The Polytope Formalism: isomerism and associated unimolecular isomerisation

This thesis concerns the ontology of isomerism, this encompassing the conceptual frameworks and relationships that comprise the subject matter; the necessary formal definitions, nomenclature, and representations that have impacts reaching into unexpected areas such as drug registration and patent specifications; the requisite controlled and precise vocabulary that facilitates nuanced communication; and the digital/computational formalisms that underpin the chemistry software and database tools that empower chemists to perform much of their work. Using conceptual tools taken from Combinatorics, and Graph Theory, means are presented to provide a unified description of isomerism and associated unimolecular isomerisation spanning both constitutional isomerism and stereoisomerism called the Polytope Formalism. This includes unification of the varying approaches historically taken to describe and understand stereoisomerism in organic and inorganic compounds. Work for this Thesis began with the synthesis, isolation, and characterisation of compounds not adequately describable using existing IUPAC recommendations. Generalisation of the polytopal-rearrangements model of stereoisomerisation used for inorganic chemistry led to the prescriptions that could deal with the synthesised compounds, revealing an unrecognised fundamental form of isomerism called akamptisomerism. Following on, this Thesis describes how in attempting to place akamptisomerism within the context of existing stereoisomerism reveals significant systematic deficiencies in the IUPAC recommendations. These shortcomings have limited the conceptualisation of broad classes of compounds and hindered development of molecules for medicinal and technological applications. It is shown how the Polytope Formalism can be applied to the description of constitutional isomerism in a practical manner. Finally, a radically different medicinal chemistry design strategy with broad application, based upon the principles, is describe

Mass spectrometric studies of ether lipids in Archaea and sediments

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been implemented as a means to separate and detect tetraether lipid cores derived from the complex lipids of Archaea. Distinct dissociation pathways during tandem mass spectrometry were noted for the lipid cores, providing information regarding their structure on-line. Analysis of cellular material from species of Methanothermobacter and Sulfolobus revealed tetraether lipid cores which contain up to four cyclopentyl rings per etherified alkyl chain, including structures identified previously in each genera. Identical structures were similarly identified in novel isolates from New Zealand hot springs. Product ions in the MS/MS spectra of the lipid cores include those formed from individual losses of both ring-containing C40 alkyl chains, allowing the reported structures to be verified with respect to the distribution of the rings within the two chains. A number of additional, hitherto unreported isomers and higher homologues of the ring-containing structures were resolved, both chromatographically and/or by characteristic product ions in MS/MS. Structures in which the two chains appear to be conjoined by a covalent link were also identified in Ignisphaera aggregans, the first such identifications in a Euryarchaeote. The array of structures revealed highlights both the complexity of the archaeal lipidome, which is more extensive than has been attributed previously, and the potential of LC-MS/MS as a powerful tool for probing tetraether lipid core structure. Ether lipid cores extracted from ancient aquatic sediments and contemporary soil were used to investigate the scope of LC-MS/MS for profiling of extremely complex distributions sourced from ecological communities as opposed to single organisms. Over 100 ether lipid components in total were identified during the studies, the vast majority of which represent novel structures. These include isoprenoid lipid cores of known archaeal origin and structures which may represent their transformation products; triolic structures in which one of the two capping glycerol moieties has been lost and chain or glycerol methylated higher homologues. A wealth of non-isoprenoid lipid cores were similarly identified, with inferred structures suggestive of a eubacterial or mixed eubacterial/archaeal origin. The components, once constrained to more specific origins, may be of chemotaxonomic value for use in modern environmental profiling or in palaeoecological reconstructions made using fossilised lipid cores

Ciguatoxins

Ciguatoxins (CTXs), which are responsible for Ciguatera fish poisoning (CFP), are liposoluble toxins produced by microalgae of the genera Gambierdiscus and Fukuyoa. This book presents 18 scientific papers that offer new information and scientific evidence on: (i) CTX occurrence in aquatic environments, with an emphasis on edible aquatic organisms; (ii) analysis methods for the determination of CTXs; (iii) advances in research on CTX-producing organisms; (iv) environmental factors involved in the presence of CTXs; and (v) the assessment of public health risks related to the presence of CTXs, as well as risk management and mitigation strategies

