No contexto de refino de petróleo, alquilação é o processo pelo qual se produz uma corrente de hidrocarbonetos chamada de alquilado, na faixa da gasolina, a partir de olefinas leves (propeno, butenos) e isobutano. A demanda por alquilado como corrente integrante do pool de gasolinas de uma refinaria tem aumentado ao longo das duas últimas décadas devido a diversos fatores, sendo o principal a adoção de normas mais restritivas para a qualidade de combustíveis automotivos. No presente trabalho foi desenvolvido e validado um modelo matemático fenomenológico capaz de representar adequadamente as reações químicas envolvidas no processo de alquilação catalítica que utiliza ácido fluorídrico como catalisador, bem como estimar o rendimento de produto e subprodutos da reação e a qualidade do alquilado, representada pelo teor de tri-metil-pentanos (TMP) e di-metil-hexanos (DMH) no alquilado. A construção do modelo foi baseada em balanços de massa e energia no conjunto reacional, utilizando mecanismos cinéticos disponíveis na literatura, sendo os seus parâmetros cinéticos estimados por regressão não linear a partir de literatura. O modelo foi validado com dados obtidos em uma unidade industrial de propriedade da Petrobrás, localizada em Cubatão. Os resultados obtidos permitem afirmar que o modelo apresentou boa resposta para a identificação do consumo de reagentes e rendimento de produtos. Sua resposta tendeu a subestimar a quantidade de frações pesadas do alquilado. / Alkylation is the process which light hydrocarbons (like butenes and iso-bute) are transformed into heavier hydrocarbons, called alkylate. The alkylate demand as a gasoline component has been growing since the middle 90s, mostly due to more severe quality requirements for gasoline. This work proposes a mathematical model that accounts for the main chemical reactions for a HF Alkylation Unit. The alkylate yield and quality, described by its composition, are also represented as well. This model as based on mass and energy balances for the alkylation reactor, using the most accepted kinetic mechanism available at literature. The model constants were estimated by non-linear regression with available data from literature. The model validation was performed comparing the simulation results with data collected at an industrial Alkylation unit at Cubatão, Brazil, without further parameter adjustment. The results show a good model response for the consumption of reagents and alky yield. The model, however, underpredicts the yield of heavier fractions.

When speciality chemicals are manufactured within the pharmaceutical industry, they are often produced in stirred batch/semi-batch reactors. A ‘methodology’ was explored, to help with the development of continuous fixed-bed catalytic reactors for this sector. This was tested on two different types of model reactions: (a) In the first, the viability of producing tertiary amines via ‘borrowing hydrogen’ was explored, and the reaction of morpholine and benzyl alcohol was studied, on Ru and Pt catalysts. This provided an opportunity for an early involvement in small-scale batch testing of catalysts, and then experiments were performed with the catalyst supported on granules in a packed bed (i.d. = 7 mm, length = 300 mm). Although it was shown that continuous processing is viable, and that high conversions (e.g. 73 to 98%, at 150 ºC) could be achieved, unfortunately further work was necessary to identify a more robust catalyst system, before moving on to pilot-scale trials. (b) In the second, the partial oxidation of benzyl alcohol to benzaldehyde was studied, using a Pt catalyst on a carbon support. This proved to be successful, and the reaction was finally demonstrated at pilot-scale. Carbon monoliths were used as catalyst supports (monolith o.d. = 19 mm; length = 50 mm long; square 0.7 mm x 0.7 mm channels; catalyst loading 2.5 and 2.7 wt% Pt). With a liquid flow of 1 L h-1 and a reactant concentration of ~1 mol L-1, operating at 110 ºC, conversion ranged from 80 to 90% and selectivity from 65 to 99%. The catalyst system was tested for 160 h of operation, and retained its performance. While testing the 2nd reaction, a pilot-scale reactor was also developed, which could be used for a variety of novel reactions. The design was flexible and it was easy to insert and remove the catalytic monoliths.

