Novel reaction products from the hypervalent iodine oxidation of hydroxylated stilbenes and isoflavones

Novel reaction pathways for the hypervalent iodine-mediated oxidation of bioactive phenols containing extended conjugated π-systems are described. Oxidation of 4-hydroxystilbenes in methanol using a hypervalent iodine-based oxidant led to the formal 1,2-addition of methoxy groups across the central stilbene double bond. Treatment of the structurally related 4-hydroxyisoflavone with di(trifluoroacetoxy)iodobenzene leads to the surprising formation of 2,4′-dihydroxybenzil. Potential mechanisms for these new reaction pathways are discussed, and the X-ray crystal structure of 2,4′-dihydroxybenzil is presented. In contrast, oxidation of the corresponding 3-hydroxystilbenes and 3-hydroxyisoflavone led to conventional dienone oxidation products. The antitumour implications of these oxidation processes are briefly highlighted; the novel 4-substituted phenolic oxidation products were found to be inactive in terms of in vitro antitumour cellular activity, whereas the 3-substituted phenol products gave novel agents with potent and enhanced antitumour activity in the HCT 116 cancer cell line. © The Royal Society of Chemistry 2005.

Molecular mechanisms of salt effects on carbon nanotube dispersions in an organic solvent (N-methyl-2-pyrrolidone)

We consider the effects of salt (sodium iodide) on pristine carbon nanotube (CNT) dispersions in an organic solvent, N-methyl-2-pyrrolidone (NMP). We investigate the molecular-scale mechanisms of ion interactions with the nanotube surface and we show how the microscopic ion-surface interactions affect the stability of CNT dispersions in NMP. In our study we use a combination of fully atomistic Molecular Dynamics simulations of sodium and iodide ions at the CNT-NMP interface with direct experiments on the CNT dispersions. In the experiments we analyze the effects of salt on the stability of the dispersions by photoluminescence (PL) and optical absorption spectroscopy of the samples as well as by visual inspection. By fully atomistic Molecular Dynamics simulations we investigate the molecular-scale mechanisms of sodium and iodide ion interactions with the nanotube surface. Our simulations reveal that both ions are depleted from the CNT surface in the CNT-NMP dispersions mainly due to the two reasons: (1) there is a high energy penalty for the ion partial desolvation at the CNT surface; (2) NMP molecules form a dense solvation layer at the CNT surface that prevents ions to come close to the CNT surface. As a result, an increase of the salt concentration increases the "osmotic" stress in the CNT-NMP system and, thus, decreases the stability of the CNT dispersions in NMP. Direct experiments confirm the simulation results: addition of NaI salt into the NMP dispersions of pristine CNTs leads to precipitation of CNTs (bundle formation) even at very small salt concentration (∼10 -3 mol L -1). In line with the simulation predictions, the effect increases with the increase of the salt concentration. Overall, our results show that dissolved salt ions have strong effects on the stability of CNT dispersions. Therefore, it is possible to stimulate the bundle formation in the CNT-NMP dispersions and regulate the overall concentration of nanotubes in the dispersions by changing the NaI concentration in the solvent. © 2012 The Royal Society of Chemistry.

Identification of the degradation mechanisms of organic solar cells:active layer and interfacial layers

