Spectral and structural studies of a new oxalato-bridged dinuclear copper(II) complex having two 3-(thiophen-2-yl)-1,10-phenanthroline ligands in a trans configuration

In this paper, spectral and structural characterizations of a new dinuclear copper(II) complex (1), formulated as [Cu₂(3-(thiophen-2-yl)-1,10-phenanthroline)₂(μ-oxalate)(DMF)₂](ClO₄)₂ (DMF = N,N′-dimethylformamide), have been described. Two five-coordinate copper(II) centers are bridged by a four-dentate oxalate dianion forming a planar molecular geometry with the Cu-Cu separation of 5.117(4) Å. The two ligands in 1 adopt a trans configuration to each other and two monodentate DMF molecules are positioned at each side of the molecular plane. In addition, typical π-π stacking interactions are found between adjacent phenanthroline and thiophene rings forming a layered packing structure. A compressed pyramidal configurational alteration is observed for each copper(II) center when the temperature is decreased from 291(2) to 100(2) K.     

Synthesis and in vitro screening of novel N-benzyl aplysinopsin analogs as potential anticancer agents

A series of novel substituted (Z)-5-((1-benzyl-1H-indol-3-yl)methylene)imidazolidin-2,4-diones (3a-f) and (Z)-5-((1-benzyl-1H-indol-3-yl)methylene)-2-iminothiazolidin-4-ones (3g-o) have been synthesized utilizing microwave irradiation. These analogs were evaluated for in vitro cytotoxicity against a panel of 60 human tumor cell lines. Compound 3i exhibits potent growth inhibition against melanoma UACC-257 (GI₅₀ = 13.3 nM) and OVCAR-8 ovarian (GI₅₀ = 19.5 nM) cancer cells while possessing significant cytotoxicity (LC₅₀ = 308 nM and LC₅₀ = 851 nM, respectively) against the same cell lines within this series of compounds. A second analog, 3a, had GI₅₀ values of 307 and 557 nM against SK-MEL-2 melanoma and A498 renal cancer cell lines, and exhibited GI₅₀ values ranging from 0.30 to 6 μM against 98% of all cancer cell lines in the 60-cell panel. Thus, (Z)-5-((5-chloro-1-(4-fluorobenzyl)-1H-indol-3-yl)methylene)-2-iminothiazolidin-4-one (3i) and (Z)-methyl 1-(4-cyanobenzyl)-3-((2,5-dioxoimidazolidin-4-ylidene)methyl)-1H-indole-6-carboxylate (3a) can be regarded as useful lead compounds for further structural optimization as antitumor agents.     

Synthesis and characterization of the novel extended TTF-type donors with thiophenic units

Two new TTF-based donors that are dithiolene ligand precursors, 3-{5-[(2-cyanoethyl)thio]-2-(5,6-dihydrothieno[2,3-d][1,3]dithiol-2-ylidene-1,3-dithiol-4-yl)thio}propanenitrile, dtdt (1) and 3-({5-[(2-cyanoethyl)thio]-2-thieno[2,3-d][1,3]dithiol-2-ylidene-1,3-dithiol-4-yl)thio}propanenitrile, α-tdt (2), were synthesized and characterized. The electrochemical properties of these compounds were studied by cyclic voltammetry (CV) in acetonitrile. Compound 1 shows two reversible oxidation process at ¹E_1/2 = 0.639 V and ²E_1/2 = 0.997 V versus Ag/AgCl. This same processes occurs at ¹E_1/2 = 0.612 V and ²E_1/2 = 0.906 V in the case of 2. The crystal structures confirm the ability of these molecules to establish interactions with their neighbours through the peripheral sulfur atoms.     

