The alkyl group is a –I + R substituent

Electronic substituent effects are usually classified as inductive (through s-bonds) and resonance effects (via p-bonds). The alkyl group has been usually regarded as a s-electron donor substituent (+I effect, according to the Ingold''s classification). However, a s-withdrawing, p-donor effect (–I + R pattern) allows explaining the actual electron-withdrawing behavior of alkyl groups when bound to sp3 carbon atoms as well as their well-known electron-releasing properties when attached to sp2 or sp atoms. Alkyl substitution effects on several molecular properties (dipole moments, NMR, IR, and UV spectra, reactivity in gas phase and solution) are discussed. Los efectos electrónicos del sustituyente se clasifican habitualmente como inductivos (a través de enlaces s) o de resonancia (mediante enlaces p). El grupo alquilo ha sido considerado habitualmente como un sustituyente dador de densidad electrónica s (+I, según la clasificación de Ingold). Sin embargo, un patrón s-aceptor p-dador (–I + R) permite explicar el comportamiento real de los grupos alquilo como atractores de electrones cuando están unidos a átomos de carbono sp3, así como sus conocidas propiedades dadoras de electrones cuando están unidos a átomos sp2 o sp. Se discuten los efectos de sustitución del grupo alquilo en varias propiedades moleculares (momentos dipolares, espectros de RMN, IR y UV, reactividad en fase gas y disolución)

Electrochemical Studies of Organic and Organometallic Compounds in the Pursuit of Electrocatalytic Carbon Dioxide Reduction

Carbon dioxide is the main contributor to the greenhouse effect in the world today; developing renewable energy sources and addressing anthropogenic CO2 release into the atmosphere are two key ways of addressing its increasing impact. Electrocatalytic reduction to products like methanol or carbon monoxide is one useful path to address the rapid increase of carbon dioxide, and the fac-M(bpy-R)(CO)3X family of complexes (M = Mn or Re; bpy-R = substituted 2,2’-bipyridine; X = Cl, Br, etc.) is one class of effective CO2 reduction catalysts. Although the capability of the rhenium complex Re(PyBimH)(CO)3Cl (PyBimH = 2-(2-pyridyl)benzimidazole) as a CO2 reduction catalyst was previously determined to be minimal, the underlying reasons why were not explained, which is odd when considering that protic sites on the ligand have been shown to increase CO2 reactivity. In this work, we show that the lack of electrocatalytic activity is due to a hydrogen atom transfer reaction that takes place upon reduction. In the process of testing for catalytic activity, a rapid method of determining the effective pKa of acidic species in acetonitrile using cyclic voltammetry was discovered and explored. The pKa of the rhenium complex was estimated through the cyclic voltammetry method to be , in reasonable agreement with DFT calculations. Because determining acidity in non-aqueous solvents is not trivial using established methods, the discovery of a method to accurately estimate the pKa of a species containing an acidic X-H bond is valuable. In addition to the organometallic rhenium complex, organic species buckminsterfullerene (C60) and benzil were explored as viable catalysts for the electrochemical reduction of carbon dioxide. Buckminsterfullerene showed minor electrochemical activity in the presence of carbon dioxide as observed by cyclic voltammetry and infrared spectroelectrochemistry. In this study, cyclic voltammetry and infrared spectroelectrochemistry showed that benzil reduces carbon dioxide at a lower overpotential than C60 and most other electrocatalysts. The production of oxalate from carbon dioxide by action of monoreduced benzil radical has been proposed, in agreement with literature. In the presence of pyridine, reactivity initially showed increased activity but did not show a linear trend in a quantified study of pyridine concentration

Spectroscopic Studies of Carbocyanine and 2,4,6- Trisubstituted Pyridine Dyes for Bioanalytical and pH Indicating Applications

