, Z= 2, and R= 0.032 for 2 453 observed and 2 029 unique reflections; (2), a= 14.186(3), b= 13.040(3), c= 11.313(2)A, Z= 2, and R= 0.043 for 1 574 observed and 1 465 unique reflections. The two structures are isomorphous with near isostructural [Cu3(bipyam–H)4X2] units in special positions of two-fold symmetry and a non-co-ordinated water molecule. The Cu3N12X2 chromophores involve nearly linear Cu3 units, Cu–Cu–Cu 178.4°(mean), terminated by the two halide anions. The four separate bipyam–H ligands act as tridentate ligands, involving co-ordination to the three separate copper(II) ions, with Cu–Cu distances of 2.471(1) and 2.468(1)A, for (1) and (2), respectively. If the Cu–Cu separations are ignored, the central Cu atom in both structures involves a four-co-ordinate rhombic coplanar CuN4 chromophore generated by the central amido nitrogens of the four bipyam–H ligands. The two terminal Cu atoms involve a square-based pyramidal CuN4X chromophore, generated by the terminal pyridine nitrogens of the four bipyam–H ligands and an axial halide anion. An average dihedral angle of 48° is involved between the planes of the pyridine rings of the individual bipyam–H ligands, which results in a spiral configuration of the [Cu3(bipyam–H)4X2] units. The spin-only magnetic moment of complex (1) is ca. 1.40 B.M. per Cu atom, consistent with antiferromagnetic coupling between the copper(II) atoms of the trimer. Both complexes are e.s.r. silent, again consistent with strong antiferromagnetic coupling. The electronic spectra of (1) and (2) have a band maximum at 15 500 cm–1, with a high-energy shoulder at 19 230 cm–1, consistent with the two different stereochemistries present.

Biologically Active Withanolides from Withania coagulans

Bioassay-directed isolation and purification of the crude extract of Withania coagulans, using two assays for cancer chemopreventive mechanisms, led to the isolation of three new steroidal lactones, withacoagulin G (1), withacoagulin H (2), and withacoagulin I (3), along with six known derivatives (4-9). The structures and absolute stereochemistry of these compounds were determined on the basis of spectroscopic analyses, including 1D and 2D NMR, mass spectrometry, and CD analyses. The structure of 1 was confirmed using X-ray diffraction methods. Compounds 1-9 inhibited nitric oxide production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells with IC(50) values in the range of 1.9-38.2 μM. Compounds 1 and 2 were the most active (IC(50) 3.1 and 1.9 μM, respectively). Withanolides 1-9 exhibited inhibition of tumor necrosis factor-α (TNF-α)-induced nuclear factor-kappa B (NF-κB) activation with IC(50) values in the range of 1.60-12.4 μM.

Anti-inflammatory sesquiterpene lactones from the flower of Vernonia cinerea

Bioassay-guided fractionation of the hexane extract from the flowers of Vernonia cinerea (Asteraceae) led to the isolation of a new sesquiterpene lactone, 8α-hydroxyhirsutinolide (2), and a new naturally occurring derivative, 8α-hydroxyl-1-O-methylhirsutinolide (3), along with seven known compounds (1 and 4-9). The structures of the new compounds were determined by 1D and 2D NMR experiments and by comparison with the structure of compound 1, whose relative stereochemistry was determined by X-ray analysis. The isolated compounds were evaluated for their cancer chemopreventive potential based on their ability to inhibit nitric oxide (NO) production and tumor necrosis factor alpha (TNF-α)-induced NF-κB activity. Compounds 1, 2, 4, 5, and 9 inhibited TNF-α-induced NF-κB activity with IC(50) values of 3.1, 1.9, 0.6, 5.2, and 1.6 μM, respectively; compounds 4 and 6-9 exhibited significant NO inhibitory activity with IC(50) values of 2.0, 1.5, 1.2, 2.7, and 2.4 μM, respectively.

Accelerated Identification of Halogenated Monoterpenes from Australian Specimens of the Red Algae Plocamium hamatum and Plocamium costatum

Two species of red algae belonging to the genus Plocamium, P. hamatum from Moreton Bay, Queensland, and P. costatum, from Pandalowie Bay, South Australia, were investigated to assess their chemical variation and as potential sources of new halogenated monoterpenes. The hyphenated technique HPLC-UV-MS-SPE-NMR was used to assess the algal extracts and to determine its potential for accelerated identification of halogenated monoterpenes generally. A combination of the hyphenated and traditional chromatographic techniques resulted in the isolation and characterization of a total of 10 halogenated monoterpene metabolites, eight of which are reported for the first time. Their structures, including configurations, were determined through interpretation of their 1D and 2D NMR, mass spectrometric, infrared, and X-ray data. The two species of Plocamium produced different secondary metabolites and contained a significant number of new polyhalogenated monoterpenes. The investigation also showed the hyphenated technique HPLC-UV-MS-SPE-NMR to be useful for preliminary investigation of the chemical content of algal extracts.

Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity

Three new withanolides, physaperuvin G (1), with physaperuvins I (2), and J (3), along with seven known derivatives (4-10), were isolated from the aerial parts of Physalis peruviana. The structures of 1-3 were determined by NMR, X-ray diffraction, and mass spectrometry. Compounds 1-10 were evaluated in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells. Compounds 4, 5, and 10 with potent nitric oxide inhibitory activity in LPS-activated RAW 264.7 cells, with IC50 values in the range of 0.32-7.8μM. In addition, all compounds were evaluated for potential to inhibit tumor necrosis factor-alpha (TNF-α)-activated nuclear factor-kappa B (NF-κB) activity with transfected human embryonic kidney cells 293. Compounds 4-7 inhibited TNF-α-induced NF-κB activity with IC50 values in the range of 0.04-5.6μM.

Temperature dependence of the crystal structure and g-values of trans-diaquabis(methoxyacetato)copper(II): Evidence for a thermal equilibrium between complexes with tetragonally elongated and compressed geometries

The crystal structures of trans-diaquabis(methoxyacetato)copper(II) and the isostructural nickel(II) complex have been determined over a wide temperature range. In conjunction with the reported behavior of the g-values, the structural data suggest that the copper(II) compound exhibits a thermal equilibrium between three structural forms, two having orthorhombically distorted, tetragonally elongated geometries but with the long and intermediate bonds to different atoms, and the third with a tetragonally compressed geometry. This is apparently the first reported example of a copper(II) complex undergoing an equilibrium between tetragonally elongated and compressed forms. The optical spectrum of single crystals of the copper(II) compound is used to obtain metal-ligand bonding parameters which yield the g-values of the compressed form of the complex and hence the proportions of the complex in each structural form at every temperature. When combined with estimates of the Jahn-Teller distortions of the different forms, the latter produce excellent agreement with the observed temperature dependence of the bond lengths. The behavior of an infrared combination band is consistent with such a thermal equilibrium, as is the temperature dependence of the thermal ellipsoid parameters and the XAFS. The potential surfaces of the different forms of the copper(II) complex have been calculated by a model based upon Jahn-Teller coupling. It is suggested that cooperative effects may cause the development of the population of tetragonally compressed complexes, and the crystal packing is consistent with this hypothesis, though the present model may oversimplify the diversity of structural forms present at high temperature.

EPR of two Cu2+ complexes showing dynamic Jahn-Teller effects

The powder electron paramagnetic resonance spectra of ∼1% Cu doped into [Zn(bipy)2(NO2)]NO3 and [Zn(bipyam)2(NO2)]NO3, bipy = 2,2′-bipyridyl, bipyam = 2,2′-bipyridylamine, over the temperature range 4.2–300 K are reported. For [Zn/Cu(bipy)2(NO2)]NO3 a spectrum characteristic of a tetragonally elongated octahedral complex with a slight orthorhombic distortion is observed below ∼50 K, but above this temperature the signals associated with the two higherg-values gradually converge. At low temperature a spectrum similar to that of the bipy complex is observed for [Zn/Cu(bipyam)2(NO2)]NO3, but between 40 and 60 K the spectrum gradually changes to one characteristic of a tetragonalg-tensor with g∥ < g⊥. The spectra may be interpreted satisfactorily with a model in which the temperature dependence of theg-vainlues is estimated from the vibronic wavefunctions of a copper(II) complex under the influence of second-order Jahn-Teller coupling and a ligand field of tetragonal symmetry perturbed by crystal lattice forces. The results are consistent with the crystal structures reported for the compounds at various temperatures.

