Attempts to Synthesize Cyclic Group 8 Metallaesters

In studying a proposed carbon monoxide reduction scheme an attempt has been made to synthesize bifunctional group 8 transition metal carbonyl complexes containing intramolecular nucleophiles. The incorporation of alkoxide nucleophiles through cyclopentadienyl ligands was hoped to encourage attack on carbonyl ligands thereby forming cyclic metallaesters. The attempts to synthesize these substituted cyclopentadienyl group 8 transition metal complexes have thus far been unsuccessful.

The Regulation of Sleep and Circadian Rhythms: The Role of Melatonin and Adenosine in Zebrafish

Sleep is a highly conserved behavioral state whose regulation is still unclear. In this thesis I initially briefly introduce the known sleep circuitry and regulation in vertebrates, and why zebrafish is seen as a good model to study sleep-regulation. I describe the existing two-process model of sleep regulation, which posits that the two processes C (circadian) and S (homeostatic) control timing of sleep-wake behavior. I then study the role melatonin plays in the circadian regulation of sleep using zebrafish. Firstly, we find that the absence of melatonin results in a reduction of sleep at night, establishing that endogenous melatonin is required for sleep at night. Secondly, melatonin mutants show a reduction in sleep in animals with no functional behavioral rhythms suggesting that melatonin does not require intact circadian rhythms for its effect on sleep. Thirdly, melatonin mutants do not exhibit any changes in circadian rhythms, suggesting that the circadian clock does not require melatonin for its function. Fourthly, we find that in the absence of melatonin, there is no rhythmic expression of sleep, suggesting that melatonin is the output molecule of process C. Lastly, we describe a connection between adenosine signaling (output molecules of process S), and melatonin. Following this we proceed to study the role adenosine signaling plays in sleep-wake behavior. We find that firstly, adenosine receptor A1 and A2 are involved in sleep- wake behavior in zebrafish, based on agonist/antagonist behavioral results. Secondly, we find that several brain regions such as PACAP cells in the rostral midbrain, GABAergic cells in the forebrain and hindbrain, Dopamine and serotonin cells in the caudal hypothalamus and sox2 cells lining the hindbrain ventricle are activated in response to the A1 antagonist and VMAT positive cells are activated in response to the A2A agonist, suggesting these areas are involved in adenosine signaling in zebrafish. Thirdly, we find that knocking out the zebrafish adenosine receptors has no effect on sleep architecture. Lastly, we find that while the A1 agonist phenotype requires the zfAdora1a receptor, the antagonist and the A2A agonist behavioral phenotypes are not mediated by the zfAdora1a, zfAdora1b and zfAdoraA2Aa, zfAdora2Ab receptors respectively.

I. Efforts toward the synthesis of aliphatic iodonium salts. II. Flourine-19 nuclear magnetic resonance spectroscopy of cyclic and bicyclic systems

The synthesis of iodonium salts of the general formula [C₆H₅IR]⁺X^-, where R is an alkyl group and x- is a stabilizing anion, was attempted. For the choice of R three groups were selected, whose derivatives are known to be sluggish in S_N1 and S_N2 substitutions: cyclopropyl, 7, 7 -dimethyl-1-norbornyl, and 9 -triptycyl. The synthetic routes followed along classical lines which have been exploited in recent years by Beringer and students. Ultimately, the object of the present study was to study the reactions of the above salts with nucleophiles. In none of the three cases, however, was it possible to isolate a stable salt. A thermodynamic argument suggests that this must be due to kinetic instability rather than thermodynamic instability. Only iodocyclopropane and 1-iodoapocamphane formed isolable iododichlorides.

Several methylated 2, 2-difluoronorbornanes were prepared with the intent of correlating fluorine -19 chemical shifts with geometric features in a rigid system. The effect of a methyl group on the shielding of a β -fluorine is dependent upon the dihedral angle; the maximum effect (an upfield shift of the resonance) occurs at 0° and 180°, whereas almost no effect is felt at a dihedral angle of 120°. The effect of a methyl group on a γ -fluorine is to strongly shift the resonance downfield when fluorine and methyl group are in a 1, 3 - diaxial-like relationship. Molecular orbital calculations of fluorine shielding in a variety of molecules were carried out using the formalism developed by Pople; the results are, at best, in modest agreement with experiment.