Prof. Nicholas H. Williams
Department of Chemistry
Professor in Physical Organic Chemistry and Director of Learning and Teaching
+44 114 222 9469
Full contact details
Department of Chemistry
13 Brook Hill
Prof. Williams obtained his BA in Chemistry from Cambridge in 1988, which was followed by an MA and PhD from the same institution in 1992. After his PhD he was a post doctoral fellow and temporary lector at Trinity College, Cambridge.
In 1994 he became a RS/NSERC Research Fellow at McGill University in Montréal. In 1996 he was appointed to a lectureship at the University of Sheffield, where he was promoted to Senior Lecturer in 2003 and then Reader in 2007. In 2011 he was promoted to Professor.
- Research interests
Our research can be broadly described as physical organic chemistry. This is the design, synthesis and systematic study of (mainly) organic molecules. The molecules we are interested in designing are ones which either show fundamental insights into mechanisms, reactivity, recognition and/or catalysis, or exploit the understanding we have to create more complex supramolecular systems. Practically, we think at the molecular level (designing organic molecules with key structural features), make them (organic synthesis), and finally discover how well they function by carefully examining their properties. Currently, we have three main strands of investigation:
Enzymes are remarkably efficient catalysts, operating under mild aqueous conditions; as man made efforts to achieve similar activity are many orders of magnitude less efficient, there is still a great deal that we do not understand. We are investigating well defined model compounds to understand how to combine several functional groups so that they work really effectively together. This helps give a deeper understanding of biological catalysis, and guides us in designing our own biomimetic catalysts. Organic ligands which can bind and control the reactivity of metal ions provide the best catalysts to date, and form the core of our models and catalysts.
We are applying the discovery that individual components of a catalyst can be brought together to achieve cooperative catalysis (i.e. the whole is more effective than the sum of the parts!) towards creating supramolecular systems which can be controlled by recognition processes. This is the type of event which takes place in signalling at cell surfaces, and we are making transmembrane signalling systems which mimic this.
Lastly, based on the discovery that calixarene-like molecules show a remarkable ability to modify the properties of surfaces, we are investigating the key molecular features that this is based on, and what properties we can bring to a wide range of materials. For example, we can already change paper from being highly water and oil absorbent to being both water and oil repellent, without observably changing its appearance. In particular, these molecules will have the potential make ordinary materials into sophisticated biomaterials by creating a new bio-active interface.
- Coordination‐cage‐catalysed hydrolysis of organophosphates : cavity‐ or surface‐based?. Chemistry – A European Journal, 26(14), 3065-3073. View this article in WRRO
- A Synthetic Vesicle-to-Vesicle Communication System. Journal of the American Chemical Society, 141(44), 17847-17853.
- Coordination Cages Based on Bis(pyrazolylpyridine) Ligands: Structures, Dynamic Behavior, Guest Binding, and Catalysis. Accounts of Chemical Research, 51(9), 2073-2082.
- Catalysis in a Cationic Coordination Cage Using a Cavity-Bound Guest and Surface-Bound Anions: Inhibition, Activation, and Autocatalysis.. Journal of the American Chemical Society, 140(8), 2821-2828. View this article in WRRO
- Front Cover: Binding of Hydrophobic Guests in a Coordination Cage Cavity is Driven by Liberation of “High-Energy” Water (Chem. Eur. J. 7/2018). Chemistry - A European Journal, 24(7), 1459-1459.
- Adhesion between oppositely charged polyelectrolytes. Journal of Adhesion, 94(1), 58-76. View this article in WRRO
- Binding of hydrophobic guests in a coordination cage cavity is driven by liberation of 'high-energy' water. Chemistry - A European Journal. View this article in WRRO
- Triggered Release from Lipid Bilayer Vesicles by an Artificial Transmembrane Signal Transduction System. Journal of the American Chemical Society, 139(44), 15768-15773. View this article in WRRO
- Simulating the reactions of substituted pyridinio-N-phosphonates with pyridine as a model for biological phosphoryl transfer.. Org Biomol Chem. View this article in WRRO
- Transition States and Control of Substrate Preference in the Promiscuous Phosphatase PP1. Biochemistry, 56(30), 3923-3933. View this article in WRRO
- Recognition-Controlled Membrane Translocation for Signal Transduction across Lipid Bilayers.. Journal of the American Chemical Society, 139(18), 6461-6466. View this article in WRRO
- How to name atoms in phosphates, polyphosphates, their derivatives and mimics, and transition state analogues for enzyme-catalysed phosphoryl transfer reactions (IUPAC Recommendations 2016). Pure and Applied Chemistry, 89(5), 653-675. View this article in WRRO
- 'Rough guide' evanescent wave optrode for colorimetric metalloporphyrine sensors. Talanta, 164, 228-232. View this article in WRRO
- The effect of magnesium ions on triphosphate hydrolysis. Pure and Applied Chemistry. View this article in WRRO
- Guest Binding and Catalysis in the Cavity of a Cubic Coordination Cage. Chemistry Letters, 46(1), 2-9.
