"Antibacterial properties of nine indium(III) complexes of substituted pyrazoles/pyrazolate and the structural and solution characterization of the mer- and trans­indium(III) complexes of 4-Me-pzH".

Two indium(III) complexes of formula mer-[InIIICl3(4-Me-pzH)3] and trans-[InIIICl2(4-Me-pzH)4]Cl·(4-Me-pzH)2·(H2O) were isolated from the same reaction mixture and crystallographically characterized. The two complexes exist in dynamic equilibrium and their dynamic behavior was probed by variable temperature 1H NMR spectroscopy in the 202 to 296 K range. Powder X-ray diffraction of the batch confirmed existence of both complexes in a 1:2 ratio. Antibacterial properties of both new complexes, in addition to seven other previously published indium(III) complexes, were investigated against three Gram-positive and four Gram-negative pathogenic bacterial strains. The results showed potential for the development of indium(III)-based antipseudomonal and antituberculosis drugs, with mer-[InCl3(4-Ph-pzH)3] being especially effective.

Mononuclear, hexanuclear and polymeric indium(III) pyrazolido complexes; structural characterization, dynamic solution studies and luminescent properties.

A new family of six mononuclear indium(III) complexes of formula mer-[InIIICl3(pz*H)3]-pz*H = pyrazole (pzH), or substituted pyrazoles: 4-Cl-pzH, 4-Br-pzH, 4-I-pzH, 4-Ph-pzH and 3,5-Me2-pzH-were synthesized by addition reactions of InCl3 and pz*H and crystallographically characterized. The fluxional behaviour of the complexes, probed by variable temperature 1H NMR spectroscopy in the 328 K to 173 K range, was attributed to (at least) four simultaneous processes: pyrazole N-H proton dissociation/association, cis/trans-pyrazole exchange, and N1/N2 tautomerization of the cis- and of the trans-pyrazoles. Three novel trianionic hexanuclear complexes of general formula (pipH)3[In6Cl6(µ3-OH0.5)2(µ-OH)6(µ-pz*)6]-pz* = pz, 4-Cl-pz and 4-Ph-pz-showing µ-hydroxo and µ-oxo bridges were synthesized from the corresponding mer-[InIIICl3(pz*H)3] and characterized by single crystal X-ray diffraction and 1H NMR. Under different solvent conditions, multicolour emitting polymeric complexes of general formula [In(µ-pz*)3]n-pz* = pz, 4-Cl-pz, 4-I-pz and 4-Ph-pz-were obtained also from mer-[InIIICl3(pz*H)3] after addition of a base. Luminescence and lifetime calculations were performed for all polymers formed.

Crystal Structure Determination and Hirshfeld Analysis of a New Alternariol Packing Polymorph.

A new polymorph of the mycotoxin alternariol is reported and characterized by single crystal X-ray diffraction. Structural data, Hirshfeld surface analysis, and 2D fingerprint plots are used to compare differences in the intermolecular interactions of the orthorhombic Pca21 Form I (previously reported) and the monoclinic P21/c Form II (herein reported). The polymorphs have small differences in planarity-7.55° and 2.19° between the terminal rings for Form I and Form II, respectively-that brings about significant differences in the crystal packing and O-H … H interactions.

Low-temperature crystal structure of 4-chloro-1H-pyrazole.

The structure of 4-chloro-1H-pyrazole, C3H3ClN2, at 170 K has ortho-rhom-bic (Pnma) symmetry and is isostructural to its bromo analogue. Data were collected at low temperature since 4-chloro-1H-pyrazole sublimes when subjected to the localized heat produced by X-rays. The structure displays inter-molecular N-H⋯N hydrogen bonding and the packing features a trimeric mol-ecular assembly bis-ected by a mirror plane (m normal to b) running through one chlorine atom, one carbon atom and one N-N bond. The asymmetric unit therefore consists of one and one-half 4-chloro-1H-pyrazole mol-ecules. Thus, the N-H proton is crystallographically disordered over two positions of 50% occupancy each.

Observation and deconvolution of a unique EPR signal from two cocrystallized spin triangles.

