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As moléculas à base de nitrogênio, NH2Ph, NH2CH2Ph e NHnBuPh foram investigadas como ligantes ancilares nos novos complexos do tipo [RuCl2 (PPh3)2 (amina) x] para a polimerização via metátese por abertura de anel (ROMP) de norborneno (NBE), norbornadieno (NBD) e diciclopentadieno (DCPD). Os complexos foram obtidos da síntese com [RuCl2 (PPh3)3] com as respectivas moléculas. E eles foram caracterizados por análise elementar de CHN, FT-IR, RMN 31P{1H}, Espectroscopia eletrônica na região do uv-vis e voltametria cíclica. Os complexos isolados foram hexacoordenados (x = 2) com NH2Ph e NH2CH2Ph, e pentacoordenado com NHnBuPh (x = 1). Além disso, os resultados sugerem que todos os ligantes estão trans-posicionados no caso do complexo com NH2Ph (complex 1) e cis no caso do complexo com NH2CH2Ph (complex 2). O complexo com NHnBuPh ( complex 3) e sugerido estar na geometria pirâmide de base quadrada, com a amina no eixo axial. Quantitativos rendimentos foram obtidos na ROMP de NBE a 50°C com 1 por 30 min e com 2 por 5 minutos. Similar resultado foi obtido com 3 at 25°C por 5 min. O valor de Mw foram na faixa de 104 e 105 g/mol,com valores de IPD entre 1,6 e 3,5. Os valores de σc foram em torno de 0,40 a 0,52. ROMP de NBE e DCPD, bem como copolimerizações foram também realizadas com melhores resultados com 3. Os resultados são discutidos em termos de densidade eletrônica e impedimento estérico das aminas como ligantes ancilares nos complexos. As reações com o complexo 2 são favoráveis pelo caráter σ-doador, enquanto que o grande ângulo de cone da NHnBuPh prove a reatividade de 3. / The nitrogen-based molecules, NH2Ph, NH2CH2Ph and NHnBuPh were investigated as ancillary ligands in the new [RuCl2 (PPh3)2 (amine) x] complex types for Ring Opening Metathesis Polymerization (ROMP) of norbornene (NBE), norbornadiene (NBD) and dicyclopentadiene (DCPD). The complexes were obtained from syntheses with [RuCl2 (PPh3)3]of and the respectively molecules and they were characterized by elementar analysis of CHN, FT-IR, NMR 31P, uv-vis spectroscopy and cyclic voltammetry. The isolated complexes were sixcoordinated (x = 2) with NH2Ph and NH2CH2Ph and pentacoordinated with NHnBuPh (x = 1). Moreover, the data suggest that all the ligands are trans-positioned in the case of NH2Ph (complex 1) and cis-positioned in the case of NH2CH2Ph (complex 2). The complex with NHnBuPh (3) was suggested to present a square pyramidal geometry with the amine in the axial axis. Quantitative yields were obtained in the ROMP of NBE at 50 °C with 1 for 30 min and with 2 for 5 min. Similar result was obtained with 3 at 25 °C for 5 min. The Mw values were in the range of 104 to 105 g/mol with PDI values between 1.6 and 3.5. The σc values were 0.40 to 0.52. ROMP of NBD and DCPD, as well copolymerizations with NBE, NBD and DCPD, were also performed with better results with 3. The results are discussed in terms of the electronic density and steric hindrance from the amines as ancillary ligands in the complexes. The reactions with complex 2 are favored by the σ-donor character of NH2CH2Ph, whereas the large cone angle of NHnBuPh provided the reactivity with 3.