- Controlled membrane translocation provides a mechanism for signal transduction and amplification. Nature Chemistry, 9, 426-430. View this article in WRRO
- Fibre optic absorbance meter with low limit of detection for waterborne cations. Sensors & Actuators: B. Chemical, 237, 1102-1107. View this article in WRRO
- The solvolysis mechanism of simple secondary tosylates in 50% aqueous TFE. Journal of Physical Organic Chemistry, 29(12), 709-717. View this article in WRRO
- The Competing Mechanisms of Phosphate Monoester Dianion Hydrolysis. Journal of the American Chemical Society, 138(33), 10664-10673. View this article in WRRO
- Double-network hydrogels improve pH-switchable adhesion. Soft Matter, 12, 5022-5028. View this article in WRRO
- Highly efficient catalysis of the Kemp elimination in the cavity of a cubic coordination cage. Nature Chemistry, 8(3), 231-236. View this article in WRRO
- Enhancing Phosphate Diester Cleavage by a Zinc Complex through Controlling Nucleophile Coordination. Chemistry - A European Journal, 21(19), 7053-7056. View this article in WRRO
- Resolving Apparent Conflicts between Theoretical and Experimental Models of Phosphate Monoester Hydrolysis. Journal of the American Chemical Society, 137(3), 1081-1093. View this article in WRRO
- Catalytic Zinc Complexes for Phosphate Diester Hydrolysis. Angewandte Chemie, 126(31), 8385-8389.
- Catalytic zinc complexes for phosphate diester hydrolysis.. Angew Chem Int Ed Engl, 53(31), 8246-8250. View this article in WRRO
- The alkaline hydrolysis of sulfonate esters: challenges in interpreting experimental and theoretical data.. J Org Chem, 79(7), 2816-2828. View this article in WRRO
- Fabrication of molecular nanopatterns at aluminium oxide surfaces by nanoshaving of self-assembled monolayers of alkylphosphonates.. Nanoscale, 5(22), 11125-11131. View this article in WRRO
- Photocatalytic nanolithography of self-assembled monolayers and proteins.. ACS Nano, 7(9), 7610-7618. View this article in WRRO
- Intramolecular general base catalysis in the hydrolysis of a phosphate diester. Calculational guidance to a choice of mechanism.. J Org Chem, 78(4), 1343-1353.
- Generic methods for micrometer- and nanometer-scale surface derivatization based on photochemical coupling of primary amines to monolayers of aryl azides on gold and aluminum oxide surfaces.. Langmuir, 29(4), 1083-1092.
- ADVANCES IN PHYSICAL ORGANIC CHEMISTRY PREFACE. ADVANCES IN PHYSICAL ORGANIC CHEMISTRY, VOL 47, 47, IX-X.
- Phase emerging from intramonolayer cycloaddition on micro-patterned monolayer. AIP Conference Proceedings, 1502(1), 171-181.
- Advances in Physical Organic Chemistry Volume 46 PREFACE. ADVANCES IN PHYSICAL ORGANIC CHEMISTY, VOL 46, 46, IX-X.
- Highly selective colorimetric sensing pyrophosphate in water by a NBD-phenoxo-bridged dinuclear Zn(ii) complex. Organic and Biomolecular Chemistry, 10(29), 5606-5612.
- β values in mechanistic studies on the transesterification of RNA models and their application in a metal ion complex promoted transesterification. Journal of Physical Organic Chemistry.
- The mechanism of cleavage and isomerisation of RNA promoted by an efficient dinuclear Zn 2+ complex. Chemistry - A European Journal, 18(2), 659-670.
- Neutralizing mutations of carboxylates that bind metal 2 in T5 flap endonuclease result in an enzyme that still requires two metal ions.. J Biol Chem, 286(35), 30878-30887.
- Activating water: Important effects of non-leaving groups on the hydrolysis of phosphate triesters. Chemistry - A European Journal, 17(52), 14996-15004.
- Brønsted analysis and rate-limiting steps for the T5 flap endonuclease catalyzed hydrolysis of exonucleolytic substrates.. Biochemistry, 49(37), 8085-8093.
