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Les virus sont au centre de problème de santé publique. En raison de l'apparition de nouveaux virus et pour certains de leur résistance aux traitements existants il est toujours d’actualité de développement de nouveaux agents antiviraux. En général, la stratégie de lutte contre les infections virales est basée sur la vaccination ou sur l'activité des petites molécules, interférant avec un ou plusieurs processus biologiques participant au cycle de vie du virus. Dans ce contexte, nous avons conçu et synthétisé des petites bibliothèques de molécules visant des propriétés anti-filovirus. Dans ce projet de recherche, nous avons mis l'accent sur le développement de composés ciblant la protéine Niemann-Pick C1, les protéases cathepsine et le processus de réplication. Lors du développement des inhibiteurs de Neimann-Pick C1 plus de 70 composés ont été synthétisés, portant le squelette pipérazine. Afin d'obtenir des inhibiteurs de cystéine cathepsines pouvant être impliqués dans la réplication du virus Ebola, nous avons synthétisé une petite bibliothèque de composés porteurs de groupement 1,3,5-triazine et possédant des activité de l’ordre du nanomolaire sur les cathepsines B, K, L et S. Enfin, pour inhiber la réplication du virus en ciblant SAH hydrolase, nous avons proposé une série de C-nucléosides carbocyclic ayant motif de 4-aza-7,9-dideazaadenosine. / The viruses cause the problem of public health. Due to the appearance of new viruses and their resistance to existing treatments there is still relevant to develop new antivirals. Generally, the strategy to combat viral infections is based on vaccination or on the activity of small molecules, interfering with one or more biological processes participating in virus life cycle. In this context, we took an effort to design and synthesize the library of small molecules possessing anti-filovirus properties. In this research project, we were focused on the developing of compounds targeting Niemann-Pick C1 protein, cathepsin proteases and replication process. In our effort into the development of the inhibitors of Neimann-Pick C1 we prepared the series of about 70 compounds, having in common the piperazine moiety. Diverse 1,4-N,N - substituents of piperazine, differencing in a size and shape were studied. In order to obtain efficient cysteine cathepsins inhibitors, we synthesized the small library of compounds bearing 1,3,5-triazine moiety. Finally, to inhibit the virus replication by targeting SAH hydrolase, we proposed the series of carbocyclic C-nucleosides having motif of 4-aza-7,9-dideazaadenosine.

Le développement de composés permettant le passage de molécules à travers la membrane cellulaire constitue un domaine de grand intérêt de la chimie et de la biochimie. Certaines maladies, comme la fibrose kystique, sont le résultat d'un dysfonctionnement du transport d'ions chlorure et bicarbonate à travers la bicouche lipidique. Ces dernières années, de nouvelles familles de transporteurs synthétiques ont fait leur apparition comme solution de remplacement aux transporteurs naturels. Cependant, la synthèse de systèmes supramoléculaires permettant le transport de larges molécules de part et d’autre de la bicouche lipidique reste, quant à elle, un défi. Ainsi nous présentons dans cette thèse deux systèmes différents: l’un permettant le transport d’ions chlorures et le second capable de combiner transport anionique et transport de macrocycles biologiquement actifs. Dans un premier temps, nous avons étudié le potentiel ionophore d’un dérivé benzimidazole. Des études mécanistiques ont été menées sur le 2,4,7-triphénylbenzimidazole afin de déterminer son mode d’assemblage dans la membrane phospholipidique, responsable de son efficacité à transporter les anions. Basé sur ces résultats, des analogues de cette molécule possédant des sites de complexation métallique ont été synthétisés afin d’augmenter l’efficacité de ces transporteurs benzimidazole et de contrôler leur auto-assemblage. Ces complexes ont été testés dans des membranes bactériennes afin d’étudier leur capacité à inhiber la croissance des bactéries et à diminuer la tolérance d’une souche bactérienne résistante envers les antibiotiques. Dans le second volet de cette thèse, nous avons étudié l’utilisation de dérivés parapluies capables de changer de conformation dépendamment de la polarité du solvant, pour le transport d’anions et de macrocycles. La synthèse et la caractérisation d’un nouvel axe et son dimère parapluie sont rapportées dans cette partie. Leur capacité à transporter les anions à travers la