No description available.

Halogen chemistry plays an important role in spring time ozone and mercury depletion events (ODEs and MDEs) and may efficiently oxidize hydrocarbons such as the important greenhouse gas methane (CH4) in the polar marine boundary layer. This thesis presents a detailed study of bromine and chlorine chemistry in the Arctic boundary layer based on measurements of bromine and chlorine containing species using chemical ionization mass spectrometry (CIMS). The capability of CIMS to accurately measure bromine oxide (BrO) was demonstrated. The first direct measurements of hypobromous acid (HOBr) were achieved. Conditions that likely favor bromine activation (e.g. high wind speeds) was presented. To advance the understanding of bromine recycling, a time dependent model was built to simulate the bromine speciation. Unexpected high levels of molecular chlorine (Cl2) were observed at Barrow, AK, which had a large impact on methane oxidation and could contribute to ozone loss and mercury oxidation at Barrow, AK. Moreover, BrO levels observed at Summit, Greenland did not explain the under prediction of hydroxyl radical (OH). However, the enhanced OH was found to be coincident with elevated reactive gaseous mercury (RGM). In addition, airborne BrO measurements were found to be generally consistent with airborne observations of soluble bromide based on the response factors of mist chamber to the bromine species and bromine chemical mechanisms.

The work presented in this thesis has broadly established a few findings about the structure¬hyperpolarizability relation in molecular compounds: First, by measuring βHRS of an organic keto-enol tautomer, benzoylacetanilide in a binary solvent, I have shown that the first hyperpolarizability can be manipulated favourably by changing the composition of the solvent or by altering the pH of the solution. BA which exists in the pure keto form in water and as a keto-enol tautomer in ethanol, co-exists in equilibrium with the keto and enol forms at pH 11 in aqueous solution. The β value of the anion form is 709 x 10¬30 esu , whereas that of the enol is 232 x 10-30 esu and of the keto is 88 x 10-30 esu. There is an enhancement of β by ~ 8 times for the anion and ~3 times for the enol compared to the keto form. This opens up the possibility of finding large nonlinearities in organic molecules by simply ionizing it. Second, in organometallic complexes of divalent Ru, the first hyperpolarizability could be manipulated by altering the valence state of the metal center by oxidation or reduction or by introducing highly polarisable halogen atoms as substitutions in ligands attached to the metal center. The enhancement of first hyperpolarizability was observed in mononuclear [RuII(acac)2(CH3CN)2] complex by 1.7 times when the metal center was oxidized from RuII to RuIII. As it is already known that the complexes like [(acac)2Ru-bptz-Ru(acac)2] produce stable mixed valent compound, the enhancement of β by ~1.6 times is appearing because of that species only. Exploring Large Nonlinearity in Tautomers In this thesis I have taken a linear ketone for studying the effect of structure on β via the enol and anion formation mediated by solvent and pH of the medium. In the present study the proton transfer in BA took place in the ground state of the ketone and the enol or anion are produced in the ground states. The proton transfer reaction (tautomerism) can also happen in the excited state as well in some molecules where there is a substantial barrier to the proton transfer reaction in the ground state. In such systems, once the ketone is excited using ultraviolet light the barrier to proton transfer in the medium is overcome and a proton transfer in the excited state takes place and the enol is produced. Since such a system will be at higher energy, it will be interesting to do a two-laser experiment where the excited state hyperpolarizability is measured in a time resolved manner and the β value is determined in the excited state. Building Molecular Nonlinearity in Step-by-Step Electron Transfer In this thesis, I have dealt with a binuclear complex of Ru(II) which in one-step electrochemical oxidation produced a mixed valence compound which had substantially higher β value compared to the unoxidized complex. In this way it is possible to build a multicentered complex and see if sequential one-electron transfer and subsequent oxidation/reduction of the metal centers produce a mixed-valent metal compound with large molecular nonlinearity. The indication from the present study is that such a scheme should double the β value in each one-electron transfer step. Also the linker group/moiety between the successive metal centers will play an important role in dictating the efficiency of electron transfer. If the metal d-electrons in a multinuclear complex are linked through a π-conjugation, one would expect manifold enhancement of β. Such metal arrays can also be designed in 2 or 3 dimensions. The dimensionality of the multinuclear metal complexes can easily be changed by supramolecular design and synthesis strategy. Such metal networks may or may not generate large β molecules since electronic polarization in such systems may not be superimposable in a coherent fashion and may not add in a positive sense. All these remain to be tested and explored in the future.

