Studies into the Synthesis of Cyclacenes

University of Minnesota Ph.D. dissertation August . 2017. Major: Chemistry. Advisor: Christopher Douglas. 1 computer file (PDF); xxv, 201 pages.Cyclacene is a unique macrocyclic hydrocarbon composed of laterally-fused benzenoid rings that has proven to be a challenging synthetic target. It is recognized as the shortest zigzag carbon nanotube (CNT) and could serve as a well-defined model to study the electronic and photophysical properties. Even prior to the discovery of CNTs, organic, physical organic, and computational chemists debated the consequences of the conjugated macrocyclic structure on the electronic and physical properties of cyclacene. This curiosity further drives the desire for experimental studies which are only possible after the successful synthesis of this molecule. Previous synthetic attempts successfully constructed the macrocyclic framework through Diels-Alder reactions, but late stage dehydrogenation and or oxidation proved problematic. Computational studies predict that one of the major challenges at the late-stage of synthetic efforts is the possibility of an open-shell singlet ground state of cyclacene, which would give the molecule a highly reactive diradical character. Another synthetic challenge associated with forming this macrocycle is its high strain energy. With these obstacles in mind, we have proposed a strategy for the synthesis of cyclacenes that should overcome these challenges because: (1) the intermediates are of approximately equal strain as the final target; (2) conjugation is completed through extrusion of a gas; (3) it allows the incorporation of substituents on the zigzag edge to increase the persistence of the final a cyclacene ring. A more detailed examination of the proposed synthetic route as well as current progress towards the synthesis of a cyclacene molecule is detailed in this dissertation

Avoidance trajectories for driver assistance systems via solvers for optimal control problems

CD-ROM, Paper No. 294, 8 pages,International audienceAvoidance trajectories for driver assistance systems is an important and active fi eld of research in car industry. Assistance systems with active braking maneuvers rely on car models, e.g. the single-track model, which are modeled as control problems. The formulation of suitable objective functions serves as a tool to realize collision detection and avoidance. In two scenarios for overtaking maneuvers, an optimal trajectory is computed via xing a secure target state or by computing reachable sets from the initial starting point. First numerical experiments show approximations to optimal trajectories, controls and reachable sets. The sensitivity analysis in both, the optimal trajectory and the reachable set, reveal parameters that signi cantly in uence the solution

Design and Synthesis of a Potential Chemotherapeutic Agent Using Goniothalamin as a Natural Product Template

Goniothalamin, a natural product extracted from the tree bark of the Goniothalamus genus, has been shown to induce apoptosis in cancer cells. It is hypothesized that goniothalamin\u27s biological activity is due to its ability to react with thiols. Goniothalamin has been shown to decrease levels of glutathione, a natural antioxidant, found in cancer cells. This causes a redox imbalance, which ultimately leads to cell death. Thiol-reactive compounds, like goniothalamin, have also been shown to inhibit nuclear factor-κB (NF-κB). NF-κB is a transcription factor that has been implicated in unregulated cell growth. Through a nine step sequence, a novle analogue of goniothalamin has been prepared that replaces the lactone core of the nature product with a cyclohexenone. The synthetic sequence features a unique enol ether protection of beta-diketone which allows facile preparation of the desired analogue. It is anticipated that the novel goniothalamin derivative will demonstrate increaed cytotoxicity against cancer cells

Orbital and millenial-scale environmental changes between 64 and 25 ka BP recorded in Black Sea sediments

