Single and multiple addition to C60. A computational chemistry study

Des del seu descobriment, a la molècula C60 se li coneixen una varietat de derivats segons el tipus de funcionalització amb propietats fisicoquímiques específiques de gran interès científic. Una sel·lecció de derivats corresponents a addicions simple o múltiple al C60 s'ha considerat en aquest treball d'investigació. L'estudi a nivell de química computacional de diversos tipus d'addició al C60 s'han portat a terme per tal de poder donar resposta a aspectes que experimentalment no s'entenen o són poc clars. Els sistemes estudiats en referència a l'addició simple al C60 han estat en primer lloc els monoiminoful·lerens, C60NR, (de les dues vies proposades per la seva síntesi, anàlisis cinètic i termodinàmic han ajudat a explicar els mecanismes de formació i justificar l'addició a enllaços tipus [5,6]), i en segon lloc els metanoful·lerens i els hidroful·lerens substituits, C60CHR i C60HR, (raons geomètriques, electròniques, energètiques i magnètiques justifiquen el diferent caràcter àcid ente ambdós derivats tenint en compte una sèrie de substituents R amb diferent caràcter electrònic donor/acceptor). Els fluoroful·lerens, C60Fn, i els epoxid ful·lerens, C60On, (anàlisi sistemàtic dels seus patrons d'addició en base a poder justificar la força que els governa han aportat dades complementàries a les poques que existeixen experimentalment al respecte).

Molybdenum eta(3)-allyl dicarbonyl complexes as a new class of precursors for highly reactive epoxidation catalysts with tert-butyl hydroperoxide

New Mo(II) diimine derivatives of [Mo(q (3)allyl)X(CO)(2)(CH3CN)(2)] (allyl = C3H5 and C5H5O; X = Cl, Br) were prepared, and [MO(eta(3)-C3H5)Cl(CO)(2)(BIAN)] (BIAN = 1,4-(4-chloro)phenyl-2,3-naphthalene-diazabutadiene) (7) was structurally characterized by single-crystal X-ray diffraction. This complex adopted an equatorial-axial arrangement of the bidentate ligand (axial isomer), in contrast with the precursors, found as the equatorial isomer in the solid and fluxional in solution. The new complexes of the type [Mo(eta(3)-allyl)X(CO)(2)(N-N)l (N-N is a bidentate chelating dinitrogen ligand) were tested for the catalytic epoxidation of cyclooctene using tert-butyl hydroperoxide as oxidant. All catalytic systems were 100% selective toward epoxide formation. While their turnover frequencies paralleled those of related Mo(eta) carbonyl compounds or Mo(VI) compounds bearing similar N-donor ligands, they exhibited similar olefin conversions in consecutive catalytic runs. The acetonitrile precursors were generally more active than the diimine complexes, and the chloro derivatives more active than the bromo ones. Combined vibrational and NMR spectroscopy and computational studies (DFT) were used to investigate the nature of the molybdenum species formed in the catalytic system with [Mo(eta(3)-C3H5)Cl(CO)(2){1,4-(2,6-dimethyl)phenyl-2.3-dimethyldiazabuta diene}] (4) and to propose that the resulting species may be dimeric bearing oxide bridges.

Heterogenisation of Os species on MCM-41 structure for epoxidation of trans-stilbene

Metal organic chemical vapour deposition technique (MOCVD) has been used to immobilise Os species onto the internal porous structure of MCM-41. Evidence suggests that volatile Os-3(CO)(12) cluster reacts with surface silanol groups of the MCM-41 via an oxidative addition reaction to yield a trinuclear HOs3(CO)(10)(OSi-) surface species. After heat treatment in air or at their very low surface coverage, these triangular sites break up to partially oxidised mononuclear surface species. In the presence of tert-butyl hydroperoxide (TBHP) as an oxidant, we demonstrate that the mononuclear species form extremely active species that catalyse the oxidation of trans-stilbene selectively to the corresponding epoxide. By carefully controlling the parameters of the MOCVD method (loading and calcination temperature), we report a new class of optimised MCM-41 porous heterogeneous catalysts carrying isolated but active Os sites for the selective oxidation of trans-stilbene in liquid phase. The reaction selectivity of the solid supported Os is apparently higher than the soluble homogeneous Os-3(CO)(12) cluster. It is envisaged that our solid supported catalysts not only facilitate separation from products but also offer an excellent utilisation of Os for catalysis. (C) 2003 Elsevier Science B.V. All rights reserved.

