No description available.

The photoaquation mechanisms for a series of Cr(III) am(m)ine complexes have been investigated using laser flash photolysis with conductivity detection. The observation of transient increases in solution conductivity at pH > 4 and a conductivity decay lifetime longer than the doublet emission decay lifetime at pH < 3, have confirmed an intermediate in the photoaquation of cis-Cr(cyclam)(NH₃)₂³⁺. Transient increases in solution conductivity characteristic of an intermediate species were also observed for Cr(en)₃³⁺, Cr(tn)₃³⁺ and Cr(sen)³⁺ at pH > 4. The conductivity changes occurring in solution have been modelled for possible photoaquation mechanisms for the am(m)ine complexes, based on numerical integration of the rate expressions for all relevant mechanistic species. The comparison of these results with experimental data indicates that the intermediates observed for Cr(en)₃³⁺, Cr(tn)₃³⁺ and Cr(sen)³⁺ are the initially formed photoproducts, Cr(NN)₂(N-N)(OH₂)³⁺, where NN = a bidentate ligand or a sen arm. These species can undergo two processes, protonation of the dangling amine arm, or deprotonation of the aquo group. At low pH the first process dominates and conductivity decays due to proton uptake are observed. As the pH of the solution increases, the second process becomes competitive, and transient increases in solution conductivity are observed when this becomes the faster process. The modelled results for cis-Cr(cyclam)(NH₃)₂³⁺ indicate that the photoaquation occurs via two modes; (i) direct loss of ammonia, and (ii) loss and recoordination of a cyclam to displace ammonia, with both modes generating the observed photoproduct, cis-Cr(cyclam)(NH₃)(OH₂)³⁺. The modelling indicates that 0.67 of the overall photochemistry occurs via the cyclam loss mode. The intermediate has been identified as the initial product of the cyclam loss mode. Cr(cyc-N)(NH₃)₂(OH₂)³⁺. The rate of reaction observed via this mode is limited by the recoordination of the cyclam amine. As this is slower than the rate of doublet decay, the conductivity lifetimes observed at pH < 3 are longer than the doublet lifetime. The slow rate of recoordination also delays the release and subsequent protonation of ammonia, allowing for competitive deprotonation of the aquo group at pH > 4, and generating the observed transient increases in solution conductivity. The relevance of these results to Cr(III) chemistry in general, including possible ²E state reaction mechanisms is discussed. The photoaquation of Cr(CN)₆³⁻ was investigated using laser flash photolysis with conductivity detection. Theory predicts that the signal magnitudes observed for this complex should be constant throughout the pH range 2.7 - 5.3. Experimental results showed that the observed signals dropped from a maximum of 120 mV at pH 2.75 to 45 mV at pH 5.25. Possible explanations for this pH dependence are presented. The stereochemistry of the thermal and photoaquation products of rac- & Λ-Cr(sen)³⁺ has been investigated using capillary electrophoresis. Two products were found in the photoaquation reactions, trans-Cr(sen-NH)(OH₂)⁴⁺ and a product resulting from loss of a secondary amine. The thermal reaction produced trans-Cr(sen-NH)(OH₂)⁴⁺ as the major product with virtually no cis-Cr(sen-NH)(OH₂)⁴⁺ enantiomers being observed. Efficient racemization of Λ-Cr(sen)³⁺ to Δ-Cr(sen)³⁺was also observed in the thermal reaction, consistent with racemization occurring via bond rupture and recoordination. The photoaquation results are discussed in terms of VC theory and a reinterpretation of conflicting literature results for the thermal and photochemical aquation of Cr(sen)³⁺ is presented. / Graduate

