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Dr James Bruce

Academic Leader, Academic Policy Group And Senior Lecturer In Organic Chemistry

School of Life, Health & Chemical Sciences

james.bruce@open.ac.uk

Biography

Professional biography

 I am a Senior Lecturer in Chemistry having joined the OU as a Lecturer in 2001. After completing my DPhil at Oxford with Prof Paul Beer I was a research fellow at the Universite Louis Pasteur in Strasbourg with Prof Jean-Pierre Sauvage and then returned to the UK as research fellow at Durham with Prof David Parker.
 

Research interests

My research interests are broadly based around supramolecular photochemistry . This research combines my  interests in non-covalent interactions and photochemistry.  The aim is to understand how these interactions can be used in the design and synthesis of novel molecular assemblies and materials.  The common theme running through the research is the use of light or light-induced processes to impart functions into these assemblies.  Spectroscopic techniques are used to study the processes occurring within these systems upon excitation with light energy.  The multidisciplinary aspect of the research is reflected in the projects, which range from those with biomedical applications to those based on functional materials and coatings

 

Luminescent sensors and probes  These systems use combinations of noncovalent interactions, such as hydrogen bonding, to bind target substrates and luminescence as the reporting signal.  By monitoring changes in the intensity, lifetime or form of the luminescence upon substrate binding, the binding affinities may be determined.  Of particular interest are systems with long-lived emission or able toundergo resonance energy transfer.  These features are ideal for sensors designed to investigate and understand the structure and function of biological systems such as oligonucleotides and cell wall receptors.  Such sensors have medical applications offering refined sensitivity in the early detection and diagnosis of disease at the molecular level particularly when targeted at biomolecules with key roles in physiological processes.

Current interest is focused on paramagnetic complexes as contrast agents for Magnetic Resonance Imaging (MRI) and luminescent complexes as labels for fluorescent microscopy and photodynamic therapy (PDT).  A primary objective of this research is to improve the specificity and selectivity of the complexes by targeting particular binding sites on cell walls or physiologically relevant molecules.  The aim is produce agents with the dual role of detecting and killing tumour cells.  The types of complex under investigation can act as photosensitizers or as radiation sensitizers as part of the cytotoxic proces

Photoactive molecular devices  There are many examples of functional molecular devices held together by non-covalent interactions occurring in nature.  Much of this research uses a biomimitic approach to duplicate natural processes, such as photosynthesis, using artificial arrays.  They have promise in the future as lean renewable energy sources if they can reproduce photosynthesis efficiently.  Non-covalent synthetic methods such as anion coordination bonding menas that a range of systems may be generated rapidly and the photophysical properties studies and fine-tuned.  The input and output signals of the device can then be regulated and such devices have potential as functional materials for use optoelectronic devices

 Functional Materials This combines my interest in photochemistry and sysnthesis to impart functionmal propertiers on larger polymweric systems such as those based on organosilicon frameworks. These can be used to arrange photoactive groups or compelxes in a defined manner that 

 

 


 

Teaching interests

My main teaching interests lie in the area of postrgraduate study and training. I was the first Graudate School Director at the OU and established the Graduate School in 2016. Prior to that I was  chair ofSTM895 - Postgraduate research skills in science, technology, maths and computing. This was  webased course that uses the VLE e-portflio to allow researchers to plan and record their skills training and this formed the basis for the Virtual  Research Environment I lead the production of in 2014. I was member of the S825 module team delivering skills training  to MSc students and am currently the chair for SXM390 a research skills based project course

My undergraduate teaching focuses on organic chemsitry and I have chaired S346 Drug Design and Synthesis module team and S344 Organic Chemistry: A synthesis approach. I have  been a member of the S205 : Molecular World and S103 Discovering Science course teams.

Impact and engagement

Member of the UKCGE Deans and Directors  of Graduate Schools Group 2016-2019

Plenary Speaker at UKCGE Worksop on PhD and part time study at a distance 2019

 