本項研究工作主要對五個結構類似的胍基配體， 即 [(2,6-Me₂C₆H₃N)C(NHPri)(NPri)]⁻ (L¹)， [(2,6-Me₂C₆H₃N)C(NHCy)(NCy)]⁻ (L²)， [(2,6-Me₂C₆H₃N)C{N(SiMe₃)Cy}(NCy)]⁻ (L³)， [(2,6-Pri₂C₆H₃N)C{N(SiMe₃)₂}(NC₆H₃Pri₂-2,6)]⁻ (L⁴) 和 [(2,6-Pri₂C₆H₃N)C(NEt₂)(NC₆H₃Pri₂-2,6)]⁻ (L⁵) 與二價鉻以及二價鑭系金屬[Sm(II)、Eu(II) 及 Yb(II)] 的配位化學進行研究，同時，一系列由 L¹ 配體所衍生的三價鑭系金屬配合物亦成功被合成。 / 第一章概括介紹了由胍基配體所構築的金屬配合物的研究背景。 / 第二章敍述了含 L¹ 與 L⁴ 的二價鉻配合物的合成、結構及其化學反應。 通過胍基鉀化合物 [KL¹･0.5PhMe] (1) 與二氯化鉻反應可得到單核二價鉻雙胍基配合物 [Cr(L¹)₂] (3)。 通過胍基鋰化合物 [LiL⁴(Et₂O)] (2) 與二氯化鉻反應，成功製備了單胍基二價鉻配合物 [Cr(L⁴)(μ-Cl)₂Li(THF)(Et₂O)] (4)。 而把二價鉻配合物 4於甲苯溶液中重結晶可得到二聚體的二價鉻配合物 [{Cr(L⁴)(μ-Cl)}₂] (5)。 另外，我們對二價鉻配合物 3 及 4 的反應特性也進行了研究。 [Cr(L¹)₂] (3) 與單質碘、二苯基硫族化合物 PhEEPh (E = S, Se, Te) 以及叠氮金剛烷反應可得相對應的三價鉻混合配體化合物，分別爲 [Cr(L¹)₂I] (6)、[Cr(L¹)₂(EPh)] [E = S (7), Se (8), Te (9)]，及四價鉻配合物 [Cr(L¹)₂{N(1-Ad)}] (10)。 透過單胍基二價鉻配合物 [Cr(L⁴)(μ-Cl)₂Li(THF)(Et₂O)] (4) 與 NaOMe反應可得甲氧基-胍基配合物 [{Cr(L⁴)(μ-OMe)}₂] (11)。 / 第三章主要報導含 L¹， L²， L³ 和 L⁵ 配基的二價鑭系配合物的合成、結構和化學反應特性。 透過 [LnI₂(THF)₂] (Ln = Sm, Eu, Yb) 與胍基鉀鹽反應，我們成功合成一系列二價鑭系絡合物，包括 [{Eu(L¹)(μ-L¹)}₂] (15)， [{Ln(L²)(μ-L²)}₂･nC₆H₁₄] [Ln = Eu, n = 2 (16); Ln = Yb, n = 0 (17)，[Yb(L²)₂(THF)₂] (18)， [Ln(L³)₂(THF)₂･0.25C₆H₁₄] [Ln = Eu (19), Yb (20)]， [{Sm(L³)(μ-I)(THF)}₂] (21) 和 [Sm(L⁵)₂] (22)。 本章亦同時探討二價鑭系配合物15， 18， 20 和 22 作爲還原劑的化學反應特性。 配合物 15 與單質碘反應可得三價銪配合物 [{Eu(L¹)₂(μ-I)}₂] (23)。 配合物 18 與二苯基硫族化合物 PhEEPh (E = S, Se) 反應，可得相對應的三價鐿配合物 [{Yb(L²)₂(μ-EPh)}₂] [E = S (24), Se (25)]。 18 與氯化亞銅反應得到三價鐿配合物 [{Yb(L²)₂(μ-Cl)}₂] (26)。 除此之外，配合物 18 與偶氮苯反應得到雙核配合物 [{Yb(L²)₂}₂(μ-η²:η²-PhNNPh)] (27)， 而 20 與偶氮苯的反應可得單核配合物 [Yb(L³)₂(η²-PhNNPh)･PhMe] (28)。 配合物 22 與二硫化碳的反應得出不對稱偶合配合物 [(L⁵)₂Sm(μ-η³:η²-S₂CSCS)Sm(L⁵)₂] (29)。 / 第四章敍述由胍基配體 L¹ 所衍生的一系列三價鑭系金屬配合物 [Ln(L¹)₃] [Ln = Ce (30), Pr (31), Gd (32), Tb (33), Ho (34), Er (35), Tm (36)] 的合成及其結構。 通過相對應的鑭系金屬三氯化物與 1 反應可得配合物 30-36。 另外， CeCl₃及 LuCl₃與 1 反應亦可合成 [{Ln(L¹)₂(μ-Cl)}₂] [Ln = Ce (37), Lu (38)]。 / 第五章總結了本項研究工作，並對本工作的未來發展作出建議。 / This research work is focused on the coordination chemistry of five closely related guanidinate ligands, namely [(2,6-Me₂C₆H₃N)C(NHPri)(NPri)]⁻ (L¹), [(2,6-Me₂C₆H₃N)C(NHCy)(NCy)]⁻ (L²), [(2,6Me₂C₆H₃N)C{N(SiMe₃)Cy}(NCy)]⁻ (L³), [(2,6Pri₂C₆H₃N)C{N(SiMe₃)₂}(NC₆H₃Pri₂-2,6)]⁻ (L⁴) and [(2,6-Pri₂C₆H₃N)C(NEt₂)(NC₆H₃Pri₂-2,6)]⁻ (L⁵), with divalent chromium and lanthanide metal ions. A series of trivalent lanthanide derivatives of the L¹ ligand were also prepared and structurally characterized in this work. / Chapter 1 gives a brief introduction to the chemistry of metal guanidinate complexes. / Chapter 2 reports on the synthesis, structure and reactivity of chromium(II) complexes derived from the bulky L¹ and L⁴ ligands. Treatment of CrCl₂ with [KL¹･0.5PhMe] (1) afforded the mononuclear Cr(II) bis(guanidinate) complex [Cr(L¹)₂] (3). Reaction of CrCl₂ with [LiL⁴(Et₂O)] (2) resulted in the isolation of ate-complex [Cr(L⁴)(μ-Cl)₂Li(THF)(Et₂O)] (4). Recrystallization of 4 from toluene gave neutral, dimeric [{Cr(L⁴)(μ-Cl)}₂] (5). The reaction chemistry of the Cr(II) complex 3 