Bonding effects and the crystal structures of (NH4)2[Cu(H2O)6](SO4)2 and its H218O substituted form at 9.5 K

The crystal structures of the Tutton salts (NH4)2[Cu(H2O)6](SO4)2, diammonium hexaaquacopper disulfate, formed with normal water and isotopically substituted H2(18)O, have been determined by X-ray diffraction at 9.5 K and are very similar, with Cu-O(7) the longest of the Cu-O bonds of the Jahn-Teller distorted octahedral [Cu(H2O)6]2+ complex. It is known that structural differences accompany deuteration of (NH4)2[Cu(H2O)6](SO4)2, the most dramatic of which is a switch to Cu-O(8) as the longest such bond. The present result suggests that the structural differences are associated with hydrogen-bonding effects rather than with increased mass of the water ligands affecting the Jahn-Teller coupling. The Jahn-Teller distortions and hydrogen-bonding contacts in the compounds are compared with those reported for other Tutton salts at ambient and high pressure.

The crystal structure and electronic properties of the complexes acetatobis(1,10-phenanthroline)copper(II) perchlorate dihydrate, acetatobis(1,10-phenanthroline)copper(II) nitrate dihydrate, and acetatobis(1,10-phenanthroline)zinc(II) tetrafluoroborate dihydrate

The crystal structure of [Cu(phen)2(O2CMe)][ClO4]·2H2O (1), [Cu(phen)2(O2CMe)][NO3]·2H2O (2), and [Zn(phen)2(O2(CMe)][BF4]·2H2O (3) have been determined by X-ray analysis. Complex (1) crystallises in the monoclinic space group P2/c with a= 9.671(3), b= 8.282(3), c= 17.595(4)A, β= 109.63(2)°, and Z= 2; (2) crystallises in the triclinic space group P with a= 14.728(2), b= 10.499(2), c= 8.603(2)A, α= 104.19(5), β= 83.97(5), γ= 96.81(5)°, and Z= 2;(3) crystallises in the monoclinic space group P2/c with a= 9.659(2), b= 8.262(2), c= 17.651(2)A, β= 109.06(5)°, and Z= 2. The MN4O2 chromophore in all three complexes has a cis-octahedral stereochemistry. In (1) and (3) the metal atoms have C2 symmetry and in (1) there is a marked cis distortion of the Cu–O distances. In (2) a distortion of the CuN4O2 chromophore towards a square pyramidal (4 + 1 + 1*) stereochemistry is present. The polycrystalline e.s.r. spectra of (1) and (2) and of 10% copper(II)-doped (3) are temperature variable, consistent with a fluxional CuN4O2 chromophore stereochemistry. The temperature variability of the single-crystal e.s.r. spectra of (1), (2), and copper(II)-doped (3) is restricted to the CuN2O2 plane, consistent with two-dimensional fluxional behaviour. The electronic reflectance spectra of (1) and (2) involve two peaks at ca. 10 000 and ca. 14 000 cm–1 and relate to the underlying static CuN4O2(4 + 1 + 1*) chromophore stereochemistry.

Influence of lattice interactions on the Jahn-Teller distortion of the [Cu(H2O)6]2+ ion: dependence of the crystal structure of K2xRb2-2x[Cu(H2O)6](SeO4)2 upon the K/Rb ratio

The temperature dependence of the structures of a wide range of mixed-cation Tuttons salts of general formula K2(x)Rb(2-2x)[Cu(H2O)6](SeO4)2 has been determined over the temperature range 90 to 320 K. Crystals with a high proportion of potassium adopt a different structure (form B) from those with a low ratio (form A). In both forms, the [Cu(H2O)6](2+) ion has an orthorhombically distorted tetragonally elongated coordination geometry, but the long and intermediate bonds occur with a different pair of water molecules in form A compared with form B. The alkali metal is surrounded by seven close oxygen atoms in form B but eight oxygen atoms in form A, and this difference in coordination number is associated with the change in the Cu-O bond distances via the hydrogen-bonding network. For crystals with between 32 and ∼41% potassium, a relatively sharp change from form B to A occurs on cooling, and the temperature at which this occurs increases approximately linearly as the proportion of potassium falls. For the whole range of mixed crystals, the bond lengths have been determined as a function of temperature. The data have been interpreted as a thermal equilibrium of the two structural forms of the [Cu(H2O)6](2+) ion that develops gradually as the temperature increases, with this becoming more pronounced as the proportions of the two cations become more similar. The temperature dependence of the bond lengths in this thermal equilibrium has been analyzed using a model in which the Jahn-Teller potential surface of the [Cu(H2O)6](2+) ion is perturbed by lattice strain interactions. The magnitude and sign of the orthorhombic component of this strain interaction depends upon the proportion of potassium to rubidium ions in the structure.