A study of how the matrix environment impacts the structure and IR spectra of N-acetylglycine conformers. The conformational composition of this compound is determined according to an analysis of the FTIR spectra of N-acetylglycine isolated in low temperature argon matrices. Bands of three N-acetylglycine conformers are identified based on the spectra: one major and two minor. The structure of all observed conformers is stabilized by different intramolecular hydrogen bonds. The Gibbs free energies of the conformers were calculated (CCSD(T)/CBS method), and these energy values were used to calculate conformer population at a temperature of 360 K, of which 85.3% belonged to the main conformer, and 9.6% and 5.1% to the minor conformers. We also determined the size and shape of the cavities that form when the N-acetylglycine conformers are embedded in the argon crystal during matrix deposition. It is established that the most energetically favorable cavity for the planar main conformer is the cavity that forms when 7 argon atoms are replaced. At the same time, bulky minor conformers were embedded into cavities that correspond to 8 removed argon atoms. We calculated the complexation energy between argon clusters and conformers, and the deformation energy of the argon crystal and the N-acetylglycine conformers. The matrix-induced shifts to the conformer oscillation frequency are calculated. Published by AIP Publishing.

This research has investigated proton-coupled electron transfer (PCET) of quinone/hydroquinone and other simple organic PCET species for the purpose of furthering the knowledge of the thermodynamic and kinetic effects due to reduction and oxidation of such systems. Each of these systems were studied involving the addition of various acid/base chemistries to influence the thermodynamics and kinetics upon electron transfer. It is the expectation that the advancement of the knowledge of acid/base catalysis in electrochemistry gleaned from these studies might be applied in fuel cell research, chemical synthesis, the study of enzymes within biological systems or to simply advance the knowledge of acid/base catalysis in electrochemistry. Furthermore, it was the intention of this work to evaluate a system that involved concerted-proton electron transfer (CPET), because this is the process by which enzymes are believed to catalyze PCET reactions. However, none of the investigated systems were found to transfer an electron and proton by concerted means. Another goal of this work was to investigate a system where hydrogen bond formation could be controlled or studied via electrochemical methods, in order to understand the kinetic and thermodynamic effects complexation has on PCET systems. This goal was met, which allowed for the establishment of in situ studies of hydrogen bonding via 1H-NMR methods, a prospect that is virtually unknown in the study of PCET systems in electrochemistry, yet widely used in fields such as supramolecular chemistry. Initial studies involved the addition of Brønsted bases (amines and carboxylates) to hydroquinones (QH2’s). The addition of the conjugate acids to quinone solutions were used to assist in the determination of the oxidation processes involved between the Brønsted bases and QH2’s. Later work involved the study of systems that were initially believed to be less intricate in their oxidation/reduction than the quinone/hydroquinone system. The addition of amines (pyridine, triethylamine and diisopropylethylamine) to QH2’s in acetonitrile involved a thermodynamic shift of the voltammetric peaks of QH2 to more negative oxidation potentials. This effect equates to the oxidation of QH2 being thermodynamically more facile in the presence of amines. Conjugate acids were also added to quinone, which resulted in a shift of the reduction peaks to more positive potentials. To assist in the determination of the oxidation process, the six pKa’s of the quinone nine-membered square scheme were determined. 1H-NMR spectra and diffusion measurements also assisted in determining that none of the added species hydrogen bond with the hydroquinones or quinone. The observed oxidation process of the amines with the QH2’s was determined to be a CEEC process. While the observed reduction process, due to the addition of the conjugate acids to quinone were found to proceed via an ECEC process without the influence of a hydrogen bond interaction between the conjugate acid and quinone. Addition of carboxylates (trifluoroacetate, benzoate and acetate) to QH2’s in acetonitrile resulted in a similar thermodynamic shift to that found with addition of the amines. However, depending on the concentration of the added acetate and the QH2 being oxidized, either two or one oxidation peak(s) was found. Two acetate