membrane des liposomes ou leur insertion dans des membranes bactériennes ont été étudiées. Les premiers essais de synthèses de rotaxanes à partir de ces dérivés parapluies pour le transport de macrocycle biologiquement actif sont rapportés. / The development of compounds able to transport molecules through cellular membranes is an emerging area of chemistry and biochemistry. Several diseases, such as cystic fibrosis, are the result of a dysfunction of chloride and bicarbonate transport across cellular membranes. In the last few years, new families of synthetic transmembrane transporters were developed in order to restore chloride transport. However, the synthesis of supramolecular systems for the transport of large molecules from one side to the other one of the lipid bilayer remains a challenge. Herein we present two different systems: one for chloride transport and a second one that combines the transport of ions and biologically active macrocycles through cellular membranes. We first present the anionophoric potential of benzimidazole derivatives. Mechanistic studies were conducted on 2,4,7-triphenylbenzimidazole to determine its self-assembly in a phospholipid membrane and its capacity to transport anions. Two analogues possessing metal coordination sites were also developed and studied for their anion transport properties, as well for the formation of metal-organic assemblies. These complexes were studied in bacterial membranes for their ability to inhibit bacterial growth and to reduce the tolerance of a resistant strain to antibiotics. In the second part of this thesis, we present the use of umbrella compounds that are able to change their conformation depending on the polarity of the environment. The synthesis and characterization of a new umbrella thread and its dimer are reported in this section. Their ability to transport anions through liposomal membranes or their insertion into more complex bacterial membranes are studied. The first attempts to assemble rotaxanes with the umbrella compounds and an active macrocycle are presented.

The synthesis and characterization of two donor acceptor type conjugated polymers were investigated. The electrochemical properties were examined using cyclic voltammetry, spectroelectrochemistry and kinetic studies. The increase in the alkyl chain length attached to the fluorene unit was investigated by the corresponding electrochemical characteristics. The synthesis was carried out via Stille coupling of 4,7- dibromo-4&#039 / -(tert-butyl)spiro[benzo[d]imidazole-2,1&#039 / cyclohexane] and 2,5- bis(tributylstannyl)thiophene with 9,9-dihexyl-9H fluorene and 9,9-didodecyl-9H fluorene respectively. Both of the polymers were neutral state green polymers. They had optical band gaps of 2.46 and 2.54 eV respectively. Increasing the chain length resulted in an increase in solubility and processibility of the polymer but also an increase in the band gap. This was due to the increased bulkyness of the alkyl group, leading to a decrease in the effective conjugation and planarity. They both had distinctive &pi / -&pi / * transitions, band structure and backbone that provides oxidative doping. P1, with the shorter alkyl chain had a lower oxidation potential than P2. Neither of the polymers was capable of being n-doped. They were both multichromic, revealing colors from neutral state green to doped state blue.

No / A library of 53 benzimidazole derivatives, with substituents at positions 1, 2 and 5, were synthesized and screened against a series of reference strains of bacteria and fungi of medical relevance. The SAR analyses of the most promising results showed that the antimicrobial activity of the compounds depended on the substituents attached to the bicyclic heterocycle. In particular, some compounds displayed antibacterial activity against two methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentrations (MICs) comparable to the widely-used drug ciprofloxacin. The compounds have some common features; three possess 5-halo substituents; two are derivatives of (S)-2-ethanaminebenzimidazole; and the others are derivatives of one 2-(chloromethyl)-1H-benzo[d]imidazole and (1H-benzo[d]imidazol-2-yl)methanethiol. The results from the antifungal screening were also very interesting: 23 compounds exhibited potent fungicidal activity against the selected fungal strains. They displayed equivalent or greater potency in their MIC values than amphotericin B. The 5-halobenzimidazole derivatives could be considered promising broad-spectrum antimicrobial candidates that deserve further study for potential therapeutic applications.

