8 research outputs found

    The synthesis of cyclic hexapeptide host molecules.

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    Beneficiation of selected pesticides and an antihyperlipidemic agent via cyclodextrin complexation and co-crystallization

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    The applications of many bioactive molecules are limited by their undesirable physicochemical properties, such as poor aqueous solubility and low thermal stability. The agrochemicals methyl- 2,5-dichlorobenzoate (fungicide, DCB) and fenthion (insecticide), as well as the medicinal compound acipimox (lipid-lowering agent) were selected for study in this context. The cyclodextrin (CD) complexes γ-CD/DCB, 2,6-dimethylated-β-CD/DCB, β-CD/fenthion, permethylated α-CD/fenthion and permethylated β-CD/fenthion, were synthesised. 1H-NMR spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and hot stage microscopy (HSM) were used to assess their stoichiometries and thermal behaviours. The complexes 2,6-dimethylated-β-CD/DCB, permethylated α-CD/fenthion and permethylated β-CD/fenthion have 1:1 host-guest stoichiometries, while those for γ-CD/DCB and β-CD/fenthion are 3:4 and 2:1 respectively. Single crystal X-ray structures were elucidated to investigate the modes of DCB inclusion and crystal packing. All of the solid complexes displayed higher thermal stabilities than those of the untreated pesticides. Furthermore, the volatility of the insecticide fenthion (a liquid at 25 ᵒC) was significantly reduced by its transformation to a solid on CDcomplex formation. The solution-state behaviour of fenthion was qualitatively evaluated using UV-visible spectrophotometry and induced circular dichroism. Phase solubility profiles at 25 ᵒC were of type Bs for solubilisation of DCB by β-CD and (2-hydroxypropyl)-β-CD, and for solubilisation of fenthion by β-CD, the respective 1:1 association constants being 737 ± 108 M⁻¹, 412 ± 53 M⁻¹ and 789 ± 170 M⁻¹. For solubilisation of fenthion by (2-hydroxypropyl)-β-CD and randomlymethylated β-CD, AN- and AP-type behaviours were recorded respectively, with association constants 1863 ± 26 M⁻¹ and 3582 ± 106 M⁻¹ respectively. Eight multi-component crystalline systems (co-crystals and salts) of acipimox were isolated via its reaction with co-formers 4-aminobenzamide, 4-aminopyridine, benzamide, isonicotinamide, tranexamic acid and urea. NMR spectroscopy revealed 1:1 stoichiometries for all products. Their designation as salts or co-crystals was based on unequivocal evidence gleaned from single crystal X-ray structural studies, these assignments being confirmed by infrared spectroscopy. The melting points and decomposition temperatures of the products containing the coformers 4- aminobenzamide, 4-aminopyridine, isonicotinamide and tranexamic acid were significantly higher than those of untreated acipimox. Equilibrium aqueous solubilities of the multicomponent systems ranged from 0.31 to 2.77 times those of untreated acipimox

    Studio di miscele multicomponente di liquidi ionici e composti molecolari

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    Ionic Liquids (ILs) are presently one of the hot topics in modern Chemistry. These compounds are basically salts having melting points below 100°C and typical features of great appeal in so many fields that I will not even attempt to number them, spanning from synthesis, industrial interest up to waste recycle . A number of 10^18 possible different ILs has been estimated and, nowadays, just a very small fraction of them is completely characterized under their physical and chemical aspects.Mixing two compounds often leads to some peculiar and unespected property of the related solution, otherwise not observable in the starting materials, thus to obtain new solvents and chemical products. That might be a more convenient route than the synthesis of a new molecule both from mere commercial and environmental considerations. The main goal of my research project is the understanding of the mechanism standing at the basis of mixing Ethylammonium Nitrate (EAN) with a number of other molecules chosen on the basis of polarity considerations. EAN is the perfect candidate for this study because it is the prototype of a wide class of ILs classified as Protic Ionic Liquids. These chemical substances are often named the "Green Solvent of the Future" and an ambitious target of my studies upon selected mixtures of ionic liquids might be, if successfully accomplished, the finding of an inexpensive protocol to deal with materials of practical use. To achieve this goal, the full characterization of chosen systems is actually mandatory and therefore several investigation techniques should be used, such as spectroscopy, calorimetry, diffraction and computational simulations

