Chiral organotin hydrides as enantioselective reducing agents

This thesis reports on the feasibility of the utilization of organotin hydrides as enaantioselective free radical reducing agents. The chiral organotin hydrides prepared contain the bulky chiral (1R,2S,5R)-menthyl substituent and in some cases also contain a stereogenic tin centre. Reaction of (1R,2S,5R)-menthylmagnesium chloride (MenMgC1) with triphenyltin chloride in THF proceeds with epimerization of the C-1 carbon of the menthyl group and results in a mixture of (1R,2S,5R)-menthyltriphenyltin and (1S,2S.5R)-menthyltriphenyltin. Addition of Lewis bases such as triphenylphosphine to the THF solution of triphenyltin chloride prior to the addition of the Grignard reagent suppresses epimerization and enables isolation of pure (1R,2S,5R)-menthyltriphenyltin. (1R,2S,5R)-Menthyltriphenyltin is the precursor for the synthesis of (1R,2S,5R)-menthyldiphenyltin hydride as well as (1R,2S,5R)-menthyl-containing organotin halide derivatives. A crystal structure of (1R,2S,5R)-menthylphenyltin dibromide and (1R,2S,5R)-menthylphenyltin dichloride confirmed the configuration of the menthyl substituent in these compounds. Reaction of MenMgC1 with diphenyltin dichloride in THF proceeds with no epimerization of the C-1 carbon of the menthyl group and bis((1R,2S,5R)-menthyl)diphenyltin is formed. A crystal structure of (1R,2S,5R)-menthyltriphenyltin confirmed the configuration of the menthyl substituent. Bis((1R,2S,5R)-menthyl)diphenyltin is used to form bis((1R,2S,5R)-menthyl)phenyltin hydride as well as other bis(1R,2S,5R)-menthyl derivatives. A series of chiral non-racemic triorganotin halides and triorganotin hydrides containing one or two (1R,2S,5R)-menthyl substituents as well as various potentially intramolecular coordination substituents were synthesized and characterized. The intramolecular substituents include the 8-(dimethylamino)naphthyl, 2-[(1S)-1-dimethylaminoethyl]phenyl, 2-(4,4-dimethyl-2-oxazoline)-5-methylphenyl and the 2-(4-(S)isopropyl-2-oxazoline)-5-methylphenyl substituents. Each compound containing a stereogenic tin centre was synthesized as diastereomeric mixtures. AM1 calculations of these compounds provide good qualitative predictability of the molecular geometries observed in the solid state as well as the diastereomeric ratios observed in solution. X-ray analysis of some of the organotin halides containing intramolecular coordination substituents revealed a tendency towards penta-coordination at the tin centre as a result of N-Sn interactions. The chiral organotin hydrides synthesized were found to be poor enantioselective free radical reducing agents. However, the addition of one molar equivalent of achiral or chiral Lewis acids to the free radical reduction reactions involving these organotin hydrides results in remarkable increases in enantioselectivity. There are numerous examples in which enantioselectivities exceed 80% and three examples of enantioselectivites which are equal and above 90% with one outstanding enantioselective outcome of ≥99%. These results appear to be the highest enantioselectivites for organotin hydride radical reductions reported to date. There is strong evidence to suggest that the chiral menthyl group of the organotin hydride directs the stereochemical outcome in the reduced product. The results also suggest that an increase in the number of menthyl substituents attached to tin or the introduction of intramolecular coordination substituents does not necessarily results in a greater increase in enantioselectivity. Preliminary studies into the synthesis of organotin hydrides containing Lewis acid functionalities are also reported. A zirconium chloride functionality was found to be incompatible with organotin hydride. However, an organotin hydride containing a trialkylboron Lewis acid functionality attached via an alkyl chain was successfully synthesized. Although this reagent was only stable in the preparative THF solution, it was still found to be effective at reducing benzaldehyde to benzyl alcohol.