DNA repair is not a single mechanism found within cells. There exists numerous different DNA repair mechanisms that function within every type of cell. The majority of these mechanisms risk accumulating mutations. However, there are a few repair mechanisms that are known to be error-free and one of these is direct reversal repair. This study focused on two proteins highly involved in direct reversal DNA repair--ALKBH2 and ALKBH3. Previous studies have shown that in mice, these two proteins play a significant role in preventing and repairing DNA damage due to methylation as well as decreasing the frequency of mutagenic alkyl adducts. The goal of this study was to characterize the roles of the direct reversal repair proteins in human cells. We expected to see a similar phenotype to that of the Alkbh2 and Alkbh3-deficient mice. Telomerase immortalized human skin fibroblasts were targeted for the ALKBH2 and ALKBH3 alleles using a RNA-guided CRISPR-Cas9 construct that was designed to induce double stranded DNA breaks within the exons and disrupt the open reading frame, eliminating protein activity. Isolated clones were analyzed using fragment analysis and DNA sequencing to characterize any alterations in the open reading frame of the genes. Through sequencing analysis, results showed that one clone was successfully targeted for one of the ALKBH3 alleles with a single nucleotide insertion in its sequence, causing a disruption of the open reading frame. Though the ultimate goal of the experiment was not attained, we concluded that HTERTG fibroblasts can be expanded to serve as a model in which to construct targeted human cell lines that have near normal karyotypes.

The palladium-catalysed asymmetric allylic alkylation is a mild and versatile bond forming reaction between a nucleophile and allylic electrophile. The wide scope of nucleophiles used, and the high regio- and stereoselectivity obtainable renders this transformation an important technique in enantioselective synthesis. The mechanism is known to go via a key palladium π-allyl intermediate, followed by nucleophilic addition occurring at the terminal allylic carbon. Both the formation of the palladium π-allyl, and the nucleophilic addition to generate the alkylated product and palladium(0) proceed with high levels of inversion of stereochemistry, and both provide an opportunity for the induction of stereochemistry. However in the case of ligand controlled nucleophilic addition memory effects have been observed. The epimerisation of the palladium π-allyl before nucleophilic attack is key to achieving high levels of selectivity when racemic starting materials and chiral ligands are employed. Previous work in the Lloyd-Jones group has determined that prolonging the lifetime of the palladium π-allyl species, either by the use of weakly coordinating counter ions or slow addition of the nucleophile reduces this memory effect, however increasing the rate of epimerisation would have a result in a similar effect. One of the mechanisms resulting in the epimerisation of the palladium π-allyl species is mediated by palladium(0), however the details of the mechanism are not well understood. We describe the synthesis of a diastereotopic palladium cyclohexenyl ester and labelled the complex with 108palladium and d3 at the cyclohexenyl ester. Using simultaneous 31P NMR and mass spectrometry, we have acquired strong evidence against mechanisms involving a single electron transfer, as proposed by Stille, of formation of a dinuclear palladium(I) species followed by an inversion event, and we have gained evidence supporting the direct nucleophilic addition of the palladium(0), resulting in inversion of stereochemistry. The differences in rates of nucleophilic attack involving monodentate and bidentate phosphine ligands on both the palladium I-cyclohexenyl ester have also been explored. Throughout the mechanistic investigation, it was noted that the 31P NMR spectroscopy experiment used gave non-quantitative results, and in fact the differences in quantification of the species varied with the spectrometer used. We also describe our investigations into where these differences arise from and an optimum set of parameters for quantitative 31P NMR spectroscopy. The conclusions are also applicable to other heternuclear NMR spectroscopic experiments.

Bibliography: leaves 213-223 / viii, 224 leaves : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Organic Chemistry, 1987

<p><b><font face="TimesNewRomanPS-BoldMT"> <p align="left">Apoptosis is a process in which a cell programmes its own death. It is a highly organized physiological mechanism in which injured or damaged cells are destroyed. Apart from physiological stimuli however, exogenous factors can induce apoptosis. Many anti-cancer drugs work by activating apoptosis in cancer cells. Natural substances have been found to have the ability to induce apoptosis in various tumour cells and these substances have been used as templates for the construction of novel lead compounds in anticancer treatment. On the other hand, alkylating agents such as cisplatin, cis- [PtCl2 (NH3) 2]have been widely used as antineoplastic agents for a wide variety of cancers including testicular, ovarian, neck and head cancers, amongst others. However, the use of cisplatin as an anticancer agent is limited due to toxicity and resistance problems. <font face="TimesNewRomanPSMT">The aim of this present study was to screen the leaves of </font><i><font face="TimesNewRomanPS-ItalicMT">Rhus laevigata</font><font face="TimesNewRomanPSMT">, a South African indigenous plant, for the presence of pro-apoptotic and anti-proliferative natural compounds and also to screen newly synthesised palladium based complexes (15 and 57) and a platinum based complex (58) for their antineoplastic activities tested against a panel of cell lines.</font></i></p> </font><font face="TimesNewRomanPS-BoldMT"> <p align="left">&nbsp / </p> </font></b></p>

