Phospholipid lung surfactant and nanoparticle surface toxicity: Lessons from diesel soots and silicate dusts

Because of their small size, the specific surface areas of nanoparticulate materials (NP), described as particles having at least one dimension smaller than 100 nm, can be large compared with micrometer-sized respirable particles. This high specific surface area or nanostructural surface properties may affect NP toxicity in comparison with micrometer-sized respirable particles of the same overall composition. Respirable particles depositing on the deep lung surfaces of the respiratory bronchioles or alveoli will contact pulmonary surfactants in the surface hypophase. Diesel exhaust ultrafine particles and respirable silicate micrometer-sized insoluble particles can adsorb components of that surfactant onto the particle surfaces, conditioning the particles surfaces and affecting their in vitro expression of cytotoxicity or genotoxicity. Those effects can be particle surface composition-specific. Effects of particle surface conditioning by a primary component of phospholipid pulmonary surfactant, diacyl phosphatidyl choline, are reviewed for in vitro expression of genotoxicity by diesel exhaust particles and of cytotoxicity by respirable quartz and aluminosilicate kaolin clay particles. Those effects suggest methods and cautions for assaying and interpreting NP properties and biological activities.     

Synthetic Diphenylacetylene-Based Retinoids Induce DNA Damage in Chinese Hamster Ovary Cells without Altering Viability

All-trans-retinoic acid (ATRA), the active metabolite of vitamin A, plays a pivotal role in cell differentiation, proliferation and embryonic development. It is an effective therapy for dermatological disorders and malignancies. ATRA is prone to isomerization and oxidation, which can affect its activity and selectivity. Novel diphenylacetylene-based ATRA analogues with increased stability can help to overcome these problems and may offer significant potential as therapeutics for a variety of cancers and neurodegenerative diseases, including amyotrophic lateral sclerosis. Here, we investigated the effects of these retinoids on cell viability and genotoxicity in the widely used model system of the rapidly proliferating Chinese hamster ovary cell line. DC360 is a fluorescent ATRA analogue and DC324 is a non-active derivative of DC360. EC23, DC525, DC540, DC645, and DC712 are promising analogues with increased bioactivity. The cytotoxic activity of the compounds was evaluated by ATP assay and DNA damage was tested by comet assay. No cytotoxicity was observed in the 10⁻⁶–10⁻⁵ M concentration range. All compounds induced DNA migration similar to ATRA, but DC324, DC360 and EC23 did so to a greater extent, particularly at higher concentrations. We believe that retinoid receptor-independent genotoxicity is a general characteristic of these compounds; however, further studies are needed to identify the molecular mechanisms and understand their complex biological functions.     

Oxalate Bridged MM Quadruply Bonded Oligomers: Considerations of Electronic Structure and Synthetic Strategies

The electronic structures of oxalate bridged oligomers of MM quadruply bonded complexes (M?=?Mo or W) have been calculated by density functional theory. The calculations predict the formation of a ?? band width ~1.0?eV. With increasing number of oxalate bridges, the metal-to-ligand (oxalate) charge transfer band moves to lower energy. Two synthetic approaches have been investigated. (1) The direct reaction between oxalic acid and the homoleptic compound M₂(T ⁱ PB)₄, where T ⁱ PB?=?2,4,6-triisopropylbenzoate and (2) the metathetic reaction between the herein reported salt Mo₂(T ⁱ PB)₂(CH₃CN)₄(BF₄)₂ and ( ⁿ Bu₄N⁺)₂(oxalate^2?). Neither reaction yielded the desired oligomers though the latter resulted in the formation of the molecular triangle [Mo₂(T ⁱ PB)₂(O₂CCO₂)]₃.     

Intermolecular recognition and crystal packing in molybdenum and tungsten coordination polymers as deduced from powder X-ray diffraction data

The molecular conformations and packing of [(tBuCO2)3M2(mu-X)M2(O2CtBu)3], where M = Mo and W, and X = oxalate and perfluoroterephthalate, determined in the solid-state from powder X-ray diffraction analysis, reveal one-dimensional coordination polymers involving pivalate-oxygen to metal interactions (X = perfluoroterephthalate), and oxalate--as well as pivalate-oxygen to metal bonds (X = oxalate), and allows explanation of the unusual state-dependent chromic properties of these compounds.     

3,6-dioxypyridazine bridged tungsten-tungsten quadruple bonds. Comparisons of electron delocalisation with oxalate bridged compounds

The preparation and characterisation of the tungsten-tungsten quadruply bonded, 3,6-dioxypyridazine bridged complex [((t)BuCO(2))(3)W(2)](2)([micro sign]-H(2)C(4)N(2)O(2)) and its single electron oxidised radical cation are reported and, when compared with related bridged dimolybdenum complexes, reveal a different mechanism of electronic coupling from that seen in related oxalate bridged systems.     