Modeling intelligent agents for web-based information gathering

The recent emergence of intelligent agent technology and advances in information gathering have been the important steps forward in efficiently managing and using the vast amount of information now available on the Web to make informed decisions. There are, however, still many problems that need to be overcome in the information gathering research arena to enable the delivery of relevant information required by end users. Good decisions cannot be made without sufficient, timely, and correct information. Traditionally it is said that knowledge is power, however, nowadays sufficient, timely, and correct information is power. So gathering relevant information to meet user information needs is the crucial step for making good decisions. The ideal goal of information gathering is to obtain only the information that users need (no more and no less). However, the volume of information available, diversity formats of information, uncertainties of information, and distributed locations of information (e.g. World Wide Web) hinder the process of gathering the right information to meet the user needs. Specifically, two fundamental issues in regard to efficiency of information gathering are mismatch and overload. The mismatch means some information that meets user needs has not been gathered (or missed out), whereas, the overload means some gathered information is not what users need. Traditional information retrieval has been developed well in the past twenty years. The introduction of the Web has changed people's perceptions of information retrieval. Usually, the task of information retrieval is considered to have the function of leading the user to those documents that are relevant to his/her information needs. The similar function in information retrieval is to filter out the irrelevant documents (or called information filtering). Research into traditional information retrieval has provided many retrieval models and techniques to represent documents and queries. Nowadays, information is becoming highly distributed, and increasingly difficult to gather. On the other hand, people have found a lot of uncertainties that are contained in the user information needs. These motivate the need for research in agent-based information gathering. Agent-based information systems arise at this moment. In these kinds of systems, intelligent agents will get commitments from their users and act on the users behalf to gather the required information. They can easily retrieve the relevant information from highly distributed uncertain environments because of their merits of intelligent, autonomy and distribution. The current research for agent-based information gathering systems is divided into single agent gathering systems, and multi-agent gathering systems. In both research areas, there are still open problems to be solved so that agent-based information gathering systems can retrieve the uncertain information more effectively from the highly distributed environments. The aim of this thesis is to research the theoretical framework for intelligent agents to gather information from the Web. This research integrates the areas of information retrieval and intelligent agents. The specific research areas in this thesis are the development of an information filtering model for single agent systems, and the development of a dynamic belief model for information fusion for multi-agent systems. The research results are also supported by the construction of real information gathering agents (e.g., Job Agent) for the Internet to help users to gather useful information stored in Web sites. In such a framework, information gathering agents have abilities to describe (or learn) the user information needs, and act like users to retrieve, filter, and/or fuse the information. A rough set based information filtering model is developed to address the problem of overload. The new approach allows users to describe their information needs on user concept spaces rather than on document spaces, and it views a user information need as a rough set over the document space. The rough set decision theory is used to classify new documents into three regions: positive region, boundary region, and negative region. Two experiments are presented to verify this model, and it shows that the rough set based model provides an efficient approach to the overload problem. In this research, a dynamic belief model for information fusion in multi-agent environments is also developed. This model has a polynomial time complexity, and it has been proven that the fusion results are belief (mass) functions. By using this model, a collection fusion algorithm for information gathering agents is presented. The difficult problem for this research is the case where collections may be used by more than one agent. This algorithm, however, uses the technique of cooperation between agents, and provides a solution for this difficult problem in distributed information retrieval systems. This thesis presents the solutions to the theoretical problems in agent-based information gathering systems, including information filtering models, agent belief modeling, and collection fusions. It also presents solutions to some of the technical problems in agent-based information systems, such as document classification, the architecture for agent-based information gathering systems, and the decision in multiple agent environments. Such kinds of information gathering agents will gather relevant information from highly distributed uncertain environments.

Perceptions and experiences of taking oral hypoglycaemic agents among people of Pakistani and Indian origin : qualitative study

Objective:  To explore British Pakistani and British Indian patients’ perceptions and experiences of taking oral hypoglycaemic agents (OHAs).
Design : Observational cross sectional study using in-depth interviews in English or Punjabi.
Setting and participants : 32 patients of Pakistani and Indian origin with type 2 diabetes, recruited from primary care and community sources in Edinburgh, Scotland.
Results : Respondents reported complex and ambivalent views about OHAs, which reflected their ambivalent attitudes towards Western drugs in general. Respondents considered OHAs to be an important part of the diabetic regimen because they perceived British healthcare professionals to be competent and trustworthy prescribers, and they considered the medicines available in Britain to be superior to those on the Indian subcontinent. Despite this, some respondents made deliberate efforts to reduce their tablet intake without being advised to do so. Reasons for this included perceptions that drugs worked by providing relief of symptoms and concerns that OHAs could be detrimental to health if taken for long periods, in conjunction with other drugs, or without traditional foods.
Conclusions : British Pakistani and Indian patients’ perceptions of their OHAs may partly derive from popular ideas about drugs on the Indian subcontinent. Cultural factors need to be understood and taken into consideration to ensure that these patients are given appropriate advice and to avoid unnecessary changes to prescriptions.

Haptically simulating soft tissue using spherical voxel and reactive agents

This thesis describes technology developed by the author enabling trainee surgeons to perform needle insertion procedures with force feedback (haptics) on a virtual patient. Addition of the sense of touch to medical simulation is arguably the most important step forward in the evolution of haptic technology to this day.

Investigation into the application of chiral organotin hydrides as enantioselective free radical reducing agents

Investigates the viability of selectively preparing molecules demonstrating the property of left or right "handedness" via free radical reactions. Experimental investigations suggested that a subtle interaction exists between the substituents of an organotin hydride and a target carbon radical during hydrogen atom transfer reactions.

Adenosine receptor agonists as potential therapeutic agents

Adenosine is a naturally occurring compound within the human body. It is known to exert a wide range of physiological effects. A range of compounds which elict a similar response to adenosine in vivo have been synthesised and evaluated as cardioprotective agents.

Hormonal breast and prostate cancer cytotoxic agents

Details 13 novel hormone compounds, designed and synthesised for the purpose of aiding the detection and treatment of breast and prostate cancers. Cellular and electromechanical studies of 3 of these synthesised hormones indicate a potential for human application.