High-resolution pollen and dinoflagellate cyst records from sediment core M72/5-25-GC1 were used to reconstruct vegetation dynamics in northern Anatolia and surface conditions of the Black Sea between 64 and 20 ka BP. During this period, the dominance of Artemisia in the pollen record indicates a steppe landscape and arid climate conditions. However, the concomitant presence of temperate arboreal pollen suggests the existence of glacial refugia in northern Anatolia. Long-term glacial vegetation dynamics reveal two major arid phases ~64–55 and 40–32 ka BP, and two major humid phases ~54–45 and 28–20 ka BP, correlating with higher and lower summer insolation, respectively. Dansgaard–Oeschger (D–O) cycles are clearly indicated by the 25-GC1 pollen record. Greenland interstadials are characterized by a marked increase in temperate tree pollen, indicating a spread of forests due to warm/wet conditions in northern Anatolia, whereas Greenland stadials reveal cold and arid conditions as indicated by spread of xerophytic biomes. There is evidence for a phase lag of ~500 to 1500 yr between initial warming and forest expansion, possibly due to successive changes in atmospheric circulation in the North Atlantic sector. The dominance of Pyxidinopsis psilata and Spiniferites cruciformis in the dinocyst record indicates brackish Black Sea conditions during the entire glacial period. The decrease of marine indicators (marine dinocysts, acritarchs) at ~54 ka BP and increase of freshwater algae (Pediastrum, Botryococcus) from 32 to 25 ka BP reveals freshening of the Black Sea surface water. This freshening is possibly related to humid phases in the region, to connection between Caspian Sea and Black Sea, to seasonal freshening by floating ice, and/or to closer position of river mouths due to low sea level. In the southern Black Sea, Greenland interstadials are clearly indicated by high dinocyst concentrations and calcium carbonate content, as a result of an increase in primary productivity. Heinrich events show a similar impact on the environment in the northern Anatolia/Black Sea region as Greenland stadials

The glacial and interglacial history of the Black Sea during the last 134 ka: About meltwater events, abrupt temperature changes, and sapropels