concentrations were studied, 10.0 mM and 30.0 mM acetate. From 1H-NMR spectra and diffusion measurements, addition of acetates to QH2 solutions causes the phenolic proton peak to shift from 6.35 ppm to as great as ~11 ppm, while the measured diffusion coefficient decreases by as much as 40 %, relative to the QH2 alone in deuterated acetonitrile (ACN-d3). From the phenolic proton peak shift caused by the titration of each of the acetates, either a 1:1 or 1:2 binding equation could be applied and the association constants could be determined. The oxidation process involved in the voltammetry of the QH2’s with the acetates at both 10.0 and 30.0 mM was determined via voltammetric simulations. The oxidation process at 10.0 mM acetate concentrations involves a mixed process involving both oxidation of QH2 complexes and proton transfer from an intermediate radical species. However, at 30.0 mM acetate concentrations, the oxidation of QH2-acetate complexes was observed to involve an ECEC process. While on the reverse scan, or reduction, the process was determined to be an CECE process. Furthermore, the observed voltammetry was compared to that of the QH2’s with amines. From this comparison it was determined that the presence of hydrogen bonds imparts a thermodynamic influence on the oxidation of QH2, where oxidation via a hydrogen bond mechanism is slightly easier. In order to understand the proton transfer process observed at 10.0 mM concentrations of acetate with 1,4-QH2 and also the transition from a hydrogen bond dominated oxidation to a proton transfer dominated oxidation, conjugate acids were added directly to QH2 and acetate solutions. Two different acetate/conjugate acid ratios were focused on for this study, one at 10.0 mM/25.0 mM and another at 30.0 mM/50.0 mM. The results of voltammetric and 1H-NMR studies were that addition of the conjugate acids effects a transition from a hydrogen bond oxidation to a proton transfer oxidation. The predominant oxidation species and proton acceptor under these conditions is the uncomplexed QH2 and the homoconjugate of the particular acetate being studied, respectively. Furthermore, voltammetry of QH2 in these solutions resembles that measured with the QH2’s and added amines, as determined by scan rate analysis. In an attempt to understand a less intricate redox-active system under aqueous conditions, two viologen-like molecules were studied. These molecules, which involve a six-membered fence scheme reduction, were studied under buffered and unbuffered conditions. One of these molecules, N-methyl-4,4’-bipyridyl chloride (NMBC+), was observed to be reduced reversibly, while the other, 1-(4-pyridyl)pyridinium chloride (PPC+), involved irreversible reduction. The study of these molecules was accompanied by the study of a hypothetical four-membered square scheme redox system studied via digital simulations. In unbuffered solutions each species, both experimental and hypothetical, were observed to be reduced at either less negative (low pH) or more negative (high pH), depending on the formal potentials, pKa’s of the particular species and solution pH. The presence of buffer components causes the voltammetric peaks to thermodynamically shift from a less negative potential (low pH buffer) to a more negative potential (high pH buffer). Both of these observations have been previously noted in the literature, however, there has been no mention, to our knowledge, of kinetic effects. In unbuffered solutions the reduction peaks were found to separate near the pKa,1. While in buffered solutions, there was a noted peak separation throughout the pH region defined by pKa’s 1 and 2 (pKa,1 and pKa,2) of the species under study. The cause for this kinetic influence was the transition from a CE reduction at low pH to an EC reduction process at high pH in both buffered and unbuffered systems. This effect was further amplified via the study of the hypothetical species by decreasing the rate of proton transfer. In an effort to further this work, some preliminary work involving the attachment of acid/base species at the electrode surface and electromediated oxidation of phenol-acetate complexes has also been studied. The attachment of acid/base species at the surface is believed to assist in the observation of heterogeneous acid/base catalysis, similar to that observed in homogeneous acid/base additions to quinone/hydroquinone systems. Furthermore, our efforts to visualize a concerted mechanism are advanced in our future experiments involving electromediated oxidation of phenol-acetate complexes by inorganic species. It may be possible to interrogate the various intermediates more efficiently via homogeneous electron-proton transfer rather than heterogeneous electron transfer/homogeneous proton transfer.