and 4 was studied. Treatment of 3 with I₂, PhEEPh (E = S, Se, Te), 1-AdN₃ (1-Ad = 1-adamantyl) gave the corresponding mixed-ligand Cr(III) complexes, namely [Cr(L¹)₂I] (6) and [Cr(L¹)₂(EPh)] [E = S (7), Se (8), Te (9)] and Cr(IV) complex [Cr(L¹)₂{N(1-Ad)}] (10). Besides, the reaction of 4 with NaOMe resulted in the isolation of the Cr(II) methoxide-guanidinate complex [{Cr(L⁴)(μ-OMe)}₂] (11). / Chapter 3 deals with the synthesis, structure and reactivity of lanthanide(II) complexes supported by the L¹, L², L³ and L⁵ ligands. Lanthanide(II) guanidinate complexes were prepared by the reactions of an appropriate lanthanide diiodide with the corresponding potassium guanidinate complexes [KL¹･0.5PhMe] (1), [KL²(THF)₀.₅]n (12), KL³ (13) and [KL⁵(THF)₂] (14). Reaction of EuI₂(THF)₂ with 1 gave the homoleptic complex [{Eu(L¹)(μ-L¹)}₂] (15). Metathesis reactions of LnI₂(THF)₂ (Ln = Yb, Eu) with 12 and 13 led to the isolation of [{Ln(L²)(μ-L²)}₂･nC₆H₁₄] [Ln = Eu, n = 2 (16); Ln = Yb, n = 0 (17)], [Yb(L²)₂(THF)₂] (18) and [Ln(L³)₂(THF)₂･0.25C₆H₁₄] [Ln = Eu (19), Yb (20)]. Direct reaction of SmI₂(THF)₂ with 13 yielded the iodide bridged Sm(II) complex [{Sm(L³)(μ-I)(THF)}₂] (21), whilst reaction of SmI₂(THF)₂ with 14 gave homoleptic [Sm(L⁵)₂] (22). The reaction chemistry of 15, 18, 20 and 22 as reducing agents was examined. Oxidation of 15 with I₂ afforded the Eu(III) complex [{Eu(L¹)₂(μ-I)}₂] (23). Reactions of 18 with PhEEPh (E = S, Se) gave the corresponding Yb(III) chalcogenide complexes [{Yb(L²)₂(μ-EPh)}₂] [E = S (24), Se (25)], whilst treatment of 18 with CuCl led to the isolation of [{Yb(L²)₂(μ-Cl)}₂] (26). Besides, addition of complex 18 to PhNNPh yielded binuclear [{Yb(L²)₂}₂(μ-η²:η²-PhNNPh)] (27), whereas treatment of 20 with PhNNPh resulted in the isolation of mononuclear [Yb(L³)₂(η²-PhNNPh)･PhMe] (28). Addition of CS₂ to 22 gave the unsymmetrical coupling product [(L⁵)₂Sm(μ-η³:η²S₂CSCS)Sm(L⁵)₂] (29). / Chapter 4 describes the preparation and structural characterization of lanthanide(III) complexes derived from L¹. A series of homoleptic lanthanide(III) tris(guanidinate) complexes [Ln(L¹)₃] [Ln = Ce (30), Pr (31), Gd (32), Tb (33), Ho (34), Er (35), Tm (36)] were prepared by the reactions of an appropriate LnCl₃ with three molar equivalents of 1. Treatment of CeCl₃ and LuCl₃ with two equivalents of 1 gave the corresponding chloride bridged guanidinate complexes [{Ln(L¹)₂(μ-Cl)}₂] [Ln = Ce (37), Lu (38)]. / Chapter 5 summarizes the findings of this study. A short description on the future prospect of this work will also be given. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Au, Chi Wai. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references. / Abstracts also in Chinese.

