Synthetic, structural and mechanistic studies of interactions of carbon, nitrogen, and oxygen nucleophiles with bis-pentamethylcyclopentadienyl zirconium and hafnium derivatives

The reactivity of permethylzirconocene and permethylhafnocene complexes with various nucleophiles has been investigated. Permethylzirconocene reacts with sterically hindered ketenes and allenes to afford metallacycle products. Reaction of these cummulenes with permethylzirconocene hydride complexes affords enolate and σ-allyl species, respectively. Reactions which afford enolate products are nonstereospecific, whereas reactions which afford allyl products initially give a cis-σ-allyl complex which rearranges to its trans isomer. The mechanism of these reactions is proposed to occur either by a Lewis Acid-Lewis Base interaction (ketenes) or by formation of a π-olefin intermediate (allenes).

Permethylzirconocene haloacyl complexes react with strong bases such as lithium diisopropylamide or methylene trimethylphosphorane to afford ketene compounds. Depending on the size of the alkyl ketene substituent, the hydrogenation of these compounds affords enolate-hydride products with varying degrees of stereoselectivity. The larger the substituent, the greater is the selectivity for cis hydrogenation products.

The reaction of permethylzirconocene dihydride and permethylhafnocene dihydride with methylene trimethylphosphorane affords methyl-hydride and dimethyl derivatives. Under appropriate conditions, the metallated-ylide complex 1, (η^5-C_5(CH_3)_5)_2 Zr(H)CH_2PMe_2CH_2, is also obtained and has been structurally characterized by X-ray diffraction techniques. Reaction of 1 with CO affords (η^5-C_5(CH_3)_5)_2 Zr(C,O-η^2 -(PMe_3)HC=CO)H which exists in solution as an equilibrium mixture of isomers. In one isomer (2), the η^2-acyl oxygen atom occupies a lateral equatorial coordination position about zirconium, whereas in the other isomer (3), the η-acyl oxygen atom occupies the central equatorial position. The equilibrium kinetics of the 2→3 isomerization have been studied and the structures of both complexes confirmed by X-ray diffraction methods. These studies suggest a mechanism for CO insertion into metal-carbon bonds of the early transition metals.

Permethylhafnocene dihydride and permethylzirconocene hydride complexes react with diazoalkanes to afford η^2-N, N' -hydrazonido species in which the terminal nitrogen atom of the diazoalkane molecule has inserted into a metal-hydride or metal-carbon bond. The structure of one of these compounds, Cp*_2Zr(NMeNCTol_2)OH, has been determined by X-ray diffraction techniques. Under appropriate conditions, the hydrazonido-hydride complexes react with a second equivalent of diazoalkene to afford η' -N-hydrazonido-η^2-N, N' -hydrazonido species.

Versuche mit einem modifizierten Rollengeschirr für Garnelenbaumkurren

With a traditional roller gear, only the rollers in the centre are working correctly. The rollers on both sides are more or less gliding on the sea bottom because their axis are not in a position perpendicular to the towing direction. Sediment is stirred up by these gliding rollers coupled with a negative bottom impact of this gear. With a modified roller gear for shrimp beam trawls the axis of all rollers are orientated 90° to the towing direction enabling all rollers to roll correctly on the sea bottom.