Organic Solar Cells (OSCs) represent a photovoltaic technology with multiple interesting application properties. However, the establishment of this technology into the market is subject to the achievement of operational lifetimes appropriate to their application purposes. Thus, comprehensive understanding of the degradation mechanisms occurring in OSCs is mandatory in both selecting more intrinsically stable components and/or device architectures and implementing strategies that mitigate the encountered stability issues. Inverted devices can suffer from mechanical stress and delamination at the interface between the active layer, e.g. poly(3-hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM), and the hole transport layer, e.g. poly(3,4-ethylenedioxythiophene):poly(p-styrene sulfonate) (PEDOT:PSS). This work proposes the incorporation of a thin adhesive interlayer, consisting of a diblock copolymer composed of a P3HT block and a thermally-triggerable, alkyl-protected PSS block. In this context, the synthesis of poly(neopentyl p-styrene sulfonate) (PNSS) with controlled molar mass and low dispersity (Ð ≤ 1.50) via Reversible Addition-Fragmentation chain Transfer (RAFT) polymerisation has been extensively studied. Subsequently, Atomic Force Microscopy (AFM) was explored to characterise the thermal deprotection of P3HT-b-PNSS thin layers to yield amphiphilic P3HT-b-PSS, indicating that surface deprotection prior to thermal treatment could occur. Finally, structural variation of the alkyl protecting group in PSS allowed reducing the thermal treatment duration from 3 hours (P3HT-b-PNSS) to 45 minutes for the poly(isobutyl p-styrene sulfonate) (PiBSS) analogous copolymer. Another critical issue regarding the stability of OSCs is the sunlight-driven chemical degradation of the active layer. In the study herein, the combination of experimental techniques and theoretical calculations has allowed identification of the structural weaknesses of poly[(4,4’- bis(2-ethylhexyl) dithieno [3,2-b:2’,3’-d]silole)-2,6-diyl-alt-(4,7-bis(2-thienyl)-2,1,3-benzothiadiazole)-5,5’-diyl], Si-PCPDTBT, upon photochemical treatment in air. Additionally, the study of the relative photodegradation rates in air of a series of polymers with systematically modified backbones and/or alkyl side chains has shown no direct correlation between chemical structure and stability. It is proposed instead that photostability is highly dependent on the crystalline character of the deposited films. Furthermore, it was verified that photostability of blends based on these polymers is dictated by the (de)stabilising effect that [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) has over each polymer. Finally, a multiscale analysis on the degradation of solar cells based on poly[4,4' bis(2- ethylhexyl) dithieno[3,2-b:2',3'-d]silole)-2,6-diyl-alt-[2,5 bis(3 tetradecylthiophen 2-yl)thiazole[5,4-d]thiazole)-1,8-diyl] and PCBM, indicated that by judicious selection of device layers, architectures, and encapsulation materials, operational lifetimes up to 3.3 years with no efficiency losses can be successfully achieved.

Organic reactions in ionic liquids:Gewald synthesis of 2-aminothiophenes catalyzed by ethylenediammonium diacetate

Ionic liquids based on 1-butyl-3-methylimidazolium tetrafluoroborate (BmimBF4) and 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6) were used as reusable alternatives to volatile organic solvents (VOCs) for ethylenediammonium diacetate (EDDA) catalyzed Gewald synthesis of 2-aminothiophenes. Significant rate enhancement and improvement of the yield were observed. The ionic liquids containing catalyst EDDA were recycled several times with no decreases in yields and reaction rates.

Organic reactions in ionic liquids:A new method for the synthesis of alkyl aryl sulfones by alkylation of sodium arenesulfinates with unactivated alkyl chlorides

A new method is reported for the synthesis of alkyl aryl sulfones by alkylation of sodium arenesulfinates with unactivated alkyl chlorides using ionic liquid based on 1-butyl-3-methylimidazolium tetrafluoroborate (BmimBF 4) mixed with water (2:1) as reaction media. The ionic liquid can be reused and the procedure gives the sulfones in moderate yields.

Organic reactions in ionic liquids:A simple and highly regioselective N-substitution of pyrrole

In ionic liquids [Bmim][PF6] or [Bmim][BF4], pyrrole replaced the halogen atom of an alkyl halide to give the corresponding N-substituted pyrrole in excellent yield. Benzenesulfonyl chloride, p-methylbenzenesulfonyl chloride and benzoyl chloride reacted similarly with pyrroles to afford the N-substituted pyrroles in quantitative yield. Michael addition reaction of pyrrole with electrophilic olefins was completed in a highly regioselective manner to afford the N-alkylpyrroles.

Organic reactions in ionic liquids:An efficient method for selective S-alkylation of 2-mercaptobenzothia(xa)zole with alkyl halides

Ionic liquids based on 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6) and 1-butyl-3-methylimidazolium tetrafluoroborate (BmimBF4) are used as reusable reaction medium in the selective S-alkylation of 2-mercaptobenzothia(xa)zole with alkyl halides in the presence of potassium carbonate. This procedure is convenient, efficient, and generally gives rise to the S-alkylated product exclusively.

Organic reactions in ionic liquids: N-alkylation of cyclic imides with alkyl halides promoted by potassium fluoride

An ionic liquid based on 1-butyl-3-methylimidazolium hexafluorophosphate is used as an efficient reusable reaction medium in the N-alkylation of cyclic imides with alkyl halides promoted by fluoride ion.