Die Verpackung und Spaltung konkatemerer DNA ist ein essentieller Prozeß bei der Reifung von Virionen. Die an diesem Prozess maßgeblich beteiligten Proteine werden als Terminase bezeichnet. Die Inhibition der HCMV Terminase bietet einen attraktiven alternativen Ansatzpunkt für die antivirale Therapie. Zur Inhibition der Terminase Aktivität wurden die neuen Benzimidazol D-Ribonukleosid Derivate BTCRB und Cl4RB auf ihre antivirale Wirkung analysiert. Die neuen Benzimidazol D-Ribonukleosid Derivate BTCRB und Cl4RB zeigten sowohl gegen den HCMV Laborstamm AD169 als auch gegen klinische HCMV-Isolaten eine Wirkung. Weiterhin wurde die Wirksamkeit der Substanzen auf anderen Herpesviren getestet. Interessanterweise zeigten BTCRB und Cl4RB sowohl einen Effekt gegen Varicella-Zoster-Virus (VZV) als auch Ratten-Cytomegalovirus (RCMV), wohingegen der Effekt gegen Herpes-simplex-Virus Typ-1 (HSV-1) und Maus-Cytomegalovirus (MCMV) gering war. Infolgedessen eignen sich beide Substanzen BTCRB und Cl4RB als attraktive alternative Inhibitoren für die weitere Entwicklung einer antiviralen Therapie. / DNA packaging is the key step in viral maturation and involves binding and cleavage of viral DNA containing specific DNA-packaging motifs. This process is mediated by a group of specific enzymes called terminase. The development for an inhibitor of HCMV terminase would be of great value, because it would act subsequent to DNA synthesis and block the first steps in viral maturation. Therefore we characterized two inhibitors targeting the HCMV terminase, 2-bromo-4,5,6-trichloro-1-(2,3,5-tri-O-acetly-ß-D-ribofuranosyl) benzimidazole (BTCRB) and 2,4,5,6-tetrachloro-1-(2,3,5-tri-O-acetly-ß-D-ribofuranosyl) benzimidazole (Cl4RB). By using viral plaque formation, viral yield, viral growth kinetics and electron microscopy, we demonstrated that two compounds BTCRB und Cl4RB are highly active against HCMV AD 169 and HCMV clinical isolates. In addition, the antiviral effect on other herpesviruses was determined. Interestingly BTCRB was active all tested herpesviruses. The best effects were observed on VZV-and RCMV-infected cells. Therefore new compounds might be promising attractive compounds for antiviral therapy in the future.

