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Synthesis and Application of Light-Activated Molecular Systems
Get PDFPhD ThesisRuthenium complexes and BODIPY dyes are two very typical types of light-activated
molecular systems which are useful in various chemistry and biology applications
such as photodynamic therapy, chemical sensors, biological labelling and imaging.
But correspondingly, these applications can face problems like cytotoxicity, poor
analyte selectivity and a weak signal-to-noise ratio (SNR). This thesis is concerned
with work focusing on the design and preparation of several novel ruthenium
polypyridyl complexes and BODIPY-based compounds for applications in
photodynamic therapy and the fluorescent sensing area. Their photochemistry
behaviours are investigated via a range of optical techniques and methods. We
hoped to discover compounds with excellent features like low toxicity, high selectivity,
good optical signal response and stable performance. The ideas are presented in six
chapters within the thesis.
Chapter 1 outlines the research directions based on ruthenium complexes and
BODIPY-based light-activated molecular systems. The literature review generally
introduces the previous discoveries of these two types of compounds, their structural
feature, principles of synthetic considerations, chemistry and some applications. A review of photochemistry principles which are related to their structures for
development in the other chapters are also reviewed as the basis of this chapter.
Chapter 2 describes the common instrumentations, general experimental set ups,
data collection and analysis methods which are applicable for the prepared samples
and some preliminary structural characterization.
Chapter 3 talks about the design of a new class of PDT agents using light-activated
small molecules like ruthenium complexes to block biological functioning, especially
targeting mitochondria and how they may interfere with critical redox reactions under
light activation. Based on our concepts the complex [Ru(bipy)2(1-hydroxyanthra-9,10
quinone)]Cl (RU1) was prepared and studied to understand the preliminary reaction
mechanisms and its excited state behaviour through a series of stability tests,
electrochemistry, UV-Visible kinetic and femtosecond transient absorption
spectroscopy experiments. Under light in the presence of H2O2 two different
reactions (fast and slow) appear to take place. The complex loses the quinone-based
ligand and a resulting Ru(III) or Ru(V) species is produced. The complex RU1 shows
good potential to consume H2O2 from the one carbon metabolism in mitochondria,
and hence may cut the energy cycle pathway of tumour cells.
Chapter 4 explored a new a julolidine-based BODIPY compound to selectively detect
sulfite in a real wine sample. A non-oxidised julolidine-based BODIPY compound
(JUL) was reacted with silver (I) ions in the presence of white light and produced its
oxidised julolidine version (OXJUL) which contains a quaternary nitrogen. This type
of oxidation reaction is highly unusual and there were no reports about it previously.
With the addition of a small amount of Na2SO3 in an aqueous solution, the
fluorescence maxima of OXJUL blue shifted from 648 nm to 608 nm over several
minutes. In the presence of a large excess of sulfite, a further slower reaction
occurred accompanied by a blue-shift of the emission to 544 nm. These series of
changes are the basis of a real-time fluorescent ratiometric sensor for the detection
of sulfite in real wine samples. Chapter 5 successfully developed a new low molecular weight BODIPY based
voltage sensitive dye (AJBD) to image and detect voltage changes in giant
unilamellar vesicles (GUVs) according to lifetime changes. Julolidine was mono
substituted in the α-position of a BODIPY core to form a neutral and lipophilic VSD
with a charge transfer feature. With the ON-OFF voltage change on the GUVs, the
fluorescence lifetime distribution ratio of AJBD showed a zigzag pattern alongside
the ON-OFF voltage changes. When the GUVs were subjected to a ramping voltage,
the lifetime distribution ratio showed a linear change in line with the voltage change.
These observations were the evidence to indicate the voltage sensitive character of
AJBD.
Chapter 6 briefly concludes the previous work and highlights the development of the
project in the future. For RU1 and RU2, we are aiming to apply it in mitochondria and
investigate its behaviour in interrupting the metabolism pathway under the light in
Newcastle University Medical School. For OXJUL and AJBD, the targets will be
following tested in cells labelling and imaging using fluorescence lifetime imaging
microscopy (FLIM) in collaboration with Central Laser Facility (CLF) in the future
The pH and Concentration of Hydrogen Peroxide – Impact upon Dental Enamel Properties and Response to Dietary Staining, Erosion, and Remineralisation
Get PDFPh. D. Thesis.Hydrogen peroxide (HP) based whitening products can damage enamel due to their pH and
concentration. This in-vitro study investigates the effect of HP pH and concentration on selected
enamel properties. In addition, combined effects of whitening/remineralisation and subsequent
resistance to simulated dietary erosion and staining were investigated.
