The ability to generate chiral building blocks is of paramount importance to organic chemists. This problem presents itself most notably at the interface of chemistry and biology, where molecules of only a single enantiomer can induce function to many biological systems. In this context, recent developments in the field of organocatalysis, most notably the employment of chiral N-heterocyclic carbenes (NHCs) have shown much promise. Our group has recently shown that one possible chiral NHC catalyzed Stetter cyclization product of a conjugated triene, a highly functionalized cyclopentenone, contains both a chiral center and an adjacent conjugated diene. This structure can be easily elaborated to a bicyclic structural motif present in some biologically active natural products from the ginkgolide family, and is difficult to access by other means. The synthesis of novel vinyl stannanes and other coupling substrates involved in the development of the aforementioned reaction discovery are described in this report.

About half a century ago, Főrster and Kasper discovered that traditional organic chromophore such as pyrene was weakened with an increase in its solution concentration. It was soon recognized that this was a general phenomenon for many aromatic compounds. This concentration-quenching effect was found to be caused by the formation of sandwich-shaped (disc-like) excimers and exciplexes aided by the collisional interactions between the aromatic molecules in the excited and ground states. In 2001, Tang¡¦group discovered such a system, in which luminogen aggregation played a constructive, instead of a destructive, role in the light-emitting process: a series of silole molecules were found to be non-luminescent in the solution state but emissive in the aggregated state. They coined the term ¡¥¡¥aggregation-induced emission¡¦¡¦ (AIE) or ¡§AIE enhancement¡¨ (AIEE) for this novel phenomenon which originated from the restricted intramolecular rotation (RIR) inherent from the chemical structures of the luminescent materials. To verify the effect of molecular structure on the AIE properties of organic and polymeric materials, four approaches were attempted in this research. (I) Aggregation-Induced Emission in Tetraphenylthiophene-Derived Organic Molecules and Vinyl Polymer Organic molecules of tetraphenylthiophene (TP) and the derived model compound of TP-Qu and vinyl polymer of PS-Qu with the pendant group of TP-Qu were prepared and characterized to identify their photoluminescent responses toward the effect of AIE. During aggregate formation, the corresponding TP solutions greatly gained the emission intensity. In contrast, TP-Qu and PS-Qu in isolated or aggregated states emitted strongly with nearly the same emission intensity. RIR is the key factor deciding the AIE effect in different states. With four small phenyl rotors around the central thiophene stator, the RIR of the TP molecules in dilute solution is low but increases upon aggregate formations. In contrast, the bulky C-2 quinoline rotor of the TP-Qu molecule enhances the RIR in isolated state. With the inherent TP-Qu pendant groups, the emissive behavior of vinyl polymer PS-Qu is similar to the TP-Qu molecule. (II) Aggregation-Induced Emission Enhancement of Diblock Copolymer Containing Tetraphenylthiophene-Quinoline Pendant Fluorphores by Selective Solvent Pairs In this study, diblock copolymer of PSQu-PBS containing 25 mol% of fluorescent PSQu segments was synthesized and its aggregation-induced emission enhancement (AIEE) behavior was characterized and compared to PSQu homopolymer with 100 mol% of fluorescent units. With fewer (25 %) fluorescent units, solutions of diblock PSQu-PBS copolymer actually have higher (or comparable) emission intensities than the homopolymer PSQu solutions. Solutions of PSQu-PBS in THF/H2O of varied compositions emit essentially with the same intensity but in contrast, emissions of PSQu-PBS in THF/hexane increase with the increasing hexane content. Copolymer micelles formed in THF/hexane mixtures are supposed to have higher extent of aggregation, leading to more pronounced AIEE effect than micelles formed in THF/H2O. (III) Tetraphenylthiophene-Functionalized Poly(N-isopropylacrylamide): Probing LCST with Aggregation-Induced Emission A hydrophobic TP center with novel AIE property was chemically linked to two poly(N-isopropylacrylamide) (PNIPAM) chains to obtain thermoresponsive polymers to study the relationships between the lower critical solution transitions (LCSTs) and the AIE-operative fluorenscence emission. Three ethynyl-terminated PNIPAMs with different molecular weights were synthesized via controlled atom transfer radical polymerization (ATRP) using ethynyl-functionalized initiator. The PNIPAMs were then coupled with diazide-funtionalized TP (TPN3) via click reaction to obtain the desired TP-embedded polymers of Px (x = 1, 2, and 3). All three polymers show AIE-property from their solution fluorescence behavior in THF/hexane mixtures. In the aqueous solution, the TP-center served as a fluorogenic probe that reveals the LCSTs of polymers and its relation to the degree of TP labeling in terms of polymer concentration. The thermoresponsiveness of Px was demonstrated by the complete emission quench when heated at temperatures above LCST. Dissociation of the TP aggregates above LCST is responsible for the emission quench. (IV) Influence of Molecular Weight on the Aggregation-Induced Emission of Vinyl Polymers Containing the Fluorescent 2,4,6-Triphenylpyridine Pendant Groups Molecular weight effect on the AIEE property of vinyl polymers containing fluorescent 2,4,6-triphenylpyridine (TPP) pendant groups was evaluated in the fourth topic. The high and low Mw vinyl polymers of PDMPS¡VL and ¡VH were prepared through Click chemistry between azide¡VTPP derivative and acetylene¡Vfunctionalized polystyrenes. Solutions of the low Mw PDMPS¡VL exhibited the normal AIEE effect with continuous emission gains with increasing extent of aggregation upon nonsolvent inclusion. On the contrast, the high Mw PDMPS¡VH solutions emitted with constant intensity on all solutions with different extent of aggregation. Despite the varied solution behavior, the solid PDMPS-L and ¡VH films are all strong deep-blue emitter with high quantum yields of 84 and 82.5%, respectively. The emission behavior was explained by the conformational difference between the PDMPS¡VL and ¡VH chains, which were approached by computer simulation in this topic.