This thesis describes new methods of carbon-carbon bond formation using metalated nitriles generated via metal exchange reactions. Sulfinylnitriles undergo a sulfinyl-metal exchange to yield lithiated, magnesiated and zincated nitriles, which can trap a range of electrophiles. The sulfinyl-metal exchange is effective with vinylic, quaternary and tertiary substitution patterns and addresses the long-standing problem of alkylating secondary nitriles. This method was then further extended to other oxidation states of sulfur, namely sulfonyl-metal exchange and relatively unknown sulfide-metal exchange. The sulfide metal exchange overcomes the problem related to the propensity of highly substituted sulfinylnitriles to eliminate. Sulfide-metal exchange is synthetically attractive because of the numerous methods for generating arylsulfides and the high tolerance of arylsulfides to numerous reagents. &lt;br&gt;A copper-catalyzed arylation reaction of aryl iodides and metalated nitriles was developed using catalytic Cu (I) and an amine ligand. A proof of principle has been established, providing a sound basis for developing the reaction. A new strategy has been developed for alkylation of alkenenitrile using LDA as base in presence of catalytic CuCN. Subsequent trapping with an electrophile, affords alkylated alkenenitriles in which the olefin is no longer in conjugation with the nitrile. &lt;br&gt;The distinct structural differences between N- & C-metalated nitriles have been harnessed in a series of chemoselective alkylations. Lithiated nitriles are found to be particularly reactive toward alkyl halides whereas magnesiated nitriles react selectively with oxygenated electrophiles. Using this strategy allows chemoselective alkylation of metalated nitriles. / Bayer School of Natural and Environmental Sciences; / Chemistry and Biochemistry / PhD; / Dissertation;

The first section of this work describes the synthesis of a library of novel rhein analogues that are potential anticancer agents. The design of these compounds takes advantage of the ability for rhein to intercalate into DNA and as the incorporation of an alkylating agent, which serves to covalently modify DNA. In three cell lines, these compounds showed potent cytotoxicity with IC50 in the low to mid-μM range. The second project was focused on the development of an efficient synthesis of 6H-Isoindolo[2,1-α]indol-6-one (24), a core structure for a number of biologically active compounds. The approach is metal-free and uses a Beckmann rearrangement followed by an intramolecular cyclization.

The reaction of the pyrrolidine enamine of cyclohexanone with several malonic acid derivatives gave good yields of the corresponding Knoevenagel adducts when one of the activating substituents was a cyano group. The above enamine, after alkylation at the 2-position with methyl acrylate, gave similar yields of Knoevenagel products. Reaction of the alkylated enamine with lithioacetonitrile gave, after acidification, an annulated product by internal Knoevenagel reaction. The latter product was also obtained by a Dieckmann ring closure reaction. The Michael reaction of the substituted Knoevenagel products was examined and found to be facile with several nucleophiles. However, no ring closure products resulting from further reaction of the intermediate dicyanomethine anions were detected.Ball State UniversityMuncie, IN 47306

Functionalization of nanoparticles often control the extent of their usage. With this in mind, I have explored methods of creating highly functionalized exfoliated graphite, by way of the Billups-Birch reduction, that can be used in the advancement of nanotechnology (i.e. biomedicine). The method explored the use of sodium as the source for the solvated electron. The results of this method produced exfoliated graphite the same size as graphene and with solubility similar to the substrates attached to it. It was further shown that functionalized graphite with a terminal carboxyl group allowed further synthesis to occur via an elimination-addition reaction after the acyl group was transformed into an acid chloride. This reaction makes it possible to create exfoliated graphite that contains any compound of interest as long as it has an oxygen or nitrogen group that is able to react with the acid chloride. Thus, these products have the potential to be used in biomedicine as drug delivery agents.