A variety of mononuclear alkene complexes, [Ir{ArNC(NR2)NAr}(cod)], and dicarbonyl complexes, [Ir{ArNC(NR2)NAr}(CO)2] (where R = Me or Et; Ar = Ph, 4-MeC6H4, 4-MeOC6H4, 2,6-Me2C6H3 or 2,6-iPr2C6H3; and cod = 1,5-cyclooctadiene), were synthesized from the neutral N,N-dialkyl-N',N"-diarylguanidines via deprotonation and transmetalation. These complexes were fully characterized by spectroscopic techniques and single-crystal X-ray diffraction. The single-crystal structure determinations show the guanidinato(1—) ligands coordinate the low valent d8 iridium(I) center in an N,N'-chelating binding mode, and the C—N bond lengths indicate a high degree of π-electron delocalization over the CN3 core. The 13C NMR chemical shifts of the alkene carbon atoms in the IrI(cod) complexes and the average CO stretching frequencies for the IrI(CO)2 complexes suggest that the guanidinato ligands function as stronger donors than related monoanionic, bidentate nitrogen-donor ligands. Intermediates in the reactions of the [Ir{ArNC(NR2)NAr}(cod)] complexes with O2 were identified and characterized as (alkene)peroxoiridium(III) species, [Ir{ArNC(NR2)NAr}(cod)(O2)], using multi-dimensional NMR and IR spectroscopy. The (alkene)persulfidoiridium(III) intermediate [Ir{PhNC(NMe2)NPh}(cod)(S2)] was identified and characterized in the reaction of [Ir{PhNC(NMe2)NPh}(cod)] with S8. It was determined that these intermediates are able to transfer oxygen or sulfur to simple organic molecules such as PPh3. The self-decay of the (alkene)peroxoiridium(III) intermediates leads to C—O bond formation and alkene oxidation, and upon addition of excess cod release of 4-cycloocten-1-one was observed. In addition, a mononuclear alkene complex, [Ir{PhNC(Me)NPh}(cod)], and a dinuclear tetracarbonyl complex, [{Ir(CO)2}2{π-PhNC(Me)NPh-κN:κN'}2], with an amidinato ligand, were synthesized and characterized. In the reaction of the IrI(cod) complex with O2, the corresponding (alkene)peroxoiridium(III) intermediate [Ir{PhNC(Me)NPh}(cod)(O2)] was observed. The reactivity of this intermediate and its decay products is similar to that of [Ir{ArNC(NR2)NAr}(cod)(O2)], with the formation of 4-cycloocten-1-one being observed upon addition of cod. Mononuclear (alkene)rhodium(I) complexes, [Rh{PhNC(NMe2)NPh}(cod)] and [Rh{PhNC(Me)NPh}(cod)], and a dinuclear complex, [{Rh(nbd)}2{π-PhNC(NMe2)NPh-κN:κN'}2], were synthesized and characterized (where nbd = norbornadiene or bicyclo[2.2.1]hepta-2,5-diene). Investigation of the reactivity of these complexes with O2 show they react very slowly or not at all.

No description available.

Méthodologie d'addition-cyclisation de guanidines et amidines sur les quinones pour la synthèse de 2-aminobenzimidazole. Application de cette stratégie à la synthèse de benzo-bis-2-aminoimmidazole, un motif important de la benzosceptrine.Valorisation de produits synthétisés par évaluation biologique : l'inhibition de kinase, la cytotoxicité sur les lignées cellulaires cancéreuses du sang. / Methodology of addition-cyclization of guanidines and amidines on quinones for the synthesis of 2-amino-benzimidazole. Applying this strategy to the synthesis of benzo-bis-2-aminoimmidazole, an analogue of benzosceptrine.Reclamation of products synthesized by biological evaluation: inhibition of kinase, cytotoxicity on cancer cell lines of blood.

