Dr Dr Lance J. Twyman
Department of Chemistry
Senior Lecturer in Chemistry
+44 114 222 9560
Full contact details
Department of Chemistry
13 Brook Hill
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 interests
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: A water-soluble dendrimers that can be used to solubilize and deliver hydrophobic drugs.
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: 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: Porphyrin cored hyperbranched polymer that can reversibly bind oxygen, as well as catalyse as series of oxidation reactions.
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: 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).
- Synthesis of oligomeric and monomeric functionalized graphene oxides and a comparison of their abilities to perform as protein ligands and enzyme inhibitors. ACS Applied Materials & Interfaces. View this article in WRRO
- Synthesis and Aggregation of a Porphyrin-Cored Hyperbranched Polyglycidol and Its Application as a Macromolecular Photosensitizer for Photodynamic Therapy. Molecular Pharmaceutics, 16(3), 1132-1139. View this article in WRRO
- Increased Oxygen Solubility in Aqueous Media Using PEG–Poly-2,2,2-trifluoroethyl Methacrylate Copolymer Micelles and Their Potential Application As Volume Expanders and As an Artificial Blood Product. ACS Applied Bio Materials, 1(3), 708-713. View this article in WRRO
- Effect of Terminal-Group Functionality on the Ability of Dendrimers to Bind Proteins. Bioconjugate Chemistry, 28(8), 2046-2050. View this article in WRRO
- Graphene Oxide-Gallic Acid Nanodelivery System for Cancer Therapy.. Nanoscale Research Letters, 11(1), 491-491. View this article in WRRO
- A convenient synthesis of a porphyrin cross-linked polymer, its application as a size selective heterogeneous catalyst and a comparison with a porphyrin-cored hyperbranched polymer. Supramolecular Chemistry, 28(7-8), 617-623.
- Self-Replicating Systems. Organic & Biomolecular Chemistry, 14(18), 4170-4184. View this article in WRRO
- Controlling microenvironments and modifying anion binding selectivities using core functionalised hyperbranched polymers. Chemical Communications (London), 52, 6131-6133. View this article in WRRO
- Exploiting dense shell/packing principles to invoke stereoselectivity in a reaction accelerated by a chiral dendrimer.. Chem Commun (Camb), 49(73), 8063-8065. View this article in WRRO
- Bimolecular catalysis and turnover from a macromolecular host system.. J Org Chem, 78(11), 5364-5371.
- Novel flame retardant poly(thiourea-sulfone-imide)s for high temperature applications: synthesis and characterization. TURKISH JOURNAL OF CHEMISTRY, 37(6), 946-958.
- Probing Dense Packed Limits of a Hyperbranched Polymer through Ligand Binding and Size Selective Catalysis.. Macromolecules (Washington, DC, U. S.), 46(17), 7055-7074.
- View this article in WRRO Delivery systems for small molecule antiprion drug candidates. PRION, 6, 99-99.
- ChemInform Abstract: Catalytic Hyperbranched Polymers as Enzyme Mimics; Exploiting the Principles of Encapsulation and Supramolecular Chemistry. ChemInform, 43(48), no-no.
- Catalytic hyperbranched polymers as enzyme mimics; exploiting the principles of encapsulation and supramolecular chemistry.. Chem Soc Rev, 41(18), 6138-6159.
- Pyridine encapsulated hyperbranched polymers as mimetic models of haeme containing proteins, that also provide interesting and unusual porphyrin-ligand geometries.. Chem Commun (Camb), 48(1), 154-156.
- Synthesis of Multiporphyrin Containing Hyperbranched Polymers. MACROMOLECULES, 44(16), 6365-6369.
- Investigating possible changes in protein structure during dendrimer-protein binding.. Org Biomol Chem, 8(22), 5056-5058.
- Pseudo-Generational Effects Observed for a Series of Hyperbranched Polymers When Applied as Epoxidation Catalysts. MACROMOLECULES, 41(21), 7776-7779.
- Dendrimers as size selective inhibitors to protein-protein binding.. Chem Commun (Camb)(36), 4351-4353.