    Towards an anthropogenic nitrogen cycle based on nitrite

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    The overall goal of this thesis was to investigate the feasibility of a new route to anthropogenic nitrogen fixation based on the oxidation of nitrogen (to give primarily nitrite), and then electrocatalytic conversion of nitrite to other N-containing species of interest, such as nitrate and nitric oxide (NO). In pursuit of this goal, the synthesis of metal-ligand coordination complexes that could act as electrocatalysts for the oxidation of nitrite to nitrate was attempted, as was the synthesis of metal-ligand coordination complexes that could act as electrocatalysts for the reduction of nitrite to NO. As a corollary to this, routes for the initial fixation reaction were also investigated, of which the ultrasonic generation of nitrite from aerated aqueous solutions was found to be the most promising. The work detailed in this thesis is organized in the following manner: In Chapter 1 we discuss coordination complexes that mimic the enzymes promoting the redox reactions of the nitrogen cycle involving nitrite as a substrate or product. During this introduction we will also give an overview of topics that are relevant to the following chapters, such as proton-coupled-electron transfer and basic kinetic treatment of catalytic reactions. Chapter 2 is a description of the different techniques used throughout this thesis. Once having set the bases, we shall start with the actual research, which corresponds to Chapters 3 to 6. Chapter 3 deals with the synthesis, characterization and catalytic properties of a copper coordination compound mimicking the active site of the copper nitrite reductase (CuNiR) class of enzymes. This chapter includes a detailed study of the kinetics and electrocatalytic properties of this complex towards the mono-electronic reduction of nitrite to nitric oxide. Chapters 4 and 5 deal with the unusual structures and spectroscopic properties of a number of new cobalt complexes that we isolated whilst trying to develop Mo(bis-dithiolene) coordination complexes that might act as analogues of the molybdenum nitrite oxidoreductase (MoNiOR), which oxidises nitrite to nitrate in nature. Our original Mo-containing targets proved impossible to obtain and are not discussed in this thesis. However, we found that cobalt readily makes coordination complexes with these bis-dithiolene ligands, which allowed us to isolate the compounds we present in Chapters 4 and 5. Hence in Chapter 4 we show the synthesis and the solvatochromic properties of mixed-ligand mono-nuclear Co-diimine o-catecholato complexes and compare these complexes with the analogous compounds prepared with o-benzenedithiolato ligands. Chapter 5 then discusses the synthesis and redox properties of a mixed-ligand di-cobalt coordination complex in which the two cobalt centres have (unprecedented) inequivalent metal coordination environments. Finally, in Chapter 6 we describe a much-underexplored way to fix nitrogen based on a sonochemical reaction. After a brief introduction we describe the optimisation of the procedure and comparisons with previous reports