In part A, the effect of varying short-chain alkyl substitution on the spectroscopic properties of cyanine dyes was examined. Molar absorptivities and quantum yields were determined for groups of pentamethine and heptamethine dyes for which the substitution of the indole nitrogen was varied. For both sets of dyes, increasing alkyl chain length did not significantly change quantum yield or molar absorptivity. These results may be useful in designing new cyanine dyes. In part B, the effect of structure on the suitability of 2,4,6-trisubstituted pyridines as color pH indicators was studied by determining spectral effects of protonation, molar absorptivities, pKa values, and the structural origin of the spectral behavior. Good color indicating properties result from aniline substitution at the 4 position of pyridine and electron donating substitution at the 2 and 6 positions of pyridine, which provide a strong red shift in the spectra and greater red shifted peak absorptivity, respectively

Synthesis of Functional Polypeptides and Development of New Synthetic Strategies toward Polypeptides

The objective of this work is to develop a new synthetic strategy for synthesizing advanced functional polypeptides or polypeptides in general. Polypeptides are amino acids based polymers with appealing properties for different applications. One of the key challenges in polypeptide research is the synthesis of functional polypeptides under mild conditions. We developed a system based on ring-opening polymerization (ROP) of N-thiocarboxyanhydrosulfides (NTAs) to synthesize polypeptides with wide range of molecular weights under mild conditions. Owing to NTAs’ good stability, our system serves as an excellent alternative to the traditional ROP of N-carboxyanhydrides (NCA). In Chapter 1, the fundamental knowledge and the cutting-edge research of polypeptides will be reviewed. The focus of the work in Chapter 2 is to develop a new class of functional polypeptide in traditional method via ROP of NCAs. This class of polypeptides combines several desired attributes for biomedical applications, which include: clickable pendant side chains for further functionalization, good water solubility, non-ionic nature to avoid unspecific interactions in biological systems, and unique secondary conformations (e.g. α-helix, β-sheet). In Chapter 3, I developed the first system to prepare polypeptides with controlled molecular weight via primary amine initiated solid-phase ring-opening polymerization (sROP) of NTAs under mild conditions in open air. Model NTA (e.g. BLG NTA, LYS NTA) monomers were synthesized for the first time, and were found to possess better thermal and moisture stability as compared to NCA analogs. The sROP proceeds by a normal amine mechanism as evidenced by matrix assisted light desorption ionization time of flight mass spectroscopy (MALDI-TOF MS). The controlled polymerization behavior of sROP is the direct result of high local monomer concentration in the solid phase, thus allowing for faster polymerization under relatively mild conditions. The work in Chapter 4 focuses on the development of solution phase polymerization of NTAs with TMG/benzoic acid as co-initiation system. PBLG with high molecular weights (33.6 kg/mol - 66.7 kg/mol) and narrow molecular weight distribution (PDI \u3c 1.12) can be readily prepared with this system. The mechanism of the TMG/benzoic acid mediated ROP of NTAs is proposed to be activated monomer mechanism (AMM)

Catálise com derivados de imidazol em reações com organofosforados : efeito do substituinte