- The one-step synthesis of a dendronized (HBP) polymer. MACROMOLECULES, 41(5), 1584-1586.
- Synthesis and characterization of immobilized PAMAM dendrons.. Chem Commun (Camb)(24), 2482-2484.
- Synthesis and aggregation of amine-cored polyamidoamine dendrons synthesised without invoking a protection/deprotection strategy. POLYM INT, 55(7), 798-807.
- Synthesis of porphyrin cored hyperbranched polymers. SUPRAMOL CHEM, 18(4), 357-360.
- Porphyrin cored hyperbranched polymers as heme protein models.. Chem Commun (Camb)(15), 1658-1660.
- Probing the onset of dense shell packing by measuring the aminolysis rates for a series amine terminated dendrimers. REACT FUNCT POLYM, 66(1), 187-194.
- Water-soluble organic dppz analogues--tuning DNA binding affinities, luminescence, and photo-redox properties.. Chem Commun (Camb)(34), 4327-4329.
- Postsynthetic modification at the focal point of a hyperbranched polymer.. J Am Chem Soc, 127(6), 1646-1647.
- Total core functionalization of a hyperbranched polymer. MACROMOLECULES, 37(20), 7428-7431.
- Synthesis of aromatic hyperbranched PAMAM polymers. TETRAHEDRON LETT, 45(2), 433-435.
- Dendrimers as Potential Drug Carriers; Encapsulation of Acidic Hydrophobes within Water Soluble PAMAM Derivatives.. ChemInform, 34(33).
- Dendrimers as potential drug carriers; encapsulation of acidic hydrophobes within water soluble PAMAM derivatives. TETRAHEDRON, 59(22), 3873-3880.
- Dendrimers as Scaffolds for the Synthesis of Spherical Porphyrin Arrays.. ChemInform, 34(18).
- Heterogeneous and Solid-Supported Dendrimer Catalysts.. ChemInform, 34(5).
- Dendrimers as scaffolds for the synthesis of spherical porphyrin arrays.. Chem Commun (Camb)(1), 38-39.
- Dendrimers and supramolecular chemistry. SUPRAMOL CHEM, 15(1), 5-23.
- Formation of A2B2 supramolecular porphyrin co-polymers.. Chem Commun (Camb)(8), 910-911.
- The effect of size on the rate of an aminolysis reaction using a series of amine terminated PAMAM dendrimers. TETRAHEDRON LETT, 43(13), 2431-2433.
- Catalysis inside dendrimers.. Chem Soc Rev, 31(2), 69-82.
- Catalysis using peripherally functionalised dendrimers. J CHEM RES-S(2), 43-59.
- Formation of A
2B 2supramolecular porphyrin co-polymers. Chemical Communications, 2(8), 910-911.
- Heterogeneous and solid supported dendrimer catalysts. J CHEM SOC PERK T 1(20), 2209-2218.
- New evidence that the Alzheimer beta-amyloid peptide does not spontaneously form free radicals: An ESR study using a series of spin-traps. FREE RADICAL BIO MED, 30(10), 1154-1162.
- The synthesis of unsymmetrical PAMAM dendrimers using a divergent/divergent approach. TETRAHEDRON LETT, 42(6), 1119-1121.
- Acceleration of an aminolysis reaction using a PAMAM dendrimer with 64 terminal amine groups. TETRAHEDRON LETT, 42(6), 1123-1126.
- 3-p-Toluoyl-2-[4 '-(3-diethylaminopropoxy)-phenyl]-benzofuran and 2-[4 '-(3-diethylaminopropoxy)-phenyl]-benzofuran do not act as surfactants or micelles when inhibiting the aggregation of beta-amyloid peptide. BIOORG MED CHEM LETT, 11(2), 255-257.
- Modulation of beta-amyloid production and fibrillization.. Biochem Soc Symp(67), 1-14.
- BENZOFURAN DERIVATIVES AS INHIBITORS OF ALZHEIMER β-AMYLOID PEPTIDE AGGREGATION. Biochemical Society Transactions, 28(5), A307-A307.