This thesis describes the investigations of leaving group effects on enzymatic catalysis by Methylyoxal synthase (MGS). MGS is a glycolytic enzyme involved m bacterial metabolism which catalyzes the irreversible elimination of dihydroxyacetone phosphate (DHAP). In order to probe the effect of various leaving groups to MGS catalysts, a range of' ’mutant’ substrates have been synthesised where the phosphate group of natural substrate DHAP has been replaced by sulfate, thiosulfate and bromo groups yielding the substtates dthydroxyacetone sulfate (DHAS), dihydroxyacetone thiosulfate (DHATS) and bromohydroxyacetone (BHA). To quantify an overall enzymatic rate acceleration detailed kinetic analysis of the solution, non-enzymatic reactions of these substrates have been made. Rates for elimination and enolization via C-1 and C-3 deprotonation respectively have been quantified for each substrate using high resolution (^1)H NMR spectroscopy for a range of pD values. From the second order rate constants for buffer catalyzed deprotonation, k(_B) (M(^-1)s(^-1)) comparisons can be made with k(_car)/K(_M) (M(^-1)s(^-1)) for the enzymatic reactions at the same pD values. The non-enzymatic reactions of DHAS were monitored in the pD range of 7.3-9.2 using phosphate and quinuclidinone buffers. Second order rate constants, k(_B) (M(^-1)s(^-1)) of 5.60 x 10(^-4), 5.28 X 10(^-3), 5.82 x l0(_-3) and 7.40 x l0(^-3) M(^-1)s(^-1) for C-1 deprotonation and 1.41 x l0(^-3), 2.24 x l0(^-3) and 3.30 x 10(^-3) for C-3 deprotonation show that increasing the pD results m an increase in the rate of buffer catalyzed deprotonation (phosphate catalyzed C-3 deprotonation was not observed at this pD). This is indicative of a general base catalyzed deprotonation mechanism. First order rate constants, k(_M) (s(^-1)) for the buffer independent catalyzed deptotonation reactions of 1.39 x 10' (^5), 1.22 X 10(^-4), 1.26 X 10(^4) and 2.04 x l0(^-4) for C-1 deprotonation and 9.66 x l0(^-5), 1.10 x 10(^-4) and 9.30 X 10(^-5) for C-3 deprotonation show that an increase 0.7 pD units leads to only a 67 % and 12 respective tacrease in the mtes of deprotonation at the C-l md C-3 positions. This is reflected in the relatively level pD rate profile of the reaction. The background, non-enzymatic reactions of DHATS were carried out in acetic acid buffers and DCl solutions, In DCl solution an average K(_int) (s(^-1)) value of 1.33 x l0(^-5) s(^-1) was obtained. For the acetate catalyzed C-1 deprotonation reactions it was found that moving from pD 3.75 to 4.38 leads to an overall 4.5 fold increase in the value of k(_int) (s(^-1)) for the buffer independent deprotonation reaction of the C-1 protons of the molecule. Values of 9.03 x l0(^-5), 1.03 x 10(^-4) and 4.07 x 10(^-4) s(^-1) were obtained for the reactions in acetate 5, 10 and 20 % f(_B) respectively. Accordingly, in the same pD range the values for the average of first order rate constants, k(_av) (s(^-1)) increase by a factor of 4.9 fold. This is believed to represent a hydroxide dependent reaction. An average k(_B) (M(^-1)s(^-1)) of 5 x 10(^-2) M(^-1)s(^-1) was obtained for the acetate catalyzed reaction at the C-1 position of the molecule. Reactions of the C-3 protons of this molecule were not quantifiable by (^-1)H NMR and thus were followed by mass spectrometry which suggests that a potential dimerisation reaction occurs following deprotonation at this position. Reactions of the C-3 protons of BHA were monitored in quinuclidinone buffet, with values of k(_B)(M(^-1)s(^-1)) = 3.35 x 10(^-3)M(^-1)s(^-1) and k(_int) (s(^-1)) = 9.35 x l0(^-5) s(^-1) obtained for the buffer catalyzed reaction and buffer-independent reaction respectively. The C-1 deprotonation reactions of BHA were monitored in acetate buffers (70-90 % f(_B)). An average k(_B) (M(^-1)s(^-1)) of 9.17 X 10(^-5) M(^-1)s(^-1) was obtained for the buffer catalyzed reaction in this pD range (5.18-6.09). In the same pD range values of k(_int) (s') - 3.7 x 10(^-6). 4.7 x l0(^-6) and 1.19 x l0(^-5) s (^1)were obtained. The reactions of DHA and DHAS were monitored m the presence of MGS (19.6 and 78.4 µg/mL). While no reaction was observable for DHA in the presence of enzyme. DHAS was found to undergo C-1 and C-3 deprotonation leading to average k(_cat)/K(_M) values of 56.5 M(^-1)s(^-1) and 43.5 M(^-1)s(^-1) for exchange and elimination respectively. The rate for elimination is approximately 90,000 fold slower than that observed for natural substrate DEHAP, k(_cat)/k(_M) = 5.2 x 10(^-6) M(^-1)s(^-1) indicating that the phosphodianior group, of DHAP is for optimal cataysis.