The interaction between molecules is essential in a wide range of biological processes. A detailed knowledge of these interactions is necessary for understanding these processes. Among the systems that involve important interactions is the immune system. NMR spectroscopy has a large number of spectral parameters that were used in this work to study antibody-antigen interactions. These same parameters were also used to begin a structural analysis of a medium-sized protein, neurophysin, that has important interactions with neurohormones, and served here as a model antigen. A set of ligands differing in size and charge was designed and used to probe the binding site of anti-phosphocholine antibodies. These ligands ranged from small organic species to medium sized proteins. Amino acids, peptides and proteins were homogeneously linked to phenyl phosphocholine and analyzed by NMR techniques. Transferred nuclear Overhauser effect measurements were used to determine the conformation of bound ligands. The conformational change observed in some ligands was explained as either due to the antibody selecting one conformation that already exists, or the antibody binding inducing a conformational change. Titration data and detailed NMR analysis showed a more rigid M3C65 antibody fragment upon binding. In summary, with eight examples of ligands and four examples of antibodies studied by NMR, a spectrum of effects was seen, including a lock-and-key model and limited local induced fit. The contribution of the carrier molecule to antibody binding was in restricting the conformation of the ligand. Bigger ligands that are expected to be more immunogenic, showed less binding avidity as determined by immunological assays. Fluorinated ligands were synthesized to determine the kinetics of binding using 19F NMR spectra. Higher concentration of a fragment of the antibody M3C65 was analyzed to determine assignments of some residues in the combining site of the antibody. High resolution NMR techniques were used to assign resonances in neurophysin. The physiological role of neurophysin includes hormone storage and stabilization of oxytocin and vasopressin against proteolytic degradation within the posterior pituitary. Neurophysin is a 10 KD protein that dimerizes at high concentrations needed for NMR studies. An organic cosolvent was used to lower the dimerization constant, and hence inrease the spectral resolution. This permitted sequence-specific assignments that were then used to identify residues in the neurophysin-hormone binding site. Chemical shift differences and conformational changes were observed for the residues glutamate 47 and leucine 50. The 3₁₀ helix was further stabilized towards a more ideal helix upon hormone-analog peptide binding. Some of the residues contributing to the monomer-monomer interface were also assigned. Dimerization ill1duced chemical shift differences and conformational changes were observed for phenylalanine 35, threonine 38, and alanine 69. Tyrosine: 49 and phenylalanine 22 were affected but to a lesser extent. One characteristic of neurophysin in all studied cases was dynamic equilibrium between different folding states.