Gastrophysa polygoni herbivory on Rumex confertus: single leaf VOC induction and dose dependent herbivore attraction/repellence to individual compounds

We report large induction (>65_fold increases) of volatile organic compounds (VOCs) emitted from a single leaf of the invasive weed mossy sorrel, Rumex confertus Willd. (Polygonaceae), by herbivory of the dock leaf beetle, Gastrophysa polygoni L. (Coleoptera: Chrysomelidae). The R. confertus VOC blend induced by G. polygoni herbivory included two green leaf volatiles ((Z)-3-hexenal, (Z)-3-hexen-1-yl acetate) and three terpenes (linalool, ß-caryophyllene, (E)-ß-farnesene). Uninjured leaves produced small constitutive amounts of the GLVs and barely detectable amounts of the terpenes. A Y-tube olfactometer bioassay revealed that both sexes of adult G. polygoni were attracted to (Z)-3-hexenal and (Z)-3-hexen-1-yl acetate at a concentration of 300 ng h⁻¹. No significant G. polygoni attraction or repellence was detected for any VOC at other concentrations (60 and 1500 ng h⁻¹). Yet, G. polygoni males and females were significantly repelled by (or avoided) at the highest test concentration (7500 ng h⁻¹) of both GLVs and (E)-ß-farnesene. Mated male and female G. polygoni might be attracted to injured R. confertus leaves, but might avoid R. confertus when VOC concentrations (especially the terpene (E)-ß-farnesene) suggest high overall plant injury from conspecifics, G. viridula, or high infestations of other herbivores that release (E)-ß-farnesene (e.g., aphids). Tests in the future will need to examine G. polygoni responses to VOCs emitted directly from uninjured (constitutive) and injured (induced) R. confertus, and examine whether R. confertus VOC induction concentrations increase with greater tissue removal on a single leaf and/or the number of leaves with feeding injury.     

Acylated triterpene saponins from the roots of Securidaca longepedunculata

Four triterpene saponins, 3-O-β-d-glucopyranosylpresenegenin 28-O-β-d-apiofuranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)-[β-d-apiofuranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-{4-O-[(E)-3,4,5-trimethoxycinnamoyl]}-β-d-fucopyranosyl ester, 3-O-β-d-glucopyranosylpresenegenin 28-O-β-d-apiofuranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)-[β-d-apiofuranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-[(6-O-acetyl)-β-d-glucopyranosyl-(1 → 3)]-{4-O-[(E)-3,4,5-trimethoxycinnamoyl]}-β-d-fucopyranosyl ester, 3-O-β-d-glucopyranosylpresenegenin 28-O-β-d-apiofuranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)-[β-d-apiofuranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-[β-d-galactopyranosyl-(1 → 3)]-{4-O-[(E)-3,4,5-trimethoxycinnamoyl]}-β-d-fucopyranosyl ester, and 3-O-β-d-glucopyranosylpresenegenin 28-O-β-d-apiofuranosyl-(1 → 3)-[α-l-arabinopyranosyl-(1 → 4)]-β-d-xylopyranosyl-(1 → 4)-[β-d-apiofuranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-{4-O-[(E)-3,4,5-trimethoxycinnamoyl]}-β-d-fucopyranosyl ester, were isolated from the roots of Securidaca longepedunculata, together with three known compounds. Their structures were established mainly by 2D NMR techniques and mass spectrometry.     

Spontaneous, intervesicular transfer rates of fluorescent, acyl chain-labeled phosphatidylcholine analogs

It was recently shown that the structure of the fluorophore attached to the acyl chain of phosphatidylcholine analogs determines their mechanism of transport across the plasma membrane of yeast cells (Elvington et al., J. Biol Chem. 280:40957, 2005). In order to gain further insight into the physical properties of these fluorescent phosphatidylcholine (PC) analogs, the rate and mechanism of their intervesicular transport was determined. The rate of spontaneous exchange was measured for PC analogs containing either NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl), Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene), Bodipy 530 (4,4-difluoro-5,7-diphenyl-4-bora-3a,4a-diaza-s-indacene), or Bodipy 581 (4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene) attached to a five or six carbon acyl chain in the sn-2 position. The rate of transfer between phospholipid vesicles was measured by monitoring the increase in fluorescence as the analogs transferred from donor vesicles containing self-quenching concentrations to unlabeled acceptor vesicles. Kinetic analysis indicated that the transfer of each analog occurred by diffusion through the water phase as opposed to transfer during vesicle collisions. The vesicle-to-monomer dissociation rate constants differed by over four orders of magnitude: NBD-PC (k_dis = 0.115 s^− 1; t_1/2 = 6.03 s); Bodipy FL-PC (k_dis = 5.2 × 10^− 4; t_1/2 = 22.2 min); Bodipy 530-PC (k_dis = 1.52 × 10^− 5; t_1/2 = 12.6 h); and Bodipy 581-PC (k_dis = 5.9 × 10^− 6; t_1/2 = 32.6 h). The large differences in spontaneous rates of transfer through the water measured for these four fluorescent PC analogs reflect their hydrophobicity and may account for their recognition by different mechanisms of transport across the plasma membrane of yeast.     

