Dr Lance J. Twyman

Lance Twyman

Senior Lecturer in Chemistry
Department of Chemistry
The University of Sheffield
Brook Hill
Sheffield S3 7HF
United Kingdom

Telephone: +44 (0) 114 222 9560
Email: l.j.twyman@sheffield.ac.uk

General

Biographical Sketch

Dr. Twyman obtained a BSc in Chemistry from King's College London in 1991, which was followed by a PhD from the University of Kent in 1995. After his PhD he became a postdoctoral research associate at the University of Cambridge and a Research Associate at Girton College. In 1997 he became a postdoctoral research fellow at the University of Oxford. In 1998 he was appointed as a lecturer at Lancaster University. In 2000 he was appointed as lecturer at the University of Sheffield, where he was promoted to senior lecturer in 2008.

Research Keywords

Biomimetics, dendritic molecules, supramolecular chemistry, encapsulation and drug delivery.

Teaching Interests

Organic Chemistry; Characterisation, Molecular Orbitals

Research

Drug delivery

The therapeutic effectiveness of any drug is often diminished by its inability to gain access to the site of action in an appropriate dose. This is often due to the poor solubility of the drug in the body’s aqueous environment. One method of aiding solubilisation is to encapsulate the drug within the hydrophobic domains of a globular polymer. In our group we are investigating the use of dendrimers (shown in Figure 1 below), hyperbranched polymers and other polymeric systems, as encapsulation and delivery agents.

Figure_1_LJT

Figure 1: A water-soluble dendrimers that can be used to solubilize and deliver hydrophobic drugs.

Supramolecular chemistry

Supramolecular chemistry can be used to form discrete self assembled structures capable of performing a variety of functions. Our interest in this area has led to the development of supramolecular polymers that form a variety of structures. These include linear and dendritic polymers for use as potential light harvesting systems. We are also investigating the use of certain diblock polymers that can self assemble into spherical materials (single and bilayered) possessing microenvironments that can be exploited as catalysts for a variety of reactions.

Figure_2_LJT

Figure 2: Schematic of a supramolecular polymer capable of bind two reactive substrates leading to catalysis.

Model enzymes and proteins - biomimetics

Over millions of years Nature has evolved a series of molecules capable of performing a variety of important biological functions. These include catalysis, transportation and signalling. We are attempting to create much simpler synthetic analogues of these molecules. The principle aim is to engineer molecules capable of outperforming the natural systems they aspire to imitate. One example could include a catalyst that works for ALL oxidations, rather than one evolved to catalyse a single specific example. Alternatively, we could construct a catalyst that can generate non-natural isomers. As well as catalysis, related systems could be developed with important medical benefits. One such area includes our work on the development of artificial blood. Towards these aims we are exploiting a number of systems, which include self assembling polymers and globular dendritic molecules such as the oxygen binding system shown in Figure 3.

Figure_3_LJT

Figure 3: Porphyrin cored hyperbranched polymer that can reversibly bind oxygen, as well as catalyse as series of oxidation reactions.

Protein binding

Proteins bind and recognise each other using large surface areas. This recognition process is vital for a variety of biological applications. Understanding these interactions, as well as being able to inhibit them, may lead the development of new therapeutic molecules. Towards these aims we are exploiting the well-defined shape and size of certain globular macromolecules. Specifically we are using a series of dendrimers to study and inhibit protein-protein binding. Our initial results clearly indicate a simple size relationship between dendrimer and selective protein binding. That is, smaller dendrimers can interact preferentially with proteins possessing smaller binding areas, whilst larger dendrimers can interact preferentially with proteins possessing larger binding areas.

Figure_4_LJT

Figure 4: Screening results for dendrimer-protein binding.) The smaller G2.5 dendrimer is the strongest binder for cytochrome-c (smaller binding area), whilst the larger G3.5 dendrimer is the best inhibitor/binder for the protein chymotrypsin (larger binding area).

Teaching

Undergraduate and postgraduate taught modules

  • Characterisation (Level 1)
    This course introduces methods of determining the composition and structure of molecules.
  • Structure Determination (Level 2)
    This module enables you to determine molecular structures from spectroscopic data.
  • Polymer Architectures (Level 4)
    This lecture course introduces the student to methods for preparing polymers of various predetermined shapes and monomer repeat unit distributions.
  • Design and Synthesis of Polymers and Controlled Structure (Postgraduate Level)

Support Teaching:

  • Tutorials: Level 1 General Chemistry
  • Tutorials: Level 2 Organic Chemistry
  • Skills for Success: Quiz Show
  • Level 3 Literature Review

Laboratory Teaching:

  • Level 4 Research Project

Publications

Journal articles

Chapters

  • () Medical Polymers, Patent Applications (pp. 409-497). John Wiley & Sons, Inc. RIS download Bibtex download

Conference proceedings papers

  • Chiba F, Hu TC, Twyman LJ & Wagstaff M (2010) Dendritic Macromolecules as Inhibitors to Protein-Protein Binding. MACROMOLECULAR SYMPOSIA, Vol. 287 (pp 37-41) RIS download Bibtex download
  • Twyman LJ, Vidal-Feran A, Bampos N & Sanders JKM (1998) Stereocontrol and rate enhancement of a Diels Alder reaction within an unsymmetrical porphyrin host. MOLECULAR RECOGNITION AND INCLUSION (pp 535-538) RIS download Bibtex download
  • BEEZER AE, MITCHELL JC, COLEGATE RM, SCALLY DJ, TWYMAN LJ & WILLSON RJ (1995) MICROCALORIMETRY IN THE SCREENING OF DISCOVERY COMPOUNDS AND IN THE INVESTIGATION OF NOVEL DRUG-DELIVERY SYSTEMS. THERMOCHIMICA ACTA, Vol. 250(2) (pp 277-283) RIS download Bibtex download