Three distinct aspects, disorder, polymorphism and co-crystal formation have been addressed in molecular crystals in terms of intra- and intermolecular interactions involving halogens, weak hydrogen bonds and van der Waals interactions. A basic introductory chapter highlights the importance of these three aspects followed by a foreword to the contents. Chapter 1 employs in situ cryo-crystallization techniques to study the crystal and molecular structures of compounds which are liquids at room temperature. Section 1.1 deals with the crystal structure analyses of low melting chloro- and bromo-substituted anilines which reveal both the importance of hydrogen bonds and weak interactions involving different halogens. The halogen⋅⋅⋅halogen interactions are compared with fluorine and iodine substituted compounds to bring out the relevance of both size and polarizability characteristics. Section 1.2 describes the crystal structures of benzyl derivative compounds utilizing the concept of in situ cryo-crystallization. This analysis brings out the correlation between acidity of benzyl derivative compounds with its preference of either a (sp2)C-H⋅⋅⋅π or (sp3)C-H⋅⋅⋅π interactions in the crystal packing. Chapter 2 consists of two sections dealing with the preference of halogen⋅⋅⋅halogen interactions in supramolecular chemistry. Section 2.1 discusses a statistically large number of crystal structures in halogen substituted benzanilide compounds. It reveals the importance of hetero halogen F⋅⋅⋅X (Cl, Br), homo halogen X⋅⋅⋅X (F, Cl, Br, I), C-X⋅⋅⋅π and C-H⋅⋅⋅F interactions in terms of their directionality and preferences to complement a primary N-H⋅⋅⋅O hydrogen bond in directing the three-dimensional supramolecular assembly. Section 2.2 deals with solvent induced polymorphism which highlights the role of weak interactions in two case studies. The preference and directionality of C-H⋅⋅⋅F and Cl⋅⋅⋅Cl interactions lead to dimorphic modifications in case of 3-chloro-N-(2-fluorophenyl)benzamide whereas in case of 2-iodo-N-(4-bromophenyl)benzamide the interactions are through C-H⋅⋅⋅π and I⋅⋅⋅I contacts. Further, the analysis is supported using morphological evidence, DSC (Differential scanning calorimetry) and Powder X-ray diffraction data. Chapter 3 has three sections, concentrating on disorder and its consequence in crystal structures. Section 3.1 discusses the apparent shortening of the C(sp3)–C(sp3) bond analysed via a variable temperature X-ray diffraction study in racemic 1,1′-binaphthalene-2,2′-diyl diethyl bis(carbonate). Variable temperature single crystal X-ray diffraction studies show that the shortening is entirely due to positional disorder and not due to thermal effects. A supercell formation at T≤150 K depicts the formation of a Z'= 2 structure. Section 3.2 deals with crystal structure analysis of Ethyl-4-(2-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate which clarifies the discrepancy in the higher value of the residual electron density in the literature in terms of positional disorder of fluorine at ortho sites. The existence of fluorine atom at the para position on the phenyl ring of another isomeric molecule leads to disorder induced conformational polymorphism through the involvement of the ethyl group. The static disorder of ethyl group which is associated with only one molecule (Z′=2) could be resolved at 120 K. This supports the results of the previous section (3.1). Section 3.3 reports crystal structure analysis of disordered fluorine in benzanilide compounds. The preference of interactions involving fluorine in either ortho sites or meta sites could be one of the reasons for the positional disorder of both possible sites. With one of the structure showing high Z′ value due to differences in the occupancy of disordered fluorine atom. CSD (Cambridge Structural Database) analysis indicates that the percentage of disorder in halogenated crystal structures having halogen atom at either ortho site or meta site decreases from fluorine to iodine. Further, the analysis points out that the disorder in fluorine containing compounds is mostly localized at the fluorine position whereas for other halogenated disordered