Antiparasitic activity of prenylated benzoic acid derivatives from Piper species

Fractionation of dichloromethane extracts from the leaves of Piper heterophyllum and P. aduncum afforded three prenylated hydroxybenzoic acids, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid, 3-[(2E,6E,10E)-11-carboxy-13-hydroxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl]-4,5-dihydroxybenzoic acid and 3-[(2E,6E,10E)-11-carboxy-14-hydroxy-3,7,15-trimethyl-2,6,10,15-hexadecatetraenyl]-4,5-dihydroxybenzoic acid, along with the known compounds, 4,5-dihydroxy-3-(E,E,E-11-formyl-3,7,15-trimethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid (arieianal), 3,4-dihydroxy-5-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 4-hydroxy-3-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid, 4-hydroxy-3-(3,7-dimethyl-2,6-octadienyl)benzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid. Their structures were elucidated on the basis of spectroscopic data, including homo- and heteronuclear correlation NMR experiments (COSY, HSQC and HMBC) and comparison with data reported in the literature. Riguera ester reactions and optical rotation measurements established the compounds as racemates. The antiparasitic activity of the compounds were tested against three strains of Leishmania spp., Trypanosoma cruzi and Plasmodium falciparum. The results showed that 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid exhibited potent and selective activity against L. braziliensis (IC₅₀ 6.5 μg/ml), higher that pentamidine used as control. Moreover, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl- 2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid showed moderate antiplasmodial (IC₅₀ 3.2 μg/ml) and trypanocidal (16.5 μg/ml) activities, respectively.     

Aryl methylene ketones and fluorinated methylene ketones as reversible inhibitors for severe acute respiratory syndrome (SARS) 3C-like proteinase

The severe acute respiratory syndrome (SARS) virus depends on a chymotrypsin-like cysteine proteinase (3CL^pro) to process the translated polyproteins to functional viral proteins. This enzyme is a target for the design of potential anti-SARS drugs. A series of ketones and corresponding mono- and di-fluoro ketones having two or three aromatic rings were synthesized as possible reversible inhibitors of SARS 3CL^pro. The design was based on previously established potent inhibition of the enzyme by oxa analogues (esters), which also act as substrates. Structure-activity relationships and modeling studies indicate that three aromatic rings, including a 5-bromopyridin-3-yl moiety, are key features for good inhibition of SARS 3CL^pro. Compound 11d, 2-(5-bromopyridin-3-yl)-1-(5-(4-chlorophenyl)furan-2-yl)ethanone and its α-monofluorinated analogue 12d, gave the best reversible inhibition with IC₅₀ values of 13 μM and 28 μM, respectively. In contrast to inhibitors having two aromatic rings, α-fluorination of compounds with three rings unexpectedly decreased the inhibitory activity.     

Counter-anions and their coordination behavior with Cu(II) complexes of thiophen-3-yl-dipicolylamine

A new ligand, 1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)-N-(thiophen-3-ylmethyl)methanamine, ThDPA, was synthesized, as a new example of an N₃S donor. Cu(II) complexes of this ligand were isolated. When Cu(NO₃)₂ was used as the metal source, a homobinuclear complex with the formula [CuThDPA(NO₃)₂]₂·H₂O, 1, with two different types of nitro coordination was isolated. 1 crystallizes in the monoclinic P2₁/n space group with a = 15.193, b = 8.181, c = 32.827 Å, β = 103.3° and V = 3971.9 Å³. In the case of CuSO₄ as the source of copper(II), uncommon sulfato-bridged structures were isolated. The homobinuclear complex crystallized in two different lattices, depending on the solvent evaporation rate. Compound 2, with the formula [CuThDPA(SO₄)]₂·3H₂O, crystallizes with 3 water molecules per binuclear structure in the monoclinic space group P2₁/c with a = 10.143, b = 17.013, c = 11.793 Å, β = 97.18° and V = 2019.1 Å³, and 3, [CuThDPA(SO₄)]₂·4H₂O, crystallizes with 4 water molecules per binuclear structure in the triclinic space group, with a = 9.2906, b = 10.7297, c = 12.7236 Å, α = 79.66, β = 72.18, γ = 67.1° and V = 1109.7 Å³.     