Diverse biological activities of polyketide natural products are often associated with specific structural motifs, biosynthetically introduced after construction of the polyketide core. Therefore, investigation of such "post-polykektide synthase (PKS)" modifications is important, and the accumulated knowledge on these processes can be applied for combinatorial biosynthesis to generate new polyketide derivatives with enhanced biological activities. In addition to the practical value, a lot of unprecedented chemical mechanisms can be found in the enzymes involved therein, which will significantly advance our understanding of enzyme catalysis. The works described in this dissertation focus on elucidating a number of post-PKS modifications involved in the biosynthesis of an insecticidal polyketide, spinosyn A, in Saccharopolyspora spinosa. First, three methyltransferases, SpnH, SpnI, and SpnK, responsible for the modification of the rhamnose moiety, have been investigated to verify their functions and to study how they are coordinated to achieve the desired level of methylation of rhamnose. In vitro assays using purified enzymes not only established that SpnH, SpnI, and SpnK are the respective rhamnose 4ʹ-, 2ʹ-, and 3ʹ-O-methyltransferase, but also validated their roles in the permethylation process of spinosyn A. Investigation of the order of the methylation events revealed that only one route catalyzed by SpnI, SpnK, and SpnH in sequence is productive for the permethylation of the rhamnose moiety, which is likely achieved by the proper control of the expression levels of the methyltransferase genes involved in vivo. The key structural feature of spinosyn A is the presence of the unique tetracyclic architecture likely derived from the monocyclic PKS product. To elucidate this "cross-bridging" process, which had been hypothesized to involve four enzymes, SpnF, SpnJ, SpnL, and SpnM, the presumed polyketide substrate was chemically synthesized using Julia-Kocienski olefination, Stille cross-coupling, and Yamaguchi macrolactonization as key reactions. Incubation of the synthesized substrate with SpnJ produced a new product where the 15-OH group of the substrate is oxidized to the ketone. Next, it was demonstrated that incubation of this ketone intermediate with SpnM produces a tricyclic compound, via a transient monocyclic intermediate with high degree of unsaturation. Whereas it was initially thought that SpnM catalyzes both dehydration and [4+2] cycloaddition in sequence, detailed kinetic analysis revealed that SpnM is only responsible for the dehydration step, and the [4+2] cycloaddition step is indeed catalyzed by SpnF. Finally, successful conversion of the tricyclic intermediate to the tetracyclic core was demonstrated using SpnL. Proposed chemical mechanisms of SpnF and SpnL, Diels-Alder and Rauhut-Currier reactions, respectively, are interesting because enzymes capable of catalyzing these reactions have yet to be characterized in vitro. This work not only establishes the biosynthetic pathway for constructing the spinosyn tetracyclic core, but also epitomizes the significance of the post-PKS modification as a rich source of new enzyme catalysis. / text

