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.

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.

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.

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.

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.

"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.

Water-Soluble Derivatives of Octanuclear Iron-Oxo-Pyrazolato Complexes; An Experimental and Computational Study.

Two water-soluble iron-pyrazolato complexes, [Fe8], have been prepared by the introduction of twelve hydroxyalkyl groups to the periphery of the approximately spherical octanuclear molecule and they are contrasted with their two organosoluble chloroalkyl analogues. All four new complexes, 1 - 4, have been characterized in solution by 1H-NMR and electrospray ionization mass spectroscopy. The one-electron reduction product of the water-soluble 3, [Fe8]-, has been structurally characterized by single crystal diffraction methods. In aqueous media, the four terminal Fe-Cl bonds of [Fe8] are partially hydrolysed and the resulting chloro/aqua/hydroxo species form supramolecular nanoscale aggregates, as determined by dynamic light scattering and electron microscopy. Preliminary computational studies by density functional theory methods have been employed in order to model the H-bonding interactions controlling the competing solvation and aggregation processes.

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.

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.

Experimental and theoretical Mössbauer study of an extended family of [Fe8(µ4-O)4(µ-4-R-px)12X4] clusters.

Six [Fe(8)(µ(4)-O)(4)(µ-4-R-pyrazolato)(12)X(4)] complexes containing an identical Fe(8)(µ(4)-O)(4) core have been structurally characterized and studied by Mössbauer spectroscopy. In each case, an inner µ(4)-O bridged Fe(III) cubane core is surrounded by four trigonal bipyramidal iron centers, the two distinct sites occurring in a 1:1 ratio. The Mössbauer spectrum of each of the clusters consists of two quadrupole doublets, which, with one exception (X = NCS, R = H), overlap to give three absorption lines. The systematic variation of X and R causes significant changes in the Mössbauer spectra. A comparison with values for the same clusters computed using density functional theory allows us to establish an unequivocal assignment of these peaks in terms of a nested model for the overlapping doublets. The changes in Mössbauer parameters (both experimental and computed) for the 1-electron reduced species [Fe(8)(µ(4)-O)(4)(µ-4-Cl-pyrazolato)(12)Cl(4)](-) are consistent with a redox event that is localized within the cubane core.

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.

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.

Mechanistic and energetic aspects of the thermal and photochemical redox chemistry of the octanuclear cubane complexes, Fe(III)(8)(mu(4)-O(4))(mu-pyrazolate)(12)X(4) (X = Cl or Br).

The mechanisms of the thermal and photochemical redox reactions of clusters [Fe(III)(8)(mu(4)-O(4))(mu-Pz)(12)X(4)] (Pz = pyrazolate anion, X = Cl or Br) were investigated in this work. Reactions of the complexes with e(-)(sol), C(*)H(2)OH, and several powerful reducing transition metal complexes were investigated using the pulse radiolysis technique. Reaction rates of the outer-sphere electron transfer reactions with transition metal complexes had to be rationalized by invoking the formation of a [Fe(III)(7)Fe(II) '(mu(4)-O(4))(mu-Pz)(12)X(4)](-) intermediate or excited state. A transient species observed in the reaction of the e(-)(sol) with the cubanes can be either an excited state or a reaction intermediate mediating the formation of the stable product, [Fe(III)(7)Fe(II)(mu(4)-O(4))(mu-Pz)(12)X(4)](-). Photoredox reactions, characteristic of the ligand X(-) to Fe(III) charge transfer excited sates, were observed in the 350 nm steady state and 351 nm laser flash irradiations of the cubanes. Quantum yields are limited by the rapid recombination of the photofragments. The charge transfer spectroscopy of the products was rationalized on the basis of parameters derived from the thermal electron transfer reactions.

Dolabellane-type diterpenoids with antiprotozoan activity from a southwestern Caribbean gorgonian octocoral of the genus Eunicea.