Frame survey of Kainji Lake, northern Nigeria, 1996

Since 1993, annual frame surveys have been conducted by the Nigerian-German Kainji Lake Fisheries Promotion Project to determine the distribution and number of fishing localities, fishing canoes and fishing gears around Kainji Lake, Nigeria. The total number of fishing localities has increased from 221 in 1993 to 286 in 1996. The fishing localities included 245 permanent fishing villages, 29 permanent fishing camps, 8 temporary fishing camps (with fishermen from Kainji Lake) and 4 temporary fishing camps (with fishermen from outside Kainji Lake area). There was an increase in the total number of fishing entrepreneurs, fishing assistants and fishing canoes over the years. A total number of 5,499 fishing entrepreneurs, 12,449 fishing assistants and 9,278 fishing canoes were recorded during the 1996 frame survey. From 1995 there was a decrease in the number of shoreline fisherfolk and a decrease in the number of transport canoes, the number of engines remained the same. During the 1996 survey, a total number of 18,655 gill nets, 1,560 drift nets, 753 beach seines, 5,548 cast nets, 7,400 longlines and 36,979 traps were recorded. The concentration of the gears (number per km shoreline) was highest in substrata 06 and 08. The total number of gill nets increased from 17,680 in 1995 to 18,655 in 1996. For the remaining 5 gear types a decrease in number was observed. Despite increasing numbers of gears on the lake, of concern is the decline recorded in all the fishing methods of the number of gears owned by individual entrepreneurs. This was most notable in the gill net and longline fisheries. These two fisheries have the lowest daily catch values and coupled with the problem of gear theft on the lake, ownership in future, may be expected to fall further. The number of larger fishing units also declined as did the number of gears new entrants enter the fishery with. The decline is particularly worrying for the beach seine fishery where diversification into other fishing methods would be beneficial in light of the present ban on seines. The group of not active fishing entrepreneurs (those who do not themselves participate in fishing activities) had the highest ownership of gears whilst the new entrants into the fishery had the lowest. There was evidence that these new entrants into the fishery were using cast nets which is worrying given the trend of using smaller mesh size of this gearSince 1993, annual frame surveys have been conducted by the Nigerian-German Kainji Lake Fisheries Promotion Project to determine the distribution and number of fishing localities, fishing canoes and fishing gears around Kainji Lake, Nigeria. The total number of fishing localities has increased from 221 in 1993 to 286 in 1996. The fishing localities included 245 permanent fishing villages, 29 permanent fishing camps, 8 temporary fishing camps (with fishermen from Kainji Lake) and 4 temporary fishing camps (with fishermen from outside Kainji Lake area). There was an increase in the total number of fishing entrepreneurs, fishing assistants and fishing canoes over the years. A total number of 5,499 fishing entrepreneurs, 12,449 fishing assistants and 9,278 fishing canoes were recorded during the 1996 frame survey. From 1995 there was a decrease in the number of shoreline fisherfolk and a decrease in the number of transport canoes, the number of engines remained the same. During the 1996 survey, a total number of 18,655 gill nets, 1,560 drift nets, 753 beach seines, 5,548 cast nets, 7,400 longlines and 36,979 traps were recorded. The concentration of the gears (number per km shoreline) was highest in substrata 06 and 08. The total number of gill nets increased from 17,680 in 1995 to 18,655 in 1996. For the remaining 5 gear types a decrease in number was observed. Despite increasing numbers of gears on the lake, of concern is the decline recorded in all the fishing methods of the number of gears owned by individual entrepreneurs. This was most notable in the gill net and longline fisheries. These two fisheries have the lowest daily catch values and coupled with the problem of gear theft on the lake, ownership in future, may be expected to fall further. The number of larger fishing units also declined as did the number of gears new entrants enter the fishery with. The decline is particularly worrying for the beach seine fishery where diversification into other fishing methods would be beneficial in light of the present ban on seines. The group of not active fishing entrepreneurs (those who do not themselves participate in fishing activities) had the highest ownership of gears whilst the new entrants into the fishery had the lowest. There was evidence that these new entrants into the fishery were using cast nets which is worrying given the trend of using smaller mesh size of this gear. (PDF contains 44 pages)

Fisheries statistical bulletin, Kainji Lake, northern Nigeria, 1997

The bulletin presents summary tables and charts on levels of fishing activity, fishing effort, yields and economic values of yields for the fisheries of Kainji Lake, Nigeria for the year 1997. Frame survey data and fishing gear measurements are also included. (PDF contains 34 pages)

Fisheries statistical bulletin, Kainji Lake, Nigeria, 1998

A tabulated summary is presented of the main fisheries data collected to date (1998) by the Nigerian-German Kainji Lake Fisheries Promotion Project, together with a current overview of the fishery. The data are given under the following sections: 1) Fishing localities and types; 2) Frame survey data; 3) Number of licensed fishermen by state; 4) Mesh size distribution; 5) Fishing net characteristics; 6) Fish yield; 7) Total annual fishing effort by gear type; 8) Total annual value of fish landed by gear type; 9) Graphs of effort and CPUE by gear type. (PDF contains 36 pages)