Organic reactions in ionic liquids: Knoevenagel condensation catalyzed by ethylenediammonium diacetate

The moisture and air stable ionic liquids 1-butyl-3-methylimidazonium tetrafluoroborate [bmim]BF4 and 1-butyl-3-methylimidazonium hexafluorophosphate [bmim]PF6 were used as ‘green' recyclable alternatives to volatile organic solvents (VOCs) for ethylenediammonium diacetate (EDDA) catalyzed Knoevenagel condensation between aldehydes or ketones with active methylene compounds. Both aldehydes and ketones gave satisfactory results. The ionic liquids containing catalyst EDDA were recycled several times with no decreases in yields and reaction rates. In the case of 2-hydroxybenzaldehyde, the reactions led to the formation of 3-substituted coumarins under standard reaction conditions.

The use of enzymes in organic solvents in polytransesterification reactions

The aim of this research project was to identify the factors affecting the porcine pancreatic lipase (PPL.)-catalysed polytransesterification of a diester and a diol in organic solvents. It was hoped that by modifying reaction conditions a commercially acceptable polymer molecular weight (Mn) of 20,000 daltons might be attained. Exploratory investigations were carried out using 1,4-butanediolibis(2,2,2- trichloroethyl) adipate and glutarate systems in diethyl ether, with and without molecular sieves. It was found that molecular sieves promoted the reaction by reducing hydrolysis of the ester end-groups, resulting in polymer molecular weights between 1.2 and 2.2 times greater than those obtainable without molecular sieves. Investigations were then concentrated on the PPL-catalysed polytransesterification of 1,4-butanediol with divinyl adipate. The particular advantage of this system is that the reaction is irreversible. The effects of varying substrate concentration, mass of drying agent, reaction solvent, reaction temperature, mass of enzyme and also enzyme immobilisation on the 1,4-butanediolidivinyl adipate system were investigated. The highest molecular weight polymer obtained for the PPL-catalysed polytransesterification of 1,4-butanedial with divinyl adipate in diethyl ether was Mn -8,000. In higher boiling ether solvents molecular weights as high as Mn -9,200 were obtained for this system at elevated temperatures. It was found that the major factor limiting polymerisation was the low solubility of the polymer in the solvent which resulted in precipitation of the polymer onto the surface of the enzyme.

The use of enzyme catalysts in organic media for the synthesis of biodegradable polyesters

The enzyme catalysed polytransesterification of diesters with diols was investigated under various conditions. The most consistent results were obtained using crude porcine pancreatic lipase (PPL) suspended in anhydrous diethyl ether. Addition of molecular sieve to the above system gave higher molecular weight products. The PPL catalysed reaction of bis(2,2,2-trichlorethyl) adipate and glutarate with butane-1,4-diol in anhydrous ether with and without molecular sieve was investigated over a range of times from 8 to 240 hours. The 72 hour adipate reaction with molecular sieve gave the highest molecular weight polymer (Mn 6,500 and Mw 9,400). The glutarate gave the maximum molecular weight polyester after 24 hours (Mn 5,700 and Mw 9,500). Occasionally the glutarate reaction produced very high molecular weight polyester-enzyme complexes. Toluene generally gave lower molecular weight products than diethyl ether. Dichloromethane and tetrahydrofuran gave mainly dimers and trimers. Alternative enzyme and diol systems were also investigated. These yielded no polymeric products. The molecular weights of the polyesters were determined by 1H NMR end-group analysis and by GPC. The molecular weights determined by NMR were on average about twice as great as those determined by GPC. The synthesis of the following diesters is described: i)Bis(2,2,2-trichloroethyl) succinate, glutarate, adipate, trans-3-hexenedioate, and trans-3,4-epoxyadipate. ii) Diphenyl glutarate and adipate.iii)Bis(2,2,2-fluoroethyl) glutarate and trans-3-hexendioate.iv) Divinyl glutarate. v) N,N'Glutaryl dicyclohexanone oxime.The polytransesterification of all the above esters with diols was investigated. The easily synthesised bis(2,2,2-trichloroethyl) glutarate and adipate gave the best results and the work was concentrated on these two esters.