This work presents a new implementation of the QP algorithm, a computer method to diagonalize the extremely large matrices arising in multimode vibronic problems. Benchmark calculations are included, showing the accuracy of the program. The QP algorithm is extended to treat multiple electronic surfaces for competitive control and this is demonstrated with an Hamiltonian including three electronic states, a model of the benzene radical cation. Finally, the evolution of zeroth-order states in a simple two electronic states, two dimensional model with a conical intersection is explored, towards building a time-dependent view of overlapping resonances coherent control.

This work presents a new implementation of the QP algorithm, a computer method to diagonalize the extremely large matrices arising in multimode vibronic problems. Benchmark calculations are included, showing the accuracy of the program. The QP algorithm is extended to treat multiple electronic surfaces for competitive control and this is demonstrated with an Hamiltonian including three electronic states, a model of the benzene radical cation. Finally, the evolution of zeroth-order states in a simple two electronic states, two dimensional model with a conical intersection is explored, towards building a time-dependent view of overlapping resonances coherent control.

A detailed understanding of natural photosynthesis provides inspiration for the development of sustainable and renewable energy sources, i.e. a technology that is capable of converting solar energy directly into chemical fuels. This concept is called artificial photosynthesis. The work described in this thesis contains contributions to the development of artificial photosynthesis in two separate areas. The first one relates to light harvesting with a focus on the question of how electronic properties of photosensitizers can be tuned to allow for efficient photo-induced electron transfer processes. The study is based on a series of bis(tridentate)ruthenium(II) polypyridyl complexes, the geometric properties of which make them highly appealing for the construction of linear donor-photosensitizer-acceptor arrangements for efficient vectorial photo-induced electron transfer reactions. The chromophores possess remarkably long lived 3MLCT excited states and it is shown that their excited-state oxidation strength can be altered by variations of the ligand scaffold over a remarkably large range of 900 mV. The second area of relevance to natural and artificial photosynthesis that is discussed in this thesis relates to the coupled movement of protons and electrons. The delicate interplay between these two charged particles regulates thermodynamic and kinetic aspects in many key elementary steps of natural photosynthesis, and further studies are needed to fully understand this concept. The studies are based on redox active phenols with intramolecular hydrogen bonds to quinolines. The compounds thus bear a strong resemblance to the tyrosine/histidine couple in photosystem II, i.e. the water-plastoquinone oxidoreductase enzyme in photosynthesis. The design of the biomimetic models is such that the distance between the proton donor and acceptor is varied, enabling studies on the effect the proton transfer distance has on the rate of proton-coupled electron transfer reactions. The results of the studies have implications for the development of artificial photosynthesis, in particular in connection with redox leveling, charge accumulation, as well as electron and proton transfer. In addition to these two contributions, the excited-state dynamics of the intramolecular hydrogen-bonded phenols was investigated, thereby revealing design principles for technological applications based on excited-state intramolecular proton transfer and photoinduced tautomerization.