A 16-line pattern has been theoretically predicted, but hitherto not reported, for the Electron Paramagnetic Resonance (EPR) spectrum of antiferromagnetically coupled CuII triangles experiencing isotropic exchange of isosceles magnetic symmetry. Now, the crystallization of such a triangular species and its X-ray structure determination in a polar space group, R3 (No. 146), has enabled its single crystal EPR study. Its detailed magnetic susceptibility, and X- and Q-band, powder and single crystal EPR spectroscopic study reveals the effect of molecular structure and of Dzyaloshinskii-Moriya interactions (DMI) on the g‖, g⊥ and A‖ parameters of the spectrum; DMI is considered for the first time in such a context. Moreover, careful analysis of the spectrum allows the deconvolution of two slightly different cocrystallized magnetic species.

A novel fungal metabolite inhibits Plasmodium falciparum transmission and infection.

BACKGROUND: Malaria transmission depends on infected mosquitoes and can be controlled by transmission-blocking drugs. The recently discovered FREP1-mediated malaria transmission pathway is an excellent target to screen drugs for limiting transmission. METHODS: To identify candidate small molecules, we used an ELISA-based approach to analyze extracts from a fungal library for inhibition of the FREP1-parasite interaction. We isolated and determined one active compound by chromatography and crystallography, respectively. We measured the effects of the bioactive compound on malaria transmission to mosquitoes through standard membrane-feeding assays (SMFA) and on parasite proliferation in blood by culturing. RESULTS: We discovered the ethyl acetate extract of the fungus Purpureocillium lilacinum that inhibited Plasmodium falciparum transmission to mosquitoes. Pre-exposure to the extract rendered Anopheles gambiae resistant to Plasmodium infection. Furthermore, we isolated one novel active compound from the extract and identified it as 3-amino-7,9-dihydroxy-1-methyl-6H-benzo[c]chromen-6-one, or "pulixin." Pulixin prevented FREP1 from binding to P. falciparum-infected cell lysate. Pulixin blocked the transmission of the parasite to mosquitoes with an EC50 (the concentration that gave half-maximal response) of 11 µM based on SMFA. Notably, pulixin also inhibited the proliferation of asexual-stage P. falciparum with an EC50 of 47 nM. The compound did not show cytotoxic effects at a concentration of 116 µM or lower. CONCLUSION: By targeting the FREP1-Plasmodium interaction, we discovered that Purpureocillium lilacinum extract blocked malaria transmission. We isolated and identified the bioactive agent pulixin as a new compound capable of stopping malaria transmission to mosquitoes and inhibiting parasite proliferation in blood culture.

Origin of Ferromagnetism and Magnetic Anisotropy in a Family of Copper(II) Triangles.

Previously reported ferromagnetic triangles (NnBu4 )2 [Cu3 (µ3 -Cl)2 (µ-4-NO2 -pz)3 Cl3 ] (1), (PPN)2 [Cu3 (µ3 -Cl)2 (µ-pz)3 Cl3 ] (2), (bmim)2 [Cu3 (µ3 -Cl)2 (µ-pz)3 Cl3 ] (3) and newly reported (PPh4 )2 [Cu3 (µ3 -Cl)2 (µ-4-Ph-pz)3 Cl3 ] (4) were studied by magnetic susceptometry, electron paramagnetic resonance (EPR) spectroscopy and ab initio calculations to assess the origins of their ferromagnetism and of the magnetic anisotropy of their ground S=3/2 state (PPN+ =bis(triphenylphosphine)iminium, bmim+ =1-butyl-3-methylbenzimidazolium, pz- =pyrazolate). Ab initio studies revealed the d z 2 character of the magnetic orbitals of the compressed trigonal bipyramidal copper(II) ions. Ferromagnetic interactions were attributed to weak orbital overlap via the pyrazolate bridges. From the wavefunctions expansions, the ratios of the magnetic couplings were determined, which were indeterminate by magnetic susceptometry. Single-crystal EPR studies of 1 were carried out to extend the spin Hamiltonian with terms which induce zero-field splitting (zfs), namely dipolar interactions, anisotropic exchange and Dzyaloshinskii-Moriya interactions (DMI). The data were treated through both a giant-spin model and through a multispin exchange-coupled model. The latter indicated that ≈62 % of the zfs is due to anisotropic and ≈38 % due to dipolar interactions. The powder EPR data of all complexes were fitted to a simplified form of the multispin model and the anisotropic and dipolar contributions to the ground state zfs were estimated.

Coordination polymers of CdII and PbII with croconate show remarkable differences in coordination patterns: a structural and spectroscopic study.

