<div>Polyamide based reverse osmosis (PA-RO) membranes are applied for the desalination of halide-containing waters such as seawater and brackish groundwater. They are the industry standard because of their high selectivity and ability to withstand a wide range of pH. However, one of their pitfalls is their propensity to undergo biofouling, which is deterioration due to biological growth. Biofouling is known to dramatically decrease membrane performance and increase energy consumption. In order to overcome biofouling, a disinfectant, typically free chlorine, is applied; however, free chlorine is known to react with the polyamide layer and result in further membrane deterioration and performance loss.<br></div><div>One topic that has garnered less attention is the application of chloramines and their interactions with the PA-RO membrane when applied as a biofouling control. Furthermore, the role of halides (e.g. chloride, bromide, and iodide) in the presence of chloramines must be further explored because they are known to react to form secondary species which are reactive toward PA-RO membranes. In Chapter 2, the PA based monomers benzanilide (BA) and N-Methyl-N-phenylbenzamide (N-CH₃-BA) were used to model the PA layer. Monomers were exposed to halide containing waters and chloraminated with pre-formed NH₂Cl over a wide range of pH. The decay and by-product formation after exposure were evaluated using HPLC-DAD, LC/MS, and/or GC/MS. Results indicated that pH of the system and bromide concentration controlled parent compound decay and brominated by-product formation, where low pH and high bromide concentrations led to the highest formation of brominated by-products.</div><div>In Chapter 3, commercially made PA-RO membranes (SWC4-LD) were chloraminated or chlorinated with and without halides over a wide pH range. Their performance was evaluated after exposure through flux experiments using a dead-end flow cell. Results indicated that exposure to free chlorine led to the greatest change in flux and monochloramine resulted in the smallest change in flux. During chloramination of the membranes, the reactors containing bromide led to further change in flux than the chloramine only conditions. This was likely due to formation of secondary species that were reactive toward the PA membrane. Furthermore, Chapter 4 summarizes overall research contributions from this work and proposes future work pertaining to this topic.</div>

Die Verwendung von nukleinsäuretemplatgesteuerten Reaktionen stellt einen innovativen Ansatz zur Therapie von Krankheiten dar, deren Ursprung in einer genetischen Veränderung von Zellen liegt. Im Rahmen der hier vorliegenden Arbeit erfolgte eine Weiterentwicklung der RNA-templatgesteuerten Acyltransferreaktion nach Seitz et al. hinsichtlich des Aufbaus von aromatischen Amidbindungen, wie sie in vielen niedermolekularen Wirkstoffen vorkommen. Als Modellverbindungen dienten die Bcr-Abl-Tyrosinkinaseinhibitoren Nilotinib, Ponatinib und GZD824, die durch zentrale Benzanilidmotive charakterisiert sind und zur Therapie der chronischen myeloischen Leukämie eingesetzt werden. Das konzipierte Reaktionssystem beruht auf dem Mechanismus der nativen chemischen Ligation, weswegen die Bcr-Abl-Inhibitoren durch die Einführung einer Thiolgruppe modifiziert werden mussten. Es wurde gezeigt, dass diese Modifikation in den meisten Fällen nur zu einer geringen Beeinträchtigung der biologischen Aktivität führt. Der RNA-templatgesteuerte Aufbau der Benzanilidstrukturen konnte sowohl mit PNA- als auch mit DNA-verknüpften Inhibitorfragmenten basierend auf Ponatinib und GZD824 erzielt werden. In Gegenwart eines komplementären RNA-Templats erfolgte die benachbarte Hybridisierung der reaktiven Konjugate, infolgedessen ein Benzoyltransfer von einem thioestermodifizierten Donor auf ein ortho-Mercaptoanilinderivat als Akzeptor stattfand. Mit PNA/PNA-Reaktionssystemen wurde auch in Abwesenheit des RNA-Templats eine signifikante Produktbildung beobachtet, was auf hydrophobe Wechselwirkungen der Konjugate zurückgeführt wurde. Unter Verwendung von DNA/DNA- bzw. PNA/DNA-Konjugatpaaren blieb die templatunabhängige Produktbildung hingegen ausreichend gering. Die entsprechenden Reaktionssysteme wurden hinsichtlich der erzielten Produktausbeuten optimiert, wobei sowohl die Linkerlänge bzw. -struktur der reaktiven Konjugate als auch die Templatarchitektur variiert wurde. / The use of nucleic acid-templated reactions represents an innovative approach to the therapy of diseases that originate in genetic alterations of cells. In this work, the RNA-templated acyl transfer reaction invented by Seitz et al. was extended towards the formation of aromatic amide bonds which occur in a variety of small molecule drugs. The Bcr-Abl tyrosine kinase inhibitors nilotinib, ponatinib, and GZD824 were used as model compounds, as they are characterized by central benzanilide motifs and find application in the treatment of chronic myeloid leukemia. The designed reaction system is based on the mechanism of native chemical ligation which required the modification of the Bcr-Abl inhibitors by introducing a thiol group. It was shown that thiolation affected the biological activity only moderately. The RNA-templated formation of the benzanilide structures was achieved with both PNA- and DNA-linked inhibitor fragments of ponatinib and GZD824. The presence of a complementary RNA template enabled adjacent binding of the reactive conjugates, triggering a rapid benzoyl transfer from a thioester-linked donor to an ortho-mercaptoaniline derivative as an acceptor. With PNA/PNA reaction systems, significant product formation was observed in absence of the RNA template, which was attributed to hydrophobic interactions between the conjugates. However, the template-independent product formation remained low when DNA/DNA or PNA/DNA conjugate pairs were used. The product yields of the corresponding reaction systems were optimized by varying the linker length and structure of the conjugates as well as the template architecture.