Highly fluorescent TPA-PBPV nanofibers with amplified sensory response to TNT

Well-aligned nanofibers were prepared from a conjugated polymer, poly(triphenylamine-alt-biphenylene vinylene) (TPA-PBPV), using a solution-assisted template wetting technique. TPA-PBPV was also coated on the surface of electrospun polyacrylonitrile (PAN) nanofiber nonwoven membrane. The extremely large surface area, highly porous fibrous structure, optical scattering and evanescent-wave guiding effect imparted these one-dimensional (1D) nanofibrous materials with highly improved sensory ability to 2,4,6-trinitrotoluene (TNT) vapors and higher quenching efficiency than that of the neat TPA-PBPV films. The results suggest that nanofibrous structures could be a promising strategy to improve the sensory efficiency of fluorescent chemosensors.

Tracking multiple mobile agents with single frequency continuous wave radar

In this paper, a novel concept to determine the velocity and the location information of multiple mobile agents using Doppler radar has been introduced. Also, an expression for the minimum number of inline sensors needed to guarantee this estimation for n number of mobile agents has been obtained. Current methods use the time derivative of the displacement of adjacent position measurements to find the velocities of agents. This method is error prone, particularly, if the agents are accelerating. In our approach we incorporate direction-of-arrival (DOA) radar which tracks the location and the velocity of each and every agent in each measurement step.

Dual responsive chemosensors for anions : the combination of fluorescent PET (Photoinduced Electron Transfer) and colorimetric chemosensors in a single molecule

The design and synthesis of two novel fluorescent PET anion sensors is described, based on the principle of ‘fluorophore-spacer-(anion)receptor’. The sensors 1 and 2 employ simple diaromatic thioureas as anion receptors, and the fluorophore is a naphthalimide moiety that absorbs in the visible part of the spectrum and emits in the green. Upon recognition of anions such as F⁻ and AcO⁻ in DMSO, the fluorescence emission of 1 and 2 was ‘switched off’, with no significant changes in the UV–vis spectra. This recognition shows a 1:1 binding between the receptor and the anions. In the case of F⁻, further additions of the anion, gave rise to large changes in the UV–vis spectra, where the λ_max at 455 nm was shifted to 550 nm. These changes are thought to be due to the deprotonation of the 4-amino moiety of the naphthalimide fluorophore. This was in fact found to be the case, using simple naphthalimide derivatives such as 6. Sensors 1 and 2 can thus display dual sensing action; where at low concentrations, the fluorescence emission is quenched, and at higher concentrations the absorption spectra are modulated.

Agents based e-commerce and securing exchanged information

Mobile agents have been implemented in e-commerce to search and filter information of interest from electronic markets. When the in format ion is very sensitive and critical, it is important to develop a novel security protocol that can efficiently protect the information from malicious tampering as well as unauthorized disclosure or at least detect any malicious act of intruders. In this chapter, we describe robust security techniques that ensure a sound security of information gathered throughout agent's itinerary against various security attacks, as well as truncation attacks. A sound security protocol is described , which implements the various security techniques that would jointly prevent or at least detect any malicious act of intruders. We reason about the soundness of the protocol using Symbolic Trace Analyzer (STA), a formal verification tool that is based on symbolic techniques. We analyze the protocol in key configurations and show that it is free of flaws. We also show that the protocol fulfils the various security requirements of exchanged information in MAS, including data-integrity, data-confidentiality, data authenticity, origin confidentiality and data non-repudiability.

Recent insights on the role of cryoprotective agents in vitrification

In recent efforts to produce cryoprotective solutions which cause either complete, or almost complete, vitrification of the cell or tissue material, increasingly complex cocktails of solutes have invariably been used. Why some of these solutes are so much more effective in suppressing ice formation than other, related solutes has never been clear. To begin to compare and contrast the role of the solute in aiding vitrification we have examined the nature of the hydrogen bonding interactions between the solute and water and between the solute molecules themselves, via proton nuclear magnetic resonance experiments. These experiments, carried out on neat samples of the solutions, show marked differences between solutes such as ethylene glycol, 1,2-propanediol, 1,3-propanediol, the family of butanediol isomers, dimethylsulfoxide, and so on, at fixed concentration. The solutions also show marked trends in the NMR chemical shift as a function of concentration in any given solution. Thus it appears that, from the point of view of the physical suppression of ice in aqueous solutions, cryoprotective agents which can act as moderately strong bases are optimum. The mechanism by which the solute promotes glass formation was also investigated in a separate series of NMR experiments using more dilute solutions of the solute in water. These experiments indicate that the role of the solute is twofold in that it must (i) effectively suppress the anomalous structuring which occurs in supercooled water and is responsible for the rapid nucleation of ice and (ii) provide a decrease in molecular mobility at low temperatures such that the nucleation probability is decreased and glass formation occurs at a relatively high temperature. It is argued that both such effects can be brought about by the strong hydrogen bonding interactions between water and solutes such as 2,3-butanediol.