The croconate dianion is a highly versatile ligand with two tautomeric forms making it useful for building large superstructures in the solid state. The single-crystal X-ray structures of PbII- and CdII-croconate coordination polymers, namely catena-poly[[[diaqualead(II)]-µ-croconato-κ4O1,O2:O3,O4] monohydrate], {[Pb(C5O5)(H2O)2]·H2O}n, 1, and catena-poly[[triaquacadmium(II)]-µ-croconato-κ4O1,O2:O3,O4], [Cd(C5O5)(H2O)3]n, 2, have been determined. Both polymers form one-dimensional (1D) structures; 1 is a nonplanar 1D zigzag coordination polymer extended along the crystallographic b axis, whereas 2 is a planar 1D ribbon parallel to the [101] direction. In 2, three H2O molecules are coordinated directly to the metal atom, while in 1, only two H2O molecules are directly coordinated to the metal atom. A third interstitial H2O molecule is involved in hydrogen bonding with O atoms of the croconate ligands of an adjacent layer and other H2O molecules, resulting in stacked double layers parallel to the [105] plane. Solid-state FT-IR and solution UV-Vis spectra also substantiate the croconate coordination.

Nitrite Reduction by Trinuclear Copper Pyrazolate Complexes: An Example of a Catalytic, Synthetic Polynuclear NO Releasing System.

Two trinuclear CuII pyrazolato complexes with a Cu3(µ3-E)-core (E = O2- or OH-) and terminal nitrite ligands in two coordination modes were characterized crystallographically, spectroscopically, and electrochemically. One-electron oxidation of the µ3-O species produces a delocalized, mixed-valent, formally CuII2CuIII-nitrite, but no nitrate. In contrast, under reducing conditions-addition of PhSH as an electron and proton donor-both complexes mediate the reduction of nitrite, releasing NO.

Spontaneous Resolution by Crystallization of an Octanuclear Iron(III) Complex Using Only Racemic Reagents.

The P and M enantiomers of the octanuclear [Fe8 (µ4 -O)4 (µ-4-Cl-pz)12 Cl4 ] complex, having T symmetry, were resolved by temporary substitution of chloride ligands by racemic 4-s Bu-phenolates and subsequent crystallization, where the (S)- and (R)-phenolates coordinate selectively to the M and P complexes, respectively. The complexes were characterized by circular dichroism analysis and X-ray structure determination. This work constitutes a rare example of enantiomeric recognition resulting in spontaneous resolution upon crystallization.

Interactions between H-bonded [Cu(µ3-OH)] triangles; a combined magnetic susceptibility and EPR study.

The X-ray crystal structure of the CuII complex [Cu3(µ3-OH)(µ-pz)3(PhCOO)3]- (pz- = pyrazolato anion) shows an isosceles triangular core, further forming a hexanuclear H-bonded aggregate. Cleavage of the H-bonds in solution results in isolated trinuclear species. Analysis of variable temperature magnetic susceptibility data of a powder sample shows an antiferromagnetically-coupled Cu3-core with a doublet ground state and isotropic exchange parameters (Jave = -355 cm-1, Hiso = -JijSiSj). The fitting of magnetic data requires the inclusion of antisymmetric exchange, AE (HAE = Gij·Si × Sj) with Gz = 31.2 cm-1 and no detectable inter-Cu3 isotropic exchange. X-band EPR spectroscopy in a frozen tetrahydrofuran solution of the compound indicates isolated Cu3-species with g‖,eff = 2.25, g⊥,eff = 1.67. The small value of g⊥,eff (≪2.0) is consistent with the presence of AE in agreement with the analysis of the magnetic measurements. The parallel component exhibits a hyperfine pattern corresponding to one I = 3/2 nucleus with A‖ = 425 MHz. This implies a specific exchange coupling scheme obeying the order |J12| = |J13| < |J23| consistent with the crystallographically determined two long and one short CuCu distances. The role of AE in modulating the hyperfine parameters in antiferromagnetic Cu3 clusters is studied. EPR spectra at X- and Q-band were performed with powder samples of the cluster at liquid helium temperatures. The spectra in both bands are consistent with two interacting Sa,b = 1/2 species in the point dipolar approximation. Fitting of the spectra reveals that each spin is characterized by g‖ = 2.24, g⊥ = 1.65 which is in agreement with an isolated Cu3 cluster in the ground state. The determined inter-spin distance of 4.4-4.5 Å is very close to the distance between the Cu(1) and Cu(1)' sites of the two trimeric units as imposed crystallographically (4.3 Å). This constitutes further verification of the specific exchange coupling scheme within each trimer. Magnetostructural correlations previously adopted for antiferromagnetically coupled Cu3 clusters are discussed in the light of the combined magnetic measurements and EPR spectroscopy.