Polished bovine enamel samples were treated with 6, 20, 40wt.% HP at pH 5, 7 and 9, for 2
hours daily for ten days. Samples were stored in artificial saliva at 37C before and after
treatment. Whitening/remineralisation investigations were performed using 6wt.% HP in
combination with either casein phosphopeptide–amorphous calcium phosphate (CPP-ACP) or
nanohydroxyapatite (nHA). Samples were then subjected to simulated dietary staining using
coffee and erosion using 0.3% citric acid (pH3.8). Measurements of enamel roughness (Ra),
hardness (HV), and colour change (E) were made before and after treatment using atomic
force microscopy, micro-hardness testing, and spectrophotometry. Mineral loss and qualitative
surface evaluations were undertaken using energy dispersive x-ray spectroscopy (EDX) and
scanning electron microscopy (SEM), respectively, after treatment.
As HP concentration increased and pH decreased there was a statistically significant increase
in E (P<0.05). Greatest increase in Ra and decrease in HV occurred in enamel treated with
pH9 40% HP. Remineralisation did not significantly affect E, Ra, and HV of whitened enamel.
CPP-ACP was effective in preventing statistically significant changes in Ra and HV values
after erosive cycling. Enamel treated with nHA exhibited the greatest dietary stain uptake. No
significant changes in enamel Ca, C, and P occurred after whitening, remineralisation, and
erosion. SEM images revealed distinct surface changes mostly in pH9 and nHA treated samples.
All whitened specimens exhibited significantly greater colour change than the control group.
Neutral HP caused the least damage to whitened enamel while producing a satisfactory
whitening effect. Remineralising agents did not reduce whitening side effects, however, CPPACP prevented significant Ra and HV changes after dietary erosion.College of Dentistry-Princess
Nourah bint Abdulrahman Universit
An exploration of meetings between parents and multiple professionals through bounded meta-study and collaborative action research
Get PDFPhD ThesisParents of children who are identified as having special educational needs and/or disabilities (SEND) are likely to experience relationships with numerous professionals, across disciplines and agencies. Parental participation in decision making is emphasised within UK SEND policy, as well as the importance of partnerships between parents and professionals. Meetings are a key feature in decision-making processes, where it is anticipated that all parties will collaborate to agree plans and provision for the child. This project presents a critical stance toward the discourses of collaboration and partnership between parents and multiple professionals, recognising the potential difficulties in actualising these concepts in practice. Meetings can act as a bounded context in which to explore relationships between parents and multiple professionals. Despite their prevalence in processes for children identified with SEND, meetings between parents and professionals appear to be an under-researched phenomenon in the UK. This project therefore seeks to contribute to literature regarding the practice of meetings and parent-professional collaboration.
This thesis is comprised of a systematic literature review and empirical study; a further chapter is presented to bridge these two papers and provide insight into decision making within the research process. Chapter one reports a systematic literature review that sought to address the question: what are parents’ experiences of working with multiple professionals during review meetings for their children identified with SEND? A bounded meta-study methodology was employed to analyse the data, methods and theoretical assumptions of five papers to construct new understandings in relation to the review question. This synthesis suggests that the unique role of the parent and their connection to the child is a key feature that permeates parental experiences of working with multiple professionals. It is proposed that meetings can be understood as professional spaces that parents enter by the nature of their role. When entering this professional space of meetings, parents’ feelings regarding how much they are valued by the team are important to their experience, in addition to their active participation being facilitated. The review offers potential implications of these findings for practice and research.
The empirical research element of this thesis aimed to be transformative in its nature and move beyond exploring experiences of meetings to actively improving practice. Chapter Three reports a collaborative action research project undertaken with a headteacher of a primary school to explore the practice of meetings between parents and multiple professionals.
The co-researcher and I chose to engage in an inquiry that we hoped would enhance our understandings and encourage reflection on our own practices. This inquiry took the form of a case study of a single meeting, where a parent, SEND co-ordinator, educational psychologist and external specialist teacher met to agree a request for the statutory assessment of a young person’s SEND needs. We chose to explore the concept of role identity amongst the meeting participants by interviewing them about their perception of their own role and that of others. We also explored how roles were constructed and how participants might be positioned through interactions by video recording the meeting. The findings from the case study were used as catalysts for discussion between the co-researcher and I. From this rich discussion, several outcomes were identified for future practice. These were concerned with how meeting facilitators might create a sense of team; foster genuine connection, understand parents’ perspectives and encourage the development of professional skills. The study demonstrates how collaborative action research processes can be useful in the development of professional learning and reflection. Key learnings from the research process are discussed
Technology-enabled planning participation: Designing & deploying digital technology to encourage citizen participation in urban planning
Get PDFPh. D. Thesis.Citizens increasingly want to formally engage with the governmental and policy processes that
manage how places change. Whilst enhancing the role of citizens in urban planning has been
a longstanding objective for academics and communities, translating these aspirations into
practice has proved to be more challenging. Although a range of conceptual ideas and
practical techniques have been developed in planning to provide opportunities to enhance
citizen involvement, these ideas and methods have faced several challenges. These include the
strict legalistic and policy parameters that determine what sort of comments that are
permissible, the governmental initiators of public engagement, and the need to understand
and utilise the often complex language of planning. And yet citizens and communities are
increasingly resorting to social media and digital communication to express their views about
urban change.