UKCGE international  conference

 WJ innovation day EDL London

External collaborations

WJ Group

Cornelius Specialities

GSK

Shimadzu

TWI LTD

Projects

Reversible polymerization for the recovery of plastics and coatings

While there has been considerable effort in developing processes and materials to make plastics recyclable and reusable, some plastics and polymeric materials remain difficult to recycle and typically end up in landfill. These materials are usually based on hard polystyrenes, epoxy resins and acrylates which are attractive to industries which require hard-wearing products, such as road marking and coatings. Furthermore, many of the current methods to make plastics recyclable or decomposable diminish their mechanical properties such as hardness and durability required for surface coatings. We have been piloting some approaches for polystyrene road studs to address this issue. These are temporary studs glued to the road to provide lane guidance during roadworks. They are currently deposited in landfill after a single use. The pilot approach used a range of surfactants and varying critical micelle concentrations to determine the optimum conditions (composition of surfactant, temperature, and time) to remove the adhesive that bonds the studs to the road. The recovered polystyrene studs will be ground and remolded and their mechanical and physical properties (e.g. hardness, hydrophobicity, glass and melting temperatures) examined and compared with newly manufactured studs. A second approach is based on current thermoplastics technologies using resins such as renewable rosin esters. These are interesting as the ester functionality is a point where additional functionality can be attached. The aim is to improve the wet weather performance of the material allowing it to be laid in wet conditions (so extending operation throughout the year), as well as lowering its application temperature from 250 °C. Other examples of additional desirable functionality are light emitting chromophores that improve the visibility of the markings in adverse conditions. The contribution to the material properties from these functionalities will be analysed using techniques such as Raman, SEM/TEM, adhesion, XRD, DSC and hardness testing. The final approach focuses on synthetic polymer chemistry and builds on pilot work we have done in preparing polymers with chemically cleavable bonds. This allows a polymer to be decomposed or decured and potentially makes it easier to remove and recover from the environment. Acrylates are increasingly being used as alternatives to thermoplastics in the road marking industry and this work will use light induced processes such as Photoinduced Electron Transfer (PET) to control the polymerisation of acrylates. This will build on the synthetic chemistry skills developed in the work with rosin esters above as well as the characterization techniques such as NMR and Fluorescence spectroscopy.

Characterisation of Reversed Phase Chromatography Peptide Separation Systems - Extension

Extension for a further 2 months to the existing 6 month research fellowship to define a method development protocol for reversed-phase separations of pharmaceutical peptides and their related impurities. The idea is to select a smaller number of columns and mobile phases that provide large differences in selectivity based on a recent PhD project [Characterisation of Reversed Phase Chromatography Peptide Separation Systems, Strathclyde Institute of Pharmacy and Biomedical Sciences, Jennifer Kathryn Field, Year of Submission 2019) 201670008]. These mobile phases will subsequently be optimised to provide not only large differences in selectivity but also acceptable limit of quantitation and peak shape as well as horizontal UV baselines. Some of the mobile phases are potentially corrosive and thus also a corrosion study will be included in the work. Finally, based on these studies, a flow scheme for rational method development will be proposed and evaluated using a series of degraded peptides. Besides automated screening this strategy also involves retention modelling in order to define optimal gradient shape and column temperature. The ambition is to publish and article as well as disseminating the results at conferences.

Characterisation of Reversed Phase Chromatography Peptide Separation Systems

The purpose of this 6 month research fellowship is to define a method development protocol for reversed-phase separations of pharmaceutical peptides and their related impurities. The idea is to select a smaller number of columns and mobile phases that provide large differences in selectivity based on a recent PhD project [Characterisation of Reversed Phase Chromatography Peptide Separation Systems, Strathclyde Institute of Pharmacy and Biomedical Sciences, Jennifer Kathryn Field, Year of Submission 2019) 201670008]. These mobile phases will subsequently be optimised to provide not only large differences in selectivity but also acceptable limit of quantitation and peak shape as well as horizontal UV baselines. Some of the mobile phases are potentially corrosive and thus also a corrosion study will be included in the work. Finally, based on these studies, a flow scheme for rational method development will be proposed and evaluated using a series of degraded peptides. Besides automated screening this strategy also involves retention modelling in order to define optimal gradient shape and column temperature. The ambition is to publish and article as well as disseminating the results at conferences.

Assessing the potential interference of extraterrestrial organic species to the application of lanthanide-based sensors.

A proposal to bring in a summer student (undergrad) to assist in the characterisation of the interaction between organic species and lanthanide-containing ligands used for organic sensors.

Markers for Meteorites (SC-10-038-VP)

Student internship funding on Markers for Meteorites.

Luminescent Lanthanide Complexes as reporters of Drug Induced Toxicity (SC-12-087-JB)

The proposed PhD will focus on the development of novel in-situ reporter agents and their application to in-vitro/in-vivo studies of drug induced toxicity. These studies will take the form of in-vitro screening studies and in vitro/in vivo mechanistic studies. The project may be considered as a series of phases or workpackages: • Phase 1: Identification of molecules to act as key determinants in the processes under study. • Phase 2: Design and synthesis of Lanthanide-based reporter agents to optimise selectivity and imaging characteristics. • Phase 3: In-vitro testing of novel reporter agent(s). This phase will include non-cellular in-vitro testing to determine the response of the agent to the marker understudy and cross-reactivity with similar target entities. • Phase 4: In-vivo testing of the reporter agent(s). In addition to studies utilising the action of the reporter, studies will be conducted to confirm the safety of the reporter agent so as to determine the utility within in vivo studies. (At GSK)

Nuffield undergraduate bursaries

The project will last for 6 weeks and will provide an OU student with the opportunity to carry out research work in our laboratories.