Orientadora: Profa. Dra. Elisa Souza OrthCoorientador: Prof. Dr. Alfredo R. Marques de OliveiraDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Exatas, Programa de Pós-Graduação em Química. Defesa : Curitiba, 28/07/2017Inclui referências: p.81-89Resumo: O imidazol e seus derivados são compostos de grande interesse devido a sua eficiencia enquanto catalisadores na transferência do grups fosforila. Nesse sentido promover a clivagem de organofosforados é bastante interessante sobre tudo devido a utilização desses compostos como pesticidas, armas químicas. Nesse trabalho foi avaliado o efeito de substituintes alcoolicos no iM z frente a reações de desfosforilação. Para isso, foram utilizados três derivados de IMZ o 1 -hidroxietil imidazol (1-HEZ), 1-hidroxipropil imidazol (1-HPZ) (sintetizados) e o 4(5) hidroximetil imidazol 4(5)HMZ (comercial). Os organofosforados escolhidos foram o tréster de fosfato dietil 2,4 dinitrofenilfosfato (DEDNPP) e o diester bis (2,4 dinitrofenil) fosfato de sódio (BDNPP). A cinética das reações foi acompanhada pela técnica de UV-Vis pelo aparecimento do produto de reação 2,4 dinitrofenolato (DNF). O mecanismo de reação foi investigado a partir das técnicas de ressonância magnética nuclear (RMN), espectrometria de massas (EM), efeito isotópico cinético (EIC), parâmetros termodinâmicos de ativação e por análise físico-químico orgânica utilizando a equação de Bronsted. Para a reação do triéster DEDNPP com os derivados o 1-HEZ e o 1-HPZ, os resultados de EIC com valores próximos de 1 e parâmetros termodinâmicos com entropia bastante negativa, evidenciaram que ambos os derivados reagem por mecanismos semelhantes de catalise nucleofílica com ataque do anel de imidazol sobre o átomo de fósforo. Na análise de RMN de P não foram detectados intermediários de reação fosforilados, devido à alta instabilidade dos mesmos, sendo observados apenas o organofosforado de partida e o produto final (fosfato de dietila). Na análise por EM foram detectadas todas as peças chave de reação, inclusive o intermediário fosforilado. Além disso, o plot de Bronsted evidenciou uma reta, típico de mecanismo concertado. As reações com o diéster de fosfato BDNPP foram estudadas com os hidroxiimidazois 1-hEz, 1-HPZ e 4(5)HMZ. Nesse caso foi observado valores de EIC secundário (i.e. entre 1 e 2) indicando que nesse caso a hidroxila poderia estar influenciando o mecanismo de reação. A partir dos valores de EIC combinado com os parâmetros termodinâmicos foi proposto um mecanismo de catálise nucleofílica combinada com a estabilização do estado de transição por uma ligação de hidrogênio do grupo hidroxila dos hidroxiimidazois. A partir do estudo por RMN de 31P para BDNPP com o 1-HEZ, foi observado o intermediário fosforilado, incomum para derivados de IMZ na posição 1, indicando que a ligação de hidrogênio com a porção fosfato pode estabilizar o intermediário de reação. Para o 4(5)HMZ foram observados, além do intermediário fosforilado, outras espécies evidenciando que a troca de posição da hidroxila tornou o mecanismo reacional mais complexo, inclusive com a detecção de um inesperado produto 0 - fosforilado. Por fim, os incrementos catalíticos observados para o DEDNPP (~105 vezes) e para o BDNPP (~106 vezes) mostraram o grande poder catalítico desses compostos e sua promissora aplicação. De maneira geral, esse estudo foi importante para elucidar o efeito de substituintes em derivados de IMZ com potencial para interações intramoleculares. Isso é promissor para compreensão de sítios enzimáticos e também para projeção de catalisadores e detoxificantes proeminentes. Palavras-chave: Hidroxiimidazol. Mecanismo de reação. Organofosforados.Abstract: Imidazole and its derivatives are compounds of great interest because of their efficiency as catalysts in phosphoryl transfer. In this sense promoting the cleavage of organophosphates is quite interesting because they are used as pesticides, chemical weapons. In this work the effect of alcoholic substituents in IMZ towards the dephosphorylation reactions was evaluated. For this, two IMZ derivatives were synthesized: 1-hydroxyethyl imidazole (1-HEZ), 1-hydroxypropyl imidazole (1-HPZ) and one commercial 4(5) hydroxymethylimidazole (4(5) HMZ) were used. The chosen organophosphates were the triester 2,4-dinitrophenyl phosphate (DEDNPP) and sodium bis (2,4-dinitrophenyl) phosphate (BDNPP). The reaction kinetics were accompanied by the UV-Vis technique by the appearance of the reaction product 2,4 dinitrophenolate (DNF). The reaction mechanism was investigated using nuclear magnetic resonance (NMR), mass spectrometry (EM), kinetic isotope effect (EIC), thermodynamic activation parameters and organic physicochemical analysis using the Bronsted equation. For the reaction with DEDNPP with the derivatives 1-HEZ and 1-HPZ,. the EIC results with values close to 1 and thermodynamic parameters with a very negative entropy showed that both derivatives react by similar mechanisms of nucleophilic catalysis, with the imidazole ring attacking the phosphorus atom. In the 31P NMR analysis no phosphorylated reaction intermediates were detected due to the high instability of the same and only the starting organophosphate and the final product (diethyl phosphate) were observed. In the MS analysis all the key pieces of reaction were detected, including the phosphorylated intermediate. In addition, the Bronsted plot showed a straight line, typical of a concerted mechanism. Reactions with the BDNPP were studied with 1-h Ez , 1-HPZ and 4 (5) HMZ hydroxyimidazoles. In this case, secondary EIC values (i.e., between 1 and 2) were observed indicating that in this case the hydroxyl could be influencing the reaction mechanism. From the EIC values combined with the thermodynamic parameters it has been proposed a nucleophilic catalysis mechanism combined with the stabilization of the transition state by a hydrogen bond of the hydroxyl group of the hydroxyimidazoles. From the 31P NMR study for BDNPP with 1-He Z, the phosphorylated intermediate, unusual for IMZ derivatives at position 1, was observed, indicating that hydrogen bonding with the phosphate moiety can stabilize the reaction intermediate. For the 4(5) HMZ, other species were observed besides the phosphorylated intermediate, evidencing that the hydroxyl position change made the reaction mechanism more complex, including the detection of an unexpected O-phosphorylated product. Finally, the catalytic increases observed for DEDNPP (~ 105-fold) and BDNPP (~ 106-fold) showed the great catalytic power of these compounds and their promising application. In general, this study was important to elucidate the effect of substituents on IMZ derivatives with potential for intramolecular interactions. This is promising for understanding enzyme sites and also for projection of prominent catalysts and detoxifiers. Key-words: Hydroxyimidazole. Reaction mechanism. Organophosphates