Historically, research projects have originated from the literature group meetings and it was at one of those late night Wednesday meetings, nascent in my graduate career, that I presented a theoretical paper over the mechanism of the Morita Baylis-Hillman reaction. Something about it caught my attention and a project was born. The Morita Baylis-Hillman reaction had been heavily studied in the literature in recent years by both experimental and computational means. Some of these computational studies had even defined a complete theoretical mechanistic energy profile for these reactions. This dissertation describes a combination of experimental and theoretical mechanistic probes, including the observation of intermediates, the independent generation and partitioning of intermediates, thermodynamic and kinetic measurements for both the main reaction and interrelated side reactions, isotopic incorporation from solvent, and kinetic isotope effects, to fully define a more realistic picture of the free-energy profile for a Morita Baylis-Hillman reaction in methanol. Although the majority of this dissertation will be about the Morita Baylis-Hillman reaction in methanol, it could not have been fully accomplished without having to study the Morita Baylis-Hillman in DMSO and the Morita Baylis-Hillman utilizing acrylonitrile as well. All of these observations will be discussed.

Described here are detailed kinetic studies probing the structural elements which are crucial for the catalytic activity of dinuclear Zn(II) complexes towards phosphate diester cleavage. First, two sets of dinuclear Zn(II) complexes (a member with and without a bridging oxyanion linker group) were synthesized and their ability to promote the cyclization of 2-hydroxypropyl-p-nitrophenyl phosphate, a common model for RNA, was compared. Kinetic studies indicated that the complexes without the oxyanion linker were more active in promoting the cyclization in methanol under pH controlled conditions at 25 degrees. Quantitative energetics analysis shows that the rate reduction is attributable to a decrease in the second-order rate constant for the cyclization reaction, which adds 3.7 and 6.5 kcal/mol of activation energy to the respective reactions mediated by the complex with the oxyanion linker. Secondly, we have investigated a series of dinuclear Zn(II) complexes that incorporate various substituents including hydrophobic and hydrogen-bonding ones. Analysis of the data at the pH optimum for each reaction indicates that the presence of the H-bonding groups and alkyl groups provides similar increases (at least an order of magnitude) of the kcat terms over the unfunctionalized complex. There is also no clear trend that H-bonding groups or the alkyl groups provide stronger binding to the substrate than the parent complex. We also describe here the preparation and kinetic analysis of a series of solid supported transition metal catalysts for the cleavage of P=O chemical warfare simulants and P=S pesticides. We report a kinetic study of a 1,10-phenanthroline:Zn(II) complex immobilized on macroporous polystyrene which is capable of accelerating the cleavage of G-agent and V-agent simulants in methanol at neutral and ambient temperature by up to one hundred thousand-fold. The materials are recoverable and can be recycled at least ten times. We have also devised a methodology for simple immobilization of an ortho-palladated dimethylbenzylamine complex on macroporous polystyrene and amorphous silica gel. We report the catalyst preparation and a detailed kinetic study of their catalysis of the methanolysis of five P=S pesticides at neutral and ambient temperature. The polymeric catalysts give over billion-fold acceleration compared to the uncatalyzed background reaction at the same pH. / Thesis (Ph.D, Chemistry) -- Queen's University, 2010-11-23 12:18:46.936

When multiple hydrogen bonds lie in-plane and parallel to each other in close proximity, they experience additional positive or negative secondary electrostatic interactions. When a pair of molecules are arranged such that every hydrogen bond acceptor is on one molecule and every hydrogen bond donor is on another, the positive secondary electrostatic interactions are maximised, and thus the association constant of the complex is enhanced. This thesis will present the development of a family of quadruple hydrogen bonded complexes containing only positive secondary interactions, which confers unprecedented stability. The complexes are sufficiently stable to maintain strong binding in polar solvents such as acetonitrile and can be switched “on” and “off” with acid and base. They will be developed into synthons for acid-base responsive supramolecular recognition, for use in stimuli-responsive supramolecular polymers and gelators.

