Polybenzimidazoles were synthesized from 3, 3', 4, 4'-tetraminobiphenyl (diaminobenzidine, or DAB) with orthoesters, carboxylic acid derivatives (an ester and an acid) and with m-benzenedialdehyde. The products were of low molecular weight, as evidenced by low inherent viscosity, except in the case of the dialdehyde plus DAB. The product of that system had inherent viscosities in the range of 0. 7 dL/g, and formed strong, flexible films. Based on these results, a dialdehyde monomer was made from naphthalene disulfonyl dihalides and p-hydroxybenzaldehyde. In addition to the aldehyde end groups, this monomer contained internal sulfonate linkages, which were intended to increase the flexibility of the target poly benzimidazole which resulted when it was condensed with DAB. These polymerizations yielded poor polybenzimidazoles, probably due to lack of purity of the new dialdehyde monomer. Another type of monomer was also produced by condensing DAB with p-hydroxybenzaldehyde. The resultant bibenzimidazole unit with two phenolic end groups shows promise for use in nucleophilic aromatic substitution polymerizations. / Graduation date: 1993

Thesis (M.S.)--Oregon State University, 1993. / Description based on title screen as viewed on April 8, 2009. "Completed 13 May 1992, Commencement June 1993." Includes bibliographical references (p. 73-75). Also available in print.

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 186-192).