The thesis entitled “Design and Synthesis of Benzimidazole Based Templates in Duplex and Quadruplex DNA Recognition and in Topoisomerase Inhibition” deals with the design and synthesis of several benzimidazole based molecules and their interaction with duplex and quadruplex DNA structures. It also elucidates the inhibition effect of the compounds on the activity of topoisomerase I enzyme of parasitic pathogen Leishmania donovani. The work has been divided into five chapters. Chapter 1: An Introduction to DNA and its Interaction with Small molecules. The first chapter provides an introduction to the double helical structure of DNA and the central dogma that suggests the flow of genetic information from DNA to RNA to protein. This chapter also presents an overview on the various types of small molecules that interact with duplex and quadruplex structures of DNA or interfere with the activity of DNA targeted enzymes like topoisomerase. This chapter describes the importance of such molecules as chemotherapeutic agents. Chapter 2 deals with three isomeric, symmetrical bisbenzimidazole derivatives bearing pyridine on the two termini. The syntheses, duplex DNA binding and computational structure analyses of the molecules have been divided into two sections. Chapter 2A: Novel Symmetrical Pyridine Derivatized Bisbenzimidazoles: Synthesis and Unique Metal Ion Mediated Tunable DNA Minor Groove Binding. The first chapter deals with the synthesis and double stranded (ds) DNA binding characteristics of the three bisbenzimidazole derivatives. Despite being positional isomers, their relative binding affinities towards ds-DNA varied considerably. Fluorescence, circular dichroism and temperature dependent UV-absorption spectroscopy have been employed to characterize ligand-DNA binding interaction. All spectroscopic studies revealed the strong A-T selective DNA binding affinities of the p- and m-pyridine derivatized molecules (p-pyben and m-pyben respectively) and indicated dramatically weak binding interaction of the ortho derivative (o-pyben) to ds-DNA. Additionally, unique transition metal ion mediated tunable DNA binding shown by o-pyben has been described in this chapter. While the ds-DNA binding characteristics of p- and m-pyben remained unaffected in presence of metal ions, that of o-pyben could be reversibly ‘switched off’ in the presence of divalent transition metal ions like Co2+, Ni2+, and Cu2+. Addition of EDTA reversed the effects and DNA binding was again observed. This interesting observation provides valuable insight into the DNA recognition property of these isomeric bisbenzimidazole derivatives. Figure 1. Molecular structures of pyridine derivatized symmetrical bisbenzimidazoles. Chapter 2B: Differential Binding of Positional Isomers of Symmetric Bisbenzimidazoles on DNA Minor-Groove: A Computational study. To explain the weak DNA binding affinity of o-pyben, compared to p- or m-pyben, detailed ab initio/DFT computational analyses of the inherent structural features of the three isomers were performed both in the gas-phase and in water. The study revealed the presence of intramolecular hydrogen bond existing in the opyben, between the benzimidazole proton (H3) and the pyridine nitrogen (N1). Additionally, potential energy scans for rotation about the bonds connecting the pyridine-benzimidazole and benzimidazole-benzimidazole fragments were performed. This revealed surprising conformational rigidity existing in the o- isomer that resisted any out-of-plane twisting of the pyridine-benzimidazole fragment. The presence of intramolecular H-bonding was further confirmed by experimental determination of pKa of the three isomers. The molecules being bisbenzimidazole derivatives bound to the minor groove of ds-DNA, the benzimidazole protons forming hydrogen bonded interactions with the DNA bases. However in the o- derivative, the intramolecular hydrogen bonding made the crucial benzimidazole protons unavailable for DNA binding thereby leading to its poor interaction with DNA. Chapter 3. Novel Series of Anthra[1,2-d]imidazole-6,11-dione Derivatives: Synthesis, DNA Binding and Inhibition of Topoisomerase I of Leishmania donovani This chapter describes the synthesis of nine imidazole fused anthraquinone derivatives and their interaction with double-stranded DNA, investigated by UV-visible absorption spectroscopy and viscometric