This research assesses the degree to which new digital technology can be designed and
deployed to enhance citizen engagement within urban planning and identify whether it offers
one potential method to address and overcome some of the challenges being experienced in
citizen engagement. Through designing, deploying and evaluating speculative digital
technologies, the research aims to understand the potential role of technology in facilitating
enhanced citizen participation in planning. Working with citizens, community organisations
and planners, the research explores the factors at play when innovative and bespoke
engagement methods are used to amplify citizens’ voices in urban change. An action research
approach was taken, which uses a continual cycle of designing and planning, deploying
different types of technologies and reflections to inform design. Three technologies were
piloted in different settings and contexts: a social media example addressing a complex
planning issues; a smart watch application to support in-place engagement; and an interactive
digital device that encourages people to communicate their feelings and aspirations through
visual and oral means. Across the three examples, over 1400 citizens participated in the
research.
Findings demonstrate how the three digital initiatives encouraged people to be expressive
when communicating complicated feelings towards urban change, and the influence different
methods have on what people communicate. They illustrate how different participation
methods can support differing levels of engagement, and how digital technologies might better
align with how citizens would like to participate.
The research critiques the suitability of current participation methods, and the extent to
which they can support a genuine discussion about where people live and what they care
about. It concludes by questioning whether current planning engagement methods can
adequately equip non-experts with the tools to participate. The overall conclusion is that by
employing digital technologies, a much more productive and fruitful conversation can be
designed to facilitate citizen participation in planning compared to traditional methods
The impact of interpersonal and institutional trust on secessionist support in established democracies: evidence from Scotland, Catalonia and Flanders
Get PDFPh. D. Thesis.The last two decades have seen a substantial increase in the number of secession attempts
taking place. Secession has therefore become a more salient issue across a growing number
of states, simply because it has become a more realistic possibility. As this is a fairly recent
phenomenon, secession has also historically been somewhat neglected by researchers, both
empirically and theoretically, and so the dynamics of support for secession have not been
analysed in as granular detail as more regular forms of voting behaviour. In explaining the
dynamics of secessionist support, this thesis will examine the impact of both interpersonal
and institutional trust on an individual’s likelihood of supporting secession.
The most commonly identified predictors of support for secession, national identity
and secessionist party identification, are generally considered to be stable variables, or at
least variables which cannot easily be affected by policy makers. Levels of trust meanwhile,
have been found to be more malleable, both at the interpersonal level and the institutional
level.
Institutional trust and in particular trust in governments, has been found to be
affected by a number of factors, including institutional performance relative to citizens’
expectations, transparency, and representation of citizens’ concerns. Levels of interpersonal
trust meanwhile, which exist horizontally between individuals and groups of individuals, can
be influenced by public policy measures, such as the promotion of civic engagement and
community building projects. Understanding the role of trust in shaping support for secession
is therefore extremely important to separatists and unionists alike, as it has the potential to
provide valuable new information about the dynamics of secessionist support, as well as the
potential measures which could be taken to address secessionist demands
Modelling Voxel Dependent Hemodynamic Response Function
Get PDFPh. D. Thesis.An important challenge of contemporary neuroscience is the detection and understanding of significant brain activity using functional
magnetic resonance imaging (fMRI). One of the many motivations of
this research, related to the data set used in this thesis, is to investigate brain activation and connectivity patterns aimed at identifying
associations between these patterns and regaining motor functionality following a stroke. Much statistical modelling has attempted to
interpret noisy fMRI data and detect changes in response to activity.