α-Rhamnosidase and β-glucosidase expressed by naringinase immobilized on new ionic liquid sol-gel matrices: Activity and stability studies

Novel ionic liquid (IL) sol-gel materials development, for enzyme immobilization, was the goal of this work. The deglycosylation of natural glycosides were performed with α-l-rhamnosidase and β-d-glucosidase activities expressed by naringinase. To attain that goal ILs with different structures were incorporated in TMOS/Glycerol sol-gel matrices and used on naringinase immobilization.The most striking feature of ILs incorporation on TMOS/Glycerol matrices was the positive impact on the enzyme activity and stability, which were evaluated in fifty consecutive runs. The efficiency of α-rhamnosidase expressed by naringinase TMOS/Glycerol@ILs matrices increased with cation hydrophobicity as follows: [OMIM] > [BMIM] > [EMIM] > [C₂OHMIM] > [BIM] and [OMIM] ≈ [E₂-MPy] ? [E₃-MPy]. Regarding the imidazolium family, the hydrophobic nature of the cation resulted in higher α-rhamnosidase efficiencies: [BMIM]BF₄ ? [C₂OHMIM]BF₄ ? [BIM]BF₄. Small differences in the IL cation structure resulted in important differences in the enzyme activity and stability, namely [E₃-MPy] and [E₂-MPy] allowed an impressive difference in the α-rhamnosidase activity and stability of almost 150%. The hydrophobic nature of the anion influenced positively α-rhamnosidase activity and stability. In the BMIM series the more hydrophobic anions (PF₆⁻, BF₄⁻ and Tf₂N⁻) led to higher activities than TFA. SEM analysis showed that the matrices are shaped lens with a film structure which varies within the lens, depending on the presence and the nature of the IL.The kinetics parameters, using naringin and prunin as substrates, were evaluated with free and naringinase encapsulated, respectively on TMOS/Glycerol@[OMIM][Tf₂N] and TMOS/Glycerol@[C₂OHMIM][PF₆] and on TMOS/Glycerol. An improved stability and efficiency of α-l-rhamnosidase and β-glucosidase expressed by encapsulated naringinase on TMOS/Glycerol@[OMIM][Tf₂N] and TMOS/Glycerol@[C₂OHMIM][PF₆] were achieved. In addition to these advantageous, with ILs as sol-gel templates, environmental friendly processes can be implemented.     

Tuning iridium(III) complexes containing 2-benzo[b]thiophen-2-yl-pyridine based ligands in the red region

Synthesis and characterization of four iridium(III) complexes containing 2-benzo[b]thiophen-2-yl-pyridine based ligands are reported. The absorption, emission, electrochemistry, and thermostability of the complexes were systematically investigated. The (btmp)₂Ir(acac) (btmp = 2-benzo[b]thiophen-2-yl-4-methyl-pyridyl, acac = acetyl acetone) was characterized using X-ray crystallography. Calculation on the electronic ground state for (btmp)₂Ir(acac) was carried out using B3LYP density functional theory, HOMO levels are a mixture of Ir and btmp ligand orbitals, while the LUMO is predominantly btmp ligand based. Introduction of substituents (CH₃, CF₃) into pyridyl ring in a typical red emitter (btp)₂Ir(acac) leads to a marked decrease in the sublimation temperature, which is more suitable for OLEDs process. Electrochemical studies showed that (btmp)₂Ir(acac) has a slightly lower oxidation potential, but (btfmp)₂Ir(acac), (btfmp)₂Ir(dbm), and (btfmp)₂Ir(pic) (btfmp = 2-benzo[b]thiophen-2-yl-5-trifluoromethyl-pyridine, dbm = dibenzoylmethane, pic = 2-picolinic acid) containing CF₃ group are much difficult to oxidate than (btp)₂Ir(acac). The emission characteristics of these complexes can be tuned by either changing the substituents and their position on 2-benzo[b]thiophen-2-yl-pyridine or using different monoanionic ligands, showing emission λ_max values from 604 to 638 nm in CH₂Cl₂ solution at room temperature.     