Vapor-liquid equilibrium and thermodynamic property estimation of CO2 - alkanolamines - water system using molecular modeling and validation with experiments

The study of phase equilibrium thermodynamics of (CO2 + alkanolamine + H2O) system is of immense significance in the context of energy efficient capture of CO2, the most alarming green- house gas in the atmosphere. Among the various methodologies available so far absorption in alkanolamine solvent is currently in use. However,alkanolamines as solvent have certain drawbacks such as solvent loss due to volatility and high regeneration costs due to the high water content, which has driven researchers for new and alternative technologies. Recently room temperature ionic liquids (ILs’); called green solvents are emerging as promising candidates to capture CO2 due to their wide liquid range, low melting point, tunable properties, negligible vapor pressure, high CO2 solubility and reasonable thermal stability. But it is difficult to realize practically owing to its high viscous and high cost, which left us so far with the alkanolamine-CO2 technology. There is a rejuvenation of interest for newer alkanolamine formulation. In view of this, present thesis aimed towards the generation of new vapor-liquid equilibrium data on(EAE+ CO2+ H2O)system along with the generation of density data on aqueous (EAE + ATM)and (EAE + MDEA)blends. The physicochemical data are considered to be a very important contribution towards the design database of gas treating process

Catalytic Stereoselective Construction of Terphenyl and Imide Atropisomers by Brønsted Basic Guanidinylated Peptides