Yau, Chung Wah. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 55-57). / Abstracts in English and Chinese. / Acknowledgement --- p.i / Abstract --- p.ii / Table of Contents --- p.iv / Index of Compounds --- p.v / Chapter 1. --- Introduction / Chapter 1.1 --- Fundamentals of inclusion chemistry --- p.1 / Chapter 1.2 --- Hydrogen bonding in supramolecular chemistry and crystal engineering --- p.3 / Chapter 1.3 --- Hydrogen-bonded rosette system --- p.4 / Chapter 1.4 --- Research plan --- p.7 / Chapter 2. --- Descriptions of crystal structures / Chapter 2.1 --- Supramolecular rosette layer and rosette ribbon constructed from guanidinium cations and hydrogen carbonate dimers /carbonate anions / Chapter 2.1.1 --- (Et4N+)[C(NH2)3+]7(C032-)3[C3N2H2(C00-)2] (1) --- p.11 / Chapter 2.1.2 --- [(n-Bu)4N+]3[C(NH2)3+]4(HC03-)4[H+{C3N2H-(C00-)(C00H)}2] (2) --- p.14 / Chapter 2.1.3 --- [(n-Bu)4N+]2[C(NH2)3+]2(HC03-)2[NCC6H4(C00-)]2 ´Ø 2H20 (3)…… --- p.16 / Chapter 2.1.4 --- "[(n-Bu)4+]8[C(NH2)3+]8(HCO3-)8[4,4'-C12H8(C00-)2]4 ´Ø 8H20 ´″…" --- p.17 / Chapter 2.2 --- Channel- and layer-type anionic host structures constructed from benzene hexacarboxylic acid and guanidinium cation / Chapter 2.2.1 --- [C6(COO-)6][C(NH2)3]6 ´Ø H20 (5) --- p.20 / Chapter 2.2.2 --- [C6(COOH)3(COO´ؤ)3][C(NH2)3+]3 ´Ø 2H20 (6) --- p.23 / Chapter 2.2.3 --- [(n-Pr)4N+][C6(COOH)5(COO-)] ´Ø 3H20 (7) --- p.27 / Chapter 2.2.4 --- [(n-Bu)4N+]4[C6(COOH)5(COO-)]2[C6(COOH)4(COO-)2]2 [C(NH2)3+]2.8H2O(8) --- p.30 / Chapter 2.2.5 --- (Et4N+)2[C6(COOH)4(COO-)2]2[C(NH2)3+]2 ´Ø 2H20 (9) --- p.35 / Chapter 2.2.6 --- (Me4N+)[C6(COOH)3(COO-)3][C(NH2)3+]2 ´Ø H20 (10) --- p.37 / Chapter 3. --- Summary and discussion / Chapter 3.1 --- Robustness of hydrogen-bonded supramolecular rosette networks --- p.40 / Chapter 3.2 --- Versatile hydrogen bonding modes of guanidinium with mellitate anions --- p.43 / Chapter 4. --- Experimental / Chapter 4.1 --- Preparation methods --- p.48 / Chapter 4.2 --- X-ray crystallography --- p.52 / Chapter 5. --- References --- p.55 / "Appendix A: Tables of atomic coordinates, thermal parameters, bond lengths and angles and hydrogen bonds" --- p.58

This thesis is an investigation into the development of amidine and guanidine based compounds to be employed as switchable surfactants. The surface activity of these molecules can be triggered by reaction with a benign gas, CO2. The ultimate application of these surfactants was to be used as emulsifying and demulsifying agents of crude oil and water emulsions. Synthesis and characterization of the following desired bases: N’-octyl-N,N-dimethylacetamidine (1), 2-octyl-2-imidazoline (2), 1-methyl-2-octyl-2-imidiazoline (3), N’-(4-heptylphenyl)-N,N-dimethylacetamidine (4), N’-(4-(octyloxy)phenyl)-N,N-dimethylacetamidine (5), N’-(4-(methyloxy)phenyl)-N,N-dimethylacetamidine (6), and N-octyl-N',N',N",N"-tetramethylguanidine (7) was carried out. Their solubility in water was quantified with NMR spectroscopy. All bases were reacted with CO2 and H2O to form bicarbonate salts, of which in situ characterization was achieved by IR and NMR spectroscopy. Percent conversion to the protonated forms at elevated temperatures was determined using NMR spectroscopy. A direct correlation between switchability and basicity was observed, as the strongest bases possessed the largest conversions to the protonated species, even at higher temperatures. The enthalpy of protonation was determined for each base through calorimetry experiments. These compounds were tested as demulsifying surfactants of crude oil and water emulsions. Demulsifying ability was determined to differ greatly with the head group structure of the various surfactants. / Thesis (Master, Chemistry) -- Queen's University, 2009-10-27 16:56:13.631

Thesis (Ph. D.)--University of Nevada, Reno, 2007. / "August, 2007." Includes bibliographical references (leaves 150-154). Online version available on the World Wide Web.