Doctor of Philosophy / Department of Chemistry / Christer B. Aakeroy / A family of three 2-aminopyrazine derivatives were prepared and co-crystallized with thirty carboxylic acids. Our theoretical charge calculations and experimental results from 90 reactions demonstrated that decreasing the charge on the hydrogen-bond acceptor sites results in a decrease of the supramolecular yield (the frequency of occurrence of the desired outcome). However, synthon crossover (undesired connectivity) was observed 7/12 times and was unavoidable due to competitive binding sites present in the N-heterocyclic bases chosen. To avoid synthon crossover, we used a strategy based on geometric bias. We utilized hydrogen-bonding two-point contacts and halogen-bonding single-point contacts for supramolecular reactions with the 2-aminopyrazine family of compounds. The desired two-point contact and single-point contact (N•••I or N•••Br) appeared in 9/9 times even in the presence of other potentially interfering intermolecular interactions. In addition, the role of charge in controlling the presence/absence of proton transfer was also highlighted. To establish a hierarchy in halogen-bonding interactions we designed and synthesized a library of eight molecules equipped with two different halogen bond donors and combined with variety of halogen-bond acceptors. 11 Halogen-bonded co-crystals were obtained; however, positional disorder of I/Br atoms obscures a complete analysis. This problem was solved by introducing asymmetry in the halogen-bond donor molecules. Finally, successfully demonstrated an unprecedented hierarchy in halogen-bond interactions based on electrostatics. We developed high-yielding Suzuki-Miyaura coupling reactions of tetraboronic pinacolyl ester cavitand to iodoarenes with a range of functional groups (electron withdrawing/donating group and a heterocycle) that show robustness and versatility, making it a ‘launch pad’ for the synthesis of many new cavitands in a facile manner. We have also successfully demonstrated cavitand functionalization from tetraaldehyde to tetraoximes using ‘solvent assisted grinding’, irrespective of the position of the aldehyde. Finally, we prepared tetra-substituted pyridyl and carboxylic acid cavitands having an ellipsoidal cavity capable of encapsulating asymmetric guest molecules and was subsequently obtained the first of its kind, C[subscript]2v symmetric molecular capsule with encapsulated asymmetric guest molecule.

6,6’-Dimethoxygossypol (DMG) is a natural product of the cotton variety Gossypium barbadense and a derivative of gossypol. Gossypol has been shown to form an abundant number of clathrates with a large variety of compounds. One of the primary reasons why gossypol can form clathrates has been because of its ability to from extensive hydrogen bonding networks due to its hydroxyl and aldehyde functional groups. Prior to this work, the only known solvate that DMG formed was with acetic acid. DMG has methoxy groups substituted at two hydroxyl positions, and consequently there is a decrease in its ability to form hydrogen bonds. Crystallization experiments were set up to see whether, like gossypol, DMG could form clathrates. The following results presented prove that DMG is capable of forming clathrates (S1 and S2) and two new polymorphs (P1 and P2) of DMG have been reported.

Choi, Kwong Shing. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

No description available.