Fisheries statistical bulletin, Kainji Lake, Nigeria, 1999

A tabulated summary is presented of the main Lake Kainji fisheries data collected to date (1999) by the Nigerian-German Kainji Lake Fisheries Promotion Project, together with a current overview of the fishery. The data are given under the following sections: 1) Fishing localities and types; 2) Frame survey data; 3) Number of licensed fishermen by state; 4) Mesh size distribution; 5) Fishing net characteristics; 6) Fish yield; 7) Average monthly CPUE by gear type; 8)Average monthly fishing activity by gear type; 9) Total annual fishing effort by gear type; 10) Total annual value of fish landed by gear type; 11) Trends of the total yield by gear type. (PDF contains 34 pages)

Nigerian German Kainji Lake Fisheries Promotion Project - approach, result, future

The paper highlighted the overall goal and purpose of the Nigerian German Kainji Lake Fisheries Promotion Project. The main goal is to increase the standard of living of fishing communities in the project area. The target groups are the fishermen and fisherwomen in the area. The project also developed in effective extension delivery system in the basin. Also developed at the project headquarters are facilities for the execution of the project. The project are able to carry out frame, gear and stock assessment surveys on the Lake and able to formulate a fisheries management plan for the fisheries of Kainji Lake

Studies of Organic Molecule Recognition by Synthetic Cyclophane Receptors in Aqueous Media

The behaviors of six new cyclophane receptors for organic guest molecules in aqueous media are reported. These new hosts are modifications of more basic parent structures, and the main goal of their examination has been to determine how the modifications affect host selectivity for cationic guests. In particular, we have been interested in determining how additional non-covalent binding interactions can complement the cation-π interactions active in the parent systems. Three types of modifications were made to these systems. Firstly, neutral methoxy and bromine substituents were added to produce four of the six new macrocycles. Secondly, two additional aromatic rings (relative to the parent host) capable of making cation-π interactions with charged guest species were appended. Thirdly, a negatively charged carboxyl group was attached to produce a cavity in which electrostatic interactions should enhance cationic guest binding. ^1H-NMR and circular dichroic techniques were employed to determine the binding affinities of a wide variety of organic guests for the parent and modified structures in aqueous media.

Bromination of the parent host greatly enhances its binding in a general fashion, primarily as the result of hydrophobic interactions. The addition of methoxy groups does not enhance binding, apparently as a result of a collapse of the hosts into a conformation that is not suitable for binding. The appendage of extra aromatic rings enhances the binding of positively charged guests, most likely in response to more complete encapsulation of guest species. The addition of a negatively charged carboxylate enhances the binding to only selective groups of cationic guests. AM1 calculations of the electrostatic potentials of several guests molecules suggests that the enhancements seen with the modified receptor compared to the parent are most likely the result of close contact between regions of highest potential on the guest and the appended carboxylate.

Pharmacology and pore-forming domains of the cystic fibrosis transmembrane conductance regulator

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel member of the ATP-binding cassette (ABC) superfamily of membrane proteins. CFTR has two homologous halves, each consisting of six transmembrane spanning domains (TM) followed by a nucleotide binding fold, connected by a regulatory (R) domain. This thesis addresses the question of which domains are responsible for Cl^- selectivity, i.e., which domains line the channel pore.

To address this question, novel blockers of CFTR were characterized. CFTR was heterologously expressed in Xenopus oocytes to study the mechanism of block by two closely related arylaminobenzoates, diphenylamine-2-carboxylic acid (DPC) and flufenamic acid (FFA). Block by both is voltage-dependent, with a binding site ≈ 40% through the electric field of the membrane. DPC and FFA can both reach their binding site from either side of the membrane to produce a flickering block of CFTR single channels. In addition, DPC block is influenced by Cl^- concentration, and DPC blocks with a bimolecular forward binding rate and a unimolecular dissociation rate. Therefore, DPC and FFA are open-channel blockers of CFTR, and a residue of CFTR whose mutation affects their binding must line the pore.

