Twyman, Lance J. , Dr

Dr Lance J. Twyman

School of Mathematical and Physical Sciences

Senior Lecturer in Chemistry

l.j.twyman@sheffield.ac.uk
+44 114 222 9560

Dainton Building

Full contact details

Dr Lance J. Twyman
School of Mathematical and Physical Sciences
Dainton Building
13 Brook Hill
91ֱ��
S3 7HF

Profile: 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 91ֱ��, where he was promoted to senior lecturer in 2008.

Research interests

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: 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: 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.

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: 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).

Publications

Journal articles

Abdullah SN, Mann G & Twyman LJ (2021) . Molecules, 26(22).
Twyman LJ & Aziz A (2019) . ACS Applied Materials & Interfaces.
Kadhim A, McKenzie LK, Bryant HE & Twyman LJ (2019) . Molecular Pharmaceutics, 16(3), 1132-1139.
Fan M, Alghassab TS & Twyman LJ (2018) . ACS Applied Bio Materials, 1(3), 708-713.
Chiba F & Twyman LJ (2017) . Bioconjugate Chemistry, 28(8), 2046-2050.
Dorniani D, Saifullah B, Barahuie F, Arulselvan P, Hussein MZ, Fakurazi S & Twyman LJ (2016) . Nanoscale Research Letters, 11(1), 491-491.
Twyman LJ & Zheng X (2016) . Supramolecular Chemistry, 28(7-8), 617-623.
Twyman LJ & Clixby G (2016) . Organic & Biomolecular Chemistry, 14(18), 4170-4184.
Twyman LJ, Mann G & Gale PA (2016) . Chemical Communications (London), 52, 6131-6133.
Ellis A, Wallace M & Twyman LJ (2013) . Chem Commun (Camb), 49(73), 8063-8065.
Ellis A, Gooch D & Twyman LJ (2013) . J Org Chem, 78(11), 5364-5371.
Ellis A & Twyman LJ (2013) . Macromolecules (Washington, DC, U. S.), 46(17), 7055-7074.
Waris G, Siddiqi HM, Twyman LJ, Hussain R, Akhter Z & Butt MS (2013) . TURKISH JOURNAL OF CHEMISTRY, 37(6), 946-958.
Luo L, Shamsudin S, Twyman L, Cecchin D, Battaglia G, Hua P, Roehl H & Chen B (2012) Delivery systems for small molecule antiprion drug candidates. PRION, 6, 99-99.
Kirkorian K, Ellis A & Twyman LJ (2012) . ChemInform, 43(48), no-no.
Kirkorian K, Ellis A & Twyman LJ (2012) . Chem Soc Rev, 41(18), 6138-6159.
Twyman LJ, Ellis A & Gittins PJ (2012) . Chem Commun (Camb), 48(1), 154-156.
Twyman LJ, Ellis A & Gittins PJ (2011) . MACROMOLECULES, 44(16), 6365-6369.
Chiba F, Mann G & Twyman LJ (2010) . Org Biomol Chem, 8(22), 5056-5058.
Zheng X, Oviedo IR & Twyman LJ (2008) . MACROMOLECULES, 41(21), 7776-7779.
Chiba F, Hu T-C, Twyman LJ & Wagstaff M (2008) . Chem Commun (Camb)(36), 4351-4353.
Lam D, Little S, Rutherford J, Twyman LJ & Zheng XW (2008) . MACROMOLECULES, 41(5), 1584-1586.
Pollock N, Fowler G, Twyman LJ & McArthur SL (2007) . Chem Commun (Camb)(24), 2482-2484.
King ASH, Martin IK & Twyman LJ (2006) . POLYM INT, 55(7), 798-807.
Twyman LJ, Ge Y & Gittins PJ (2006) . SUPRAMOL CHEM, 18(4), 357-360.
Twyman LJ & Ge Y (2006) . Chem Commun (Camb)(15), 1658-1660.
Burnett J, King ASH & Twyman LJ (2006) . REACT FUNCT POLYM, 66(1), 187-194.
Phillips T, Rajput C, Twyman L, Haq I & Thomas JA (2005) . Chem Commun (Camb)(34), 4327-4329.
Gittins PJ & Twyman LJ (2005) . J Am Chem Soc, 127(6), 1646-1647.
Gittins PJ, Alston J, Ge Y & Twyman LJ (2004) . MACROMOLECULES, 37(20), 7428-7431.
Twyman LJ, King ASH, Burnett J & Martin IK (2004) . TETRAHEDRON LETT, 45(2), 433-435.
Beezer AE, King ASH, Martin IK, Mitchel JC, Twyman LJ & Wain CF (2003) . ChemInform, 34(33).
Beezer AE, King ASH, Martin IK, Mitchell JC, Twyman LJ & Wain CF (2003) . TETRAHEDRON, 59(22), 3873-3880.
Ballester P, Gomila RM, Hunter CA, King ASH & Twyman LJ (2003) . ChemInform, 34(18).
King ASH & Twyman LJ (2003) . ChemInform, 34(5).
Ballester P, Gomila RM, Hunter CA, King ASH & Twyman LJ (2003) . Chem Commun (Camb)(1), 38-39.
Gittins PJ & Twyman LJ (2003) . SUPRAMOL CHEM, 15(1), 5-23.
Twyman LJ & King ASH (2002) . Chem Commun (Camb)(8), 910-911.
Burnett JL, King ASH, Martin IK & Twyman LJ (2002) 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.