Marine Toxins from Harmful Algae and Seafood Safety

The rapid expansion of aquaculture around the world is increasingly being impacted by toxins produced by harmful marine microalgae, which threaten the safety of seafood. In addition, ocean climate change is leading to changing patterns in the distribution of toxic dinoflagellates and diatoms which produce these toxins. New approaches are being developed to monitor for harmful species and the toxins they produce. This Special Issue covers pioneering research on harmful marine microalgae and their toxins, including the identification of species and toxins; the development of new chemical and biological techniques to identify and monitor species and toxins; the uptake of marine biotoxins in seafood and marine ecosystems; and the distribution and abundance of toxins, particularly in relation to climate change

Physiological plasticity of marine phytoplankton revealed by untargeted metabolomics

The majority of the earth's surface is covered by oceans. Within their photic zones, microscopically small algae are fixing carbon dioxide in form of organic molecules, thus building the base of the marine food web. The metabolic plasticity of these algae allows them to respond to ecological changes such as grazing, thereby increasing their fitness and survival. However, most of the metabolites produced by microalgae are not yet known. State-of-the-art metabolomics techniques allow the untargeted and sensitive analysis of intra- and extracellular metabolites both in laboratory cultures and the ocean. The aim of this thesis was to describe physiological plasticity of marine microalgae with regard to grazing interactions. Thus, I conducted a comprehensive review on metabolomics in the field of chemical ecology, and introduced a systematically optimized and standardized protocol for the metabolic analysis of marine algae. Furthermore, I developed a UHPLC-APCI-HRMS analysis for the simultaneous profiling of volatile and non-volatile oxylipins - two compound classes that are released by microalgae as grazing defence, and that had to be analysed separately in the past. To better understand the influence of algal physiology on trophic interactions with marine grazers, I described the physiological plasticity of the abundant cold-water species Phaeocystis pouchetii in laboratory cultures, identified by an untargeted metabolomics approach endo- and exometabolites that are potential physiological markers for different growth phases, and used these markers to characterize natural P. pouchetii blooms in the Northeast Atlantic. In addition, I showed that during filtration of P. pouchetii metabolites can be released which influence the specific growth of marine bacteria. In summary, this thesis provides new insights into the role of physiological and thus functional parameters in the ecology of marine algal communities.Der Großteil der Erde wird von Meerwasser bedeckt, in welchem mikroskopisch kleine Algen Kohlenstoffdioxid in Form organischer Moleküle fixieren, und somit die Basis der marinen Nahrungskette bilden. Ihr plastischer Zellstoffwechsel ermöglicht es Algen, auf ökologische Veränderungen wie z.B. Fraß zu reagieren, und erhöht somit deren Fitness und Überleben. Moderne Metabolomics-Methoden erlauben die nichtselektive, sensitive Messung intra- und extrazellulärer Metabolite sowohl in Laborkulturen als auch im Meer. Das Ziel dieser Arbeit war es, die physiologische Plastizität mariner Mikroalgen in besonderem Hinblick auf Räuber-Beute-Beziehungen zu beschreiben. So verfasste ich einen Übersichtsartikel zur Anwendung von Metabolomics im Bereich der chemischen Ökologie, und stellte ein systematisch optimiertes und standardisiertes Protokoll zur metabolomischen Analyse mariner Algen in Form eines Buchkapitels zusammen. Weiterhin entwickelte ich eine UHPLC-APCI-HRMS Methode zur simultanen Messung flüchtiger und nichtflüchtiger Oxylipine - zwei Substanzklassen, die von Kieselalgen zum Fraßschutz freigesetzt werden, und die in der Vergangenheit nur getrennt analysiert werden konnten. Um den Einfluss der Zellphysiologie auf trophische Interaktionen mit marinem Zooplankton besser zu verstehen, beschrieb ich die physiologische Plastizität der abundanten Kaltwasserart Phaeocystis pouchetii in Laborkulturen, identifizierte mithilfe einer nichtselektiven Metabolomanalytik intra- und extrazelluläre Metabolite, die sich als physiologische Marker für verschiedene Wachstumsphasen eignen, und nutzte diese Marker zur Charakterisierung natürlicher P. pouchetii-Blüten im Nordostatlantik. Weiterhin zeigte ich, dass bei Filtration von P. pouchetii Stoffwechselmetabolite freigesetzt werden, welche das spezifische Wachstum von Bakterien beeinflussen. Diese Arbeit gewährt neue Einblicke in die Bedeutung physiologischer und somit funktioneller Parameter für die Ökologie mariner Algengemeinschaften