No description available.

Over the past decade, the field of photoredox catalysis has garnered increasing amounts of attention in the organic chemistry community due to its wide applicability in sustainable free radical-mediated processes. Several examples have demonstrated that under carefully optimized conditions, efficient and highly selective processes can be developed through excitation of a photosensitizer using inexpensive, readily available light sources. Furthermore, these reactions can generally be performed under milder conditions than thermal reactions, as all the energy required to overcome the reaction barrier is supplied by light. Despite all these recent advancements in the field, many of these discoveries often lack in depth investigations into the excited state kinetics and underlying mechanisms. Furthermore, the vast majority of these transformations are photocatalyzed by ruthenium and iridium polypyridyl complexes. Not only are these precious metal catalysts extremely costly, but these metals are also known to be toxic, limiting their potential use in the development of pharmaceutical protocols. Herein, we present our solutions to these shortcomings, which involve a three-prong approach in the development of novel protocols, understanding the underlying mechanisms through detailed kinetic analysis, and by the development of new tools to facilitate mechanistic investigation for practitioners who may not possess specialized photochemical equipment. In this work, we were the first to demonstrate that radicals derived from amines, commonly employed as “sacrificial” electron-donors, can also act as reducing agents in photoredox transformations. We also present examples in which Methylene Blue, an inexpensive, non-toxic organic dye, can be employed as a viable alternative to ruthenium complexes for photoredox transformations. By employing a photosensitizer with more favourable excited state kinetics for electron-transfer, we successfully demonstrated that Methylene Blue could be used to increase the efficiency of a previously developed photoredox transformation. While employing organic dyes is an excellent strategy to lowering the cost of photoredox transformations, another viable strategy is to employ heterogeneous semiconductors. Titanium dioxide is an example of a semiconductor which is often employed in photocatalytic applications due to its low cost, desirable redox properties, and high chemical stability which allows for continued use. However, titanium dioxide has seen limited use in organic synthesis due to the requirement of UV irradiation for excitation. Herein, we present a process which led to the discovery of visible light photochemistry with titanium dioxide, generated through the adsorption of indole substrates creating a new, visible light absorbing complex. Employing this strategy, we were able to promote the photocatalytic Diels–Alder reaction of indoles with electron-rich dienes, giving access to valuable tetrahydrocarbazole scaffolds. Finally, in order to facilitate the characterization of chain processes in photoredox catalysis, we have successfully developed a visible light actinometer based on the ubiquitous photocatalyst, Ru(bpy)3Cl2. This actinometer offers many advantages compared to other visible light actinometers, such as completely eliminating the need for spectral matching, as the actinometer is also the photocatalyst. This technique should provide researchers with a mechanistic tool to properly characterize chain propagation in the transformation of interest.

