No description available.

No description available.

One of the most critical factors in the success of a solid phase synthesis is the choice of linker. The linker must be stable during synthesis then cleaved under conditions that do not damage the product. Ideally then the cleavage conditions should be both mild and selective. For this reason resin/linker systems such as 3 have been designed for cleavage by enzyme. 3 was synthesised using a variety of spacers and solid supports, starting from either soluble linker 1 or support bound aldehyde 2. Activation of the ethylthiolate group of 3 and subsequent displacement by primary and secondary alcohols gave 4 in good yield. Both enzymatic and acidic cleavage of alcohol from 4 was investigated. As the acid stability of 4 could be modulated depending on the nature of the spacer it was possible to induce cleavage under very mild acidic conditions. (Fig. 9898) The utility of 3 was demonstrated by coupling of Fmoc serine methyl ester through the side-chain hydroxyl functionality and subsequent elaboration to a pentapeptide (H-SAVSS-OMe). This approach could find application in the synthesis of cyclic peptides and peptides with modified C-termini.

This work presents a systematic approach to the identification of possible by-products in process synthesis. The objective is to discover all possible reactions that might take place in a reaction system, in addition to already known main reactions. These side reactions may generate species in minor quantities which can be difficult to separate and therefore be into the recycle system. These species can thus remain in the process and accumulate. A literature survey indicated that generic languages for chemical reactions have been developed recently by other workers. These have adopted the concepts of fundamental chemistry with the aim of identifying major chemical reactions. For the purpose of the present work, strict interpretation of chemistry was not considered necessary since the aim was to generate minor species which <I>might</I> be formed. The work covers aspects of molecular representation, reaction generation and thermodynamic evaluation for screening. Molecular properties are estimated using group contribution methods. Unlikely species are ruled out using both stoichiometric and thermodynamic tests. The approach was first tested by comparison with experimental work, on the partial wet oxidation of p-coumaric acid and alkylation of toluene with ethanol. This shows favourable results. Process case studies were then undertaken including vinyl chloride monomer and the preparation of R-134a and R-22. These processes have been used to study the effect of by-product build-up. The study involved separation simulation to investigate the separability of the components. This confirmed that many potential by-products would be difficult to separate and might tend to accumulate in recycles. The results show that the approach has a promise for identifying possible side reactions, by-products and the problems that they will cause in a continuous process. Thus in the long term the approach affects the possibility of reducing and eliminating pilot plant studies in moving from laboratories to full scale processes.

Investigations into the role of alkenes as promoters of benzyneformation from N-Nitrosoacetanilide, using furan as a benzyne trap showed that the ability of the alkene to trap and efficiently delocalise free radicals involved in competing processes was of primary importance, while the resistance of the radical-alkene adduct to subsequent oxidation appeared to be an additional controlling factor. Thus good benzyne promotion was observed using dibenzofulvene and 1, 1-(bis-4-biphenylyl)ethene while 1, 1-dibenzoylethene showed no promoting effect. The use of 1,1-diphenylethene as a promoter with ring-substituted N-nitrosoacetanilides showed that while yields of 4-t-butylbenzyne derived from _N-nitroso-4-t-butylacetanilidc were significantly increased with respect to the reaction in the absence of alkene, no significant effects were observed on the yields of arynes derived from N-nitroso-4-methoxyacetanilide and N-nitroso-4-methylacetanilide; the formation of free radical derived products was suppressed in each case. N-Nitroso-2- and 4-chloroacetanilides in benzene and 1,1-diphenylethene underwent substitution of chloride by acetate and formed diazonium chlorides. N-Nitroso-2- and 4-acetoxyacetanilides decomposed via the intermediacy of benzoquinone monodiazides and carbenes as was shown by the isolation of 1,4dioxa-2, 3-benzofulvalene from the decomposition of N-nitroso-2-acetoxyacetanilide in p-xylene. N-Nitroso-2-thioacetoxyacetanilide decomposed in benzene to yield 1, 2, 3-benzothiadiazole. In the reaction of diaroyl peroxides with dimethyl acetylenedicarboxylate (DMAD) to form tetramethyl naphthalen-1, 2, 3, 4-tetracarboxylates low yields were shown, by measurement of carbon dioxide evolution, to be in part due to inefficient decarboxylation of the aroyloxy radicals; aroic acid formation was insignificant. The decomposition of dicinnarnoyl peroxide in DMAD gave no cyclised product while bis-a-methylcinnamoyl peroxide in DMAD gave a low yield of dimethyl 3-methylnaphthalen-1, 2-dicarboxylate.