Organotellurium compounds for metal organic vapour phase epitaxy

The infra-red detector material cadmium mercury telluride can be grown by the technique of Metal Organic Vapour Phase Epitaxy using simple alkyl telluride compounds as the source of tellurium. New tellurium precursors are required in order to overcome handling and toxicity problems and to reduce the growth temperature in preparing the material. A range of diaryltellurium(IV) dicarboxylates and some 2-(2'-pyridyl)phenyl-tellurium(II) and tellurium(IV) monocarboxylates have been synthesised and characterised by infra-red, 13C N.M.R. and mass spectroscopy. Infra-red spectroscopy has been used to determine the mode of bonding of the carboxylate ligand to tellurium. Synthetic methods have been devised for the preparation of diorganotritellurides (R2Te3) and mixed diorganotetrachalcogenides (RTeSeSeTeR). A mechanism for the formation of the tritellurides based on aerobic conditions is proposed. The reaction of ArTe- with (ClCH2CH2)3N leads to tripod-like multidentate ligands (ArTeCH2CH2)3N which form complexes with the ions Hg(II), Cd(II), Cu(I), Pt(II) and Pd(II). Synthetic routes to aryltelluroalkylamines and arylselenoalkylamines are also reported. The crystal structure of 2-(2'-pyridyl)phenyltellurium(II) bromide has been solved in which there are six molecules present within the unit cell. There are no close intermolecular Te---Te interactions and the molecules are stabilised by short Te---N intramolecular contacts. The crystal structure of 2-(2'-pyridyl)phenylselenium(II)-tribromomercurate(II) is also presented. A study of the Raman vibrational spectra of some tellurated azobenzenes and 2-phenylpyridines shows spectra of remarkably far superior quality to those obtained using infra-red spectroscopy.

The mechanisms of melt stabilisation of polyolefins

The effects of melt stabilisers on the oxidative degradation of polyolefins (polypropylene, low density polyethylene) have been studied under a variety of processing conditions . The changes in the both chemical and physical properties of unstabilised polymers occurring during processing were found to be strongly dependent on the amount of oxygen present in the mixer. 2 ,6 ,3' ,5' -tetra-tert-butyl-4'-phenoxy-4-methylene-2, 5-cyclohexadiene-1- one (galvinoxyl), iodine, nitroxyl radicals and cupric stearate were found to be very efficient melt stabilisers particularly when processed in a restricted amount of air. The mechanisms of their melt stabilising action have been investigated and a common cyclical regenerative mechanism involving both chain-breaking electron acceptor (CB-A) and chain-breaking electron donor (CB-D) antioxidant activity was found to be involved in each case. 2,6,3',5'-tetra-tert-butyl-4'-hydroxy phenyl-4-rrethylene-2,5-cyclohexadiene- 1-one (hydrogalvinoxy1), 4-hydroxy, 2,2,6, 6-tetra methyl-N-hydroxy piperidine and hydrogen iodide were formed together with olefinic unsaturation in the substrates during the melt processing of the polymers containing galvinoxyl, 4-hydroxy, 2,2,6, 6-tetra methyl piperidine oxyl and iodine respectively. No bonding of the melt stabilisers to the polymers was found to occur. Cupric stearate was found to undergo a similar redox reaction during its action as a melt stabiliser with the formation of unsaturation in the polymer. Evidence for the above processes is presented. The behaviours of melt stabilisers in the subsequent thermal and photooxidation of polyolefins have also been studied. Galvinoxyl which is very effective under both mild and severe processing canditions has been found to be an effective antioxidant during thermal oxidation (oven ageing) and it is also moderately good. as a photo-stabiliser. Iodine and cupric stearate acted efficiently during melt stabilisation of polymers, however they were both ineffective as thermo-oxidative antioxidants and UV stabilisers. Although the melt stabilisation effectiveness of stable nitroxyl radicals (e.g. 4-hydroxy, 2,2,6,6-tetra methyl piperidineoxyl and Bis- (2,2,6 ,6-tetra methyl-4- piperidinyl-N-oxyl) sebacate) is not as high as that of galvinoxyl during processing particularly in excess of air, they have been found to be much more efficient as UV stabilisers for polyolefins. The reasons for this are discussed.