Over the past twenty years molecules capable of templating their own synthesis, so called self–replicating molecules have gained prominence in the literature. We show herein that mixing the reagents for replicating molecules can produce a network of self–replicators which coexist and that the networks can be instructed by the addition of preformed template upon initiation of the reaction. Whilst self–replicating molecules offer the simplest form of replication, nature has evolved to utilise not minimal self–replication but reciprocal replication where one strand templates the formation of not an identical copy of itself but a reciprocal strand. Efforts thus far at producing a synthetic reciprocal replicating system are discussed and an alternative strategy to address the problems encountered is proposed and successfully implemented. The kinetic behaviour of a self–replicating reaction bears two distinctive time periods. Upon initiation, the reaction proceeds slowly as no template exists to catalyse the reaction. Upon production of the template, the reaction proceeds more rapidly via template direction. During this slow reaction period, the system is prone to mistakes as the reaction is slow and unselective. The creation of an [A•B] binary complex through non–covalent recognition of reagents allows for the reaction to proceed at an accelerated rate upon initiation however products of such a reaction are usually catalytically inert and do not promote further template directed reaction. A strategy to combine the desired behaviour of an [A•B] binary complex with the further template directed autocatalytic self–replicating reaction is described and implemented. Supramolecular polymers consist of repeating monomers which are held together by non–covalent interactions. The strong association of a self–replicating template dimer is comparable to that of supramolecular polymers reported thus far in the literature which are produced by cumbersome standard linear synthetic procedures. Herein the application of self–replication to the field of supramolecular polymer synthesis is discussed. As the autocatalytic reaction to produce the template monomers occurs under the same conditions as required to allow polymerisation to proceed, the polymer is able to spontaneously form in situ by self–replicating supramolecular polymerisation.

A presente dissertação tem por objetivo o estudo dos rearranjos de Pummerer, ainda não descritos na literatura para &#945;-alquiltio-sulfóxidos. É apresentado um apanhado bibliográfico que consta de duas partes: a) Um relato dos trabalhos sobre os rearranjos de Pummerer com os sulfóxidos que não possuem átomo de enxofre na cadeia carbônica. b) Um resumo dos trabalhos que estudam algumas reações de &#945;-alquiltio-sulfóxidos. Na primeira parte desta revisão é dado destaque às possibilidades mecanísticas da reação de Pummerer, apontando-se a sua dependência dos diversos fatores, tais como as estruturas do sulfóxido, do reagente de Pummerer e das condições experimentais empregadas. Na segunda parte são destacadas a acidez aumentada do grupo metilena de &#945;-alquiltio-sulfóxidos e a sua fácil hidrólise ácida, características estas de grande importância para o nosso estudo da reação de Pummerer com os referidos compostos. No presente trabalho são preparados quatro sulfóxidos: metil n-propilsulfóxido (I) metil metiltiometilsulfóxido (II) etil etiltiometilsulfóxido (III) e fenil feniltiometilsulfóxido (IV), todos eles já descritos na literatura. São descritas as reações do etil etiltiometilsulfóxido (III) com anidrido acético. O rearranjo de Pummerer não ocorre em condições brandas, havendo recuperação do sulfóxido de partida. Em condições mais enérgicas e isolado o ortotritioformiato de etila. É relatada a reação do mesmo sulfóxido (III) com ácido clorídrico aquoso, na qual houve recuperação de grande parte do produto de partida e formação de pequenas quantidades do dietildissulfeto. São apresentadas as reações do metil metiltiometilsulfóxido (II), etil etiltiometilsulfóxido (III) e fenil feniltiomtilsulfóxido (IV) com cloreto de tionila. Em todas elas, em vez do cloro ditioacetal esperado, produto normal do rearranjo de Pummerer ocorre formação de clorometil-sulfetos correspondentes em rendimentos de 70-90%, ao lado de dissulfetos correspondentes. Finalmente é relatada a reação do etil etiltiometilsulfóxido (III) com cloreto de benzoila. Nesta reação há também ausência do produto normal do rearranjo de Pummerer e formação de dois produtos principais: clorometilsulfeto e tioformiato de etila, ao lado de