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Doctor of Philosophy(PhD) / The present study deals with the synthesis and characterization of six tri-palladium complexes code named MH3, MH4, MH5, MH6, MH7 and MH8 that contained two planaramine ligands bound to the central or each of the terminal metal ions. The activity of the compounds against human cancer cell lines: A2780, A2780cisR and A2780ZD0473R, cell uptake, levels of DNA-binding and nature of interaction with salmon sperm and pBR322 plasmid DNA have also been determined. Whereas cisplatin binds with DNA forming mainly intrastrand GG adduct that causes local bending of a DNA strand, the tri-palladium complexes are expected to bind with DNA forming a number of long-range interstrand GG adducts that would cause a global change in DNA conformation. Among the designed complexes, MH6 that has two 2-hydroxypyridine ligands bound to each of the two terminal palladium ions is found to be most active. The compound also has the highest cell uptake and Pd-DNA binding levels. In contrast, MH8 which has two 4-hydroxypyridine ligands bound to each of the two terminal palladium ions is found to be least active. The results indicate that, as applied to the terminal metal centres, 2-hydroxypyridine would be more activating than 4-hydroxypyridine perhaps because of greater protection provided to the terminal centres from coming in contact with the solvent molecules. In contrast, when bound to the central metal centre, 4-hydroxypyridine appears to play a slightly greater activating role than 2-hydroxypyridine or 3-hydroxypyridine, suggesting that non-covalent interactions such as hydrogen bonding associated with the ligand rather than its steric effect may be a more important determinant of antitumour property. The results illustrate structure-activity relationships and suggest that the tri-palladium complex containing two 2-hydroxypyridine ligands bound to each of the three metal centres or the compound that contains two 2-hydroxypyridine ligands bound to each of the two terminal metal centres and two 4-hydroxypyridine ligands bound to the central metal centre, may be much more active than any of the designed complexes.

Includes bibliographies. / xi, 240 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The complexation of a range of monovalent and divalent metal ions by the aliphatic bridge cryptands C22C2 and C22C8; and the complexation of alkali metal ions by the pendant arm tetraaza macrocycle 1,4,7,10-tetrakis(2-methoxyethyl)1,4,7,10-tetraazacyclododecane, and the factors effecting complex stability and lability, have been investigated. / Thesis (Ph.D.)--University of Adelaide, Dept. of Chemistry, 1995

Src Homology 3 (SH3) domains are small protein- protein interaction domains that bind to proline-rich peptides, mediating a range of important biological processes. Because the deregulation of events involving SH3 domains forms the basis of many human diseases, the SH3 domains are appealing targets for the development of potential therapeutics. Previously in the field, no examples of entirely small-molecule ligands for the SH3 domains have been identified. However, in our research group, we have discovered a class of heterocyclic compounds that bind to the Tec SH3 domain at conserved residues in the proline-rich peptide binding site, with weak to moderate affinity. The highest affinity of these was 2- aminoquinoline (Kd = 125 mM). In this thesis, a range of approaches are described, that were intended to contribute towards development of higher affinity small-molecule ligands for the Tec SH3 domain. Preliminary experiments, involving testing a variety of compounds structurally related to 2- aminoquinoline, provided new structure activity information, and led to a better understanding of the 2-aminoquinoline/SH3 domain binding event. The major component of this thesis is a thorough investigation into the synthesis of a range of 2- aminoquinoline derivatives. N-Substituted- 2-aminoquinolines were synthesised, however these compounds bound the SH3 domain with slightly lower affinity than 2-aminoquinoline. 6- Substituted-2-aminoquinolines were subsequently prepared, and ligands were identified with up to six-fold improved affinity relative to 2-aminoquinoline, and enhanced selectivity for the Tec SH3 domain. The techniques used for the ligand binding studies were Nuclear Magnetic Resonance (NMR) chemical shift perturbation and Fluorescence Polarisation (FP) peptide displacement assays. As part of the ligand binding studies, it was intended that the 3D tructure of a 2- aminoquinoline ligand/SH3 complex would be obtained using NMR methods, provided that a ligand was identified that bound the SH3 domain in slow exchange on the NMR timescale. However, this goal was not fulfilled. Despite this, the work presented in this thesis provides a solid foundation for the development of potent 2-aminoquinoline ligands for SH3 domains, with engineered specificity. / Thesis (Ph.D.)--School of Molecular and Biomedical Science, 2005.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.