Different structures of non-viral cationic polymer delivery vehicles, including charge center type, molecular weight and degradability, could significantly affect toxicity, release of nucleic acid and transfection efficiency. Poly(glycoamidoamine)s (PGAAs) contained different carbohydrate and secondary amine moieties and showed high transfection efficiency to different cell lines in a nontoxic manner. The "proton sponge hypothesis" has attempted to relate the buffering capacity to endosomal release of polyethylenimine (PEI) based polyplexes, which could contribute to high transfection efficiency. Secondary amine structures rendered PGAAs buffering capacity around physiological pH. To test the feasibility of the mechanism for PGAAs, new no buffering capacity guanidine or methylguanidine containing poly(glycoamidoguanidine)s (PGAGs) were synthesized. PGAGs formed stable polyplexes with pDNA from N/P (# secondary amine or guanidine group on polymer backbone / # phosphate group on pDNA backbone) ratio 3. PGAG based polyplexes expressed low cytotoxicity and were internalized by 90% of cells at N/P 25. Furthermore, two PGAG based polyplexes showed higher transfection efficiency from N/P 5 to 30 than their PGAA based analogs. These data suggested the low transfection could be due to the difficulties to release pDNA from polyplexes; also, the "proton sponge theory" could not explain the higher transfection efficiency by some PGAGs. Degradation of delivery vehicles could potentially release pDNA in cells and increase transfection efficiency. PGAAs degraded rapidly at physiological conditions and the proposed mechanism was amide hydrolysis. Typically, amide groups are stable and hydrolyze slowly in absence of enzyme. Different models mimicking PGAAs were synthesized to study the fast hydrolysis. Amide groups showed asymmetric hydrolysis. Different hydrolysis behaviors suggested neighboring group participation of two terminal groups to induce rapid amide hydrolysis. These new models could potentially be used to design new polymer delivery vehicles with various degradation profiles. / Master of Science

Le traitement des douleurs sévères repose dans la plupart des cas sur l’utilisation d’analgésiques opiacés. Cependant après administration répétée d’analgésique morphinique, on observe une tolérance aux agents morphiniques. Au niveau moléculaire, l’hypothèse physiopathologique met en avant la participation de systèmes ‘’dits anti-opiacés’’, comme le système du neuropeptide FF (NPFF). Dans un premier temps, une méthode de synthèse a été développée pour introduire divers α-aminoacides sur les chlorures d’α-hétéroaryle correspondants. Cette méthode originale, faisant appel aux conditions et catalyseurs décrits par Buchwald, a conduit à la découverte de ligands puissants de ces récepteurs. D’autre part, notre travail s’est basé sur la conception, la synthèse et l’étude des relations structure-activité d’autres familles de ligands pour les récepteurs du NPFF. Plusieurs séries de molécules ont été étudiées, parmi elles deux grandes familles : les aminoguanidines hydrazones et les quinolin-2-yl guanidines. Cette étude nous a permis d’identifier plusieurs ligands actifs in vitro (nanomolaire) et in vivo sur les récepteurs du NPFF. Ainsi nous disposons actuellement de ligands sélectifs vis-à-vis des deux récepteurs du NPFF. Une difficulté de synthèse des aryl/hétéroaryl guanidines a été rencontrée, en particulier avec les anilines appauvries en électrons. Pour cela nous avons développé une méthode de guanidinylation directe des halogénures d’aryle/hétéroaryle catalysée par le cuivre. Cette méthode de synthèse de dérivés de guanidines N-monosubstituées s’est montré très efficace, généralisable à quasiment tous les systèmes