Targeting radiotherapy with DNA binding metal complexes of amino acids.

This was to fund an undergraduate student, Kirsten Hawkins, who has approached the department for a summer placement.New approaches that localise radiosensitivity within tumours have the potential to improve the effectiveness of radiotherapy and reduce side effects for patients. Here we developed compounds, known as radiosensitisers, containing heavier elements such as metals that produce electrons upon radiotherapy. These electrons promote localised DNA damage in cancer cells leading to their death. Careful design of the complexes aimed to promote their localisation in the DNA of cancer cells so that those that these are most damaged upon radiotherapy. It is significant that we developed one copper containing compound that exhibited a comparatively low cytotoxicity in HEK293T cells (human embryonic kidney cells) over 24 h, for example it was approximately 45 times less cytotoxic to these cells in comparison to the anticancer drug cis-platin. This suggests its further study in targeted radiotherapy where the cytotoxicity in cancer cells would be turned on by the application of the radiotherapy. It is significant that we developed one copper containing compound that exhibited a comparatively low cytotoxicity in HEK293T cells (human embryonic kidney cells) over 24 h, for example it was approximately 45 times less cytotoxic to these cells in comparison to the anticancer drug cis-platin. This suggests its further study in targeted radiotherapy where the cytotoxicity in cancer cells would be turned on by the application of the radiotherapy. Abi Barbour, an A-S level student, also worked on this project under the Nuffield Research Placement scheme and as a result achieved her Gold Crest award.

Publications

Book Chapter

Photophysical aspects of Lanthanide(III) complexes (2001)

Journal Article

Method Development for Reversed-Phase Separations of Peptides: A Rational Screening Strategy for Column and Mobile Phase Combinations with Complementary Selectivity (2022)

Investigation into reversed-phase chromatography peptide separation systems part V: Establishment of a screening strategy for development of methods for assessment of pharmaceutical peptide's purity (2022)

Synthesis of Organosilicon Ligands for Europium (III) and Gadolinium (III) as Potential Imaging Agents (2020)

Influence of the initial chemical conditions on the rational design of silica particles (2018)

Targeting tumour energy metabolism potentiates the cytotoxicity of 5-aminolevulinic acid photodynamic therapy (2013)

Fully protected glycosylated zinc (II) phthalocyanine shows high uptake and photodynamic cytotoxicity in MCF-7 cancer cells (2013)

Antioxidant inhibitors potentiate the cytotoxicity of photodynamic therapy (2012)

Near IR-emitting DNA-probes exploiting stepwise energy transfer processes (2007)

Synthesis of asymmetrically substituted cyclen-based ligands for the controlled sensitisation of lanthanides (2007)

Organic photochemistry (2007)

Synthesis of asymmetrically substituted 1,4,7,10-tetraazacyclododecanes for the triggered near infrared emission from lanthanide complexes (2006)

Correlation of optical and NMR spectral information with coordination variation for axially symmetric macrocyclic Eu(III) and Yb(III) complexes: axial donor polarisability determines ligand field and cation donor preference (2003)

Structural, Luminescence, and NMR Studies of the Reversible Binding of Acetate, Lactate, Citrate, and Selected Amino Acids to Chiral Diaqua Ytterbium, Gadolinium, and Europium Complexes (2002)

Synthesis of a linear bis-porphyrin with a Ru(phen)(2)(2+)-complexed 2,2 '-bipyridine spacer (2002)

Synthesis, characterisation and application of lanthanide cyclen complexes in organic synthesis (2002)

Survey of factors determining the circularly polarised luminescence of macrocyclic lanthanide complexes in solution (2002)

Modulation of the water exchange rates in [Gd-DO3A] complex by formation of ternary complexes with carboxylate ligands (2001)

Experimental assessment of lanthanide ion donor preference: spectroscopic and theoretical dissection of static charge and dynamic polarisation contributions to axial ligation in a C-4-symmetric chiral europium complex (2001)

Excitement in F-block: responsive lanthanide complexes (2001)

Patent

Detection, Monitoring and Treatment of Cancer (2003)

Presentation / Conference

Supporting part time and distance PGR students (2018)

Creating a Virtual Research Environment to build a research Community (2014)

Potentiation of AlPcS2 mediated photodynamic therapy by energy metabolism inhibitors in human tumour cell lines (2009)

Glucosamine improves the efficiency of photodynamic therapy (PDT) (2008)

Synthetic approaches to combining sensing and sensitizing in a single luminescent agent (2008)

Magnetic resonance imaging (MRI) contrast agents that target the brain (2005)

Aptamers as new tools for disease diagnosis and therapy (2003)