After a general introduction about the properties and preparation of organofluorine compounds (Chapter 1), this thesis is divided into two parts focussing on the development of new methods for C-F bond formation (Part A) as well as studies towards the development of novel fluorinating reagents (Part B). Part A: New Methods for Carbon-Fluorine Bond Formation Part A consists of two chapters outlining the development of a Pd-catalysed hydrofluorination of alkenylarenes (Chapter 2) as well as a halofluorination of alkynes (Chapter 3). Chapter 2 This chapter describes the development of a novel, regioselective, syn-specific hydrofluorination of alkenylarenes under Pd-catalysis leading to the formation of benzylic fluorides. An extensive substrate scope is presented together with a model of the catalytic cycle, based on observations during the development of this reaction, deuterium labelling experiments as well as mechanistic control experiments starting from isolated palladacycles. Chapter 3 In this chapter the development of a novel iodo- as well as bromofluorination of internal and terminal alkynes, leading to the formation of (E)-halofluoroalkenes, is presented. For the former substrate class, the effects of steric as well as electronic bias on regioselectivity are discussed. For the latter substrate class, this methodology could be extended to the corresponding double iodofluorination, and for both transformations it was found to exclusively lead to the fluorination of the internal carbon. An extensive substrate scope as well as different iodofluorination-cross-coupling sequences including Suzuki, Sonogashira and Ullmann couplings, are illustrated. A representative reaction was successfully carried out on gram-scale and an iodofluorination-Suzuki-coupling sequence was used to prepare a fluorinated tamoxifen derivative. Part B: Hydrogen-Bonded Fluoride Complexes as Novel Reagents for Carbon-Fluorine Bond Formation Part B consists of two chapters describing structural as well as reactivity studies of fluoride-alcohol (Chapter 4) and fluoride-urea complexes (Chapter 5). Chapter 4 In this chapter the synthesis of 19 novel hydrogen-bonded tetraalkylammonium fluoride-alcohol complexes is described. For a subset of 15, the solid-state structures as determined by single-crystal X-ray diffraction experiments are presented. Trends of reactivity and selectivity were determined using these complexes as sources of fluoride anion in a model SN2 reaction. Preliminary results from in silico modelling of the fluoride-alcohol system provide a basis for explaining the results. Chapter 5 This chapter summarises the synthesis and solid-state structures of 20 hydrogen-bonded fluoride complexes using the urea and related squaramide and amide motifs. Also, the size of the tetraalkylammonium counter-cation was varied to study the influence on the solid-state structure. The reactivity and selectivity of a series of complexes was studied using the same model SN2 reaction as in Chapter 4 and results were compared accordingly. Different UV-vis and NMR spectroscopic techniques were used to study the behaviour of the fluoride-urea system in solution. Preliminary results demonstrate the use of 1,3-diarylureas as organocatalysts for nucleophilic fluorination.

by Zhou ping. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (p. 160-170). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Proton-transfer reactions are one of the most fundamental chemical reactions. However, the chemical dynamics of these processes remain elusive due to the difficulty of modeling these reactions. Establishing an experimental model system and using infrared absorption and two-dimensional infrared (2D IR) spectroscopies as means for detection, the chemical dynamics of the protonation states that are involved in a ground-electronic-state proton-transfer reaction in solution can be determined. In this study, experimental models are established with formic acid and nitrogenous bases in a low dielectric solvent. A hydrogen bond forms between the acid and the base, which will allow for the proton to transfer between the two molecules to form the neutral and the ion-pair protonation states. The carbon-deuterium (C-D) stretch and the carbonyl (C=O) stretch of the formic acid molecule are used as the reporter groups for the 2D IR measurements. The results of the C-D stretch demonstrate that there is a high sensitivity to the deprotonation, vibrational coupling, and vibrational dynamics trends that are linked to the solute-solvent interactions. The results of the C=O stretch demonstrate a sensitivity to the deprotonation and conformational disorder in which the position of the C=O changes the dynamics of the protonation state. Although, a proton-transfer is not detected, the experimental model system provides an understanding of the features that govern the chemical dynamics of proton-transfer reactions.

The synthesis or the interaction between two or more molecules is known as supramolecular chemistry. The concept of supramolecular chemistry can be applied to the design of new pharmaceutical materials affording new compositions of matter with desirable composition, structure and properties. The design of a two-molecule, or binary, compound using complementary molecules represents an example of an application of crystal engineering. Crystal engineering is the understanding of intermolecular interactions, in the context of crystal packing, in the design of new solid materials. By identifying reliable connectors through molecular recognition or self-assembly, one can build predictable architectures. The study of supramolecular synthesis was accomplished using known pharmaceutical molecules such as Nifedipine (calcium channel blocker used for cardiovascular diseases) and Phenytoin (used as an anticonvulsant drug) and model compounds containing synthons common in pharmaceutical drugs (Crown ethers and Trimesic acid with ether linkages and carboxylic acid dimers, respectively) with complementary molecular additives. The co-crystals formed were characterized by various techniques (IR, m.p., XPD, single X-ray diffraction) and preliminary results were found to exhibit characteristics different from the parent compounds as a direct result of hydrogen bonding and self-assembly interactions. These crystalline assemblies could afford improved solubility, dissolution rate, stability and bioavailability.