Magnetic resonance imaging contrast enhancement in vitro and in vivo by octanuclear iron-oxo cluster-based agents.

A water-soluble octanuclear cluster, [Fe8], was studied with regard to its properties as a potential contrast enhancing agent in magnetic resonance imaging (MRI) in magnetic fields of 1.3, 7.2 and 11.9 T and was shown to have transverse relaxivities r2 = 4.01, 10.09 and 15.83 mM s-1, respectively. A related hydrophobic [Fe8] cluster conjugated with 5 kDa hyaluronic acid (HA) was characterized by 57Fe-Mössbauer and MALDI-TOF mass spectroscopy, and was evaluated in aqueous solutions in vitro with regard to its contrast enhancing properties [r2 = 3.65 mM s-1 (1.3 T), 26.20 mM s-1 (7.2 T) and 52.18 mM s-1 (11.9 T)], its in vitro cellular cytotoxicity towards A-549 cells and COS-7 cells and its in vivo enhancement of T2-weighted images (4.7 T) of a human breast cancer xenografted on a nude mouse. The physiologically compatible [Fe8]-HA conjugate was i.v. injected to the tumor-bearing mouse, resulting in observable, heterogeneous signal change within the tumor, evident 15 min after injection and persisting for approximately 30 min. Both molecular [Fe8] and its HA-conjugate show a strong magnetic field dependence on r2, rendering them promising platforms for the further development of T2 MRI contrast agents in high and ultrahigh magnetic fields.

Crystal structure and conformational analysis of doxorubicin nitrate.

Crystal structure determination of doxorubicin nitrate, (DoxH)NO3, systematic name (7S,9S)-7-{[(2R,4S,5S,6S)-4-azaniumyl-5-hy-droxy-6-methyl-oxan-2-yl]-oxy}-6,9,11-trihy-droxy-9-(2-hy-droxy-acet-yl)-4-meth-oxy-8,10-di-hydro-7H-tetra-cen-5,12-dione nitrate, shows two formula units present in the asymmetric unit. In the crystal lattice, hydrogen-bonded pairs of (DoxH+) cations and segregation of the aglycone and sugar moieties are observed. Inspection of mol-ecular overlays reveals that the conformation of (DoxH)NO3 resembles that of DNA-inter-calated, but not of protein-docked (DoxH)+. The structure was refined as a two-component twin.

Towards ionic liquids with tailored magnetic properties: bmim+ salts of ferro- and antiferromagnetic Cu triangles.

Complexes (bmim)2[Cu3(µ3-Cl)2(µ-pz)3Cl3] (1), (bmim)[Cu3(µ3-OH)(µ-pz)3Cl3] (2) and (bmim)2[Cu3(µ3-OH)(µ-Cl)(µ-pz)3Cl3] (3) were synthesized (bmim+ = 1-butyl-3-methylimidazolium, pz- = pyrazolato anion). Dianionic complexes 1 and 3 were obtained as crystalline solids, whereas the monoanionic complex 2 was obtained as a viscous paste. Magnetic susceptibility and X-band EPR studies revealed intramolecular ferromagnetic interactions for 1 with small magnetoanisotropy in its ground state (D3/2∼ 10-3 cm-1) and intramolecular antiferromagnetic interactions for 2 and 3 (-285 and -98 cm-1 average J, respectively) with important magnetic anisotropy in their ground states stemming from a combination of low magnetic symmetry and antisymmetric exchange interactions. Thermal studies revealed a clear melting point of 140 °C for 1, which is lower than that of its PPN+ and Bu4N+ analogues (1PPN and 1Bu4N, respectively, PPN+ = bis(triphenylphosphine)iminium). Upon cooling, 1 remains molten down to 70 °C. Mixtures of the salts 1, 1PPN and 1Bu4N, exhibited modified melting behaviours, with the mixtures exhibiting lower melting points than those of either of their pure components.

Crystal structure of µ6-chlorido-nona-kis-(µ-4-chloro-pyrazolato)bis-µ3-methoxo-hexa-copper(II).