Antibacterial phenolic components from Eriocaulon buergerianum

Five phenolic components, 1,3,6-trihydroxy-2,5,7-trimethoxyxanthone (1), 7,3′-dihydroxy-5,4′,5′-trimethoxyisoflavone (2), toralactone-9-O-β-d-glucopyranoside (3), patuletin-3-O-[2-O-E-feruloyl-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside] (4), patuletin-3-O-[β-d-glucopyranosyl-(1 → 3)-2-O-E-caffeoyl-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside] (5), along with 19 known compounds were isolated from Eriocaulon buergerianum (Eriocaulaceae). Their structures were determined by spectroscopic and chemical methods. All 24 isolated compounds were tested against the pathogenic bacteria Staphylococcus aureus (ATCC 25923); as a result, 10 compounds were found to exhibit antibacterial activity with MICs ranging from 32 to 256 μg/ml.     

Green tea epigallocatechin-3-gallate inhibits microsomal prostaglandin E2 synthase-1

Prostaglandin (PG)E₂ is a critical lipid mediator connecting chronic inflammation to cancer. The anti-carcinogenic epigallocatechin-3-gallate (EGCG) from green tea (Camellia sinensis) suppresses cellular PGE₂ biosynthesis, but the underlying molecular mechanisms are unclear. Here, we investigated the interference of EGCG with enzymes involved in PGE₂ biosynthesis, namely cytosolic phospholipase (cPL)A₂, cyclooxygenase (COX)-1 and -2, and microsomal prostaglandin E₂ synthase-1 (mPGES-1). EGCG failed to significantly inhibit isolated COX-2 and cPLA₂ up to 30 μM and moderately blocked isolated COX-1 (IC₅₀ > 30 μM). However, EGCG efficiently inhibited the transformation of PGH₂ to PGE₂ catalyzed by mPGES-1 (IC₅₀ = 1.8 μM). In lipopolysaccharide-stimulated human whole blood, EGCG significantly inhibited PGE₂ generation, whereas the concomitant synthesis of other prostanoids (i.e., 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid and 6-keto PGF_1α) was not suppressed. Conclusively, mPGES-1 is a molecular target of EGCG, and inhibition of mPGES-1 is seemingly the predominant mechanism underlying suppression of cellular PGE₂ biosynthesis by EGCG.     

Carboxy-derived (tpy)2Ru complexes as sub-units in supramolecular architectures: The solubilized ligand 4′-(4-carboxyphenyl)-4,4″-di-(tert-butyl)tpy and its homoleptic Ru(II) complex

We herein describe the synthesis and characterization of a series of homoleptic, Ru(II) complexes bearing peripheral carboxylic acid functionality based upon the novel ligand 4′-(4-carboxyphenyl)-4,4″-di-(tert-butyl)tpy (L₁), as well as 4′-(4-carboxyphenyl)tpy (L₂) and 4′-(carboxy)tpy (L₃) (where tpy = 2,2′: 6′,2″-terpyridine). Inspection of the metal-based oxidations (E_1/2 = 1.22-1.42 V) indicates an anodic shift (∼0.2 V) for (L₃)₂Ru²⁺ (3b) (E_1/2 = 1.40 V) relative to (L₂)₂Ru²⁺ (2b) (E_1/2 = 1.22 V). The metal-based oxidation (E_1/2 = 1.22 V) and ligand-based reductions (E_1/2 = −1.25 to −1.52 V) of (L₁)₂Ru²⁺ (1) are essentially invariant relative to those of the structural analogue 2b (PF₆)₂, which suggests no significant electronic effect caused by the tert-butyl groups. This is supported by invariance in the metal-to-ligand charge transfer bands in both the electronic absorption (494-489 nm) and emission spectra (654-652 nm). However, contrary to 2b, complex 1 is both very soluble and exhibits a highly porous solid-state structure with internal cavity dimensions of 15 Å × 14 Å due to the preclusion of inter-annular interactions by the bulky tert-butyl substituents.     