aromatiques et hétéroaromatiques. Enfin, quelques observations inattendues au cours de la réalisation de la réaction de Buchwald ont été décrites. / The treatment of severe pain involves in most cases the use of opioid analgesics such as morphine or fentanyl. However, after repeated administration of narcotic analgesics, a tolerance to opioid agents is observed. This result needs to gradually increase the dose of drug to obtain the desired analgesic effect. At the molecular level, the pathophysiological hypothesis emphasizes the participation of so-called ''anti-opioid'' systems, like the neuropeptide FF (NPFF) system. Initially, a synthetic method was developed to introduce various α-amino acids on various α-heteroaryl chlorides. This original method, using the conditions and catalysts described by Buchwald, led to potent NPFF receptor ligands. Then, our work was based on the design, synthesis and study of structure-activity relationships of other ligands for NPFF receptors. Several series of molecules have been studied. Among them two large families were selected: aminoguanidine hydrazones and quinolin-2-yl guanidines. This study allowed us to identify several potent ligands in vitro (nanomolar Ki) and active in vivo. So we have now selective ligands towards the two NPFF receptors. A loss of reactivity during the synthesis of aryl / heteroaryl guanidines was observed, in particular with electron deficient anilines. For these compounds we developed a new method of direct guanidinylation of aryl and heteroaryl halides catalyzed by copper. This method of synthesis of N-monosubstituted guanidines is very effective, generalizable to almost all aromatic and heteroaromatic systems. Finally, some unexpected observations during the completion of Buchwald reaction were described.

The N-methyl-D-aspartate (NMDA) receptors are highly regulated ligand-gated ion channels, which are affected by many substrates. Overactivation of the NMDA receptor can lead to hyperexcitability and a number of neurotoxic effects and neurological diseases. Agmatine has been demonstrated to act allosterically as an inhibitory modulator at the polyamine recognition sites of the NMDA receptor complex. The present study synthesized and evaluated a library of agmatine analogs for their ability to displace tritiated MK-801 from NMDARs in P2 membrane preparations from rat brains at ligand concentrations of 1 mM and 50 uM. A full dose-response curve was generated for the most active compounds, in the presence and absence of a pathological level of spermidine (100 uM). A forty-five member subset of arylidenamino-guanidino compounds was synthesized and all were demonstrated to be NMDA receptor inhibitory modulators in the above assay. Three of these compounds generated biphasic curves, indicating activity at two binding sites: the postulated high-affinity agmatine binding site, and a low-affinity site (perhaps the channel itself). (4-Chlorobenzylidenamino)-guanidine hydrochloride demonstrated an IC50 of 3.6 uM at the former site and 124.5 uM at the latter. Several computer models were generated to direct further synthesis. Based on the structure-activity relationship of the arylidenamino-guanidino compounds, a pharmacophore model of the agmatine binding site of the NMDAR was proposed.