Twyman LJ, King ASH & Martin IK (2002) . Chem Soc Rev, 31(2), 69-82.
Twyman LJ & King ASH (2002) Catalysis using peripherally functionalised dendrimers. J CHEM RES-S(2), 43-59.
Twyman LJ & King ASH (2002) . Chemical Communications, 2(8), 910-911.
King ASH & Twyman LJ (2002) . J CHEM SOC PERK T 1(20), 2209-2218.
Turnbull S, Tabner BJ, El-Agnaf OMA, Twyman LJ & Allsop D (2001) 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.
Martin IK & Twyman LJ (2001) Acceleration of an aminolysis reaction using a PAMAM dendrimer with 64 terminal amine groups. TETRAHEDRON LETT, 42(6), 1123-1126.
Martin IK & Twyman LJ (2001) The synthesis of unsymmetrical PAMAM dendrimers using a divergent/divergent approach. TETRAHEDRON LETT, 42(6), 1119-1121.
Allsop D, Gibson G, Martin IK, Moore S, Turnbull S & Twyman LJ (2001) 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.
Allsop D, Twyman LJ, Davies Y, Moore S, York A, Swanson L & Soutar I (2001) . Biochem Soc Symp(67), 1-14.
Turnbull S, Moore S, Twyman LJ & Allsop D (2000) . Biochemical Society Transactions, 28(5), A307-A307.
Twyman LJ (2000) Post synthetic modification of the hydrophobic interior of a water-soluble dendrimer. TETRAHEDRON LETT, 41(35), 6875-6878.
Allsop D, Davies Y, Moore S & Twyman L (2000) . Biochemical Society Transactions, 28(1), A14-A14.
Twyman LJ & Allsop D (1999) 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.
Gale PA, Twyman LJ, Handlin CI & Sessler JL (1999) A colourimetric calix[4]pyrrole-4-nitrophenolate based anion sensor. CHEM COMMUN(18), 1851-1852.
Twyman LJ & Sanders JKM (1999) A general route for the synthesis of flexible porphyrin dimers. TETRAHEDRON LETT, 40(36), 6681-6684.
Twyman LJ, Beezer AE, Esfand R, Hardy MJ & Mitchell JC (1999) The synthesis of water soluble dendrimers, and their application as possible drug delivery systems.. TETRAHEDRON LETT, 40(9), 1743-1746.
Twyman LJ, Beezer AE, Esfand R, Mathews BT & Mitchell JC (1998) The synthesis of chiral dendrimeric molecules based on amino acid repeat units. J CHEM RES-S(12), 758-759B.
Marty M, Clyde-Watson Z, Twyman LJ, Nakash M & Sanders JKM (1998) Acceleration of a hetero-Diels-Alder reaction by cyclic metalloporphyrin trimers. CHEM COMMUN(20), 2265-2266.
Clyde-Watson Z, Vidal-Ferran A, Twyman LJ, Walter CJ, McCallien DWJ, Fanni S, Bampos N, Wylie RS & Sanders JKM (1998) Reversing the stereochemistry of a Diels-Alder reaction: use of metalloporphyrin oligomers to control transition state stability. NEW J CHEM, 22(5), 493-502.
Esfand R, Beezer AE, Mitchell JC & Twyman LJ (1996) Synthesis, complexation and pharmaceutical applications of tetra-directional cascade dendrimers. Pharmaceutical Sciences, 2(3), 157-159.
TWYMAN L, BEEZER AE & MITCHELL JC (1994) THE SYNTHESIS OF CHIRAL DENDRITIC MOLECULES BASED ON THE REPEAT UNIT L-GLUTAMIC ACID. TETRAHEDRON LETT, 35(25), 4423-4424.
TWYMAN LJ, BEEZER AE & MITCHELL JC (1994) AN APPROACH FOR THE RAPID SYNTHESIS OF MODERATELY SIZED DENDRITIC MACROMOLECULES. J CHEM SOC PERK T 1(4), 407-411.
Chen Z & Twyman LJ () . ACS Applied Polymer Materials.
Twyman LJ & King ASH () . ChemInform, 33(31), no-no.
Twyman LJ, King ASH & Martin IK () . ChemInform, 33(22), no-no.
Twyman LJ & Sanders JKM () . ChemInform, 30(44), no-no.
Twyman LJ, Beezer AE, Esfand R, Mathews BT & Mitchell JC () . ChemInform, 30(18), no-no.
Twyman LJ, Beezer AE, Esfand R, Hardy MJ & Mitchell JC () . ChemInform, 30(17), no-no.
MARTY M, CLYDE-WATSON Z, TWYMAN LJ, NAKASH M & SANDERS JKM () . ChemInform, 30(6), no-no.

Chapters

() , Patent Applications (pp. 409-497). John Wiley & Sons, Inc.

Conference proceedings papers

Chiba F, Hu TC, Twyman LJ & Wagstaff M (2010) . MACROMOLECULAR SYMPOSIA, Vol. 287 (pp 37-41)
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)
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)

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)

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