structures, the disorder appears at other parts of the molecule. Chapter 4 discusses co-crystal formation and analysis of intermolecular interactions. It consists of two sections. Section 4.1 discusses co-crystal formation of nicotinamide with benzoic acid and seven other derivatives by changing the functional group at different positions of benzoic acid. Hydroxyl (-OH) group at 4/3-postion of benzoic acid prefers phenol⋅⋅⋅pyridine synthon when at 2-position it prefers acid⋅⋅⋅pyridine synthon. The preference of amide anticatemer over dimer synthon is supported by additional C-H⋅⋅⋅O hydrogen bonds. In case of 3,5-dinitro-2-hydroxy benzoic acid, the disorder in hydroxyl (-OH) group at ortho site leads to salt formation. Section 4.2 describes co-crystal study of adenine and thymine (AT) as free nucleobases. This result reveals the formation of AT (2:1) complex with both Hoogsteen and “quasi-Watson-Crick” hydrogen bonds. The hydrogen bonded bases using the Hoogsteen and the “quasi-Watson-Crick” interactions generate a hexagonal supramolecular motif. Four water molecules are located inside the hexagonal void of this complex. A high temperature study on the same crystal shows that at 313K, one of the water molecules escapes from the lattice resulting in the small change in unit cell parameters. However, the space group remains the same and the hexagonal void remains unaltered. With further increase in temperature, the crystal deteriorates irreversibly which clearly brings out the importance of water molecule in the molecular recognition of adenine-thymine complex. Chapter 5 discusses crystal structure analysis of trans-atovaquone (antimalarial drug), its new polymorph form including one stereoisomer (cis) and five other derivatives with different functional groups. Based on the conformational features of these compounds and the characteristics of the nature of hydrogen bonding and other weak intra and intermolecular interactions, docking studies with cytochrome bc1 complex provide valuable insight into the atomistic details of protein-inhibitor interactions. The docking results reveal that atovaquone and its derivatives, owing to their nature of hydrogen bond and the propensity towards the formation of weaker hydrogen bonds involving the chlorine atom as well appear as good candidates for drug evaluation.

No description available.

The purpose of this research was to investigate the kinetics and mechanisms of the photocatalytic degradation of organic substances in the presence of anions (bromide and chloride), using titanium dioxide as a photocatalyst. Tris(hydroxymethyl)aminomethane (Tris) and methanol were the organic substances used as probes. Photocatalytic degradation of the probes produces formaldehyde through reaction with hydroxyl radicals at the surface of the photocatalyst. The product was quantified using a modified Hantzsch reaction and UV-Vis spectroscopy at the fixed wavelength 368 nm. It was found that having bromide present in the reaction mixture resulted in an increase in the rate of formation of formaldehyde from Tris, while it resulted in a decrease from methanol. Bromide on the surface of the photocatalyst reacts with the hydroxyl radicals to form reactive halogen species (RHS). This study proposes that the RHS Br2•- oxidises the probe into a cation radical, which initialises the probe degradation and the subsequent formation of formaldehyde. Conversion from hydroxyl radicals to RHS leads to a greater selectivity in formaldehyde production. Increased selectivity of attack towards electron-rich centres can explain the observed results with the different probes in this study. A linear combination expression of the total production of formaldehyde was developed, through which the X-factor, a ratio of the production of formaldehyde by RHS relative to the production of formaldehyde by hydroxyl radicals, was calculated. However, no realistic values were obtained when calculating the X-factor for different anion concentrations, thus indicating that factors other than competition kinetics affect the degradation. No conclusions could be drawn regarding the effect of chloride on the formation of formaldehyde