Quantification of cis and trans influences in [PtX(PPh3)3] complexes. A P NMR study

In [PtX(PPh₃)₃]⁺ complexes (X = F, Cl, Br, I, AcO, NO₃, NO₂, H, Me) the mutual cis and trans influences of the PPh₃ groups can be considered constants in the first place, therefore the one bond Pt-P coupling constants of P_(cis) and P_(trans) reflect the cis and trans influences of X. The compounds [PtBr(PPh₃)₃](BF₄) (2), [PtI(PPh₃)₃](BF₄) (3), [Pt(AcO)(PPh₃)₃](BF₄) (4), [Pt(NO₃)(PPh₃)₃](BF₄) (5), and the two isomers [Pt(NO₂-O)(PPh₃)₃](BF₄) (6a) and [Pt(NO₂-N)(PPh₃)₃](BF₄) (6b) have been newly synthesised and the crystal structures of 2 and 4·CH₂Cl₂·0.25C₃H₆O have been determined. From the ¹J_PtP values of all compounds we have deduced the series: I > Br > Cl > NO₃ > ONO > F > AcO > NO₂ > H > Me (cis influence) and Me > H > NO₂ > AcO > I > ONO > Br > Cl > F > NO₃ (trans influence). These sequences are like those obtained for the (neutral) cis- and trans-[PtClX(PPh₃)₂] derivatives, showing that there is no dependence on the charge of the complexes. On the contrary, the weights of both influences, relative to those of X = Cl, were found to depend on the charge and nature of the complex.     

Photoluminescent metal(II)-organic complexes with two distinct atropisomeric units from axially prochiral ligands through C-H?O hydrogen bonds (M = zinc, cobalt, nickel)

By taking advantage of rich-electron modification of pyridine-3,5-dicarboxylates, three photoluminescent isostructural metal-organic complexes, namely, [M(Hsmpdc)₂(H₂O)₄] · 6H₂O (smpdc = 2,6-dimethyl-4-(thiophen-2-yl)pyridine-3,5-dicarboxylate, M = Zn (1), Co (2) and Ni (3)), were synthesized and characterized by single crystal X-ray analyses. There are interesting hydrogen-bonded M²⁺(H₂O)₈ ionic clusters in the structures of title compounds. And of the most interesting is that S- and R-atropisomeric units are constructed from axially prochiral organic ligands through C-H?O hydrogen bonds. Strong photoluminescent emission at 543 nm with obvious red shift might make compound 1 a potentially photoactive solid-state material for its thermal and chemical stability.     

Discovery of ((1S,3R)-1-isopropyl-3-((3S,4S)-3-methoxy-tetrahydro-2H-pyran-4-ylamino)cyclopentyl)(4-(5-(trifluoromethyl)pyridazin-3-yl)piperazin-1-yl)methanone, PF-4254196, a CCR2 antagonist with an improved cardiovascular profile

We describe the systematic optimization, focused on the improvement of CV-TI, of a series of CCR2 antagonists. This work resulted in the identification of 10 (((1S,3R)-1-isopropyl-3-((3S,4S)-3-methoxy-tetrahydro-2H-pyran-4-ylamino)cyclopentyl)(4-(5-(trifluoromethyl)pyridazin-3-yl)piperazin-1-yl)methanone) which possessed a low projected human dose 35-45 mg BID and a CV-TI = 3800-fold.     

