Yes / We deposited Os atoms on S- and Se-doped boronic graphenic surfaces by electron bombardment of micelles containing 16e complexes [Os(p-cymene)(1,2-dicarba-closo-dodecarborane-1,2-diselenate/dithiolate)] encapsulated in a triblock copolymer. The surfaces were characterized by energy-dispersive X-ray (EDX) analysis and electron energy loss spectroscopy of energy filtered TEM (EFTEM). Os atoms moved ca. 26× faster on the B/Se surface compared to the B/S surface (233 ± 34 pm·s–1 versus 8.9 ± 1.9 pm·s–1). Os atoms formed dimers with an average Os–Os distance of 0.284 ± 0.077 nm on the B/Se surface and 0.243 ± 0.059 nm on B/S, close to that in metallic Os. The Os2 molecules moved 0.83× and 0.65× more slowly than single Os atoms on B/S and B/Se surfaces, respectively, and again markedly faster (ca. 20×) on the B/Se surface (151 ± 45 pm·s–1 versus 7.4 ± 2.8 pm·s–1). Os atom motion did not follow Brownian motion and appears to involve anchoring sites, probably S and Se atoms. The ability to control the atomic motion of metal atoms and molecules on surfaces has potential for exploitation in nanodevices of the future. / We thank the Leverhulme Trust (Early Career Fellowship No. ECF-2013 414 to NPEB), the University of Warwick (Grant No. RDF 2013-14 to NPEB), the EPSRC (EP/G004897/1 to RKOR), and ERC (Grant No. 247450 to PJS) for support.

The research presented herein is concerned with the chemical modification of polysulfone towards the synthesis of a hollow fibre boronic acid fixed carrier membrane system for saccharide separation. Chapter 1 firstly introduces the area of boronic acids as chemosensors, in particular for detecting saccharides. Secondly, membrane separation techniques are discussed focussing on hollow fibre membranes and their synthesis. Chapter 2 discusses the potential of boronic acid fixed carrier hollow fibre membranes for saccharide separation. Three general routes are highlighted to achieve the desired boronic acid appended polymers: electrophilic aromatic substitution, lithiation and functional monomer polymerisation. Chapter 3 describes the various attempts at achieving the target polymer via electrophilic aromatic substitution methodology. Chapter 4 describes the various attempts at achieving the target polymer via lithiation methodology. Chapter 5 investigates the ability to create functional monomers with which functional polymers can be polymerised from. Chapter 6 describes the synthesis and characterisation of the compounds discussed in chapters 3, 4 and 5.

La modification d’oligonucléotides est un domaine attrayant de la chimie organique. De nombreuses études se sont intéressées à la génération de liens internucléosidiques artificiels à visée thérapeutique, diagnostic ou encore pour des applications en chimie prébiotique. Ce manuscript de thèse rapporte la synthèse et l’étude de biocompatibilité d’acides nucléiques modifiés à leurs extrémités 5’ par un acide boronique. Les comportement des oligomères boroniques a été évalué en présence de différentes classes d’enzymes telles que les ligases, les polymérases ou encore les phosphodiestérases. Les résultats de biocompatibilité obtenus en présence de ces enzymes nous ont permis d’utiliser ces acides nucléiques modifiés comme de réels outils de diagnostic pour réaliser de la détection de point de mutation ou encore de la détection de péroxynitrite in-cellulo. / The modification of oligonucleotides is an attractive field of organic chemistry. Many studies have focused on the generation of artificial internucleoside linkages for therapeutic, diagnostic or for applications in prebiotic chemistry. This thesis manuscript reports the synthesis and study of nucleic acids biocompatibility modified at their 5 'ends by a boronic acid function. The behavior of boronic oligomers was assessed in the presence of different classes of enzymes, such as ligases, polymerases or phosphodiesterases. The biocompatibility results obtained in the presence of these enzymes allowed us to use these modified nucleic acids as real diagnostic tools to achieve mutation point detection or detection of peroxynitrite in-cellulo.

Since its discovery in 1979, the Suzuki-Miyaura (SM) reaction has become one of the most widely utilised tools for carbon-carbon bond formation. The palladium catalysed coupling of an organoboron and organohalide compounds proceeds through a three-stage mechanism of oxidative addition, transmetalation and reductive elimination. The transmetalation of boronic acids to a palladium(II) complex has been widely studied. However, very little is known about the transmetalation of boronic esters, which are commonly used as an alternative to unstable boronic acids. Whether these species undergo direct transmetalation or prior hydrolysis to the boronic acid under SM conditions remains unknown. This research aimed to elucidate the mechanism of this cross-coupling process. Initial results under typical SM conditions created a biphasic reaction, promoted by the inorganic base and solvent composition, and showed that the boronic esters and corresponding boronic acid couple at the same absolute rate. This is thought to be a consequence of the formation of a biphasic mixture, rendering phase transfer the turnover-limiting step. The conditions were thus adapted to maintain a monophasic system using an organic soluble base, 2-tert-butyl-1,1,3,3-tetramethylguanidine, enabling the focus to be transmetalation as the turnover-limiting step. These new conditions show a significant difference in both reaction rate and induction period when using a boronic ester compared to the corresponding boronic acid. The use of guanidine was also shown to have an interesting effect on the boronic acid/ester species by 19F and 11B NMR. Further studies found the use of guanidine to create a boronate species, with this species being an aryl trihydroxyboronate or the hydroxyl"ate"-complex of the boronic ester, depending on the presence of diol in the system. Formation of a boronate species was found to be crucial for efficient cross-coupling. When testing weaker bases, unable to form a boronate species, poor SM cross-coupling conversion was found using the newly developed phosphine-free guanidine conditions, showing the importance of the boronate species under these conditions. The results suggest that depending on the strength of base used, the pathway of transmetalation pathway can be switched, between the boronate pathway and the oxo-palladium pathway, under the specific conditions developed.