Aziridine synthesis via nucleophilic attack of carbene equivalents on imines: the aza-Darzens reaction

The development of new methods for the efficient synthesis of aziridines has been of considerable interest to researchers for more than 60 years, but no single method has yet emerged as uniformly applicable, especially for asymmetric synthesis of chiral aziridines. One method which has been intensely examined and expanded of late involves the nucleophilic addition to imines by anions bearing a-leaving groups; by analogy with the glycidate epoxide synthesis, these processes are often described as "aza-Darzens reactions". This Microreview gives a summary of the area, with a focus on contemporary developments. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Engineering of a monodisperse core-shell magnetic Ti-O-Si oxidation nanocatalyst

There has been limited development in catalyst carriers for magnetic separations where superparamagnetic nanoparticles of a high saturation magnetization with no coercivity are required to isolate expensive catalyst reagent that are subjected to repeated magnetic cycles. By using simple stepwise layer-by-layer nanochemistry techniques, we show that an fee FePt nanomagnet can be created inside each silica particle with tailored dimensions to great precision. Subsequent engineering of the external surface with Ti-O-Si species in an optimum structure to create a unique interface gives high activity and excellent selectivity of the composite material for the trans-stilbene oxidation to the corresponding epoxide in the presence of tert-butyl hydroperoxide. Thus, a new magnetic separable epoxidation catalyst is described. This work clearly demonstrates the significance of nanoengineering of a single catalyst particle by a bottom-up construction approach in modern catalyst design, which could lead to new catalytic. properties.

Kinetic models as a route to control acrylamide formation in food

Reports that heat processing of foods induces the formation of acrylamide heightened interest in the chemistry, biochemistry, and safety of this compound. Acrylamide-induced neurotoxicity, reproductive toxicity, genotoxicity, and carcinogenicity are potential human health risks based on animal studies. Because exposure of humans to acrylamide can come from both external sources and the diet, there exists a need to develop a better understanding of its formation and distribution in food and its role in human health. To contribute to this effort, experts from eight countries have presented data on the chemistry, analysis, metabolism, pharmacology, and toxicology of acrylamide. Specifically covered are the following aspects: exposure from the environment and the diet; biomarkers of exposure; risk assessment; epidemiology; mechanism of formation in food; biological alkylation of amino acids, peptides, proteins, and DNA by acrylamide and its epoxide metabolite glycidamide; neurotoxicity, reproductive toxicity, and carcinogenicity; protection against adverse effects; and possible approaches to reducing levels in food. Cross-fertilization of ideas among several disciplines in which an interest in acrylamide has developed, including food science, pharmacology, toxicology, and medicine, will provide a better understanding of the chemistry and biology of acrylamide in food, and can lead to the development of food processes to decrease the acrylamide content of the diet.

Equol: a comparison of the effects of the racemic compound with that of the purified S-enantiomer on the growth, invasion, and DNA integrity of breast and prostate cells in vitro

It has been postulated that the R- and S-equol enantiomers have different biological properties given their different binding affinities for the estrogen receptor. S-(-)equol is produced via the bacterial conversion of the soy isoflavone daidzein in the gut. We have compared the biological effects of purified S-equol to that of racemic (R and S) equol on breast and prostate cancer cells of varying receptor status in vitro. Both racemic and S-equol inhibited the growth of the breast cancer cell line MDA-MB-231 (> or = 10 microM) and the prostate cancer cell lines LNCaP (> or = 5 microM) and LAPC-4 (> or = 2.5 microM). The compounds also showed equipotent effects in inhibiting the invasion of MDA-MB-231 and PC-3 cancer cells through matrigel. S-equol (1, 10, 30 microM) was unable to prevent DNA damage in MCF-7 or MCF-10A breast cells following exposure to 2-hydroxy-4-nonenal, menadione, or benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide. In contrast, racemic equol (10, 30 microM) prevented DNA damage in MCF-10A cells following exposure to 2-hydroxy-4-nonenal or menadione. These findings suggest that racemic equol has strong antigenotoxic activity in contrast to the purified S-equol enantiomer implicating the R-, rather than the S-enantiomer as being responsible for the antioxidant effects of equol, a finding that may have implications for the in vivo chemoprotective properties of equol.