titrations. Figure 2. Molecular structures of the imidazole fused anthraquinone derivatives. All the molecules showed intercalative mode of binding to double stranded DNA, though their relative binding affinities were different. Next their inhibitory effects on the catalytic activity of topoisomerase I enzyme of Leismania donovani were investigated. L. donovani is the causative agent for human visceral leishmaniasis; a fatal disease affecting liver and spleen. Five out of the nine derivatives tested, proved to be extremely efficient inhibitors of the enzyme. Of them, three showed greater inhibition potency than camptothecin, a well-established topoisomerase I inhibitor and the precursor for several clinically useful anti-tumor drugs. The molecules were shown to inhibit by the stabilization of enzyme-DNA cleavable complex, and the inhibition efficiency was found to be highly dependent on the pKa of the side-chain nitrogen. These results provide useful insights towards developing more potent inhibitors of the parasitic enzyme. As the compounds are synthetically facile, chemically stable and possess long shelf life, they should be attractive candidates for design of novel family of topoisomerase I inhibitor. Indeed the nature of amine based side chain and its pKa would hold the key in such design. Chapter 4 deals with a series of symmetrical bisbenzimidazole derivatives in which the benzimidazole units have been connected via different aromatic linkers. The syntheses, duplex DNA interaction, topoisomerase inhibition and quadruplex DNA stabilization shown by these four molecules have been divided into two sections. Chapter 4A. Synthesis, Duplex DNA Binding and Topoisomerase I Inhibition by Symmetrical Bisbenzimidazole Derivatives with Aromatic Linkers. This chapter describes the synthesis of four symmetrical bisbenzimidazole derivatives bearing aromatic linkers, phenyl, naphthyl or anthryl between the benzimidazole rings. Next their interaction with duplex DNA was investigated using fluorescence and temperature dependent UV absorption spectroscopy and viscometric titration techniques. Addition of DNA caused fluorescence enhancement of the molecules implying their interaction with duplex DNA. All the four molecules on binding to double helical DNA induced thermal stabilization of the latter. Viscometric titration of calf thymus DNA with the four compounds revealed a partial-intercalative mode of binding for the anthracene derivatized molecule 4. Next, their inhibitory effects on the catalytic activity of topoisomerase I enzyme were studied. The anthracene derivatized compound (4) showed high inhibition of the enzyme catalyzed relaxation of supercoiled plasmid DNA. Naphthalene derivatized compound (3) exhibited weak inhibition whereas the derivatives bearing 1,4- and 1,3-disubstitued benzene (1 and 2 respectively) units showed no inhibition. Figure 3. Molecular structures of the symmetrical bisbenzimidazole derivatives. Chapter 4B. Quadruplex DNA Stabilization by Symmetrical Bisbenzimidazole Derivatives with Aromatic Linkers. The ability of the aforementioned molecules to stabilize G-quadruplex structures was investigated next. DNA quadruplex secondary structures are potential molecular targets for new generation chemotherapeutic drugs; hence there is an impetus in developing quadruplex targeting molecules. The Tetrahymena thermophilia telomeric sequence 5´-(T2G4)4-3´ was selected for the studies as it exhibits interesting structural polymorphism depending on whether quadruplex formation occurs in presence of Na+ or K+. Circular dichroism and fluorescence anisotropy techniques were used to study the interaction of these newly synthesized molecules with quadruplex DNA. Also thermal stabilization of quadruplex structure induced by the molecules was determined by temperature dependent UV absorption studies. The compounds 1, 3 and 4 stabilized Na+ induced quadruplex without causing any structural alterations of the latter. However, the m-phenyl linker bearing molecule 2, above a certain [ligand]/[DNA] concentration ratio, caused uniquestructural alteration of the Na+ induced quadruplex such that the CD-signature of the latter resembled that of a K+ induced quadruplex structure. This result was corroborated by quadruplex thermal melting data and fluorescence anisotropy. Interestingly this ligand was also able to induce secondary structure