This dissertation describes our studies on the development of tetramethylguanidine (TMG)-based peptides as a new class of Brønsted basic catalysts and their application to challenging atroposelective reactions. The enhanced basicity of these peptides has enabled us to access novel reactivity to synthesize scaffolds of interest containing one or more stereogenic axes with high levels of catalyst control.Chapter 1 serves as an introduction to the concept of chirality, with a focus on its connection to the functional role of natural and synthetic molecules. An important subset of chirality is atropisomerism, which arises from restricted bond rotation most commonly between sp2–sp2 atoms. Atropisomerism is a critical consideration to drug development and we describe strategies prepare axially chiral biaryls. We also discuss the inspirations behind applying miniaturized peptides as catalysts in diverse asymmetric transformations. Chapter 2 outlines our motivations to pursue the novel class of TMG-based peptides, and our development of a modular synthetic route to build a library of these catalysts. We also highlight the properties of guanidines responsible for their reactivity, seminal work in the area of asymmetric guanidine catalysis, and challenges to address in the field. Chapter 3 discusses our development of an atroposelective ring-opening of biaryl lactones catalyzed by our new tetramethylguanidylalanine (Tmga) peptides. Optimization of this system revealed critical insights on the impact of solvent effects on pKa magnitudes and inhibition of reversible reaction pathways. We were able to design a Tmga peptide catalyst that could catalyze the ring-opening of buttressed lactones in up to 93:7 er. Chapter 4 details our studies on the catalyst-controlled synthesis of two-axis terphenyl atropisomers. The chemistry proceeds through a sequence of two distinct dynamic kinetic resolutions: first, an atroposelective ring opening of Bringmann-type lactones installs a first-axis while “turning on” the second step, stereoselective arene halogenation, which delivers the two-axis product. Notably, the TMG-based peptide enabled the first reported efficient atroposelective chlorination. In addition, a complementary bromination was established through chiral anion phase transfer catalysis by C2-symmetric phosphoric acids. These studies were done in collaboration with the Toste Group at UC Berkeley, and we established the fully catalyst-controlled stereodivergent synthesis of all possible chlorinated and brominated diastereomers with significant levels of enantioselectivity. Chapter 5 presents a novel atroposelective cyclization strategy to prepare axially chiral N-aryl maleimides and similar scaffolds. To date, a catalytic ring-closure to atropisomeric imides remains unreported, and previous approaches are limited to desymmetrizations. This reaction is catalyzed by Brønsted basic Tmga peptides, and we found that other catalyst types were not sufficiently reactive to deliver the product. In our studies, we observed a striking enantiodivergency that occurs by simple modulation of the substitution pattern on the D-proline residue. Accordingly, we present the full optimization of peptide catalysts, most recent results, and preliminary mechanistic insights on the reaction process. Ultimately, the studies presented herein unveil a new class of guanidinylated peptide catalysts which are significantly more basic than our group’s previously reported tertiary amine containing peptides. These TMG peptides can enable challenging reactivity with high levels of stereoselectivity and catalyst control, and we outline new strategies for the stereodivergent syntheses of multi-axis and imide-based atropisomer scaffolds