Ligand substituents effect on 10Dq

Reaction of 5,6-dihydro-5,6-epoxy-1,10-phenanthroline (L) with Ni(ClO4)(2)center dot 6H(2)O in methanol in 3:1 M proportion at room temperature yields [NiL3](ClO4)(2)center dot 2H(2)O. The X-ray crystal structure of the cation Nil(3)(2+) has been determined. Aminolysis of the three epoxide rings in NiL32+ by 4-substituted anilines in boiling water without any Lewis acid catalyst gives a family of Ni(II) complexes with octahedral NiL62+ core. In these complexes, crystal field splitting 10Dq varies from 11601 to 15798 cm(-1) in acetonitrile. The variation in 10Dq is found to be satisfactorily linear (r(2) = 0.951) with the Hammett sigma(R) parameter of the substituent on the anilino fragment. 10Dq increases with the increase in the electron donation ability of the substituent.

Regulation of KCa2.3 andendothelium-dependent hyperpolarization (EDH) in the rat middle cerebral artery: the role of lipoxygenase metabolites and isoprostanes

Background and Purpose. In rat middle cerebral arteries, endothelium-dependent hyperpolarization (EDH) is mediated by activation of calcium-activated potassium(KCa) channels specifically KCa2.3 and KCa3.1. Lipoxygenase (LOX) products function as endothelium-derived hyperpolarizing factors (EDHFs) in rabbit arteries by stimulating KCa2.3. We investigated if LOX products contribute to EDH in rat cerebral arteries. Methods. Arachidonic acid (AA) metabolites produced in middle cerebral arteries were measured using HPLC and LC/MS. Vascular tension and membrane potential responses to SLIGRL were simultaneously recorded using wire myography and intracellular microelectrodes. Results. SLIGRL, an agonist at PAR2 receptors, caused EDH that was inhibited by a combination of KCa2.3 and KCa3.1 blockade. Non-selective LOX-inhibition reduced EDH, whereas inhibition of 12-LOX had no effect. Soluble epoxide hydrolase (sEH) inhibition enhanced the KCa2.3 component of EDH. Following NO synthase (NOS) inhibition, the KCa2.3 component of EDH was absent. Using HPLC, middle cerebral arteries metabolized 14C-AA to 15- and 12-LOX products under control conditions. With NOS inhibition, there was little change in LOX metabolites, but increased F-type isoprostanes. 8-iso-PGF2α inhibited the KCa2.3 component of EDH. Conclusions. LOX metabolites mediate EDH in rat middle cerebral arteries. Inhibition of sEH increases the KCa2.3 component of EDH. Following NOS inhibition,loss of KCa2.3 function is independent of changes in LOX production or sEH inhibition but due to increased isoprostane production and subsequent stimulation of TP receptors. These findings have important implications in diseases associated with loss of NO signaling such as stroke; where inhibition of sEH and/or isoprostane formation may of benefit.

Pharmacogenetics of Warfarin: Development of a Dosing Algorithm for Brazilian Patients

A dosing algorithm including genetic (VKORC1 and CYP2C9 genotypes) and nongenetic factors (age, weight, therapeutic indication, and cotreatment with amiodarone or simvastatin) explained 51% of the variance in stable weekly warfarin doses in 390 patients attending an anticoagulant clinic in a Brazilian public hospital. The VKORC1 3673G>A genotype was the most important predictor of warfarin dose, with a partial R(2) value of 23.9%. Replacing the VKORC1 3673G>A genotype with VKORC1 diplotype did not increase the algorithm`s predictive power. We suggest that three other single-nucleotide polymorphisms (SNPs) (5808T>G, 6853G>C, and 9041G>A) that are in strong linkage disequilibrium (LD) with 3673G>A would be equally good predictors of the warfarin dose requirement. The algorithm`s predictive power was similar across the self-identified ""race/color"" subsets. ""Race/color"" was not associated with stable warfarin dose in the multiple regression model, although the required warfarin dose was significantly lower (P = 0.006) in white (29 +/- 13 mg/week, n = 196) than in black patients (35 +/- 15 mg/week, n = 76).