pequenas quantidades de dissulfeto e ácido benzoico. Na discussão dos resultados obtidos são destacados dois aspectos de maior-importância nas reações dos &#945;-alquil-tio-sulfóxidos: a supressão do produto de rearranjo de Pummerer e a formação de clorometil-sulfetos nas reações com cloreto de tionila e cloreto de benzoila. São relatadas as medidas de basicidades relativas pelo emprego de dois doadores de prótons, pirrol e fenol, através do método de espectroscopia no infra-vermelho do etil etiltiometilsulfóxido (II) e metil metiltiometilsulfóxido (II) em comparação com os sulfóxidos correspondentes não substituidos. Os dados obtidos voNH e voOH indicam uma diminuição de basicidade do oxigênio sulfinílico, resultante da introdução de um átomo de enxofre na posição 2 dos sulfóxidos. É sugerida a diminuição de basicidade e em consequência da nucleofilicidade do oxigênio sulfinílico como responsável pela diminuição da reatividade com os reagentes de Pummerer. É proposto o mecanismo de três passos para a formação de clorometil-sulfetos nas reações com cloreto de tionila e cloreto de benzoila. A formação de ortotritioformiato de etila e tioformiato de etila nas reações com anidrido acético e cloreto de benzoila, respectivamente é interpretada como decorrente do rearranjo de Pummerer. / This thesis investigates the Pummerer rearrangements not described in the literature, for some &#945;-alkylthio-sulphoxides. A literature report divided in two parts is presented: a) Pummerer rearrangements of the sulphoxides not containing sulphur atom in the carbon chain. b) Some investigations on the reactions of &#945;-alkylthio-sulphoxides. In the first part, the mechanistic aspects of the Pummerer rearrangement are described being emphasized their dependence on several factors, such as the structure of the sulphoxide and Pummerer reagent, and experimental conditions. In the second part the increased acidity of the methylene group of the &#945;-alkylthio-sulphoxides and its easy hydrolysis are appointed, as they are of great importance for our study of the Pummerer rearrangement. In the present work: 1. Four sulphoxides already described in the literature are prepared: methyl methylthiomethylsulphoxide (I), methyl n-propylsulphoxide (II), ethyl ethylthiomethylsulphoxide (IV), and phenyl phenylthiomethylsulphoxide (IV). 2. The reactions of ethyl ethylthiomethylsulphoxide (III) with acetic anhydride are described. The Pummerer rearrangement does not occur in mild conditions being recovered the starting material. In more drastic condition the ethyl trithioformate is isolated. 3. The reaction of the same sulphoxide (III) with hydrochloric diluted acid is reported to give mostly starting material and small amount of diethyldisulphide. 4. The reactions of methyl methylthiomethylsulphoxide (I), ethyl ethylthiomethylsulphoxide (III) and phenyl phenylthiomethylsulphoxide (IV) with thionyl chloride are presented. In all cases instead of the expected chloro dithioacetal, the normal Pummerer rearrangement product, chloromethylsulphides were identified in the 70-90% yield in mixture with small amounts of the corresponding disulphides. 5. The reaction of ethyl ethylthiomethylsulphoxide (III) with benzoyl chloride is reported. Again the absence of the normalPummerer rearrangement product with formation of chloromethyl sulphoxide and small amount of disulphide are observed. However, an addicional product, ethylthioformate, was also produced. 6. The suppression of the normal Pummerer rearrangement product and formation of chloromethyl-sulphides in the reaction with thionyl chloride and benzoyl chloride are discussed. The relative basicity measurements using pirrol and phenol as proton donors by IR spectroscopy are reported for ethyl ethylthiomethylsulphoxide (III) and methyl methylthiomethylsulphoxide (I) and compared to the corresponding unsubstituted sulphoxides. The obtained data (voNH and voOH) indicate a decrease of basicity of sulphinyl group by replacement of &#946;-methylene group by sulphur atom in the sulphoxides studied. Is suggested that decrease in basicity and consequently of nucleophilicity of the oxygen atom is responsible for the decrease of reactivity toward Pummerer reagents. A three step mechanism is proposed for the formation of chloromethyl-sulphides in the reactions with thionyl chloride and benzoyl chloride. The formation of ethyl orthotriethyl thioformate and ethyl thioformate as secondary products in the reactions with acetic anhydride and benzoyl chloride respectively is interpreted as resulting from the Pummerer rearrangement.