formation in randomly oriented ss-DNA, akin to K+ induced quadruplex structure, even in the absence of Na+ or K+. Chapter 5. Synthesis and DNA Binding of Novel Biscationic Dimers of Bisbenzimidazole Systems. This chapter describes the design, synthesis and ds-DNA binding properties of four dicationic dimers of bisbenzimidazoles. Targeting long base pair sequences in double helical DNA is a key issue in chemical biology and connecting different DNA binding modules by appropriate linkers is an attractive strategy for achieving the same. The precursor monomer unit was a bisbenzimidazole derivative and an analogue of Hoechst 33258. Two such moieties were connected via bisoxyethylenic or 6- or 3-methylenic or piperazinyl units to achieve linker of varying length, rigidity and hydrophilicity. To study the interaction of the dimers with duplex DNA, fluorescence and circular dichroism spectroscopy were used. Two of the dimers, (bbim-2ox-bbim and bbim-6met-bbim) bearing long flexible spacers, were able to target 13-AT base pairs long oligonucleotide sequences in a 1:1 binding mode with an affinity 8-10 times better than the precursor monomer or Hoechst 33258. Also thermal denaturation experiments showed high duplex stabilization induced by the same two dimers. All studies indicated a bidentate mode of binding where both the arms of the dimers participated in DNA binding. The molecules bearing the short and rigid linkers (bbim-3met-bbim and bbimpiper- bbim) on the other hand showed low binding affinity towards duplex DNA, as indicated by fluorescence, circular dichroism and thermal melting studies. The short linkers probably did not favor simultaneous binding of both the monomeric arms of the dimers to DNA minor groove. The work reported in this chapter indicates the strong influence of the length and nature of linker in determining drug/DNA binding affinity. Figure 4. Molecular structures of dicationic dimeric bisbenzimidazole derivatives.(Refer PDF File)

L'urée, apportée dans les engrais, fournit aux plantes l'azote nécessaire à leur croissance. Dans le sol, elle est convertie en ammoniac par les uréases, puis, via le procédé de nitrification, est oxydée en nitrites, puis en nitrates, éléments essentiels pour la nutrition des plantes. Mais, cet apport artificiel conduit à de nombreux déséquilibres écologiques dus à d'importants rejets d'azote au niveau atmosphérique et aquatique. C'est pourquoi les inhibiteurs d'uréases et de la nitrification, qui régulent la présence des différentes formes de l'azote dans le sol, sont d'un intérêt majeur en agriculture. Dans le cadre du projet AZOSTIMER, nous avons voulu améliorer l'efficacité du MBT, inhibiteur de la nitrification, et du NBPT, inhibiteur d'uréases. Nous avons tout d'abord souhaité améliorer l'hydrosolubilité, et ainsi la biodisponibilité du MBT et d'un homologue, le MBI, par mise à profit du concept de prodrogue. Ces molécules ont été conjuguées à des sucres par synthèse glycosidique et une famille d'inhibiteurs glycosylés a été préparée. Par la suite, les propriétés physico-chimiques (solubilité, stabilité), biologiques (écotoxicité, activité) et le comportement dans les sols (dégradabilité, mobilité) ont été évalués. Dans un second temps, nous avons voulu prolonger l'activité du NBPT dans les sols acides en limitant sa dégradation, soit par encapsulation dans une formulation, soit par modulations chimiques. De nombreuses formulations du NBPT ont été développées puis évaluées (stabilité en milieu acide, activité dans les sols). Des phosphoramides ont été synthétisés et évalués afin de mettre en évidence des relations structure-stabilité chimique et structure-activité.

Šio eksperimentinio darbo tikslas buvo įvertinti 1,4-dihidropiridino ir benzimidazolo junginių poveikį jūros kiaulyčių širdies papiliarinių raumenų izometrinei funkcijai bei žmogaus kraujagyslių segmentų susitraukimui ir atsipalaidavimui. Buvo atlikti eksperimentiniai tyrimai su izoliuotais jūros kiaulyčių širdies papiliarinių raumenų preparatais ir izoliuotais žmogaus v.saphena magna ir a.thoracica interna kraujagyslių segmentais. Kraujagyslių preparatai gauti iš pacientų, kuriems buvo atliekamos širdies vainikinių arterijų jungčių suformavimo operacijos LSMU ligoninės Kauno klinikos Kardiochirurgijos klinikoje. Žmogaus izoliuotų kraujagyslių preparatų tyrimams išduotas Kauno regioninio bioetikos komiteto leidimas