The hexa-nuclear title compound, [{Cu3(µ3-OCH3)(µ-C3H2ClN2)3}2(µ-C3H2ClN2)3(µ6-Cl)] or [Cu6(C3H2ClN2)9(CH3O)2Cl], crystallizes in the space group Pbcn, with individual mol-ecules being located on a twofold rotation axis. The mol-ecule adopts a trigonal prismatic shape, with two trinuclear units linked by three 4-chloro-pyrazolate ligand bridges by encapsulating a Cl- anion in a µ6-coordination mode. In the crystal, individual mol-ecules are stacked into rods parallel to [1-10] that are arranged in a pseudo-hexa-gonal packing. Cohesion between mol-ecules is accomplished through weak C-H⋯Cl inter-actions.

A Redox-Induced Spin-State Cascade in a Mixed-Valent Fe3 (µ3 -O) Triangle.

One-electron reduction of a pyrazolate-bridged triangular Fe3 (µ3 -O) core induces a cascade wherein all three metal centers switch from high-spin Fe3+ to low-spin Fe2.66+ . This hypothesis is supported by spectroscopic data (1 H-NMR, UV-vis-NIR, infra-red, 57 Fe-Mössbauer, EPR), X-ray crystallographic characterization of the cluster in both oxidation states and also density functional theory. The reduction induces substantial contraction in all bond lengths around the metal centers, along with diagnostic shifts in the spectroscopic parameters. This is, to the best of our knowledge, the first example of a one-electron redox event causing concerted change in multiple iron centers.

A [Cu3(µ3-O)]-pyrazolate metallacycle with terminal nitrate ligands exhibiting point group symmetry 3.

The trinuclear triangular cuprate anion of the title compound, tris-[bis-(tri-phenyl-phospho-ranyl-idene)ammonium] tris-(µ2-4-chloro-pyrazolato-κ(2) N:N')-µ3-oxido-tris-[(nitrato-κ(2) O,O')cuprate(II)] nitrate monohydrate, (C36H30P2N)[Cu3(C3H2ClN2)3(NO3)3O]NO3·H2O, has point group symmetry 3., with the µ3-O atom located on the threefold rotation axis. The distorted square-pyramidal coordination sphere of the Cu(II) atom is completed by two N atoms of trans-bridging pyrazolate groups and a chelating nitrate anion. The complex anion is slightly bent, with the nitrate and pyrazolate groups occupying positions above and below the Cu3 plane, respectively. In the crystal, weak O-H⋯O and C-H⋯O hydrogen bonds, as well as π-π inter-actions, are present.

Uracil Nucleosides with Reactive Group at C5 Position: 5-(1-Halo-2-sulfonylvinyl)uridine Analogues.

The transition-metal-catalyzed or radical-mediated halosulfonylation of 5-ethynyluridine provided (E)-(1-halo-2-tosylvinyl)uridines. These (ß-halo)vinyl sulfones undergo efficient stereoselective addition-elimination with amines or thiols to provide Z-ß-aminovinyl or E-ß-thiovinyl sulfones tethered to the C5 position of the uracil ring.

Synthesis of 8-(1,2,3-triazol-1-yl)-7-deazapurine nucleosides by azide-alkyne click reactions and direct C-H bond functionalization.

Treatment of toyocamycin or sangivamycin with 1,3-dibromo-5,5-dimethylhydantoin in MeOH (r.t./30 min) gave 8-bromotoyocamycin and 8-bromosangivamycin in good yields. Nucleophilic aromatic substitution of 8-bromotoyocamycin with sodium azide provided novel 8-azidotoyocamycin. Strain promoted click reactions of the latter with cyclooctynes resulted in the formation of the 1,2,3-triazole products. Iodine-mediated direct C8-H bond functionalization of tubercidin with benzotriazoles in the presence of tert-butyl hydroperoxide gave the corresponding 8-benzotriazolyltubercidin derivatives. The 8-(1,2,3-triazol-1-yl)-7-deazapurine derivatives showed moderate quantum yields and a large Stokes shifts of ~ 100 nm.

A trigonal prismatic Cu6-pyrazolato complex containing a µ6-F ligand.

The encapsulation of a fluoride ion in a trigonal prismatic CuII6-pyrazolato cage results in a small expansion of the Cu6-host. The structural, electronic and magnetic features of the Cu6-complex, containing an endohedral fluoride in the rare µ6-F coordination mode, are compared with those of the parent complex with a vacant Cu6-cage.