Organochlorine and trace metal residues in adult southern bent-wing bat (Miniopterus schreibersii bassanii) in Southeastern Australia

In recent times, the apparent population decline of the southern bent-wing bat (Miniopterus schreibersii bassanii) at Bat Cave, Naracoorte has been ascribed to pesticide use in the region, following the finding of organochlorine and orgaonophosphate insecticide residues in bat guano. Adult southern bent-wing bats were collected from Bat Cave and Starlight Cave in 2003. Organochlorine contaminants were detected in all carcass samples: p,p′-DDE was by far the most dominant contaminant with concentrations ranging from 11 000 to 59 000 ng g⁻¹, followed by p,p′-DDT (110–1600 ng g⁻¹), p,p′-DDD (35–620 ng g⁻¹), ∑PCBs (33–490 ng g⁻¹), ∑chlordane and related compounds (7.9–270 ng g⁻¹), HCB (1.6–120 ng g⁻¹), HP epox. (3.1–230 ng g⁻¹), TCPMOH (3.8–38 ng g⁻¹), ∑HCHs (1.4–9.6 ng g⁻¹), and TCPMe (0.1–4.2 ng g⁻¹) (all values on lipid-weight basis). No significant difference in DDE, DDD, DDT, ∑DDT, ∑PCB, trans-chlordane, heptachlor epoxide, trans-nonachlor, α-HCH, β-HCH, γ-HCH, TCPMOH or TCPMe concentrations were observed either between sexes within sites, or between sites (p > 0.05). However, there were significant differences in HCB and oxychlordane concentrations between sexes and between sites (p < 0.05), between site differences in cis-nonachlor concentrations in male bats (p < 0.05), and cis-chlordane concentrations between sexes at Starlight Cave, and between males of each site (p < 0.05). There were also significant differences in the liver concentrations of some metals between sexes within sites (Ag, Cd, Co, Cu, Pb, Se, Zn), and between sites (Ag, Cd, Co, Cu, Hg, Pb, Se, V, Zn). Clustering or grouping of sites was observed when the OC data was expressed on a lipid-weight basis. These inter-site differences in OC concentrations reflect local exposure over a period of time, and do not unambiguously support any suggestion that we are witnessing incipient speciation. However, for conservation purposes, it may be prudent to assume that there are two sub-populations of M. s. bassani feeding in different locations in this region of southern Australia, rather than the single homogeneous population suggested by genetic studies.

syn-Facial hetero-bridged [n]polynorbornanes : a new class of polarofacial framework molecules composed of fused 7-oxa- and 7-azanorbornanes

New oxygen-bridged norbornane-fused cyclobutene epoxides and bis-(cyclobutene epoxides) are described and shown to react stereoselectively with 7-azanorbornenes to produce syn-facial N,O-bridged polynorbornanes and stereorandomly with 7-oxanorbornenes to produce O,O-bridged polynorbornanes as mixtures of syn-facial and anti-facial products.[1] Polarofacial systems containing up to six syn-facial norbornane bridges are described, while systems with seven co-facial oxygen atoms have been prepared by incorporating terminal epoxide rings to O5-[5]polynorbornanes. Ester-substituted 1,3,4-oxadiazoles are shown to be useful reagents for coupling 7-oxanorbornanes and produce predominantly syn-facial O-bridged polarofacial systems together with their anti-facial isomers.

Potential antiarrhythmic and cardioprotective agents based on adenosine

N-Ethylcarboxamidoadenosine (12) was synthesised from adenosine (1) and the 6-chloro-2’,3’-O-isopropylidene-AT-ethylcarboxamidoadenosine (25) was synthesised from inosine (19). Employing molecular modelling techniques and the results from previous structure activity relationships it was possible to design and synthesise a N6-substituted N-ethylcarboxamidoadenosines which possessed an oxygen in the N6-substituent either in the form of an epoxide (which was obtained by cpoxidising an alkene with m-CPBA or dimethyldioxirane) or in the form of a cyclic ether as was the case for N6-((tetrahydro-2H--pyran--2-yl)methyl-N-ethylcarboxamidoadenosine (78). These compounds were tested for their biological activity at the A1 adenosine receptor by their ability to inhibit cAMP accumulation in DDT, MF2 cells. The EC50 values obtained indicated that the N6-(norborn-5-en-2-yl)-N-ethylcarboxamidoadenosines were the most potent. Of theseN6-(S-endo-norbrn-5-en-2-yI)-N-ethylcarboxaniidoadenosine (56) was the most potent (0.2 nM). N6-(exo-norborn-5-en-2-yl)-2-iodo-N-ethylcarboxamidoadenosine (79) was synthesised from guanosine (22) and was also evaluated for its potency at the A, receptor (24.8 ± 1.5 nM). At present 79 is being evaluated for its selectivity for the A1 receptor compared to the other three receptor subtypes (A2a, A2b, A3). A series of N6-(benzyl)-N-ethylcarboxamidoadenosines were synthesised with substitutions at the 4-position of the phenyl ring. Another series of compounds were synthesised which replaced the methylene spacer between the N6H and the N6-aromatic or lipophilic substituent The replacement groups -were carbonyl and trans-2- cyclopropyl moieties. The N6-acyl compounds were obtained by reacting 2’,3’-O- di(tert-butyldimethylsilyl)-AT-ethylcarboxamidoadenosinc (59) with the appropriate acid chloride and then deprotecting with lelrabutylammonium fluoride in tetrahydrofuran. The compound N6-(4-(1,2-dihydroxy)ethyl)benzyl-N- ethylcarboxamidoadenosine (125) was synthesised by the reaction of 4-(1,2-0- isopropylidene-ethyl)benzyl aminc (123) with 6-chloro-2,3-0-isopropylidene-N- ethylcarboxamidoadenosine (25). Compound 123 was synthesised from an epoxidation of vinylbenzyl phthalimide (118) followed by an acidic ring opening to yield the diol which was isopropylidenated to yield 4-(l,2-O-isopropylidene- elhyl)benzyl phlhalimide (122), It was hoped that the presence of the diol functionality in 125 would increase water solubility whilst maintaining potency at the A3 receptor.