However due to the large data sets usually involved in fMRI modelling,
here as many as 150, 000 measurements in localised spatial volumes
known as voxels at each time point, many simplifying assumptions are
usually made to make computation feasible. This is known to have a
negative impact on detecting voxel activation. In this work we fit a
space-time model to a fMRI data set using a sequential approach to
allow for scalability. However, the main contribution of this work is
an alternative method to detect activation in the brain. Here we take
the novel approach of using topological data analysis to investigate
the model residuals to detect changes in the fMRI data. In particular
we analyse the spatial distribution of topological features of the residuals to provide a test for normality, and also by providing a method
to analyse how the spatial distribution of such features change over
time, we are able to detect changes in the data in response to activity
where conventional methods cannot. A recommendation for future
work is to also investigate how topological features change for different filtration levels of the field, as this may provide new insights on
brain activation
Molecular genetic studies of inherited cystic kidney disease in Oman
Get PDFPh. D. ThesisInherited kidney diseases are fundamental causes of chronic kidney disease (CKD) and
end stage kidney disease (ESKD); accounting for approximately 20% of all CKD cases
and up to 10% of adults and over 70% of children reaching ESKD.
Oman is the second largest country in the South East of Arabian Peninsula. Omani
population is characterized by large family size, presence of tribal and geographical
settlements and higher rates of consanguineous marriages, which facilitate the study of
autosomal recessive disorders. Rare genetic disorders create considerable burden on
healthcare system in Oman and are major causes of congenital abnormalities and perinatal
deaths in hospitals. The prevalence of inherited kidney disease was estimated to be high,
but there is a lack for a comprehensive data. Therefore, this study aimed to evaluate the
magnitude of inherited kidney disease in this population and identify the molecular
genetic causes of inherited cystic kidney diseases in Omani patients. First, I performed a
population-based retrospective analysis of ESKD patients commencing RRT from 2001
to 2015 using the national renal replacement therapy (RRT) registry and evaluated the
epidemiological and etiological causes of ESKD with focused attention on inherited
kidney diseases. Second, I designed a targeted gene panel (49 genes) and used massive
parallel sequencing technologies for the molecular genetic diagnosis of cystic kidney
disease in 53 patients. An overall molecular genetic diagnostic yield of 75% was
achieved; with 46% of detected causative variants were novel genetic findings. Third, I
evaluated the utility of molecular genetic testing in patients with autosomal recessive
polycystic kidney disease (ARPKD) and described the clinical and genetic profile of this
cohort. Finally, whole exome sequencing (WES) was used to determine the genetic
causes of CKD in 11 unrelated children suspected with recessively inherited kidney
diseases. Definite genetic diagnosis was achieved in 54.5% of cases, reflecting the
importance of genomic implications in those with uncertain aetiology causing CKD. This
study creates a solid basis reflecting the genotype-phenotype of some inherited kidney
diseases in Omani population and reveals the enormous diagnostic power of genomic
technologies.The Research Council (TRC), Ministry of Health (MOH), Ministry
of Higher Education (MOHE
Polymer Immobilised Ionic Liquid Supported Catalysts: Synthesis, Characterisation and Applications
Get PDFPhD ThesisDue to increasing demand for synthetic commodities, to reduce the overall
environmental impact of existing chemical processes, a sustainable approach is
required. In order to accomplish this, it will be necessary to use highly efficient, durable,
and scalable catalyst technologies which are low in energy consumption and waste
production. In addition, bio-renewable feedstock will also be required due its
abundancy and availability. In this regard, chapter 1 provides an overview of the unique
physicochemical properties and concepts of ionic liquids (ILs). The incorporation of ILs
can produce functional materials, which in turn, can be used for the sustainable
conversion of bio-renewable feedstock.
Chapter 2 discusses the rational design and synthesis of a range of ruthenium
nanoparticle (RuNP) catalysts, in which, the catalysts were tested in the hydrogenation
of the benchmark substrate acetophenone. The overall aim of this work was to
investigate the effect of the interactions between the ruthenium and the polymer
support on the catalyst performance and selectivity. The resulting catalysts were highly
active and selective in the hydrogenation of a range of , -unsaturated ketones,
aldehydes, and the study was extended to include bio-derived substrates. In total four
reactions were tested, namely the hydrogenation of acetophenone, furfural, levulinic
acid and ethyl levulinate. The low ruthenium loadings and the reusability of these
heterogenous catalysts, in addition to the use of water as the co-solvent/solvent, has
provided a sustainable hydrogenation method, which is among one of the highest
reported on comparison with the literature. Chapter 3 covers the application of the
RuNPs for the hydrazine-mediated reduction of a broad range of nitroaromatics to their
corresponding aromatic amines under mild conditions with low catalyst loadings.
Chapter 4 details the synthesis of a set of imidazolium polystyrene-based
Brønsted acid catalysts immobilised with peroxophosphotungstate anions. These
efficient and selective catalysts were tested, as catalysts for the alcoholysis of furfuryl
alcohol to produce alkyl levulinates, under batch as well as continuous flow regimes.