Ten new diterpenes, 1-10, having a dolabellane skeleton were isolated from a Colombian gorgonian coral of the genus Eunicea. Their structures, as well as those of known compounds 11-18, were determined on the basis of spectroscopic analysis and, in some instances, by chemical conversion and X-ray crystallographic analysis. The absolute structure of 7 was established by chemical conversion from 11, a co-occurring dolabellane congener of known absolute structure. Most of these diterpenoids showed antimalarial activity against the protozoan parasite Plasmodium falciparum.

Current and future applications of magnetic resonance imaging (MRI) to breast and ovarian cancer patient management.

Magnetic resonance imaging (MRI) is occupying an increasing niche in the clinical diagnostic workup of several cancers, including breast cancers. Despite the high level of implementation of mammography, it has become apparent that MRI can play at least a complementary role in the imaging and diagnosis of primary breast cancers, including ductal carcinoma in situ, the earliest stage of breast cancer that is associated with an increased risk of invasive breast cancer. This can also be said of inflammatory breast cancer, of low incidence but with high impact on overall breast cancer mortality rates, and for which mammography is not ideal due to the typically diffused nature of this disease. Much of the value of breast MRI is dependent on its high sensitivity, resulting from the use of contrast agent enhancement in the detection of breast cancer. Interest has also increased in the application of diffusion-weighted MRI for early assessment of treatment response in this disease. Regarding ovarian and other gynecological cancers, MRI has already demonstrated value in the evaluation of patients with ovarian masses, uterine leiomyoma, endometrioma, and cervical cancer. Features on MRI suggestive of malignant ovarian tumors are varied, and span irregular or solid components to a cystic mass, prominent septations, evidence of peritoneal, hematogenous, or lymphatic spread, or local invasion. The majority of ovarian malignancies are diagnosed in advanced, incurable stages, where exploratory laparotomy provides the opportunity for maximal debulking. Although a role for MRI has yet to be established in this initial setting or in staging, some studies have shown that high sensitivity may be achieved with contrast agent-enhanced MRI for detection of recurrent disease, including demonstration of macroscopic intraabdominal dissemination and the hallmark omental "cake". Efforts in recent years have been focused on design of MRI contrast agents (MRI-CAs), which either target biomarkers, or take advantage of the different physiology of cancerous cells. MRI-CAs based on gadolinium complexes, ferrumoxides, or other metallic nanoparticles have been investigated. This review will focus on the recent progress in the application of MRI to the imaging of breast and ovarian cancers, and present a possible role for molecularly-targeted contrast agents in enriching the context for MRI-based diagnosis.

Metal tetraphosphonate "wires" and their corrosion inhibiting passive films.

Herein, we describe the preparation and characterization of five new divalent metal tetraphosphonates, M-HDTMP [M = Mg(2+), Ca(2+), Sr(2+), Ba(2+), and Cu(2+); HDTMP = hexamethylenediaminetetrakis(methylenephosphonate) dianion]. Materials {Sr[(HDTMP)(H(2)O)(6)] x 2 H(2)O}(n) (1), {Ba[(HDTMP)(H(2)O)(6)] x 2 H(2)O}(n) (2), and {Cu[(HDTMP)(H(2)O)(4)] x 6 H(2)O}(n) (3), as well as (en)(HDTMP) x 2 H(2)O (en = ethylenediammonium cation) have been structurally characterized. Structures depend on the coordination requirements of the M(2+) center and waters of crystallization content. The formation and characterization of effective anticorrosion passive films of M-HDTMP (M = Sr(2+) and Ba(2+)) are also reported.

Euryjanicin A: a new cycloheptapeptide from the Caribbean marine sponge Prosuberites laughlini.

A new proline-containing cycloheptapeptide, euryjanicin A (1), has been isolated from the marine sponge Prosuberites laughlini indigenous to Puerto Rico, and its structure established by an X-ray crystal structure determination. The absolute configuration of each amino acid residue was determined by Marfey's method.

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.