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Monanchora arbuscula (DUCHASSAING & MICHELOTTI, 1864) (Crambeidae) à uma esponja incrustante, maciÃa ou ramificada com atà 15 cm de altura. Cor, variando de salmÃo a vermelho vivo ou rosa claro, provida de canais esbranquiÃados conspÃcuos. Estudos anteriores de M. arbuscula levaram a obtenÃÃo de alguns alcalÃides guanidÃnicos policÃclicos; ptilocaulina, 8b-hidroxiptilocaulina, dehidrobatzelladina C, crambescidina 800 e isoptilocaulina. Neste trabalho, o extrato hidroalcoÃlico da esponja M. arbuscula, coletada no Parque Estadual Marinho âPedra da Risca do Meioâ, na costa Fortalezense, foi particionado com CH2Cl2/H2O (3:1) fornecendo assim o extrato bruto, o qual foi submetido a uma partiÃÃo lÃquido-lÃquido utilizando os solventes Ãter de petrÃleo, diclorometano, acetato de etila e metanol. Sucessivas cromatografias em gel de sÃlica, SEPHADEX LH-20 e/ou HPLC das fraÃÃes diclorometano, acetato de etila e metanol levaram ao isolamento dos alcalÃides guanidÃnicos mirabilina B, 8b-hidroxiptilocaulina, ptilocaulina, 1,8a;8b,3a-desidro-8βâhidroxiptilocaulina, 1,8a;8b,3a-desidro-8α-hidroxiptilocaulina, 3,3a;8b,8a-desidro-8-hidroxiptilocaulina. Mirabilina B, 1,8a;8b,3aesidro- 8βâhidroxiptilocaulina e 1,8a;8b,3a-desidro-8α-hidroxiptilocaulina estÃo sendo citados pela primeira vez para a espÃcie e 3,3a;8b,8a-desidro-8-hidroxiptilocaulina, no melhor do nosso conhecimento, à inÃdito na literatura. Ensaios para a avaliaÃÃo da atividade citotÃxica frente as linhagens de cÃlulas tumorais cÃlon (HCT-8), melanona (MADMB-435), leucemia (HL-60) e glioblatoma (SF-295), indicaram atividade para o extrato bruto, fraÃÃes e os compostos isolados ptilocaulina e 8b-hidroxiptilocaulina. O alcalÃide 8b-hidroxiptilocaulina mostrou-se ativo aos fungos Microsporum canis e Trichophyton rubrum, enquanto ptilocaulina ao Microsporum canis. Mirabilina B mostrou atividade leishmanicida frente a Leishmania chagasi e amazonesis. As estruturas das substÃncias isoladas foram elucidadas atravÃs de mÃtodos espectroscÃpicos, principalmente RMN, incluindo seqÃÃncias de pulsos uni e bidimensionais e comparaÃÃo com dados da literatura. / Monanchora arbuscula (DUCHASSAING & MICHELOTTI, 1864) (Crambeidae) is an incrustant sponge, massive or branched with 15 cm high. Its color ranges from salmon to bright red or light pink with white conspicuous channels. Previous studies of M. arbuscula led to the isolation of some polycyclic guanidine alkaloids; ptilocaulin, 8bhydroxyptilocaulin, dehydrobatzelladine C, crambescidin 800 and isoptilocaulin. In this work, the hydroethanol extract from M. arbuscula collected at â Pedra da Risca do Meioâ Marine State Park, in Fortaleza coast zone was partitioned with CH2Cl2/H2O (3:1) affording the crude extract which was submitted to liquid-liquid partition using petroleumether, dichloromethane, ethyl acetate and methanol as the solvents. Successive chromatograghy over silica gel, SEPHADEX LH-20 and/or HPLC of all solvent fractions led to the isolation of the guanidine alkaloids: mirabilin B, 8bβ-hydroxyptilocaulin, ptilocaulin, 1,8a;8b,3a-didehydro-8βâhydroxyptilocaulin, 1,8a;8b,3a-didehydro-8α-hydroxyptilocaulin, 3,3a;8b,8a-didehydro-8-hydroxyptilocaulin. Mirabilin B, 1,8a;8b,3adidehydro- 8βâhydroxyptilocaulin, 1,8a;8b,3a-didehydro-8α-hydroxyptilocaulin are reported for the first time for the species while 3,3a;8b,8a-didehydro-8-hydroxyptilocaulin has not being reported in the literature yet. Pharmacological assays revealed weak citotoxic activity against 4 cancer cell lines: HCT-8 (human colon carcinoma), MADMB-435 (melanoma), HL-60 (human leukemia) and SF-295 (glioblastoma). The assays indicated activity for the crude extract, several fractions and the isolated compounds ptilocaulin and 8bβ-hydroxyptilocaulin. The alkaloid 8b-hydroxyptilocaulin indicated antifungal activity against Microsporum canis and Trichophyton rubrum, while ptilocaulin against Microsporum canis, Mirabilin B antiprotozoal activity against Leishmania chagasi and amazonesis. Structure elucidation of the isolated substances was performed through spectroscopic methods, mainly NMR, including uni and bidimensional pulses sequences, and comparison with data from literature.