Substitution chemistry of MM quadruply bonded complexes (M = Mo or W) supported by the anion of 2-hydroxy-6-methylpyridine

The compounds M(2)(mhp)(4), where M = Mo or W and mhp is the anion formed from deprotonation of 2-hydroxy-6-methylpyridine, are shown to react with carboxylic acids RCOOH to give an equilibrium mixture of products M(2)(O(2)CR)(n)(mhp)(4-n) where R = 2-thienyl and phenyl. The equilibrium can be moved in favor of M(2)(O(2)CR)(4) by the addition of excess acid or by the favorable crystallization of these products. The latter provides a facile synthesis of the W(2)(O(2)CR)(4) compound where R = 9-anthracene. Reactions involving 2,4,6-triisopropyl benzoic acid, TiPBH, yield M(2)(TiPB)(2)(mhp)(2) compounds as thermodynamic products. Reactions involving Me(3)OBF(4) (1 and 2 equiv.) yield the complexes Mo(2)(mhp)(3)(CH(3)CN)(2)BF(4) and Mo(2)(mhp)(2)(CH(3)CN)(4)(BF(4))(2), respectively. The latter compound has been structurally characterized and shown to have mirror symmetry with two cis mhp ligands: MoMo = 2.1242(5) A, Mo-O = 2.035(2) A, Mo-N(mhp) = 2.161(2) A, and Mo-N(CH(3)CN) = 2.160(3) and 2.170(3) A. Reactions involving Mo(2)(mhp)(3)(CH(3)CN)(2)(2+) and Mo(2)(mhp)(2)(CH(3)CN)(4)(2+) with (n)Bu(4)NO(2)CMe (1 and 2 equiv.) yield the complexes Mo(2)(mhp)(3)(O(2)CMe) and Mo(2)(mhp)(2)(O(2)CMe)(2) which are shown to be kinetically labile to ligand scrambling. Reactions between Mo(2)(mhp)(3)(CH(3)CN)(2)(+)BF(4)(-) (2 equiv.) and [(n)Bu(4)N(+)](2)[O(2)C-X-CO(2)](2-) yielded dimers of dimers [Mo(2)(mhp)(3)](2)(micro-O(2)C-X-CO(2)] where X = nothing, 2,5- or 3,4-thienyl and 1,4-C(6)H(4). Reactions between Mo(2)(mhp)(2)(CH(3)CN)(4)(2+)(BF(4)(-))(2) and tetra-n-butylammonium oxalate and terephthalate yield compounds [Mo(mhp)(2)bridge](n) which by MALDI-TOF MS are proposed to be a mixture of molecular squares (n = 4) and triangles (n = 3) along with minor products of [Mo(2)(mhp)(3)](2)(bridge) and Mo(2)(mhp)(4) that arise from ligand scrambling.     

2,5-Dianilinoterephthalate bridged MM quadruply bonded complexes of molybdenum and tungsten

From the reactions between 2,5-dianilinoterephthalic acid and M2(O2CBut)4 in toluene the dicarboxylate bridged complexes [(ButCO2)3M2]2{micro-1,4-(CO2)(2)-2,5-(NHPh)2C6H2}, (M=Mo) and (M=W) have been isolated. The compounds are air sensitive, sparingly soluble in aromatic hydrocarbons but appreciably soluble in tetrahydrofuran. Electronic structure calculations employing density functional theory on the model compounds [(HCO2)3M2]2{micro-1,4-(CO2)(2)-2,5-(NHPh)2C6H2}, indicate that the ground state structure contains a planar bridge and that for molybdenum the HOMO is a bridge based molecular orbital. However, the compounds show reversible oxidation waves (CV and DPV) that for both M=Mo and W are metal based oxidations. Furthermore, the cations + and + are shown to be valence trapped and fully delocalized respectively. The magnitude of the electronic coupling of the two M2 centers, Hab, can be estimated as 383 cm-1 for + and 1500 cm-1 for + based on the corresponding low energy IVCT or charge resonance bands.     

Ring-opening polymerization of l-lactide by organotin(IV)alkoxides,R2Sn(OPr)2: Estimation of the activation parameters

The ring-opening polymerization of l-lactide, l-LA, to give poly-l-lactide by R₂Sn(OPrⁱ)₂ compounds, where R = Buⁿ and p-XC₆H₄ (X = CF₃, F, H, Me and OMe) has been studied in benzene over a temperature range. There is a relatively small variation in ΔH^≠ as a function of R with all the values falling within the range 11 ± 2 kcal mol⁻¹. The entropy of activation, ΔS^≠, is consistently large and negative, −50 ± 5 eu, supporting the view that the ring-opening event, the enchainment step involves a highly ordered transition state. The crystal and molecular structures of the compounds Ph₂Sn(OPrⁱ)₂, (p-FC₆H₄)₂Sn(OPrⁱ)₂ and (p-Me₂NC₆H₄)₃SnOPrⁱ are also reported. While the latter compound is monomeric in the solid state the former are both dimeric with a pair of bridging OPrⁱ ligands.