No description available.

In recent years, the use of microwave irradiation to accelerate chemical reactions has become increasingly popular. A protocol for the synthesis of esters <i>via</i> reaction of carboxylic acids with <i>O-</i>alkylisoureas under microwave heating was studied. Efficient processes were developed using pre-formed <i>O</i>-alkylisoureas or <i>via</i> an in-situ formation sequence starting from primary and secondary alcohols. It was demonstrated that under these microwave conditions ester formation with primary and secondary alcohols proceeded in good yields and, in the latter case, with clean inversion of configuration of the esters. <i>O</i>-alkylisoureas were used as reactive intermediate also in the alkylation of substituted phenols. A PASP procedure was also developed by employing pre-formed polymer-supported isoureas, and by an efficient “catch and release” esters formation procedure in which alcohols are caught on resin as isoureas by reaction with immobilised carbodiimide, and released as ester by subsequent treatment with a carboxylic acid. Polymer-supported isoureas were also employed in the synthesis of 2-oxazolines.

The low air stability of many primary phosphines has made them an under-utilised class of ligand, however they are versatile starting materials due to the possibility of functionalising the weak phosphorus hydrogen bonds, which can lead to a library of new phosphorus compounds. The work presented herein details the synthesis of the first air-stable fluorescent primary phosphines based on the fluorophore Bodipy (Chapter 2). The primary phosphines are shown to be air-stable in solution and in the solid state by 31P NMR spectroscopy and by DFT computational analysis, which is in accord with our group’s model of phosphine air-stability. In Chapters 3 and 4 we show the primary phosphines can be readily functionalised via hydrophosphination and formylation reactions to give novel fluorescent tertiary monodentate and tridentate derivatives. Fluorescent primary phosphines and their functionalisation via hydrophosphination reactions. Remarkably the phosphorus moieties have minimal influence on the photophysical properties, showing only a slight reduction in fluorescence quantum yields from the parent Bodipy dyes; the fluorescence is not ‘switched off’, which is the case for many amines and the few examples of phosphines conjugated to other fluorophores. In Chapter 4 we show these novel fluorescent phosphines coordinate to a range of low oxidation state(I-III) transition metals including those in groups 6, 9, 10 and 11. Surprisingly the presence of the heavy metals does not turn off the emission of the Bodipy dye; the complexes also showed high thermal and air stability in solution. These complexes have the potential to be used as multi-functional radiopharmaceutical complexes, for which the following functions were sought after (i) a polydentate ligand to ensure the complex is kinetically inert and thermodynamically stable; (ii) a radioactive metal centre, which will allow in vivo nuclear imaging using a gamma scanner; (iii) a fluorophore, which will provide in vitro fluorescence imaging and (iv) a target-specific group to transport the radiolabel to a specific receptor site in the body for iii a given disease. This combination of modalities would allow images obtained from fluorescence cell imaging to be correlated with in vivo radioimaging, to gain a greater understanding of the true fate of these agents within the body. The last chapter shows how the fluorescent rhenium(I) phosphine complexes can be made target-specific, and details the synthesis of a 99mTc radio-analogue containing a fluorescent tridentate phosphine rhenium(I) centre, which showed high levels of stability in biological media. Fluorescent rhenium(I) phosphine complexes, which have a carboxylic acid tag for peptide coupling, allowing the preparation of a target-specific fluorescent potential radiopharmaceutical, and a 99mTc/Re(I) fluorescent tridentate phosphine complex. Finally a number of the complexes are uptaken into cervical and prostate cancer cells and viewed by fluorescence confocal microscopy. Most of the complexes showed no toxicity towards the cells and have the potential to be used as a diagnostic tool.