A series of rhenium(I) complexes with monodentate benzazole ligands containing the fac-[Re(CO)3]+ was synthesized. The rhenium(I) compound [ReCl(Hmbt)2(CO)3] was prepared from the reaction of [Re(CO)5Cl] and 2-aminobenzothiazole (Hmbt) in toluene. The ligand coordinates in a monodentate manner via the thiazole nitrogen atom. A similar reaction between [Re(CO)5Cl] and N-(1,3-benzothiazol-2-yl)-2- chloroacetamide (Hbct) resulted in the formation of [ReCl(Hbct)(CO)3(NCMe)], where only one ligand binds per rhenium in a monodentate fashion. The reaction of ligands 2-mercaptobenzimidazole (Hmbi) (dibenzothiazol-2-yl)tetraazathiapentalene (Hdbt) with rhenium(I) gave [ReCl(Hmbi)2(CO)3] and [ReCl(Hdbt)2(CO)3] respectively. The study on the coordination behaviour between ethyl-(1H-benzimidazol-2-yl-sulfanyl) acetate (Hbsa) and [Re(CO)5Cl] surprisingly gave the dimeric species (μ-Cl)2[Re(Hbsa)(CO)3]2, where the two rhenium atoms are bridged by two chloro ligands. The coordination of Hbsa occurs through the imidazole nitrogen, leaving the ethoxy tail free on each Hbsa ligand. The coordination behaviour of benzimidazole and benzothiazole derivatives gave rhenium complexes in oxidation states I, III and V, where all the ligands coordinate as bidentate N,N-chelating ligands. The study on 2-(2-aminophenyl)-1-benzothiazole (Hapt) and 2-(2-aminophenyl)-1-benzimidazole (H2apz) with [ReVOCl3(PPh3)2] resulted in the formation of [ReVOCl2(apt)(OPPh3)] and [ReVCl2(apz)(PPh3)2](ReO4), respectively. 1,2-Bis(2-benzimidazole)-1,2-ethanediol (Hbed) and 2,6-bis(2- benzimidazol-2-yl)pyridine (H2bip) were studied towards rhenium(I) and rheniumV) respectively. The former gave a dimeric species (μ-bbi)[Re(CO)4]2 (H2bbi – bisbenzimidazole) by reaction with [Re(CO)5Cl], whereas H2bip produced the rhenium(III) cationic salt [ReCl3(H3bip)(PPh3)]Cl, where the ligand coordinates as a cationic H3bip+ with protonation of an uncoordinated imidazole nitrogen atom. The pyridine derivatives 2-hydrazino-pyridinyl-2-benzothiazole (Hhpt) and (E)-1-benzo[d]thiazol-2-yl)-2- (pyridin-2-ylmethylene)hydrazine (btp) were reacted with [Re(CO)5Cl]. The neutral complex [ReCl(Hhpt)(CO)3] was isolated upon reaction with Hhpt, where Hhpt coordinates as a neutral bidentate ligand. The reaction of [Re(CO)5Cl] with btp gave two different complexes when using different solvents. In methanol, [ReCl(btp)(CO)3] was isolated, whereas in toluene, the conjugate of btp (btp1) was formed which resulted in the formation of [ReCl(btp1)(CO)3]. The study on potentially bidentate thiourea derivatives containing a benzothiazole moiety towards [ReI(CO)3]+ and [ReVO]3+ cores gave rise to a wide variety of complexes. The reaction of [Re(CO)5Cl] with N-phenyl-N-(2-benzothiazole)thiourea (Hpbt) produced the rhenium(I) complex [Re(Hpbt)(pbt)(CO)3]. Hpbt coordinates both as a monodentate neutral ligand and as a bidentate monoanionic chelate. The study of the reaction between trans-[ReOCl3(PPh3)2] and Hpbt gave the rhenium(V) product [ReOCl2(pbt)(PPh3)], with pbt acting as a bidentate ligand. The reaction of 1-(1,3- benzothiazol-2-yl)-3-benzoylthiourea (Hbbt) with [Re(CO)5Cl] led to the isolation of [ReCl(Hbbt)(CO)3]. Similar reaction of Hbbt with trans-[ReOCl3(PPh3)2] gave the unique compound [ReOCl2(Hbnt)(PPh3)], where the ligand coordinates via the ketonic oxygen and a methine carbon. The complex [Re(Hmby)(mby)(CO)3] was isolated upon reacting [Re(CO)5Cl] with methylbenzothiazol-2-ylidenecarbamodithioate (Hmby), with Hmby coordinating as a monodentate neutral ligand and mby as a bidentate monoanionic chelate. The coordination behaviour of N-(benzothiazol-2-yl)-S,S’- dimethyldithiocarboimine (Hbdc) towards rhenium(I) led to the formation of [ReCl(Hbdc)(CO)3]. The reactivity of 1-(benzothiozol-2-yl)-3,3-dimethylthiourea (Hbdm), a derivative of Hmby, was studied with trans-[ReOCl3(PPh3)2] and trans- [ReO(OEt)I2(PPh3)2] producing the square pyramidal compound [ReOCl(bdm)2] and the salt [Re(bdm)2(MeCN)2]I3, respectively. Pyrazole derivatives containing a benzothiazole ring were studied towards rhenium in oxidation states +I and +V. The reaction between 2-(3,5-dimethylpyrazol-1-yl)benzothiazole (Hdmp) and [Re(CO)5Cl] gave the neutral rhenium complex [ReCl(Hdmp)(CO)3], whereas its reaction with [ReOCl3(PPh3)2] surprisingly results in the formation of a dimeric complex (μ-O)[ReOCl2(Hdmp)]2. The study on the reactivity of 1-(benzo[d]thiazol-2-yl)-4-methyl-1H-pyrrol-2-ol (Hbtm) with [Re(CO)5Cl] gave the unexpected trimer [Re(btm)(CO)3]3 containing the fac-[Re(CO)3]+ core. The ligand btm forms a bridge between each rhenium metal, serving as a bidentate ligand to one rhenium, and a monodentate ligand to another rhenium atom. The study on the coordination chemistry between trans-[ReOCl3(PPh3)2] and Hbtm gave two different complexes when using different solvents. In ethanol, [ReOCl(btm)(btm1)] formed, whereas [ReOCl(btm1)(btz)] (Hbtz = 1-(benzo[d]thiazol-2-yl)-4-(1-iminoethyl)-3- methyl-1H-pyrazol-5-ol) was isolated in acetonitrile. The reaction of cis-[ReO2I(PPh3)2] also gave two different products when using different solvents, where the respective solvents coordinate to the metal. The rhenium(V) compound [ReO(OMe)(btm)(btm1)] was formed in methanol, whereas [ReO(OEt)(btm)(btm1)] was formed in ethanol. The coordination chemistry of 2-(2-Benzothiazoleyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Hbth) was studied towards [Re(CO)5Cl] and trans-[ReOCl3(PPh3)2]. The resulting complexes which formed are [ReCl(Hbth)(CO)3] and [ReOCl(bth)(bth1)] respectively. The reactivity of potentially tridentate Schiff base ligands towards rhenium(I) and (V) was studied. The rhenium(I) precursor [Re(CO)5Cl] was reacted with (E)-1- (benzo[d]thiazol-2-yl)-2-(phenol-2-ylmethylene)hydrazine (H3bph) to give [ReCl(CO)3(H3bph)], which contains the kinetically inert fac-[Re(CO)3]+ core coordinated to a neutral bidentate ligand. The reaction of [ReO2(py)4Cl] with H3bph gave the dimeric species (μ-O)[ReO(Hbph)(py)]2, where the ligand coordinates as a tridentate dianionic chelate. A similar complex was isolated with (E)-1- (benzo[d]thiazol-2-yl)-2-(2,4-dihydroxy-2-ylmethylene)hydrazine (H3bdh) to give (μ-O)[ReO(Hbdh)(py)]2. The reaction of trans-[ReOCl3(PPh3)2] with H3bph afforded [Re(abt)(imp)Cl2(PPh3)] (abt = 2-aminobenzothiazole, imp = 2-(iminomethyl)phenol), where the ligand broke up into two fragments, both of which coordinated without any modification. The dioxo rhenium precursor cis-[ReO2I(PPh3)2] gave [ReO(Hbdh)(imp)] upon reaction with H3bdh. Ligand imp coordinates as a bidentate monoanionic ligand via the imine nitrogen and deprotonated phenolic oxygen and ligand Hbdh coordinatesas a tridentate dianionic chelate.

