Synthetic, structural, spectroscopic and theoretical study of a Mn(III)-Cu(II) dimer containing a Jahn-Teller compressed Mn ion.

The heterobimetallic complex [Cu(II)Mn(III)(L)(2)(py)(4)](ClO(4))·EtOH (1) built using the pro-ligand 2,2'-biphenol (LH(2)), contains a rare example of a Jahn-Teller compressed Mn(III) centre. Dc magnetic susceptibility measurements on 1 reveal a strong antiferromagnetic exchange between the Cu(II) and Mn(III) ions mediated through the phenolate O-atoms (J = -33.4 cm(-1)), with magnetisation measurements at low temperatures and high fields suggesting significant anisotropy.

Assessment of the time-dependent inhibition (TDI) potential of test compounds with human liver microsomes by IC50 shift method using a nondilution approach.

Time-dependent inhibition (TDI) of hepatic cytochrome P450 (CYP) enzymes is increasingly implicated in the majority of clinically relevant drug-drug interactions (DDIs). A time-dependent inhibitor or its reactive metabolite irreversibly inactivates CYP enzymes, thereby inhibiting the metabolism of other drugs. As the majority of marketed drugs are metabolized by CYP enzymes, their inhibition has important clinical consequences, such as in decreasing the metabolic clearance of a co-administered drug (victim drug).

Assessment of P-glycoprotein substrate and inhibition potential of test compounds in MDR1-transfected MDCK cells.

P-glycoprotein (P-gp) is the most widely studied drug transporter due to its potential role in drug disposition and efficacy, and drug-drug interactions (DDI). It is abundantly expressed in both the intestinal wall and blood-brain barrier where it serves as a drug permeability barrier while simultaneously facilitating drug elimination in the liver and kidney. It is also abundantly expressed in tumors where it can facilitate the elimination of chemotherapeutics, a phenomenon known as multidrug resistance (MDR).

Aminotroponiminatogermaacid halides with a Ge(E)X moiety (E = S, Se; X = F, Cl).

Fluorination of aminotroponiminate (ATI) ligand-stabilized germylene monochloride [(t-Bu)(2)ATI]GeCl (1) with CsF gave the aminotroponiminatogermylene monofluoride [(t-Bu)(2)ATI]GeF (2). Oxidative addition reaction of compound 2 with elemental sulfur and selenium led to isolation of the corresponding germathioacid fluoride [(t-Bu)(2)ATI]Ge(S)F (3) and germaselenoacid fluoride [(t-Bu)(2)ATI]Ge(Se)F (4), respectively. Similarly, reaction of aminotroponiminatogermylene monochloride [(i-Bu)(2)ATI]GeCl (9) with elemental sulfur and selenium gave the aminotroponiminatogermathioacid chloride [(i-Bu)(2)ATI]Ge(S)Cl (11) and aminotroponiminatogermaselenoacid chloride [(i-Bu)(2)ATI]Ge(Se)Cl (12), respectively.

A computational examination on the structure, spin-state energetics and spectroscopic parameters of high-valent Fe(IV)=NTs species.

The imidoiron(IV) species are relatively less explored compared to the oxoiron(IV) intermediates. Recently, generation and characterization of a novel imido/oxoiron(iv) species ([(N(4)Py)Fe(IV)=X](2+) X = NTs; 1, O; 2) has been reported with an S = 1 ground state. Although the ground state for 1 and 2 are the same, they are reported to be distinctly different in other aspects.

Is a radical bridge a route to strong exchange interactions in lanthanide complexes? A computational examination.

The origin of very strong antiferromagnetic exchange in N(2)(3-) bridged complex, [{[(Me(3)Si)(2)N](2)Gd(THF)}(2)(μ-η(2):η(2)-N(2))](-) (1) has been probed using density functional theory (DFT) combined with molecular orbital (MO) and natural bond orbital (NBO) analysis. The analysis helps us to propose a generic mechanism of coupling for a {2p-4f} class of compounds.

