Includes bibliographical references. / x, 187 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 Physical and Inorganic Chemistry, 1994?

Thesis (Ph.D.)--Tufts University, 2003. / Adviser: Elena V. Rybak-Akimova. Submitted to the Dept. of Chemistry. Includes bibliographical references (leaves 168-179). Access restricted to members of the Tufts University community. Also available via the World Wide Web;

Thesis (Ph. D.)--University of Oregon, 2007. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 243-262). Also available for download via the World Wide Web; free to University of Oregon users.

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Thesis (M.S.)--University of Texas at Dallas, 2008. / Includes vita. Includes bibliographical references (leaves 85-88)

Thesis (Ph.D.) - University of Queensland, 2004. / Includes bibliography.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 229-247).

The thesis describes the development of a new set of macrocycles that could be used as part of an existing modular set of components, that when assembled, probe the structure-activity relationship of ion transporters. A property directed synthesis approach was adopted in which the properties, rather than the specific chemical makeup of the final target, guide the synthetic path. This allows for incorporation of the favorable properties and avoidance of the troublesome aspects of the current set of macrocycles into the synthetic design of the new modular components. As components in a modular set, the macrocycles are required in sufficient yield, so the property directed synthesis must provide an economical and efficient route to the targets. Molecular mechanics was used as a tool to estimate the length and rigidity of the macrocyclic systems. The design was also dictated by the need to incorporate high yielding methods for macrocyclization into the synthesis. All targets are formally meta cyclophanes involving overall axial symmetry to limit regioisomerism. The syntheses of 23, 25, 27, and 28 were based on the macrocyclization of bis-α- halo amides with bis-nucleophiles. Target 22 incorporated the bis-chloroamide of meta-phenylene diamine and a diol 23 derived from 1,3 bisbromomethyl benzene and butane diol. Conditions sufficient to deprotonate 23 apparently resulted in concomitant deprotonation of the amides leading to complex mixtures of products. Based on these observations the secondary amides of 23 were replaced with the homologous N-Me tertiary amides to give target 25. As anticipated, macrocyclization of 23 and the bis-chloramide of N,N’ dimethyl metaphenyiene diamine gave 25a in a yield of 7%. The design requires additional functional groups at the 5 and 5’ positions of the cyclophane. The chemistry leading to combinations of nitro and t-Boc protected amino groups in these positions was explored. Additional side reactions of the alkoxide nucleophile with nitro substituted aromatics precluded the desired macrocyclization reactions, and in all cases complex product mixtures were obtained. Additionally, the diol component 23 was replaced with a diol 26 of similar length in which the ether linkages were replaced by secondary amides. This gave a further target 27. In this series as well the side reaction of alkoxide with the nitro aromatic resulted in destruction of starting materials without production of product macrocycle. A corresponding target incorporating a dithiol in place of the diol 23 was explored in a preliminary fashion, but the physical properties of the dithiol complicated the purification of the precursor. The synthesis of a series of tetraester macrocycles derived from isophthalic acid and diols was explored. Direct condensation of 5-nitro isophthaloyl chloride and 1,8-octanediol gave a series of symetrical 2+2, 3+3, and 4+4 tetraesters in high conversion. A step-wise synthesis from the mono-tetrahydropyranyl derivative of 1.8-octane diol gave the 2+2 macrocycle 67 substituted with nitro and t-Boc protected amino in the 5 and 5’ positions in an overall yield of 16%. The efficiency of the synthesis of 67 is analysed using plan graphs as initially described by Hendrickson for natural products synthesis. The synthesis plan is compared with the actual performance in terms of reagent consumption, total weight manipulated, and the time for the synthesis. These results are compared with the synthesis of a comparable target in the existing series of macrocycles. Although tetraester 67 is somewhat less efficiently prepared than earlier examples, it is better functionalized to lead to candidate ion transporters. / Graduate