    Synthesis and Chemistry of Isoprekinamycin and Analogues

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    A methodology was studied to set up the benzo[a]fluorene skeleton, which provides a potential route to the total synthesis of isoprekinamycin (IPK) (1-112) and analogues of this natural product that contains an unusual diazo group so as to study the relationship of the structure and bioactivities. Basically the strategy involved a Suzuki coupling between the bromoindenone 2-64 as an AB ring building block and the pinacol boronate 2-89 as a D ring building block to generate a diaryl intermediate 2-90 that incorporates the A, B and D ring of isoprekinamycin. The diaryl intermediate was cyclized via a Dieckmann-like reaction to provide the full ABCD benzo[a]fluorene ring system that incorporates a cyano group at the carbon atom intended to become the carbon of the diazo group in the final structure. This intermediate was subjected to a sequence of reactions involving hydrolysis of the cyano group to the amide followed by a modified Hofmann rearrangement that provided the C-N bond at the correct position for creation of the diazo group in a three step sequence. This methodology provided a model of IPK 2-58 with the longest linear path of the synthesis being thirteen steps and in a 7% yield overall. A total synthesis of IPK which followed the method developed in the model synthesis was then attempted. In this IPK synthesis, the key Dieckmann-like cyclization that proceeded very selectively in the model synthesis proved to be problematic as a result of a competing aldol reaction involving the B-ring ketone group. This problem was eventually solved by reducing the ketone with LiAlH(n-Bu)(i-Bu)2 to produce a reduced aluminate intermediate which served as a protecting group through several steps to the full benzo[a]fluorene system that provided a sample of IPK, after appropriate functional group modification. The synthetic compound was shown to be identical with a sample of the natural product. The synthesis represents the first total synthesis of IPK and was achieved with an overall yield of 6% and the longest linear path being fourteen steps. An examination of the crystallographic data for the model compound 2-58 and IPK provided structure confirmation of the proposal that the diazonium ion character of the diazo group in IPK is enhanced by the presence of intramolecular H-bonding An analogue of IPK was designed, incorporating a side chain at C3 of the D ring in order to improve solubility and potentially the affinity of the molecule for DNA. An intermediate 4-74 that contains a carbamate group intended to serve as the precursor of the diazo group of the IPK analogue, was synthesized using the same strategy as the model of IPK through eleven steps in 14% yield overall. Another benzo[a]fluorene 5-28 was synthesized in 6% overall yield, via an eleven steps sequence initiated from commercial available 3-methylsalicylic acid. This benzo[a]fluorene is intended to be a key intermediate for the total synthesis of fluorostatin A and for the synthesis of analogues of IPK with a side chain at the C4 of the D ring. A discussion of potential significance of the proposed analogues and how they might be best achieved synthetically from the intermediates prepared in this study is provided.1 yea

    Synthesis of novel chiral pyrrolidine-type (salen)Mn(III) complexes.

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    The thesis reports the total syntheses of new chiral pyrrolidine-type salen ligands 5.4 and their corresponding Mn(III) complexes 5.5. The salen ligands were synthesized by condensation of tras-(3R,4R)-diaminopyrrolidine (3.12) or trans-(3R,4R)-1-benzyl-3,4-diaminopyrrolidine (3.10) with two equivalents of (R)-3-formyl-2-hydroxy-2'-phenyl-1,1'-binaphthalene [(R)-4.9]. The salen ligands were transformed to their corresponding Mn(III) complexes following a general procedure. The catalytic performances of the synthesized (salen)Mn(III) complexes in asymmetric epoxidation of 1,2-dihydronaphthalene were tested. In chapter 1, a review of asymmetric epoxidation of alkenes is given. Emphasis is placed on the development and some of the important designs of chiral salen ligands and their corresponding (salen)Mn(III) complexes. In chapter 2, the nature of the research project is outlined. In chapter 3, the syntheses of trans-(3R,4R)-diaminopyrrolidine trihydrochloride salt (3.9), trans-(3R,4R)-1-benzyl-3,4-diaminopyrrolidine (3.10) and its trihydrochloride salt (3.11) are reported. These compounds were prepared from (2R,3R)-(-i-)-tartaric acid via multi-step syntheses. Extensive studies on optimization of these transformations are reported. Chapter 4 records the synthesis of (R)-3-formyl-2-hydroxy-2'-phenyl-1,1'-binaphthalene [(R)-4.9] from 2-naphthol via a seven-step synthetic procedure. Extensive studies on these transformations are described, especially on the oxidative coupling of 2-naphthol and on the optical resolution of racemic 2,2'-dihydroxy-1,1'-binaphthalene. In chapter 5, the preparations of salen ligands 5.4 and their corresponding Mn(III) complexes 5.5 are reported. The applications of synthesized Mn(III) complexes in asymmetric epoxidation of 1,2-dihydronaphthalene were carried out. In chapter 6, an overall conclusion of the work is given

    IMA2010 : Acta Mineralogica-Petrographica : abstract series 6.

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