On the controversy of metal ion composition on amine oxygenase (AurF): a computational investigation.

An energetics-spectroscopic approach based on DFT method reveals that the active site structure of AurF has {Fe(III)(2)O} central core with one protonated terminal glutamate.

Computational insight into a gold(I) N-heterocyclic carbene mediated alkyne hydroamination reaction.

A gold(I) N-heterocyclic carbene (NHC) complex mediated hydroamination of an alkyne has been modeled using density functional theory (DFT) study. In this regard, alkyne and amine coordination pathways have been investigated for the hydroamination reaction between two representative substrates, namely, MeC≡CH and PhNH(2), catalyzed by a gold(I) NHC based (NHC)AuCl-type precatalyst, namely, [1,3-dimethylimidazol-2-ylidene]gold chloride. The amine coordination pathway displayed a lower activation barrier than the alkyne coordination pathway.

What controls the magnetic interaction in bis-μ-alkoxo Mn(III) dimers? A combined experimental and theoretical exploration.

The synthesis and magnetic characterisation of a series of bis-μ-alkoxide bridged Mn(III) dinuclear complexes of general formula [Mn(III)(2)(μ-OR)(2)(biphen)(2)(ROH)(x)(L)(y)] (where R = Me, Et; H(2) biphen = 2,2'-biphenol and L = terminally bonded N-donor ligand) is described, doubling the literature basis set for this type of complex. Building on these findings we have categorised all known μ-OR bridged Mn(III) dinuclear complexes into one of three classifications with respect to their molecular structures. We have then employed DFT and MO calculations to assess all potential magneto-structural correlations for this class of compound in order to identify the structural requirements for constructing ferromagnetic family members.

Species-dependent and receptor-selective action of bilobalide on the function of constitutive androstane receptor and pregnane X receptor.

Bilobalide is a naturally occurring sesquiterpene trilactone with therapeutic potential in the management of ischemia and neurodegenerative diseases such as Alzheimer's disease. In the present study, we investigated the effect of bilobalide on the activity of rat constitutive androstane receptor (rCAR) and rat pregnane X receptor (rPXR) and compared that with human CAR (hCAR) and human PXR (hPXR). Bilobalide activated rCAR in a luciferase reporter gene assay and increased rCAR target gene expression in cultured rat hepatocytes, as determined by the CYP2B1 mRNA and CYP2B enzyme activity (benzyloxyresorufin O-dealkylation) assays.

Speciation of uranyl ions in fulvic acid and humic acid: a DFT exploration.

The speciation of uranyl ions in fulvic acid (FA) and humic acid (HA), based on models of larger sizes, is systematically studied using density functional theory (DFT). Four uranyl binding sites are suggested for FA and based on their energetics, the preferential binding sites are proposed. The computed binding sites include two chelating types, one through the carboxylate group and one via the hydroxo group.

Density functional studies on dinuclear {Ni(II)Gd(III)} and trinuclear {Ni(II)Gd(III)Ni(II)} complexes: magnetic exchange and magneto-structural maps.

Theoretical calculations using density functional methods have been performed on two dinuclear {Ni(II)-Gd(III)} and two trinuclear {Ni(II)-Gd(III)-Ni(II)} complexes having two and three μ-OR (R = alkyl or aromatic groups) bridging groups. The different magnetic behaviour, having moderately strong ferromagnetic coupling for complexes having two μ-OR groups and weak ferromagnetic coupling for complexes having three μ-OR groups, observed experimentally is very well reproduced by the calculations. Additionally, computation of overlap integrals MO and NBO analysis reveals a clear increase in antiferromagnetic contribution to the net exchange for three μ-OR bridged {Ni-Gd} dimers and also provides several important clues regarding the mechanism of magnetic coupling.

Magnetic exchange interactions and magneto-structural correlations in heterobridged μ-phenoxo-μ(1,1)-azide dinickel(II) compounds: a combined experimental and theoretical exploration.