Screening of site-directed mutants for altered DPC binding affinity reveals that TM-6 and TM-12 line the pore. Mutation of residue 5341 in TM-6 abolishes most DPC block, greatly reduces single-channel conductance, and alters the direction of current rectification. Additional residues are found in TM-6 (K335) and TM-12 (T1134) whose mutations weaken or strengthen DPC block; other mutations move the DPC binding site from TM-6 to TM-12. The strengthened block and lower conductance due to mutation T1134F is quantitated at the single-channel level. The geometry of DPC and of the residues mutated suggest α-helical structures for TM-6 and TM-12. Evidence is presented that the effects of the mutations are due to direct side-chain interaction, and not to allosteric effects propagated through the protein. Mutations are also made in TM-11, including mutation S1118F, which gives voltage-dependent current relaxations. The results may guide future studies on permeation through ABC transporters and through other Cl^- channels.

Characterization of rural livelihood of Lake Chad basin fishermen

The study examined the characterization of rural livelihood of the fishermen in the Nigeria portion of Lake Chad Basin are as part of European Commission (EC) founded project entitled "Sustainable development of continental fisheries; a regional study of policy options and policy formation mechanisms for the Lake Chad Basin" Wealth ranking exercise which was not based on real income but on production capacity of the fishermen was carried out in twenty (20) villages survey on the western part of the region using Rapid Rural Appraisal Technique with semi- structured interviews. The different activities carried out by the villagers for living were identified according to their socio-economic status. This was followed by an assessment of the socio-economic characterization within each wealth group. Series of comparative analysis of the ethnic composition, accessibility of fishing gear ownership by the population were done. The results show that the 3 wealth groups in the region include the rich (Group 1) the middle class (Group 2) and the poor (Group 3). It was identified that fishing is just one component of the socio-economic production system along side farming, livestock rearing and trading which are closely integrated. The diversified livelihood system being practiced in the Chad Basin region are not only less vulnerable but also more sustainable

Impact of radio broadcast on fish production and conservation in Kainji Lake basin

The decline in fishermen catches of Lake kainji, which went down from 28,639.6t in 1970 to 6.048t in 1974 (Ita 1982) prompted the promulgation of fisheries edict banning beach seines and other obnoxious fishing gear by Kebbi and Niger State governments in 1997 as a measure to prevent depletion of fisheries resources in the lake. Radio as a medium of communication was adopted as the method to disseminate information in the fisheries edict to the fisherfolks in order to bring about positive changes. Radio Niger, Koro station, was involved in the broadcast. Fisherfolk listened to the broadcast 32 times a week. Frame survey data and radio impact assessment studies were used to assess the effect of the broadcast on the number of beach seines and other obnoxious fishing gears on the lake which were banned in the fisheries edicts. It was revealed that the number of beach decreased drastically from 582 in 1997 to 122 in 1999 and to only 17 in 2001

Directed evolution of terpene synthases for non-natural substrates

Terpenes represent about half of known natural products, with terpene synthases catalyzing reactions to increase the complexity of substrates and generate cyclizations of the linear diphosphate substrates, therefore forming rings and stereocenters. With their diverse functionality, terpene synthases may be highly evolvable, with the ability to accept a wide range of non-natural compounds and with high product selectivity. Our hypothesis is that directed evolution of terpene synthases can be used to increase selectivity of the synthase on a specific substrate. In the first part of the work presented herein, three natural terpene synthases, Cop2, BcBOT2, and SSCG_02150, were tested for activity against the natural substrate and a non-natural substrate, called Surrogate 1, and the relative activities on both the natural and non-natural substrates were compared. In the second part of this work, a terpene synthase variant of BcBOT2 that has been evolved for thermostability, was used for directed evolution for increased activity and selectivity on the non-natural substrate referred to as Surrogate 2. Mutations for this evolution were introduced using random mutagenesis, with error prone polymerase chain reactions, and using site-specific saturation mutagenesis, in which an NNK library is designed with a specific active site amino acid targeted for mutation. The mutant enzymes were then screened and selected for enhancement of the desired functionality. Two neutral mutants, 19B7 W367F and 19B7 W118Q, were found to maintain activity on Surrogate 2, as measured by the screen.