No description available.

Peritoneal carcinomatosis is a complex clinical-pathological condition and most patients with this disease would die within 6 months. The disadvantage of systemic cancer therapy is that only a small portion of the administered drug can reach the tumor cells, and side effects could occur due to its wide distribution in the body. In recent years, cytoreductive surgery combined with intraperitoneal chemotherapy has been the effective way for the treatment of peritoneal carcinomatosis. But the anticancer agents in aqueous form can be easily absorbed through capillaries below the large serosal surface into the systemic circulation, and it is difficult to retain the drug at a high concentration for a long time in the peritoneal cavity. The ideal drug for intraperitoneal chemotherapy should have a high molecular weight, a prolonged retention in the peritoneal surface, and increase drug exposure to tumor cells, decrease drug absorption and hence reduce systemic toxicity. ABZ (albendazole) with its properties of poor water solubility and strong anticancer effects could be a potential effective agent for the treatment of peritoneal carcinomatosis. The aims of this study are: to compare oral versus i.p administration of ABZ, study pharmacokinetic characteristics of ABZ in i.p administration; to study the efficacy ofABZ on early, middle and later stages of cancer development, to find out the possible antitumor effect of ABZ in suppressing cancer cell proliferation, ascites control and longer survival of mice with peritoneal carcinomatosis; to solve the occurring problems during ABZ i.p administration, reduce side effects and increase the drug efficacy; to investigate possible mechanisms ofABZ suppressing tumor proliferation and ascites formation. A series of experiments were designed in order to achieve the study objectives. The pharmacokinetic study of ABZ gives some dynamic characteristics by oral versus i.p administration in rabbits. Three sets of experiments of ABZ treatment were performed on different stages peritoneal carcinomatosis arising from the OVCAR-3 cancer cells in nude mice, from which the efficacy of ABZ in suppressing tumor growth and ascites formation by i.p administration is clearly demonstrated. The increased solubility of ABZ with three surfactants and in human ascites was carried out in different tests, and the combination of ABZ with Tween 80 has achieved better control of peritoneal carcinomatosis when given by i.p administration. The results from this study have revealed for the first time the capacity of ABZ suppressing VEGF (vascular endothelial growth factor) and ascites formation profoundly, confirmed that ABZ has potent anti-proliferation effects on ovarian cancer cells (OVCAR3); it suppressed tumor growth in early stage of cancer development; and prolonged survival of all ABZ treated mice by i.p administration. The major contributions from this study are: ABZ i.p treatment increases survival, inhibits ascites production, reduces tumor burden at relatively early stage of cancer, changes tumor morphology and reduces vascular density, reduces CA-125 (cancer antigen 125) and VEGF level, decreases in vitro VEGF secretion, and down regulates VEGF mRNA expression. The study results concluded that ABZ could be a potential anticancer agent for the treatment of peritoneal carcinomatosis by i.p administration. The significance of this study is that the fundamental results obtained from all experiments, including the major contributions and other associated works, have provided the scientific foundation for a clinical trial. Currently the maximum tolerated dose of ABZ i.p treatment in mice is on going before clinical trial and studies in related area of ABZ anticancer pathways are continuing in our laboratory.