The syntheses of three structurally isomeric pentacoordinate [special characters omitted]-donor macrobicyclic ligands are reported. The isomers differ only in the identity of the two nitrogen atoms of the cyclam ring across which the [special characters omitted] fragment ("sulphur bridge") has been linked. The first isomer, 15-Thia-1,5,8,12- tetraazabicyclo[10.5.2]nonadecane (L1), consists of a 9-membered [special characters omitted]-donor ring fused to the 14-membered 1,5,8,11-tetraazacyclotetradecane (cyclam) ring. The ligand was synthesized by a copper(II) templated ring closure followed by borohydride reduction. A novel side product (4), a monoamide derivative of (L1), was also isolated and characterized. The second isomer, 17-Thia-1,5,8,12-tetraazabicyck)[6.6.5]nonadecane (L2), consists of linking the sulphur bridge across the diagonally opposed [1,8]-nitrogens. The ligand was synthesized by cyclizing cyclam (1,4,8,11-tetraazacyclotetradecane) with thiodiglycolic acid chloride under high dilution conditions. The third isomer, 14-Thia- 1,4,8, 11-tetraazabicyclo[9.5.3]nonadecane (L3), consists of linking the sulphur bridge across the adjacent [1,5]-nitrogens of the cyclam ring. The ligand was synthesized by cyclization of 1-thia-4,8-diazacyclododecane (20) with N,N’ –bis(α-chloro amido)diaminopropane (27) which afforded the diamide derivative, 14-Thia-1,4,8,11- tetraazabicyclo[9.5.3]nonadecane-3,9-dione (30), in high yield. Reduction of 30 with diborane gave the third structural isomer, (L3). A novel, convenient synthesis of 1-thia-4,8-diazacyclododecane-3,9-dione (23) from diaminopropane and thiodiglycolic acid chloride was developed. It was shown that high dilution conditions were necessary to obtain high product yields. The nature of the product obtained from reduction of 23 was shown to depend on the conditions used. In the presence of excess borane and methanol, the major product was a boron complex of the reduced ligand. Several changes to the conditions used avoided production of the boron complex and yielded the intended product (20) in sufficient quantity. The parent 1-Thia-4,7-diazacyclononane ([9][special characters omitted]) and 1,4,8,11- tetraazacyclotetradecane ([14][special characters omitted]) ligands exhibit first order coupling behaviour as a result of time averaging of molecular motions. However, the ambient temperature [special characters omitted] spectrum of the [9][special characters omitted] bicyclic free ligand (L1) exhibited second-order couplings and line broadening indicative of an exchange process. This result indicates that the rigidity of the macrobicyclic structure has hindered certain molecular motions. The variable-temperature [special characters omitted] spectra of (L1) were recorded in deuterated chloroform. It was found that the geminal coupling (> 15 Hz) of the [special characters omitted] (propylene fragment) methylene group approached 0 Hz as the temperature was raised beyond 40°C. It is believed that nitrogen inversion processes are responsible for the collapse of these signals. In order to determine if the rigidity of the [special characters omitted] macrobicyclic free ligand structure would have a significant effect on the chemistry of the metal complexes, the copper(II) and nickel(II) complexes of each of the [special characters omitted] isomers (L1-L3) were prepared and characterized. Any differences observed between these isomers can be attributed to ring strain effects. Electronic spectroscopy of the copper(II) complexes determined the absorption maxima of the [special characters omitted] isomers to be 532, 532.5 and 603 nm respectively. ESR spectroscopy showed each complex to have similar [special characters omitted] values (2.092, 2.090 and 2.089), and the frozen solution (77 K) spectra were indicative of tetragonally elongated axial symmetry [special characters omitted] with the unpaired electron predominantly in the [special characters omitted] orbital. The synthesis and characterization of the corresponding nickel(II) complexes of each ligand are reported. The electronic spectra of each of the [special characters omitted](acetate)2 and [special characters omitted] isomers were consistent with that expected for [special characters omitted] coordination of nickel(II). Electrochemical studies of the nickel(II)/(III) oxidations showed that there was a 170 mV difference between the [special characters omitted] values of the [special characters omitted] and [special characters omitted] complexes. These results implied that the (L1) and (L3) bicycle isomers are similar in coordination properties such that significant differences were not observed. The coordination properties of the third [special characters omitted] bicycle (L2) differ markedly from those of the other two isomers. That the unique diagonally bridged structure resulted in significantly different absorption maxima and redox potentials, indicates that the coordination of the [special characters omitted] donor set has been perturbed (relative to the (L1) and (L3) bicyclic ligands) by the strain energies unique to that isomer. The molecular structures of the [special characters omitted] and [special characters omitted] complexes were determined by X-ray crystallographic techniques. The cobalt(Ill) complex was shown to contain "true" octahedral coordination. The palladium(ll) complex was shown to consist of square planar [special characters omitted] coordination with the axial sulphur donor positioned 2.87Å from the palladium atom with the M-S vector deviating 16° from the perpendicular to the [special characters omitted] plane. / Graduate

Macrocyclic ligands containing nitrogen and sulphur donor atoms, as well as with pyridine or thiophene pendant arms were synthesized. The Co(II), Ni(II), Cu(II) and Pd(II) complexes have been characterized by crystallography, UV/Vis, NMR or ESR spectroscopy and the redox chemistry have been studied by cyclic voltammetry (CV). The Pd(II) complex of [14]aneNS3 (1,4,7-trithia-11-azacyclotetradecane), is square-planar whereas the structures of Pd(II) macrocyclic complexes with pyridine or thiophene pendent arms may be described as pseudo five-coordinate. There is considerable interaction between the apical sulphur donor atom and the palladium metal centre. In solution, the Pd(II) complex of py[14]aneNS3 (N-(2’-pyridylmethyl)- 1,4,7-trithia-11-azacyclotetradecane) exhibits fluxional behavior. There is an exchange process involving the metal-coordinated and -uncoordinated thioether atoms. By analyzing the NMR spectra obtained at different temperatures, the mechanism for the fluxional process is proposed. The cyclic voltammograms of the Pd(II) macrocyclic complexes showed irreversible reduction to Pd(I) and no oxidation to Pd(III) could be detected in the potential range studied. In the case of the Pd(II) complex with thiophene pendent arms, a quasi-reversible reduction to Pd(I) was observed. This unique behavior is rationalized as due to the proximity of a thiophene moiety in the apical position which inhibits dimerization to the Pd(I) generated, due to steric reasons. The Ni(II) complex of py[14]aneS3 is peudo-octahedral whereas the Co(Il) complex exists as two linkage isomers. In the nitrate salt, [special characters omitted], the cobalt centre is octahedral, being coordinated to only the nitrogen donors from the ligand and the remaining coordination sites are occupied by acetonitrile and oxygen atoms from two nitrate groups. In the perchlorate salt, [special characters omitted], solution studies (ESR and CV) suggest that the cobalt(II) ion is being coordinated by the nitrogen and sulphur donor atoms from the ligand. The Cu(II) complexes of these mixed donor ligands have also been studied and their spectroscopic (UV/Vis and ESR) characteristics and Cu(II)/Cu(I) reduction potential were compared to the type I Blue copper protein. / Graduate