The discovery and mechanistic investigation of a new class of photochemical reactions of benzophenones and related compounds is documented in this Thesis. Their photobehaviour in aqueous solvent media varied dramatically from their well-known behaviour in organic solvents and suggests unique and unprecedented mechanistic pathways. The aqueous photoredox chemistry of various substituted benzophenones was initially explored. Particular attention was paid to 3-(hydroxymethyl)benzophenone (47), which upon photolysis in acidic aqueous media undergoes an intramolecular photoredox reaction to produce 3-formylbenzhydrol (61). Extensive investigation into the mechanistic behaviour of 3-(hydroxymethyl)benzophenone (47) produced evidence of a unique solvent-mediated, acid catalysed photoreaction. A mechanism has been proposed for the intramolecular photoredox reaction that proceeds via the protonated triplet state. This protonated triplet state subsequently promotes the deprotonation of the benzylic carbon before rearranging to form the redox product. The modification of the benzylic carbon with an alkyl group or with a phenyl group resulted in only slight changes in the photobehaviour. In both cases intramolecular photoredox reactions were observed although significantly more oligomeric side products were observed in some cases. To more fully elucidate the photobehaviour and to test the generality of the photoredox reaction, a variety of structurally related hydroxyalkyl aromatic carbonyls were synthesized and studied. Alternative chromophores were explored using xanthone and fluorenone derivatives. Both types of derivative compounds underwent an intramolecular photoredox reaction, supporting the assertion that the intramolecular photoredox reaction could be considered a general feature of aromatic carbonyls under aqueous conditions. However, significant differences in photoreactivity were also observed. It was found that 2-(hydroxymethyl)xanthone (53) exhibited sufficient photoactivity that the intramolecular photoredox reaction was observable even under neutral conditions whereas 2-(hydroxymethyl)fluorenone (54) was nearly photoinert. The last topic focuses on the extension of the electronic transmission from the carbonyl functional group to the benzylic alcohol by insertion of an additional phenyl group. The addition of the phenyl group also provided a bichromophoric molecule, rather than the monochromophoric substrates studied to this point. The substituent’s position played an important role in the photobehaviour, in that both of the meta- and ortho- substituted compounds underwent intramolecular photoredox reaction, while the para- substituted compound primarily exhibited photobehaviour indicative of hydrogen abstraction.

This Thesis aims to examine the effects of substituents on the adjacent proton accepting phenyl ring with respect to a new type of excited state intramolecular proton transfer (ESIPT) process discovered by Wan and co-workers. Therefore, a number of 2-phenylphenols 23-28 were synthesized with electron-donor and electron-acceptor substituents such as methyl, methoxy, and ketone moieties on the adjacent proton accepting phenyl ring. The results obtained from examination of photochemical deuterium exchange showed that all derivatives except for ketone 27 underwent deuterium exchange (Фex = 0.019 - 0.079), primarily at the 2’-position on photolysis in D2O-CH3CN. In general, compounds with methoxy moiety (ies) on the adjacent proton accepting ring showed higher deuterium exchange yields. Diol 28 has the potential to undergo photosolvolysis as well as ESIPT process since it has both a benzyl alcohol and a phenol chromophore on the same molecule. Irradiation of 28 in 1:1 H2O-CH3OH gave the corresponding methyl ether product in high yield. Photolysis of 28 in 1:1 D2O-CH3OH also showed that ESIPT competes very well with photosolvolysis. Thus, this work has established that ESIPT can compete efficiently with photosolvolysis. Semi-empirical AM1 (examination of HOMOs and LUMOs) calculations show a large degree of charge transfer in the electronic excited state (except 27), from the phenol ring to the attached phenyl ring of the studied compounds. The AM1 calculation for ketone 27 showed that the carbonyl oxygen is more basic than the carbon atoms of the benzene ring, which explains the lack of deuterium exchange observed for 27.