Studies on DNA methylation and mechanisms of hypomethylation

The methylation of cytosinc residues in DNA is thought to play an important role in the regulation of gene expression, with active genes generally being hypomethylated. With this in mind peptides were synthcsised to mimic the cytosine-5 methylation activity carried out by DNA mcthylase, which however, showed no ability to carry out this function. The imidazotetrazinoncs are a novel group of antitumour agents which have demonstrated good activity against a range of murinc tumours and human tumour xenografts, and hypomethylation of DNA has been implicated in the mechanism of action. Studies have been conducted on the mechanism by which such agents cause hypomethylation, using DNA methylase partially purified from murine L1210 leukaemia cells. Unmodified calf thymus DNA does not inhibit the transfer of methyl groups from SAM to M.lysodeikticus DNA by partially purified DNA methylase. However, if the calf thymus DNA is modified by alkylating agents such as imida-zotetrazinones or nitrosoureas, the treated DNA becomes an inhibitor of the methylation reaction. This has been correlated with the induction of DNA damage, such as single strand breaks, since X-ray treated DNA and deoxyribonuclease treatment produces a similar effect. The mechanism of inhibition by the drug treated or damaged DNA is thought to occur by binding of the enzyme to an increased concentration of non-substrate DNA, presumably by the occurrence of single strand breaks, since neither sonication nor treatment with the restriction enzyme Mspl caused an inhibition. Attempts were made to elucidate the strict structure activity relationship for antitumour activity observed amongst the imidazotctrazinones. The transfection of a murine colon adcnocarcinoma cell line (MAC 13) with DNA extracted from GM892 or Raji cells previously treated with either the methyl (temozolomide) or ethyl (ethazolastone) imidazotetrazinone was performed. X-irradiated DNA did not cause any suppression of cell growth, suggesting that it was not due to physical damage. Transfection of MAC 13 cells with DNA extracted from GM892 cells, was more effective at inhibiting growth than DNA from Raji cells. Temozolomide treated cellular DNA was a more potent growth inhibitor than that from ethazolastone treated cells. For both agents the growth inhibitory effect was most marked with DNA extracted 6h after drug addition, and after 24h no growth suppression was observed. This suggested that the growth inhibitory effect is due to a repairable lesion. .The methylation of M.lysodeikticus DNA by DNA methylase is inhibited potently and specifically by both hereto and homoribo and dcoxyri-bopolynucleotides containing guanine residues. The inhibitory effect is unaffected by chain length or sugar residue, but is abolished when the O-6 residue of guanine is substituted as in poly d(OGG)2o. Potent inhibition is also shown by polyinosinic and polyxanthylic acids but not by polyadenylic acid or by heteropolymers containing adcnine and thymine. These results suggest that the 6 position of the purine nucleus is important in binding of the DNA methylase to particular regions of the DNA and that the hydrogen bonding properties of this group are important in enzyme recognition. This was confirmed using synthetic oligonucleotides as substrates for DNA methylase. Enzymatic methylation of cytosine is completely suppressed, when O6 methylguanine replaces guanine in CG sites.

Interactions between organic polymers and cement hydration products

Organic substances, particularly polymers, are finding increasing use in modifying the properties of cements and concrete. Although a significant amount of research has been conducted into the modification of the mechanical properties of cements by polymers, little is known about the nature of the interface and interactions taking place between the two phases. This thesis addresses the problem of elucidating such interactions. Relevant literature is reviewed, covering the general use of polymers with cements, the chemistry of cements and polymers, adhesion and known interactions between polymers and both cements and related minerals. Although several polymer systems were studied, two in particular were selected, as being well characterized. These were: - 1) polymethyl methacrylate (PMMA), the polymer derived from methyl methacrylate (MMA), and 2) an amine-cured epoxy resin system. By this approach, a methodology was developed for the examination of other polymer/cement interactions. Experiments were conducted in five main areas:- 1) polymer-cement adhesion and the feasibility of revealing interfacial regions mechanically, 2) chemical reactions between polymers and cements, 3) characterization of cement adhesion surfaces, 4) interactions affecting overall polymerisation rates, and 5) studies of polymer impregnated cements. The following conclusions were reached:- 1) The PMMA/cement interface contains calcium methacrylate as an interfacial reaction product, water being a reactant. Calcium methacrylate is detrimental to the properties of PMMA/cement composites, being highly water-soluble. 2) The pore surface of cement accelerates the polymerisation of MMA, leading to an increased molecular weight compared to polymerisation of pure MMA, minerals in hydrated cement powders having the opposite effect. 3) The investigation of reaction products presents a number of experimental problems, selection of appropriate techniques depending upon the system studied. For the two systems examined in detail, ion chromatography proved particularly useful; DTA, IRS and XPS indicated reactions, though the data was hard to interpret; XRD proving inconclusive. 4) It is impractical to reveal interfacial regions mechanically, but may be accomplished by chemical means.