Nr. BE–2–64, data 2010–11–05. Buvo tiriamas 1,4-dihidropiridinų bei benzimidazolo junginių poveikis izometrinei jūros kiaulyčių širdies papiliarinių raumenų funkcijai, registruojant preparatų elektromechaninį susitraukimo jėgos ir transmembraninio veikimo potencialus. Eksperimentiniai tyrimai, atlikti in vitro sąlygomis, įvertinant 1,4-dihidropiridinų bei benzimidazolo junginių poveikį žmogaus izoliuotų kraujagyslių (v.saphena magna ir a.thoracica interna) segmentų susitraukimui ir atsipalaidavimui, skirtingų ekstraląstelinio Ca2+ koncentracijų įtaką tiriamųjų junginių poveikiui kraujagyslių segmentų susitraukimui ir atsipalaidavimui. Tiriamieji 1,4–dihidropiridinų junginiai sintezuoti Latvijos Organinės Sintezės institute. / This study aim was to evaluate the effects of 1,4-dihydropiridines and benzimidazole deriva¬tives on the isometric function of guinea pig papillary cardiac muscles and the contraction and relaxation of vascular segments in humans. The experiments were carried out on isolated samples of human great saphenous vein (v. saphena magna) and internal thoracic artery (a. tho¬racica interna). The vein and arteries samples were taken from patients who underwent coronary artery bypass. The study was approved by the Regional Ethics Committee of the Biomedical Research on 05/11/2010, license No. BE-2-64, Kaunas, Lithuania. The inotropic activity and transmembrane AP duration of the dihydropyridine derivatives were evaluated on the guinea-pig papillary muscles and aorta vascular samples. Synthesis of 1,4-dihydropyridine derivatives were performed in Latvian Organic Synthesis institute. During this study were performed the evaluation of 1,4-dihydropyridines and benzimidazole derivatives on contraction force and action potential in guinea pig papillary muscles. Effects of 1,4-dihydropyridines and benzimidazole derivatives on contraction and relaxation of the segments of the great sa¬phenous vein (v. saphena magna) and internal thoracic artery (a. tho¬racica interna) in humans, the extra-cellular concentration of Ca2+ and the effect of the studied compounds and were evaluated. Also assessment of preventive effect of the calcium channel blockers and benzimidazole derivative on contraction... [to full text]

Polymer electrolyte membrane fuel cells (PEMFCs) are one of the most promising clean technologies under development. However, the main obstacles for commercialising PEMFCs are largely attributed to the technical limitations and cost of current PEM materials such as Nafion. Novel poly(2,5-benzimidazole) (ABPBI)/POSS based polymer composite electrolyte membranes with excellent mechanical and conductivity properties were developed in this project including (I) ABPBI, polybenzimidazole (PBI) and their copolymers were synthesised by solution polymerisation and their chemical structures were confirmed by FTIR and elemental analysis. ABPBI/ActaAmmonium POSS (ABPBI/AM) and ABPBI/TriSilanolPhenyl POSS (ABPBI/SO) composites were also synthesised in situ. High quality polymer and composite membranes were fabricated by a direct cast method; and (II) The mechanical and thermal properties, microstructure and morphology, water and H3PO4 absorbility and proton conductivity of phosphoric acid doped and undoped ABPBI and ABPBI/POSS composite membranes were investigated. SEM/TEM micrographs showed that a uniform dispersion of POSS nano particles in ABPBI polymer matrix was achieved. The best performances on both mechanical properties and proton conductivities were obtained from the ABPBI/AM composite membrane with 3 wt% of POSS (ABPBI/3AM). It was found that both the water and H3PO4 uptakes were increased significantly with the addition of POSS due to formation of hydrogen bonds between the POSS and H2O/H3PO4, which played a critical role in the improvement of the conductivity of the composite membranes at temperatures over 100oC. ABPBI/3AM membranes with H3PO4 uptake above 117% showed best proton conductivities at both hydrous and anhydrous conditions from room temperature to 160oC, which is comparable with the conductivity of commercial Nafion 117 at 20oC in water-saturated condition, indicating that these composite membranes could be excellent candidates as a polymer electrolyte membrane for high temperature applications. A new mechanism for illustrating the improved proton conductivity of composite membranes was also developed.