Doctor of Philosophy(PhD), / This thesis describes the synthesis of terminal and internal amino and amidoalkynes and their hydroamination (cyclisation) catalysed by the complex (bis(N-methylimidazol-2-yl)methane)dicarbonylrhodium(I) tetraphenylborate (1). A series of analogous palladium complexes were also prepared and investigated for catalytic hydroamination. The scope of the rhodium(I) complex (1) for the intramolecular hydroamination of more complex amino and amidoalkyne substrates was investigated. This was made possible with the synthesis of aliphatic substrates, namely, 4 pentyn 1 amide (3) and 5 hexyn 1 amide (4) and a number of aromatic substrates, namely, 1, 4 diamino-2, 5 diethynylbenzene (5), 1, 4-diamino-2, 5 bis(phenylethynyl)benzene (6), 2, 3-diamino-1, 4-diethynylbenzene (7), 2, 3-diamino-1, 4-bis(phenylethynyl)benzene (8), 1, 5-bis(acetamido)-2, 4-diethynylbenzene (9), N-(acetyl)-2-ethynylbenzylamine (10) and N-(acetyl)-2-(phenylethynyl)benzylamine (11). The rhodium(I) complex (1) catalytically cyclised the aliphatic 4 pentyn 1 amide (3) regioselectively to the 6 membered ring, 3, 4 dihydro 2 pyridone (64) as the sole product. Attempts to cyclise 5 hexyn 1 amide (4) to produce either the 6 or 7 membered ring were unsuccessful. Compounds 5, 6, 7 and 8 were doubly cyclised to 1, 5 dihydro pyrrolo[2, 3 f]indole (71), 1, 5-dihydro-2, 6-diphenyl-pyrrolo[2, 3 f]indole (73), 1, 8-dihydro-pyrrolo[2, 3 g]indole (74) and 1, 8-dihydro-2, 7-diphenyl-pyrrolo[2, 3 g]indole (75) respectively. The aromatic amides with terminal acetylenes 9 and 10 cyclised to give 1, 7 diacetyl pyrrolo[3, 2 f]indole (76) and N (acetyl) 1, 2 dihydroisoquinoline (77) respectively. However, attempts to cyclise 11 were unsuccessful. Thus the rhodium(I) complex (1) successfully catalysed via hydroamination both terminal and internal acetylenic amine and amide substrates, to give pyridones, indoles and isoquinolines. Cationic and neutral palladium complexes incorporating the bidentate heterocyclic nitrogen donor ligand bis(N-methylimidazol-2-yl)methane (bim; 2) were synthesised: [Pd(bim)Cl2] (15), [Pd(bim)2][BF4]2 (17) [Pd(bim)(Cl)(CH3)] (14), [Pd(bim)(CH3)(NCCH3)][BF4] (16). All of the complexes were active as catalysts for the intramolecular hydroamination reaction, using the cyclisation of 4 pentyn 1 amine (21) to 2 methyl 1 pyrroline (22) as the model test reaction. Percentage conversions, turnover numbers and reaction profiles for each complex were compared to the rhodium(I) complex (1). These studies have shown that the catalytic activity was not significantly dependent on the bim donor ligand or the choice of metal. Substitution of the bim (2) ligand with the COD ligand and the use of methanol as the solvent did impact significantly on the efficiency of the hydroamination reactions.

Os corantes benzazólicos fluorescentes por ESIPT são conhecidos pela sua grande estabilidade e variabilidade no comprimento de onda da sua emissão de fluorescência. Novos derivados, nomeados HBs, foram estudados como corantes para sangue por possuírem grupos sulfônicos na sua estrutura molecular, o que é característico dos corantes proteicos utilizados para a análise de sangue. Estudos sobre essa aplicação foram desenvolvidos nesse trabalho, visando estabelecer vantagens e desvantagens em comparação aos reagentes mais utilizados. Os resultados foram satisfatórios para essa utilização, sendo tão sensível quanto o Amido Black e permitindo a combinação de técnicas com diferentes reveladores, sendo eles: Amido Black, Cianoacrilato e Luminol. Este trabalho também estudou a síntese do Luminol reproduzindo metodologias descritas na literatura, além da síntese do isômero Isoluminol. A obtenção de um produto com alto grau de pureza é difícil. Como são necessárias várias etapas, o rendimento do produto não é alto. / The benzazole fluorescent dyes by ESIPT are known for their high stability and fluorescence emission wavelength variability. New derivatives, appointed HBs, were studied as blood enhancement dyes once they have sulfonic groups in its molecular structure, which is characteristic of protein dyes used for blood analysis. Studies about this application were developed in this work, in order to establish its advantages and disadvantages compared to commonly used reagents. The results were satisfactory for the referred use, being as sensitive as Amido Black and allowing for techniques combination with different developers: Amido Black, Cyanoacrylate and Luminol. This work also studied the Luminol synthesis by reproducing methodologies described in the literature, as well as the isomer Isoluminol synthesis. The obtaining of a product with high purity is difficult. As several steps are required, the product yield is not high.