Approaches to the synthesis of peptide substituted frameworks

The 1,3 dipolar cycloaddition between carbonyl ylids (generated from cyclobutene epoxides flanked by esters) and norbornyl alkenes – the ACE reaction – offers a facile method for the construction of polynorbornyl molecular frameworks. This reaction has, as described in this dissertation, underpinned the construction of molecular frameworks that have peptides and amino acids attached. Such highly rigid peptide-frameworks are of use in the field of peptidomimetics; the template molecule governs the final positioning of any attached groups such that a precise arrangement of amino acids can be achieved without the need to construct entire proteins. In the course of any ACE reaction the ester flanked cyclobutene epoxide is transformed to a 1,3 dipole, the esters serve to stablise this reactive intermediate and are as a consequence incorporated in the reaction product. Modification of these esters provides pseudo-equatorial points for peptide attachment. These methyl esters were replaced with tert-butyl esters to provide pseudo-axial attachment points that could be selectively addressed. The optimal strategy for peptide-framework construction involved direct condensation of carboxyl protected amino acids to bicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid as well as condensation of amino acids to cyclobutene epoxides derived from this acid. The ACE reaction of (±) bicycloheptene-2-endo-carboxylic acid derivatives with cyclobutene epoxides synthesised from such racemic acid derivatives provided a mixture of enantiomers and meso compounds. In order to control the position of the attachment points – and hence the final location of the attached peptides – the ACE reaction required chiral starting materials. Accordingly, all peptidoframeworks were derived from the chiral (2S)-(-)-bicycloheptene carboxylic acid. The ACE reaction of this (S)-norbornene with the (S)-epoxide provided a peptide framework in which the attached amino acids were positioned pseudo-axially. Deprotection of the amino acid allowed peptide chain building in the pseudo-axial direction. Using this strategy a framework with an alanine residue and a triglycine peptide was synthesised. By combining this strategy with the ter-butyl ester variant a framework with pseudo-axial alanine and pseudo-equatorial glycine residues was manufactured.

Time-of-flight secondary ion mass spectrometry investigation of epoxy resin curing behavior in real time

Time-of-flight secondary ion mass spectrometry and principal components analysis were used in real time to monitor the progress of curing reactions on the surface of a diglycidyl ether of bisphenol A (DGEBA) and diglycidyl ether of bisphenol F (DGEBF) epoxy resin blend reacted with the diamine hardener isophorone diamine at different time intervals. Molecular ions in the mass spectra that characterized the curing reactions steps, including blocking, coupling, branching, and crosslinking, were identified. The aliphatic hydrocarbon ions were correlated to the curing reaction rate, and this indicated that coupling and branching occurred much faster than the blocking and crosslinking curing reactions steps. The total conversion of the coupling and branching reaction steps were followed on the basis of changes with time in the relative ion intensity of molecular ions assigned to the DGEBA/DGEBF, aliphatic hydrocarbon, epoxide, and aromatic ring structures. Indicative measures of crosslinking density were monitored through the observation of changes in the ratio of the relative intensities of the aliphatic hydrocarbon and hydroxyl molecular ions over time. The curing reaction conversion was established by the observation of the changes in the relative ion intensity of the molecular ions that were related to the DGEBA/ DGEBF molecules.