The Black Sea experienced fundamental environmental changes during the last glacial-interglacial transitions. During the last 670,000 years, the Black Sea was at least twelve times connected to Mediterranean Sea, received saltwater via the Bosporus strait, and evolved to a brackish anoxic water body. A lowered global sea level during glacials caused isolation of the basin from the open ocean, and the Black Sea became limnic and well-oxygenated. The last glacial-interglacial history of the Black Sea is relatively well understood and demonstrates the high sensitivity of this basin to global climate and environmental changes. Previous studies particularly focussed on the evolution during the last glacial with meltwater pulses, warming during the glacial-interglacial transition, and the development from a ventilated lake to the present euxinic/brackish water body. Apart from the interglacial warming, the Black Sea sediments clearly recorded short-term abrupt temperature changes associated with cooling during Heinrich events and the Younger Dryas as well the Bølling-Allerød warming, which occurred over the northern hemisphere. However, our knowledge about the Black Sea history before 40,000 BP is comparatively poor even though crucial for understanding hemisphere-wide atmospheric teleconnection patterns and climate mechanisms during older glacials and interglacials. A multiproxy approach has been applied on three gravity cores and surface sediment from the southeastern Black Sea comprising ostracod geochemistry (Mg/Ca, Sr/Ca, U/Ca, 87Sr/86Sr), major and trace elements (Al, Ca, Fe, K, Ti, Mo, Re, Sr, W, Zr) and organic biomarkers (n-alkanes, alkenones, UK’37-palaeotemperatures, glycerol dialkyl glycerol tetraethers, TEX86-palaeotemperatures, BIT-index). The cores cover the last 134,000 a and provide new findings concerning the last and penultimate glacial-interglacial transitions (12,000- 0 a BP; 134,000-120,000 a BP) as well as the abrupt climate changes during the last glacial period (64,000-20,000 a BP). The major topics of this work are i) the penultimate glacial-interglacial transition (Saalian-Eemian), ii) the environmental conditions in the Black Sea “Lake” during abrupt climate oscillations of the last glacial period, iii) and the comparison of the redox evolution during Eemian and Holocene sapropel formation. Two meltwater pulses caused a pronounced freshening of the Black Sea “Lake” during the ending penultimate glacial, which originated from the melting Fennoscandian Ice Sheet. Due to unusually high radiogenic Sr-isotope signatures of benthic ostracods, a potential Himalayan source communicated via the Caspian Sea is also likely. During the glacial-interglacial transition the temperatures in the Black Sea increased from 9°C to 17°C and the associated global sea-level rise allowed the reconnection between the Mediterranean and Black Seas around 128,000 a BP. Eemian sapropel formation started shortly after the intrusion of saltwater and the water body became gradually euxinic. In comparison with the Holocene sapropel, the Eemian proxy records imply warmer and stronger euxinic conditions and distinctly higher enrichments of redox-sensitive trace elements like e.g. Mo, Re, and W. Because the seawater forms the ultimate source for several trace metals, these enrichments were most likely favoured by the higher salinity due to a ca. 10 m higher sea level and enhanced Mediterranean Sea - Black Sea water exchange. Based on biomarker analyses, lake surface temperatures could be calculated for the first time for the period between 64,000 and 20,000 a BP, which includes the Marine Isotope Stage (MIS) 3. Abrupt stadial/interstadial temperature changes with amplitudes of up to 4°C in the Black Sea “Lake” clearly resemble the Greenland Dansgaard-Oeschger pattern. However, an exceptional cooling during the so-called Heinrich events is not evident from our cores. This finding agrees with modelling results proposing a deeper penetration of regular Dansgaard-Oeschger cycles into the Eurasian continent when compared with the Heinrich events. During the warm and more humid interstadials, the Black Sea “Lake” became fresher and more productive and the water level probably increased. During the colder and more arid stadials the freshwater supply was decreased and productivity was low. Aridity and stronger westerly winds favoured the input of aeolian transported detritus. The long-term pattern from 64,000 to 20,000 a BP demonstrates a strong influence of orbital-driven changes in the Eurasian ice volume and associated atmospheric circulation patterns over the Black Sea region. The present multi-proxy study demonstrates that the sediments from the SE Black Sea clearly record not only orbital- but also millennial-scale climate and environmental changes and thus represent an important continental archive for climate change bridging the North Atlantic-Eurasian corridor.Das Schwarze Meer (SM) war im Zuge der Wechsel von Glazialen (G) zu Interglazialen (IG) fundamentalen Umweltveränderungen ausgesetzt. Während der letzten 670 ka war das SM mindestens 12x mit dem Mittelmeer (MM) verbunden, wodurch salziges Wasser über den Bosporus eintrat und ein brackischer, anoxischer Wasserkörper entstand. Ein niedriger Meeresspiegel während der G bedingte jedoch die Isolation vom offenen Ozean und das SM entwickelte sich erneut zu einem limnischen und durchlüftetem System. Die Entwicklung des SM während des letzten G-IG Übergangs (TI) ist weitgehend bekannt. Es hat sich gezeigt, dass das SM besonders sensibel auf globale Klima- und Umweltveränderungen reagiert. In früheren Arbeiten wurde besonderes Augenmerk auf Schmelzwasserereignisse, den Temperaturanstieg während TI sowie die Entwicklung von einem oxischen See zum heutigen euxinischen Brackwasserkörper gerichtet. Abgesehen von der Erwärmung zum IG, haben die Sedimente aber auch abrupte, kurzfristige Temperaturveränderungen archiviert, die im Zusammenhang mit denen auf der Nordhemisphäre auftretenden Abkühlungen während der Heinrich Ereignisse (HE) und der Jüngeren Dryas aber auch mit der Erwärmung während des Bølling-Allerøds stehen. Jedoch ist unser Kenntnisstand hinsichtlich der Zeit vor 40 ka BP für das SM begrenzt. Die Entwicklungsgeschichte während früherer G und IG ist jedoch unerlässlich für unser Verständnis der atmosphärischen Fernwirkung und klimatischer Prozesse im globalen Kontext. An 3 Schwerelotkernen und Oberflächensedimenten aus dem südöstlichen SM wurde im Rahmen dieser Arbeit ein Multiproxy-Ansatz angewandt, der die Analyse der Geochemie von Ostrakoden, Haupt- und Spurenelemente sowie organische Biomarker der Sedimente umfasste. Die Kerne erfassen die letzten 134 ka und liefern neue Einblicke in die letzten beiden G-IG Übergänge. Weiterhin wurden abrupte Klimaschwankungen während des MIS 3 detailliert untersucht. Die primären Inhalte dieser Arbeit umfassen i) den vorletzten G-IG Übergang, ii) die Umweltbedingungen des limnischen SM während abrupter Klimaschwankungen im MIS 3 und iii) den Vergleich der Entwicklung der Redoxbedingungen während der Sapropelbildung im Eem und Holozän. Während des ausgehenden vorletzten G führten 2 Schmelzwasserereignisse zu einer erheblichen Süßwasserzufuhr in das damalige limnische SM. Ähnlich des letzten G könnte dieses Schmelzwasser seinen Ursprung im schwindenden Fennoskandischen Eisschild gehabt haben. Die Analyse von Sr-Isotopen in Ostrakodenschalen zeigte jedoch eine erheblich radiogenere Signatur an, die auf einen zusätzlichen Beitrag von Schmelzwasser aus dem Himalaya, das über das Kaspische Meer transportiert wurde, hindeutet. Im Verlauf der TII stiegen die Temperaturen von ca. 9°C auf ca. 17°C an. Der globale Meeresspiegelanstieg führte vor etwa 128 ka zur Wiederverbindung des MM mit dem SM. Im Zuge des Salzwassereinstroms entwickelten sich euxinische Bedingungen und die Bildung des sog. Eem-Sapropels setzte ein. Im Vergleich zum Holozän-Sapropel lassen die Analysen des Eem-Sapropels wärmere und stärker euxinische Bedingungen vermuten, die mit erheblich höheren Anreicherungen von redox-sensitiven Spurenelementen einhergehen. Da das Meerwasser die entscheidende Quelle für eine Vielzahl von Spurenmetallen darstellt, wurden diese hohen Anreicherungen insbesondere durch den etwa 10m höheren Meeresspiegel und dem daran gekoppelten höheren Salzgehalt bzw. dem stärkeren Wasseraustausch zwischen MM und SM begünstigt. Basierend auf Biomarker-Analysen konnten erstmals Oberflächenwassertemperaturen des SM für den Zeitraum zwischen 64 und 20 ka BP berechnet werden. Abrupte Grönland Stadial (GS)/Interstadial (GIS)-assoziierte Temperaturschwankungen mit Amplituden von bis zu 4°C spiegeln eindeutig die Dansgaard-Oeschger (DO) Zyklen wider. Außergewöhnliche Abkühlungen während der HE zeichnen sich in den Kernen allerdings nicht ab. Diese Beobachtung deckt sich mit Modellergebnissen, die im Vergleich zu den HE auf eine stärkere Ausdehnung der regulären DO-Zyklen in den Eurasischen Kontinent hindeuten. Die warmen und humiden GIS zeichnen sich zudem durch einen reduzierten Salzgehalt und eine erhöhte Produktivität aus. Es ist außerdem anzunehmen, dass der Seespiegel während der GIS anstieg. Während der kälteren und ariden GS nahmen Süßwasserzufuhr und Produktivität hingegen ab. Trockenere Bedingungen und stärkere Westwinde begünstigten äolischen Eintrag von detrischem Material. Langfristig gesehen war das SM zwischen 64 und 20 ka BP stark durch die orbital gesteuerten Veränderungen des Eurasischen Eisschildes und den verbundenden atmosphärischen Zirkulationsmustern geprägt. Diese Arbeit belegt, dass die Sedimente des südöstlichen SM die Klima- und Umweltveränderungen nicht nur im orbitalen sondern auch im kurzzeitigen Maßstab aufgezeichnet haben. Damit stellt das SM, inmitten des Atlantisch-Eurasischen Sektors, ein überaus wichtiges kontinentales Archiv für Klimaentwicklungen dar