Mining Uranium from Seawater: A Coordination Chemistry Approach

Poly(acrylamidoxime) fibers are the current state-of-the-art adsorbent for mining uranium from seawater. However, the amidoxime group is not perfectly selective towards the uranyl cation, in particular, competition with transition metal cations remains a major challenge. In order for subsequent generations of chelating polymer adsorbents to be improved, the coordination chemistry of amidoxime-uranyl and -transition metal cation complexes needs to be better understood. While the coordination mode of amidoxime-uranyl complexes has been established in the literature, a number of amidoxime-transition metal cation complex binding motifs can be observed on the Cambridge Structrural Database. Likewise, the formation constants, or log K values, of a number of essential amidoxime-uranyl and -transition metal cation complexes remain largely unresolved due to the wide range of conflicting acid dissociation constants, or pKa [pKa] values, that have been reported for representative acyclic amidoxime ligands in the literature. Therefore, in Chapter 2 we use spectroscopic titrations to resolve the pKa values of acetamidoxime and benzamidoxime. Subsequently, we use those pKa values to develop computational protocols for predicting the pKa values of aqueous oxoacid ligands. In Chapters 3 and 4, we computationally investigate the binding motif of formamidoximate-dioxovanadium(V) and –oxovanadium(IV) complexes, major competing ions in seawater by utilizing density functional theory and wave-function methods in conjunction with continuum solvation calculations. Our investigations of these formamidoximate complexes universally identified the most stable binding motif to be a tautomerically rearranged imino hydroxylamine chelate formed via coordination of the imino nitrogen and hydroxylamine oxygen. In Chapter 5, we build on the design principles acquired in Chapters 2-4 to design a ligand, salicylaldoxime that is more selective towards utanyl than competing transition metal cations. Finally, in Chapter 6 we potentiometrically determine the proton affinity distribution of the classical poly(acrylamidoxime) fiber between pH 2 and pH 10 via the Stable Numerical Solution of the Adsorption Integral Equation Using Splines (SAIUS) algorithm. This work lays the foundation for resolving the metal cation affinity distribution of the poly(acrylamidoxime) fibers, which can aid in improving the uranium selectivity of subsequent generations of chelating polymers

Transition Metal Hydrides that Mediate Catalytic Hydrogen Atom Transfers

Radical cyclizations are important reactions in organic chemistry. However, they are seldom used industrially due to their reliance on neurotoxic trialkyltin hydride. Many substitutes for tin hydrides have been developed but none have provided a general solution to the problem. Transition metal hydrides with weak M-H bonds can generate carbon centered radicals by hydrogen atom transfer (HAT) to olefins. This metal to olefin hydrogen atom transfer (MOHAT) reaction has been postulated as the initial step in many hydrogenation and hydroformylation reactions. The Norton group has shown MOHAT can mediate radical cyclizations of ɑ,ω dienes to form five and six membered rings. The reaction can be done catalytically if 1) the product metalloradical reacts with hydrogen gas to reform the hydride and 2) the hydride can perform MOHAT reactions. The Norton group has shown that both CpCr(CO)₃H and Co(dmgBF₂)₂(H₂O)₂ can catalyze radical cyclizations. However, both have significant draw backs. In an effort to improve the catalytic efficiency of these reactions we have studied several potential catalyst candidates to test their viability as radical cyclization catalysts. I investigate the hydride CpFe(CO)₂H (FpH). FpH has been shown to transfer hydrogen atoms to dienes and styrenes. I measured the Fe-H bond dissociation free energy (BDFE) to be 63 kcal/mol (much higher than previously thought) and showed that this hydride is not a good candidate for catalytic radical cyclizations. I have investigated the dynamics of Co(dmgBF₂)₂(H₂O)₂ under hydrogen gas to attempt to observe its hypothesized cobalt hydride. Under large pressures up to 70 atm we see two species one which we assign as the cobalt hydride and one which we assign as a ligand protonated Co(I) complex. These are supported by high pressure NMR studies of the same complexes. By varying the H₂ pressure, we can calculate the hydrogen atom donor ability of the mixture formed under H₂ as 50 kcal/mol. This makes this mixture a very good H• donor. The Norton group has shown that vanadium hydrides have very weak V-H bonds that donate H* rapidly. However, they cannot be made catalytic under hydrogen gas. I have attempted to regenerate these vanadium hydrides by a sequential reduction then protonation of the metalloradical. With HV(CO)₄dppe this only produced hydrogen gas, presumably by one electron reduction of HV(CO)₄dppe. However, with HV(CO)₄dppf this does not readily occur and this hydride could potentially be a catalyst for radical cyclizations. Many radical cyclizations involve vinyl (sp²) radicals. I have shown that both the CpCr(CO)₃H and the Co(dmgBF₂)₂(H₂O)₂ systems can catalytically perform metal to alkyne hydrogen atom transfers (MAHAT's) and that these reactions can be used to perform radical cyclizations very efficiently