from Tris and methanol, as the results were ambiguous. / Syftet med denna studie var att undersöka mekanismer och kinetik bakom fotokatalytisk nedbrytning av organiska molekyler i närvaro av anjoner (bromid och klorid), där titandioxid användes som fotokatalysator. Tris(hydroxymetyl)aminometan (Tris) och metanol var de organiska substanserna som studerades. Den fotokatalytiska nedbrytningen av proberna resulterar i formaldehyd via reaktion med hydroxylradikaler på fotokatalysatorns yta. Produkten kan sedan kvantifieras genom en modifierad version av Hantzsch-reaktionen följt av UV-Vis spektroskopi vid en fixerad våglängd på 368 nm. Studien kom fram till att närvaron av bromid i reaktionslösningen resulterade i en ökad produktionshastighet av formaldehyd från Tris, medan det resulterade i en minskning från metanol. Bromid på ytan av fotokatalysatorn reagerar med hydroxylradikaler och bildar reaktiva halogena molekyler (RHS). Denna studie föreslår att RHS:en Br2•- oxiderar proben till en radikalkatjon, som initierar nedbrytningen av proben och efterföljande bildning av formaldehyd. Omvandling från hydroxylradikaler till RHS leder till högre selektivitet av bildning av formaldehyd. Ökad selektivitet av attacker mot elektronrika center kan förklara de observerade resultaten med de olika proberna i denna studie. Ett linjärkombinationsuttryck av den totala produktionen av formaldehyd utvecklades, från vilket X-faktorn, ett förhållande av produktionen av formaldehyd via RHS relativt till produktionen av formaldehyd via hydroxylradikaler, kunde beräknas. Inga realistiska värden erhölls dock vid beräkningen av X-faktorn för olika anjonskoncentrationer, vilket indikerar att andra faktorer än konkurrenskinetik påverkar nedbrytningen. Inga slutsatser kunde dras gällande klorids effekt på bildningen av formaldehyd från Tris och metanol, då resultaten var tvetydiga.

Doctor of Philosophy / Department of Chemistry / Christer B. Aakeroy / A family of bis-pyridine based pharmaceutical active ingredients were synthesized and co-crystallized with four iodoperfluoroalkanes. Thirteen new crystal structures that are driven by I‧‧‧N(py) halogen bonds, are presented and compared with that of their hydrogen-bonded analogues. Halogen bonded co-crystals exhibit two different structural arrangements, as opposed to layered architectures observed in hydrogen bonded co-crystals. In order to explore the effect of aromatic stacking interactions on hydrogen and halogen bond driven co-crystallization process, we utilized a series of aromatic hydrogen and halogen bond donors in combination with bis-pyridine based pharmaceutical active ingredients. Aromatic stacking between the donor and the acceptor were limited, due to the lack of complementarity between the donor and the acceptor in terms of size, shape and geometry. In that case, homomeric interactions between the single components were translated into the structure of the binary co-crystals. According to our charge calculations, similarly activated hydrogen and iodine atoms possess similar electrostatics. Therefore, we wanted to investigate the interchangeability of hydrogen bonds and halogen bonds by utilizing 2-aminopyrimidine as the backbone for C(sp)-H and C(sp)-I functionalities which makes self-complementary ribbons via NH‧‧‧N synthons. Our results show that the ethynyl proton is capable of acting as a synthon mimic of ethynyl iodine by interchangeable C(sp)-H‧‧‧N hydrogen bonds and C(sp)-I‧‧‧N halogen bonds. We exploited the halogen bonding donor capability of iodo, bromo and chloro ethynyl functionalities towards a series of halide ions. Based on the grinding experiments these donors showed 90%, 70% and 50% success rates towards halides. Among the halides, chlorides exhibited the highest red shift compared to bromides and iodides. We synthesized a series of cavitands functionalized with hydrogen bond donor and acceptor groups and studied their binding preferences towards a series of active ingredients. We have shown that suitably functionalized cavitands can act as carriers of active ingredients and especially, selective binding of aspirin is demonstrated using a two-point binding mode.