With the rapidly increasing interest in the field of glycomics, which is the comprehensive study of the roles carbohydrates play in a living system, urgent need for developing quick and highly selective carbohydrate sensors is growing. The boronic acid group, with its electron-deficient structure (6 valence electrons with an open shell), acts as a Lewis acid with high intrinsic affinity towards Lewis bases such as fluoride, cyanide and hydroxyl groups. Specifically, formation of a 5- or 6- membered ring between the boronic acid moiety and a1,2- or 1,3-diol in aqueous solution has been fully explored as a strategy of carbohydrate sensor design. Along this line, those binders were termed as ¡°boronolectins¡± because of their similar functions as lectins. One challenge in developing boronic acid-based carbohydrate sensors is to enhance the discriminating ability among various carbohydrate analytes with diverse building blocks and complex linkage patterns. One approach is using polypeptide or oligonucleotide as a backbone or scaffold with functionalized boronic acid moiety to create a molecular library, and then selecting binders with favorable properties. The work presented here includes three general research parts: synthesis of a naphthalimide-based boronic acid-conjugated thymidine triphosphate (NB-TTP), fluorescence property studies of NB-TTP incorporated DNA (NB-DNA), and cellular imaging studies using NB-TTP: 1) 4-Amino-1,4-naphthalimide (Nap) was chosen as the fluorophore because of its relatively long excitation and emission wavelengths, and stability. The synthesis of naphthalimide-based boronic acid (NB) followed similar route as previously published work. Tethering of boronic acid moiety and TTP was accomplished through Cu(I)-catalyzed azide-alkyne cyclization (CuAAC), known as click chemistry. The synthesized NB-TTP showed fluorescence enhancements at long wavelength (¦Ëem: 540 nm) upon sugar addition. 2) NB-TTP was incorporated into DNA through Klenow fragment-catalyzed primer extension reactions. Different DNA sequences were designed with varying number and spacing for NB-TTP incorporation. The preliminary study provided certain insight into several factors that affect the fluorescent properties of different NB -DNA. 3) NB-TTP was added into Hela cell culture medium to study its cell imaging properties. With the observation under fluorescent microscope, it was demonstrated that NB-TTP showed good cell membrane permeability and significant accumulation in cell nucleus.

Conducting polymers have been widely explored for many different purposes including sensing. In thisthesis the conducive properties of pyrrole and the carbohydrate binding properties of boronic acid iscombined to make a reagent-free detector for carbohydrates. The polymer is manufactured in form ofparticles in the μm scale to create a porous film which has a high surface to volume ratio.The material was characterised and the binding properties were evaluated for galactose and glucose.Proof of binding was found via both electrochemical methods and QCM-D. A correlation between R2 value and concentration of substrate was found which enables measurement of concentration of carbohydratesin unknown samples.

Phosphorylated molecules play vastly important roles in the environment and biological systems. The main focus of this work sought to expand the current collection of synthetic phosphate receptors to include the binding of oligosaccharide phosphates. To this end, the synthesis of a boronic acid - appended porphyrin whose selectivity could be tuned through nucleic acid selection was pursued through a number of synthetic routes. Though difficulties were encountered with synthetic reactivities and product solubility, these efforts culminated in the development of a bis-boronic acid-substituted porphyrin soluble in DMSO/water mixtures that displays fluorescence quenching upon the addition of specific saccharide derivatives. In efforts to ease the synthetic burden, the creation of a DNA-based self-assembled receptor system was also investigated. Further, this work included the synthesis of phosphorylated derivatives of gemcitabine, a nucleoside chemotherapeutic drug, with the goal of developing targeted delivery systems for the improved treatment of cancer. Progress in each of these areas is discussed. / text