Fabacyl acetate, a germination stimulant for root parasitic plants from Pisum sativum

A germination stimulant, fabacyl acetate, was purified from root exudates of pea (Pisum sativum L.) and its structure was determined as ent-2′-epi-4a,8a-epoxyorobanchyl acetate [(3aR,4R,4aR,8bS,E)-4a,8a-epoxy-8,8-dimethyl-3-(((R)-4-methyl-5-oxo-2,5-dihydrofuran-2-yloxy)methylene)-2-oxo-3,3a,4,5,6,7,8,8b-decahydro-2H-indeno[1,2-b]furan-4-yl acetate], by 1D and 2D NMR spectroscopic, ESI- and EI-MS spectrometric, X-ray crystallographic analyses, and by comparing the ¹H NMR spectroscopic data and relative retention times (RR_t) in LC-MS and GC-MS with those of synthetic standards prepared from (+)-orobanchol and (+)-2′-epiorobanchol. The ¹H NMR spectroscopic data and RR_t of fabacyl acetate were identical with those of an isomer prepared from (+)-2′-epiorobanchol except for the opposite sign in CD spectra. This is the first natural ent-strigolactone containing an epoxide group. Fabacyl acetate was previously detected in root exudates of other Fabaceae plants including faba bean (Vicia faba L.) and alfalfa (Medicago sativa L.).     

Time-resolved OH → EH transition of the aberrant ba3 oxidase from Thermus thermophilus

The kinetics of single-electron injection into the oxidized nonrelaxed state (O_H → E_H transition) of the aberrant ba₃ cytochrome oxidase from Thermus thermophilus, noted for its lowered efficiency of proton pumping, was investigated by time-resolved optical spectroscopy. Two main phases of intraprotein electron transfer were resolved. The first component (τ ∼ 17 μs) reflects oxidation of Cu_A and reduction of the heme groups (low-spin heme b and high-spin heme a₃ in a ratio close to 50:50). The subsequent component (τ ∼ 420 μs) includes reoxidation of both hemes by Cu_B. This is in significant contrast to the O_H → E_H transition of the aa₃-type cytochrome oxidase from Paracoccus denitrificans, where the fastest phase is exclusively due to transient reduction of the low-spin heme a, without electron equilibration with the binuclear center. On the other hand, the one-electron reduction of the relaxed O state in ba₃ oxidase was similar to that in aa₃ oxidase and only included rapid electron transfer from Cu_A to the low-spin heme b. This indicates a functional difference between the relaxed O and the pulsed O_H forms also in the ba₃ oxidase from T. thermophilus.     

Structural, magnetic and spectroscopic characterization of two unusual end-on bis(μ-acetato/μ-nitrato) bridged copper(II) complexes with N′-[phenyl(pyridin-2-yl)methylidene]furan-2-carbohydrazide and (2E,4Z)-N,2-dimethylhepta-2,4,6-trienamide-1-phenyl-1-pyridin-2-ylmethanimine (1:1) as capping ligands

Two new binuclear end-on bis(μ-acetato/μ-nitrato) bridged complexes with two NNO donor ligands, viz., [(L¹)Cu(μ-CH₃COO)₂Cu(L¹)]·4,4-bipy 1 and [(L²)Cu(μ-NO₃)₂Cu(L²)] 2 where [L¹ = N′-[phenyl(pyridin-2-yl)methylidene]furan-2-carbohydrazide, L² = (2E,4Z)-N,2-dimethylhepta-2,4,6-trienamide-1-phenyl-1-pyridin-2-ylmethanimine (1:1) μ-CH₃COO⁻ = μ-acetato and μ-NO₃⁻ = μ-nitrato) have been prepared and physiochemically characterized. These complexes are structurally characterized by X-ray crystallography. In both complexes, the two copper centers are linked by two acetate or two nitrate groups in end-on bonding fashion. The copper-copper separation is 3.279 Å for 1 and 3.459 Å for 2. The copper ions are pentacoordinated in both complexes. The coordination geometry may be described as close to square pyramidal (SP) stereochemistry with slight distortion to trigonal bipyramidal (TBP) stereochemistry. The polycrystalline epr spectra of these two complexes exhibit the properties commensurate with S = 1 systems. The magnetic moment (μ_eff) for these complexes are below the theoretical value suggesting antiferromagnetic exchange between the copper(II) ions. The cyclic voltammograms (CV) of the two complexes have been investigated. Superoxide dismutase (SOD) activity of these complexes has also been measured. These complexes can catalyze the dismutation of superoxide.