Sulfoxide-ligand exchange (SLE) and asymmetric halogen-metal exchange (AHME) processes were separately examined for the enantioselective synthesis of functionalized alpha-haloalkylmetal (carbenoid) reagents. Carbenoids derived from SLE were used to effect stereospecific reagent-controlled homologation (StReCH) of boronic esters and those generated via AHME were engaged in Darzens-type chemistry with aldehydes. Abstract for Part 1. Scalemic syn alpha-chloroalkylsulfoxides p-TolS(O)CHClR [R = allyl, (1,3-dioxolan-2-yl)methyl, proparygyl, and 2-(benzyloxy)ethyl] were prepared from the corresponding thioethers by Jackson-Ellman-Bolm catalytic enantioselective sulfoxidation [cat. VO(acac)₂, tert-leucinol derived chiral Schiff base ligand, aq. H₂O₂, CHCl₃; 76-80% yield, >98% ee] followed by non-racemizing chlorination mediated by N-chlorosuccinimide in the presence of potassium carbonate (84-86% yield, syn:anti ≥ 20:1). The corresponding anti diastereoisomers were accessed from their syn epimers by sodium hexamethyldisilazide mediated deprotonation (THF, –78 °C) followed by treatment with either CH₃OH or CD₃OD to yield alpha-[¹H] or alpha-[²H] isotopomers, respectively (88% yield, anti:syn ≥ 17:1). Allyl and (1,3- dioxan-2-yl)methyl substituted chlorosulfoxides reacted with R'Li (t-BuLi or PhLi, THF, –78 °C) to give the expected products of SLE [p-TolS(O)R' and LiCHClR or LiCDClR]; however, neither the benzylether nor propargyl substituted substrates gave wholly satisfactory results under the same reaction conditions. The functionalized carbenoid reagents so obtained, 1-chloro-3-butenyllithium and 1-chloro-2-(1,3- dioxolan-2-yl)ethyllithium, were applied to the StReCH of B-(2-chloropyrid-5-yl) pinacol boronate but only the latter gave acceptable yields of chain extended products. The anti alpha-[²H]-chlorosulfoxide dioxolanyl bearing carbenoid precursor gave superior results to the analogous syn or anti alpha-[¹H]-chlorosulfoxides for StReCH of the B-pyridyl boronate [79% conversion, ≥ 89% ee (99% stereofidelity), vs. ≤ 68% conversion for non-deuterated chlorosulfoxides]. The origin of this isotope effect was traced to a deleterious proton transfer pathway between the alpha- chloroalkyllithium reagent and its chlorosulfoxide precursor. Sequential double iterative StReCH of B-(2-chloropyrid-5-yl) pinacol boronate with two separate portions of (S)-1-[²H]-1-chloro-2-(1,3-dioxolan-2-yl)ethyllithium (generated via SLE with phenyllithium) followed by oxidative work-up (with KOOH) gave (1R,2R)-1,2- [²H]₂-2-(2-chloropyrid-5-yl)-1,2-bis[(1,3-dioxolan-2-yl)methyl]ethanol (40% yield, ≥ 98% ee, dr = 85:15). Substitution of the (R)-configured carbenoid for its antipode in the second StReCH stage above gave the unlike (1S,2R)-isomer of the same pyridylethanol derivative (49% yield, ≥ 98% ee, dr = 79:21). The unlike diastereoisomer was advanced to the trifluoroacetamide of (1R,2R)-1,2-[2H]2-1- amino-2-(2-chloropyrid-5-yl)cyclohex-4-ene (6 steps, 5% overall yield); the non- deuterated isotopomer of this compound was previously advanced to the analgesic alkaloid (–)-epibatidine by Corey and co-workers. Abstract for Part 2. Scalemic planar chiral N,N-dialkyl 2-iodoferrocene carboxamides envisioned as recyclable precursors to ferrocenyl metal reagents for AHME, were prepared from ferrocene carboxylic acid by a three step sequence of: acid chloride formation [(COCl)₂ and cat. DMF)], aminolysis (with R₂NH, R = Me, Et, i-Pr; 65- 80% yield over 2 steps), and sec-butyllithium/(–)-sparteine mediated enantioselective directed ortho-metallation (DoM) followed by iodinolysis (87% yield, ≥ 96% ee). Attempts to access more elaborate 5-substituted 2-iodoferrocene carboxamides via DoM/iodinolysis of ortho-substituted ferrocene carboxamides (Me, Ph, or SiMe₃ substituents) mostly failed; however, analogous trisubstituted ferrocene oxazolines could be synthesized. Treatment of N,N-diisopropyl 2-iodoferrocene carboxamide (298, ≥ 96% ee) with n-BuLi (THF, –78 °C) resulted in complete conversion to the corresponding lithioferrocene (327) via I/Li interchange; subsequent iodinolysis initiated reverse Li/I exchange and returned iodoferrocene 298 without diminished enantiomeric excess, establishing configurational stability for the lithiated ferrocene intermediate. Prochiral (RCHI₂) and racemic (RCHICl) geminal dihalide substrates for AHME studies were prepared by electrophilic quench of dihalomethylsodiums with either Ph(CH₂)₃I or Me₃SiCl (50-78% yield). Of the four dihalides so produced, only prochiral substrate Me₃SiCHI₂ engaged in I/Li exchange with scalemic lithioferrocene 327 resulting in regeneration of its precursor iodoferrocene 298 and the formation of a putative chiral carbenoid Me₃SiCHLiI. Trapping of the carbenoid with aldehydes RCHO (R = Ph, 4-MeOC₆H₄, Ph(CH₂)₂, c-C₆H₁₁) in the presence of Me₂AlCl gave the expected epoxysilane products (35-40% yield, cis:trans ≥ 2:1) but without discernable enantiomeric excess. Hypotheses to account for the apparent lack of stereoinduction in this AHME cycle are presented. Comparable experiments using analogous magnesiated ferrocenes failed to produce putative carbenoid species from the same set of geminal dihalide substrates. / Graduation date: 2012

Non-covalent interactions taking place in solution are essential in chemical and biological systems. The solvent environment plays an important role in determining the geometry and stability of interactions. This thesis examines aromatic stacking interactions, alkyl-alkyl interactions, edge-to-face aromatic interactions, halogen bonds and hydrogen…hydrogen interactions in solution. Chapter 1 briefly introduces the different classes of non-covalent interactions, in addition to the state-of-the-art models and methods for investigating these weak interactions. The chapter finishes with a focus on dispersion interaction in alkanes and arenes. Chapter 2 investigates dispersion interactions between stacked aromatics in solution using a new class of complexes and thermodynamic double mutant cycles (DMCs). In extended aromatics, dispersion was detected as providing a small but significant contribution to the overall stacking free energies. Chapter 3 concerns the experimental measurement of alkyl-alkyl dispersion interactions in a wide range of solvents using Wilcox torsion balances. The contribution of dispersion interactions to alkyl-alkyl association was shown to be very small, with DMC, QSPR method and Hunter's solvation model. Chapter 4 studies edge-to-face aromatic interactions in series of solvents. In the open system, edge-to-face aromatic interactions were found to be sensitive to the solvent environment. The solvent effects were complicated and cannot be rationalised by a single parameter. Further analysis is needed. Chapter 5 describes a preliminary approach to investigate organic halogen…π interactions in solution using supramolecular complexes and torsion balances. Chapter 6 is a preliminary investigation of the ability of hydrogen atoms to act as H bond acceptors in silane compounds. Computations and 1H NMR demonstrated a weak interaction between silane and perfluoro-tert-butanol.

The Raman linewidths of the carbon-halogen stretching mode was measured as a function of temperature in ethyl bromide, isopropyl chloride, isopropyl bromide, t-butyl chloride, t-butyl bromide, chlorobenzene, bromobenzene, iodobenzene and o-dichlorobenzene. The vibrational relaxation times showed a very clear trend. Together with earlier work on methyl iodide, these results provide evidence that the vibrational dephasing efficiencies (T^-1_iso) of the carbon-halogen mode vary in the order of Cl > Br > I. Vibrational dephasing times were calculated from the Fischer-Laubereau Isolated Binary Collision Mode. If further work shows this transferability to extend to other types of skeletal modes in molecular systems, this would have significant ramifications on future vibrational lineshape studies.