This investigation presents the syntheses, crystal structures, magnetic properties, and density functional theoretical modeling of magnetic behavior of two heterobridged μ-phenoxo-μ(1,1)-azido dinickel(II) compounds [Ni(II)(2)(L(1))(2)(μ(1,1)-N(3))(N(3))(H(2)O)]·CH(3)CH(2)OH (1) and [Ni(II)(2)(L(2))(2)(μ(1,1)-N(3))(CH(3)CN)(H(2)O)](ClO(4))·H(2)O·CH(3)CN (2), where HL(1) and HL(2) are the [1+1] condensation products of 3-methoxysalicylaldehyde and 1-(2-aminoethyl)-piperidine (for HL(1))/4-(2-aminoethyl)-morpholine (for HL(2)), along with density functional theoretical magneto-structural correlations of μ-phenoxo-μ(1,1)-azido dinickel(II) systems. Compounds 1 and 2 crystallize in orthorhombic (space group Pbca) and monoclinic (space group P2(1)/c) systems, respectively. The coordination environments of both metal centers are distorted octahedral.

A periodic mixed gaussians-plane waves DFT study on simple thiols on Au(111): adsorbate species, surface reconstruction, and thiols functionalization.

Here we present DFT calculations based on a periodic mixed gaussians/plane waves approach to study the energetics, structure, bonding of SAMs of simple thiols on Au(111). Several open issues such as structure, bonding and the nature of adsorbate are taken into account. We started with methyl thiols (MeSH) on Au(111) to establish the nature of the adsorbate.

Differential effect of meclizine on the activity of human pregnane X receptor and constitutive androstane receptor.

Conflicting data exist as to whether meclizine is an activator of human pregnane X receptor (hPXR). Therefore, we conducted a detailed, systematic investigation to determine whether meclizine affects hPXR activity by performing a cell-based reporter gene assay, a time-resolved fluorescence resonance energy transfer competitive ligand-binding assay, a mammalian two-hybrid assay to assess coactivator recruitment, and a hPXR target gene expression assay. In pregnane X receptor (PXR)-transfected HepG2 cells, meclizine activated hPXR to a greater extent than rat PXR.

Human pregnane X receptor agonism by Ginkgo biloba extract: assessment of the role of individual ginkgolides.

Ginkgo biloba extract activates pregnane X receptor (PXR), but how this occurs is not known. Therefore, we investigated the mechanism of PXR activation by the extract and the role of five individual terpene trilactones in the activation. In a cell-based reporter gene assay, G.

Placental biglycan expression is decreased in human idiopathic fetal growth restriction.

Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. The majority of FGR cases are idiopathic and are associated with placental insufficiency, which can result from placental thrombosis. Evidence suggests that Dermatan Sulfate (DS) is an important anti-coagulant in placentae of uncomplicated pregnancies.

Decorin expression is decreased in human idiopathic fetal growth restriction.

Fetal growth restriction (FGR) is a clinically significant pregnancy disorder in which the fetus fails to achieve its full growth potential in utero. Most cases of FGR are idiopathic and are associated with placental thrombosis. Previous studies suggest that proteoglycans, such as decorin, that contain the glycosaminoglycan dermatan sulfate are the principal anticoagulants in the normal placenta.

Modulation of CYP1B1 and CYP1A1 gene expression and activation of aryl hydrocarbon receptor by Ginkgo biloba extract in MCF-10A human mammary epithelial cells.

The aryl hydrocarbon receptor (AhR) signaling pathway regulates the production of CYP1B1 and CYP1A1, which catalyze the bioactivation of various procarcinogens. In the present study, we investigated the effect of Ginkgo biloba extract and some of its chemical constituents on CYP1B1 and CYP1A1 gene expression and AhR activity in cultured MCF-10A human mammary epithelial cells. Treatment of MCF-10A cells with noncytotoxic concentrations of G.