The Suzuki-Miyaura Cross-Coupling of aryl halides and aryl boronic esters has become one of the most important and oft used C-C bond forming reactions in industry and academia alike. Recently, substantial effort has been invested in expanding this reaction to include alkyl boronic esters as coupling partners, though until recently, success has been limited to primary alkyl boronic esters. Secondary alkyl boronic esters, with the inherent possibility of being chiral, have proven to be more difficult to couple. As a means of expanding our program on the enantio- and regioselective hydroboration of styrene derivatives, we sought to develop conditions that could couple benzylic (secondary) boronic esters. Not only was the coupling to aryl iodides achieved in moderate to good yield with a commercially available (and relatively cheap) catalyst system and phosphine, but the coupling reaction proceeds with almost complete retention of the stereochemistry installed during the hydroboration reaction. Interestingly, these conditions leave primary (linear) alkyl boronic esters completely untouched. Further examination of the chemoselectivity of the reaction revealed that, despite being unable to cross-couple strictly aliphatic secondary boronic esters, our silver-mediated protocol was able to effectively cross-couple chiral allylic boronic esters in high yield and good regioselectivity. The asymmetric syntheses of novel secondary boronic esters have also been developed to overcome the substrate limitations of the hydroboration reaction. Together with our effective cross coupling strategy, these novel chiral boronic esters have led to the synthesis of exciting new classes of molecules, most notably, the asymmetric triarylmethanes. Finally, the stability of mesoporous silica supports used in Pd catalysis was assessed. Though silica supports effectively reduce Pd-contamination in reaction mixtures to sub-ppm levels, their long-term reusability is hindered by material degradation caused by harsh reaction conditions. It was found that aqueous base, required for the Suzuki-Miyaura reaction, is responsible for silica degradation and the collapse of mesostructure. Interestingly, it was determined that the reaction itself had a protective effect on the material, with the boric acid side-product mitigating the deleterious effect of the base. / Thesis (Ph.D, Chemistry) -- Queen's University, 2011-09-19 14:53:49.444

Trichloroethylene, a simple and very inexpensive material, has been identified as a tri- and tetrafunctionalizable building block. A combination of selective palladium-catalyzed cross-coupling reactions with standard lithiation and electrophilic quenching yields a wide variety of unsaturated linear or cyclic compounds in excellent yields in few synthetic steps. Dichlorovinyl ethers, obtained from a nucleophilic displacement reaction with trichloroethylene, are the basic starting materials. Two sets of conditions have been developed to achieve the reaction of either electron-rich or –deficient phenols with trichloroethylene to give the resultant dichlorovinyl ethers in high yields. Site selective palladium-catalyzed cross-coupling for the specific functionalization of a single C-Cl bond was developed, and could install alkyl, alkenyl, alkynyl and (hetero)aryl moieties. The resulting electrophiles could be reacted with a second organometallic nucleophile forming trisubstituted, electron-rich alkenes, dienes, trienes or enynes in only two or three steps. Alternatively, the product from the first cross-coupling reaction could be isolated, deprotonated and quenched with an electrophile, then cross-coupled with a second organometallic nucleophile to give tetrasubstituted, electron-rich alkenes and dienes. In the course of studying the site selective cross-coupling, it was found that prolonged exposure of the C1-functionalized materials to palladium promoted an intramolecular C-H activation, forming 2-substituted benzofurans. This reaction proved to be very general, and a wide variety of benzofurans were synthesized, containing both electron-withdrawing and electron-donating group groups in the donor arenes, as well as alkyl, alkenyl, alkynyl and aryl functionalities at the 2-position. This method was also extended to the synthesis of 2-substituted indoles from anilines, trichloroethylene and boronic acids.

Trichloroethylene, a simple and very inexpensive material, has been identified as a tri- and tetrafunctionalizable building block. A combination of selective palladium-catalyzed cross-coupling reactions with standard lithiation and electrophilic quenching yields a wide variety of unsaturated linear or cyclic compounds in excellent yields in few synthetic steps. Dichlorovinyl ethers, obtained from a nucleophilic displacement reaction with trichloroethylene, are the basic starting materials. Two sets of conditions have been developed to achieve the reaction of either electron-rich or –deficient phenols with trichloroethylene to give the resultant dichlorovinyl ethers in high yields. Site selective palladium-catalyzed cross-coupling for the specific functionalization of a single C-Cl bond was developed, and could install alkyl, alkenyl, alkynyl and (hetero)aryl moieties. The resulting electrophiles could be reacted with a second organometallic nucleophile forming trisubstituted, electron-rich alkenes, dienes, trienes or enynes in only two or three steps. Alternatively, the product from the first cross-coupling reaction could be isolated, deprotonated and quenched with an electrophile, then cross-coupled with a second organometallic nucleophile to give tetrasubstituted, electron-rich alkenes and dienes. In the course of studying the site selective cross-coupling, it was found that prolonged exposure of the C1-functionalized materials to palladium promoted an intramolecular C-H activation, forming 2-substituted benzofurans. This reaction proved to be very general, and a wide variety of benzofurans were synthesized, containing both electron-withdrawing and electron-donating group groups in the donor arenes, as well as alkyl, alkenyl, alkynyl and aryl functionalities at the 2-position. This method was also extended to the synthesis of 2-substituted indoles from anilines, trichloroethylene and boronic acids.