Such generated levulinates are highly desirable as bio-renewable fuel additives
Quantum mechanical bespoke force fields for computer-aided drug design
Get PDFPhD ThesisThe ability to accurately model complex biological processes such as protein-ligand
binding with an atomistic level of detail is critical to their thorough understanding.
Typically a molecular mechanics simulation is used, which represents the system
using a force eld that is a physically motivated linear combination of empirically
parameterised potentials. Traditionally their parameterisation has involved the
recreation of experimental and quantum mechanical data for a target set of representative
structures, ranging from small molecules to peptides. This potentially limits the
progress of general transferable force elds to time and labour-intensive incremental
improvements. In this thesis, we aim to challenge this \parameterise once and
transfer" philosophy, with that of a transferable parametrisation methodology that
can be readily applied to new systems with a consistent level of accuracy. We
collect together recently developed force eld parameterisation techniques from the
literature to develop a protocol suitable to derive virtually all required force eld
parameters for small molecules directly from quantum mechanics. This protocol
forms the basis of the QUantum mechanical BEspoke force eld (QUBE) and is
delivered to users through a reliable and extensible software toolkit named QUBEKit.
Here we extensively benchmark the methodology and software presented through
typical force eld performance metrics which involve the prediction of thermodynamical
properties of small organic molecules. In this regard, we achieve very competitive
accuracy with popular general transferable force elds such as OPLS which have
been extensively optimised to reproduce such properties. We also demonstrate how
the QUBE force eld is a suitable alternative in a computer-aided drug design setting
via the retrospective calculation of the relative binding free energies of 17 inhibitors
of p38 MAP kinase. Again good agreement with both experiment and transferable
force elds is achieved despite this being the rst generation of the force eld. The
results of this work are then particularly important to those studying systems which
are not covered or inaccurately represented by standard transferable force elds, as
we present an accurate framework towards their complete parameterisation
The effects of surface architecture and physics on bacterial biofilm growth
Get PDFPh. D. ThesisBacteria are ubiquitous in the environment and can adhere onto abiotic or biotic surfaces to form biofilms. These three-dimensional (3D) communities of sessile cells are encased in a matrix of extracellular polymeric substances (EPS). Bacterial biofilms can be detrimental to human health, causing infections and diseases. Notably, bacterial biofilms are robust structures and are difficult to treat via traditional antibiotic therapy. The EPS matrix acts as a barrier to agents trying to access the interior of the biofilm, subsequently triggering the development of antibiotic resistance, which has been shown for both Staphylococcus epidermidis and Pseudomonas aeruginosa. Physical strategies, in particular the use of rationally surface design, have gained interests and present us with an effective approach to prevent bacterial adherence and biofilm growth without the requirement for antimicrobials.
In this study, we aim to develop biomaterial surfaces via surface modifications that can control bacterial growth, as well as investigate the bacterial-material interactions on these surfaces. We firstly designed and fabricated nano-pillar structured surfaces via electron-beam lithography and polymer moulding technique. The results showed that rod-shaped Pseudomonas aeruginosa can align within the pillars if the space is comparable to the bacteria size; and the extended bacterial growth showed that fibrous network was formed and can help to connect isolated bacterial clusters within the pillars thereby aid in the continuous biofilm growth. Therefore, biomimetic hierarchical structured surfaces were fabricated based on the natural rose-petal via the same method of replicating nano-pillars. The key results showed that hierarchical structures are more effective in delaying biofilm growth of Staphylococcus epidermidis and Pseudomonas aeruginosa compared to the unitary structure. The nano-folds across the hemispherical micro-papillae restrict initial attachment of bacterial cells and delay the direct contacts of cells via cell alignment, and the hemispherical micro-papillae arrays isolate bacterial clusters and inhibit the formation of a fibrous network. Finally, we made two kinds of slippery surfaces via infusing the silicone oil. These slippery surfaces showed superior anti-wetting properties and exhibited excellent “self-cleaning” effects. Additionally, either slippery surface can prevent around 90% of bacterial biofilm growth of Staphylococcus epidermidis and Pseudomonas aeruginosa after 6 days, as compared with the unmodified control PDMS surfaces.
This study detailed investigated the different bacterial responses when making contacts with artificial biomaterial surfaces. Multiply imaging techniques such as fluorescent microscopy,
scanning electron microscopy and wettability analysis were adopted in this study, will instruct researchers to reveal the physic-chemical interactions of bacteria and materials. Particularly, the anti-biofilm surface design in this study will give insights to develop a more effective way for controlling robust biofilm growth, thereby paving a high way for preventing infection or fouling problems in either medical or industry contexts