The research presented throughout this dissertation demonstrates the potential of miniemulsion polymerization to co-encapsulate silicon quantum dots (SiQDs) within polymeric nanoparticles and shows that the optical properties of SiQDs can be manipulated by their co-encapsulation with metal nanoparticles. In Chapter 1, the current state of the art in the preparation of inorganic/polymer composite nanoparticles via miniemulsion polymerization, utilizing inorganic species ranging from semiconductor nanocrystal quantum dots, metal nanoparticles, magnetic and oxide nanoparticles, is reviewed. A brief discussion on the properties of SiQDs, which are the inorganic entities of interest in this work, is presented. Chapter 2 describes the synthesis and characterization of encapsulated alkylated SiQDs within polymer nanoparticles composed of the monomers styrene and 4-vinylbenzaldehyde via miniemulsion polymerization. It was shown that the polymer nanoparticle surfaces, which display aldehyde groups, can be further decorated with organic molecules through the formation of imine, oxime or hydrazone bonds. The preparation of two-component polymer composite nanoparticles encapsulating both SiQDs and gold nanoparticles (AuNPs) is presented in Chapter 3. These Au-Si polymer composite nanoparticles display plasmon-enhanced fluorescence of the SiQDs attributable to the localized surfaced plasmon resonance of AuNPs co-encapsulated within the polymer nanoparticles. A preliminary study of Au-Si polymer composite nanoparticles in inkjet printing is also discussed. Chapter 4 presents the development of multicomponent polymer composite nanoparticles which co-encapsulate SiQDs and Au-Ag alloys NPs encoded with Raman-active molecules within polymer nanoparticles. The multicomponent polymer composite nanoparticles exhibit the simultaneous effects of surface-enhanced Raman scattering and metal-enhanced fluorescence as a consequence of the close proximity of the co-encapsulated SiQDs and Raman-active Au-Ag NPs. In Chapter 5, the conclusions and future directions of this study are discussed. This research moves iii towards the development of novel inorganic/polymer composite nanoparticles which may offer potential as new chemical probes with applications in biology, sensing and anti-counterfeiting.

Uses for fluorescent dyes are diverse and increasingly important with compounds having many uses in medicinal, chemical and physical fields - amongst others. The creation of new fluorescent dyes helps to push the boundaries of molecular photonics alongside the further study of the underlying principles involved in the systems. This thesis concentrates largely on the synthesis and characterisation aspects of novel fluorescent dyes, though the analysis of the resultant photophysical data also features prominently. Chapter 1 is an introduction to fluorescence from some of the more basic principles involved in the field. A discussion and comparison of intrinsic and extrinsic fluorescent dyes is followed by a brief discussion of a series of examples of fluorescent molecular sensors. As bodipy dyes feature heavily throughout the thesis the second half of the introduction is focused solely on this topic. This half of the chapter centres around the synthetic approaches towards bodipy, modifications to the bodipy core and the resulting photophysics. Photo-induced electron transfer and fluorescence energy transfer is introduced from basic principles along with selected literature examples that demonstrate these processes in systems that incorporate bodipy. Chapter 2 discusses the synthesis and photophysics of a new class of fluorescent dyes based on a highly substituted terephthalate core. The initial aim of the chapter was to create fluorescent systems based on a xanthene core, this was found to be non-fluorescent. As such attention was turned towards a terephthalate intermediate which demonstrated strong and highly red shifted fluorescence in solution, as well as solid state fluorescence. A meso-perfluorinated phenyl ring causes a marked increase in fluorescence quantum yield, along with a pronounced red-shift, relative to the equivalent meso-phenyl variant. This observation lead to a series of Fn-aryl (n = 1,2,3,5) bodipy dyes being synthesised. Chapter 3 subsequently investigates the relationship between the number and position of fluorine atoms on the aryl moiety, and the resultant photophysical measurements. High fluorescence quantum yields were observed with ortho-substitution of fluorine atoms, a trend that was mirrored with the fluorescence lifetime. Mono-ortho fluorine substitution iii of the aryl group was also found to make the bodipy prochiral pathing the way towards axially chiral bodipy compounds. Chapter 4 follows on from chapter 4 by taking prochiral bodipy compounds to there chiral conclusion. In this chapter several synthetic approaches towards axially chiral (AxC) bodipy compounds are discussed. Included in these synthetic approaches is a completely novel route towards asymmetric bodipy cores thus AxC-bodipy compounds. This chapter represents the first examples of AxC bodipy compounds to exist with future developments in the field aimed at enhanced fluorescence sensing in chiral media and facile enantiomeric determination via circularly-polarised fluorescence measurements. Chapter 5 is an in-depth experimental section where the synthesis and characterisation of each compound is detailed. Also provided are the details for each chemical used, purification and drying methods for each solvent used and techniques used for proper characterisation of all of the compounds.