The intramolecular Buchner reaction of α-diazo-β-ketonitriles : development and application to the total synthesis of (+)-Salvileucalin B

Since its discovery in 1896, the Buchner reaction has fascinated chemists for more than a century. The highly reactive nature of the carbene intermediates allows for facile dearomatization of stable aromatic rings, and provides access to a diverse array of cyclopropane and seven-membered ring architectures. The power inherent in this transformation has been exploited in the context of a natural product total synthesis and methodology studies.

The total synthesis work details efforts employed in the enantioselective total synthesis of (+)-salvileucalin B. The fully-substituted cyclopropane within the core of the molecule arises from an unprecedented intramolecular Buchner reaction involving a highly functionalized arene and an α-diazo-β-ketonitrile. An unusual retro-Claisen rearrangement of a complex late-stage intermediate was discovered on route to the natural product.

The unique reactivity of α-diazo-β-ketonitriles toward arene cyclopropanation was then investigated in a broader methodological study. This specific di-substituted diazo moiety possesses hitherto unreported selectivity in intramolecular Buchner reactions. This technology was enables the preparation of highly functionalized norcaradienes and cyclopropanes, which themselves undergo various ring opening transformations to afford complex polycyclic structures.

Finally, an enantioselective variant of the intramolecular Buchner reaction is described. Various chiral copper and dirhodium catalysts afforded moderate stereoinduction in the cyclization event.

Developing peptide based capture agents for diagnostics and therapeutics

Iterative in situ click chemistry (IISCC) is a robust general technology for development of high throughput, inexpensive protein detection agents. In IISCC, the target protein acts as a template and catalyst, and assembles its own ligand from modular blocks of peptides. This process of ligand discovery is iterated to add peptide arms to develop a multivalent ligand with increased affinity and selectivity. The peptide based protein capture agents (PCC) should ideally have the same degree of selectivity and specificity as a monoclonal antibody, along with improved chemical stability. We had previously reported developing a PCC agent against bovine carbonic anhydrase II (bCAII) that could replace a polyclonal antibody. To further enhance the affinity or specificity of the PCC agent, I explore branching the peptide arms to develop branched PCC agents against bCAII. The developed branched capture agents have two to three fold higher affinities for the target protein. In the second part of my thesis, I describe the epitope targeting strategy, a strategy for directing the development of a peptide ligand against specific region or fragment of the protein. The strategy is successfully demonstrated by developing PCC agents with low nanomolar binding affinities that target the C-terminal hydrophobic motif of Akt2 kinase. One of the developed triligands inhibits the kinase activity of Akt. This suggests that, if targeted against the right epitope, the PCC agents can also influence the functional properties of the protein. The exquisite control of the epitope targeting strategy is further demonstrated by developing a cyclic ligand against Akt2. The cyclic ligand acts as an inhibitor by itself, without any iteration of the ligand discovery process. The epitope targeting strategy is a cornerstone of the IISCC technology and opens up new opportunities, leading to the development of protein detection agents and of modulators of protein functions.

A survey of fisherfolk involved in artisanal fisheries in some selected areas of Ikorodu in Lagos State

The study focused on men and women involved in artisanal fisheries in some selected areas of Ikorodu Local government in Lagos State. The random sampling technique was used to select 50 fishermen each at Ibeshe and Baiyeku sites. The results revealed that majority of the fishermen were male, christian, semi-illiterate, and married. Data were collected on capital sources, labour used, income, gear techniques and type of fish caught. Analysis showed that the highest sources of capital were from personal savings (50%). Majority of labour used were hired labour, 44% at Ibeshe and 50% at Baiyeku. Highest monthly income ranged between N10, 000 - N25, 000 at both sites. Planks were mostly used at both sites for fishing boats as well as means of transport (Ibeshe 68%, Baiyeku 72%). Common fishing gear was the gill net, The fishes caught were found to be of various tyupes. Ethalmalosa fimbriata constituted the highest fish species caught by weight and number at both sites (50%). However, the problems of capital source were most peculiar coupled with high cost of fishing materials and labour scarcity