- Post synthetic modification of the hydrophobic interior of a water-soluble dendrimer. TETRAHEDRON LETT, 41(35), 6875-6878.
- Modulation of β-amyloid production and fibrillisation. Biochemical Society Transactions, 28(1), A14-A14.
- A short synthesis of the beta-amyloid (A beta) aggregation inhibitor 3-p-toluoyl-2-[4 '-(3-diethylaminopropoxy)-phenyl]-benzofuran.. TETRAHEDRON LETT, 40(52), 9383-9384.
- A colourimetric calixpyrrole-4-nitrophenolate based anion sensor. CHEM COMMUN(18), 1851-1852.
- A general route for the synthesis of flexible porphyrin dimers. TETRAHEDRON LETT, 40(36), 6681-6684.
- The synthesis of water soluble dendrimers, and their application as possible drug delivery systems.. TETRAHEDRON LETT, 40(9), 1743-1746.
- The synthesis of chiral dendrimeric molecules based on amino acid repeat units. J CHEM RES-S(12), 758-759B.
- Acceleration of a hetero-Diels-Alder reaction by cyclic metalloporphyrin trimers. CHEM COMMUN(20), 2265-2266.
- Reversing the stereochemistry of a Diels-Alder reaction: use of metalloporphyrin oligomers to control transition state stability. NEW J CHEM, 22(5), 493-502.
- Synthesis, complexation and pharmaceutical applications of tetra-directional cascade dendrimers. Pharmaceutical Sciences, 2(3), 157-159.
- THE SYNTHESIS OF CHIRAL DENDRITIC MOLECULES BASED ON THE REPEAT UNIT L-GLUTAMIC ACID. TETRAHEDRON LETT, 35(25), 4423-4424.
- AN APPROACH FOR THE RAPID SYNTHESIS OF MODERATELY SIZED DENDRITIC MACROMOLECULES. J CHEM SOC PERK T 1(4), 407-411.
- ChemInform Abstract: Catalysis Using Peripherally Functionalized Dendrimers. ChemInform, 33(31), no-no.
- ChemInform Abstract: Catalysis Inside Dendrimers. ChemInform, 33(22), no-no.
- ChemInform Abstract: A General Route for the Synthesis of Flexible Porphyrin Dimers.. ChemInform, 30(44), no-no.
- ChemInform Abstract: The Synthesis of Chiral Dendrimeric Molecules Based on Amino Acid Repeat Units.. ChemInform, 30(18), no-no.
- ChemInform Abstract: The Synthesis of Water Soluble Dendrimers and Their Application as Possible Drug Delivery Systems.. ChemInform, 30(17), no-no.
- ChemInform Abstract: Acceleration of a Hetero-Diels-Alder Reaction by Cyclic Metalloporphyrin Trimers.. ChemInform, 30(6), no-no.
- Medical Polymers, Patent Applications (pp. 409-497). John Wiley & Sons, Inc.
Conference proceedings papers
- Dendritic Macromolecules as Inhibitors to Protein-Protein Binding. MACROMOLECULAR SYMPOSIA, Vol. 287 (pp 37-41)
- Stereocontrol and rate enhancement of a Diels Alder reaction within an unsymmetrical porphyrin host. MOLECULAR RECOGNITION AND INCLUSION (pp 535-538)
- MICROCALORIMETRY IN THE SCREENING OF DISCOVERY COMPOUNDS AND IN THE INVESTIGATION OF NOVEL DRUG-DELIVERY SYSTEMS. THERMOCHIMICA ACTA, Vol. 250(2) (pp 277-283)
- Teaching interests
Organic Chemistry; Characterisation, Molecular Orbitals.
- Teaching activities
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)
- Tutorials: Level 1 General Chemistry
- Tutorials: Level 2 Organic Chemistry
- Skills for Success: Quiz Show
- Level 3 Literature Review
- Level 4 Research Project
- Characterisation (Level 1)