Thesis (Ph. D.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains xi, 179 p. : ill. Includes abstract. Includes bibliographical references (p. 88-94).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1943. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph.D.)--Murdoch University, 2007. / Thesis submitted to the Division of Science and Engineering. Includes bibliographical references (leaves 136-160)

La presente Memoria se orientó al estudio y caracterización electro-analítica de una serie de derivados N-(4-R-benzoil)-2-(2-nitrofenil)-1-H-benzimidazoles como sustratos de interés biológico. Los compuestos estudiados fueron sintetizados a partir de 2-(o-nitrofenil)-benzimidazol, generado por condensación entre 1,2-diamino-benceno y 2-nitrobenzaldehído. Posterior reacción del benzimidazol con una serie de cloruros de aroílo, generó la serie de cuatro N-(4-R-benzoil)-2-(2-nitrofenil)-1-H-benzimidazoles en buen rendimiento (R = NO2, Cl, F), con la excepción del producto denominado PMNB (R = OCH3), que obtuvo un rendimiento promedio de un 5%. Los estudios analíticos posteriormente a la síntesis, fueron desarrollados para los compuestos denominados PNB (R= NO2) y PFNB (R= F) y correspondieron al desarrollo y la puesta punto de metodologías analíticas reproducibles y selectivas, y su posterior aplicación en la caracterización de éstos. Dichos estudios se llevaron a cabo usando las técnicas de polarografía de pulso diferencial (PPD), polarografía tast (PTAST), espectrofotometría UV-Vis y cromatografía líquida de alta eficiencia (HPLC). En una primera etapa se llevó a cabo el estudio de influencia del pH por PPD y PTAST, el que por razones de estabilidad fue realizado en un rango de pH entre 2,0 hasta 8,2 para ambos compuestos. En este rango de pH, PFNB y PNB exhibieron dos y tres señales de reducción respectivamente: una señal principal (dos en el caso de PNB) debida a la reducción del grupo nitro y una secundaria, probablemente correspondiente al enlace azometino presente en el anillo benzimidazólico. Ambas señales son dependientes de pH, desplazándose hacia potenciales más negativos mientras más alcalino es el pH. En una segunda etapa se desarrollaron tres metodologías analíticas para la cuantificación de los compuestos en estudio (PPD, HPLC y espectrofotometría UV-Vis), las cuales exhibieron valores adecuados de reproducibilidad (CV< 4,5%) y repetibilidad (CV< 4%), presentando linealidad en un amplio rango de concentración (4,0×10-6 M a 1,0×10-4 M) para ambos compuestos. Por espectrofometría UV-Vis se determinaron las constantes de acidez para cada compuesto, debidas al nitrógeno ubicado en la posición 3 del anillo imidazólico, en ambos casos. Los valores de pKa determinados fueron de 4,79 ± 0,06 para PNB y 4,86 ± 0,06 para PFNB. Utilizando la técnica de HPLC se determinaron los coeficientes de partición respectivos, presentando valores de log P de 2,77 para PNB y de 3,18 para PFNB. Además, por medio de la técnica de PPD se llevó a cabo un estudio preliminar de estabilidad para PNB a pH 3,0 y a temperatura ambiente, observándose que el decaimiento se ajusta a una cinética de seudo orden cero (k= 1,9571×10-7 M/min), con una vida media de alrededor de 4 horas para una concentración inicial de 1×10-4 M.