- A Simple Arg to Lys Mutant of Protein Phosphatase 1 Exhibits Catalytic Efficiencies toward Monoanionic Substrates Superior to Wild Type. FASEB JOURNAL, 24.
- Atomic details of near-transition state conformers for enzyme phosphoryl transfer revealed by MgF-3 rather than by phosphoranes.. Proc Natl Acad Sci U S A, 107(10), 4555-4560.
- Phosphate ester analogues as probes for understanding enzyme catalysed phosphoryl transfer. FARADAY DISCUSS, 145, 281-299.
- MgF(3)(-) and alpha-galactose 1-phosphate in the active site of beta-phosphoglucomutase form a transition state analogue of phosphoryl transfer.. J Am Chem Soc, 131(45), 16334-16335.
- Mechanism and transition state structure of aryl methylphosphonate esters doubly coordinated to a dinuclear cobalt(III) center.. J Am Chem Soc, 131(35), 12771-12779.
- Generation of Bioactive Materials with Rapid Self-Assembling Resorcinarene-Peptides. ADV MATER, 21(28), 2909-2915.
- Dinuclear Zn(II) Complex Promotes Cleavage and Isomerization of 2-Hydroxypropyl Alkyl Phosphates by a Common Cyclic Phosphate Intermediate. J AM CHEM SOC, 131(11), 4159-4166.
- Kinetic analysis of beta-phosphoglucomutase and its inhibition by magnesium fluoride.. J Am Chem Soc, 131(4), 1575-1588.
- Three metal ions participate in the reaction catalyzed by T5 flap endonuclease.. J Biol Chem, 283(42), 28741-28746.
- Mechanistic study of protein phosphatase-1 (PP1), a catalytically promiscuous enzyme.. J Am Chem Soc, 130(41), 13673-13682.
- Amphiphilic spin probes based on disulfide-bridged bisnitroxides. TETRAHEDRON LETT, 49(41), 5887-5889.
- Dineopentyl phosphate hydrolysis: Evidence for stepwise water attack. J ORG CHEM, 73(18), 6960-6969.
- Cleavage and isomerization of UpU promoted by dinuclear metal ion complexes. J AM CHEM SOC, 130(13), 4232-+.
- Anionic charge is prioritized over geometry in aluminum and magnesium fluoride transition state analogs of phosphoryl transfer enzymes.. J Am Chem Soc, 130(12), 3952-3958.
- ORGN 724-Comparative mechanistic studies on the catalytically promiscuous serine/threonine protein phosphatase-1 (PP-1) and the dinuclear cobalt(III) complex [Co2(tacn)2(OH)3](ClO4)3. ABSTR PAP AM CHEM S, 234.
- Trimorphism in solid resorcinarenes.. Chem Commun (Camb)(17), 1748-1750.
- Mechanistic study of PP-1, a catalytically promiscuous enzyme. ABSTR PAP AM CHEM S, 233, 613-613.
- Monofunctionalised resorcinarenes. TETRAHEDRON LETT, 48(8), 1317-1319.
- Evaluation of anti-inflammatory and antimicrobial resorcinarene-peptides for biomaterial modification. European Cells and Materials, 14(SUPPL.3), 23.
- Evaluation of anti-inflammatory and antimicrobial resorcinarene-peptides for biomaterial modification. European Cells and Materials, 14(SUPPL.3), 126.
- Transmission of binding information across lipid bilayers.. Chemistry, 13(25), 7215-7222.
- Efficient Phosphodiester Binding and Cleavage by a ZnII Complex Combining Hydrogen-Bonding Interactions and Double Lewis Acid Activation. Angewandte Chemie, 118(42), 7214-7217.
- Efficient phosphodiester binding and cleavage by a ZnII complex combining hydrogen-bonding interactions and double Lewis acid activation.. Angew Chem Int Ed Engl, 45(42), 7056-7059.
- A Trojan horse transition state analogue generated by MgF3- formation in an enzyme active site.. Proc Natl Acad Sci U S A, 103(40), 14732-14737.
- Comparing a mononuclear Zn(II) complex with hydrogen bond donors with a dinuclear Zn(II) complex for catalysing phosphate ester cleavage.. Chem Commun (Camb)(17), 1845-1847.
- The time required for water attack at the phosphorus atom of simple phosphodiesters and of DNA. P NATL ACAD SCI USA, 103(11), 4052-4055.
- Evaluation of anti-inflammatory calixarene-peptides for biomaterial modification. European Cells and Materials, 11(SUPPL.2), 26.
- A highly reactive mononuclear Zn(II) complex for phosphodiester cleavage.. J Am Chem Soc, 127(39), 13470-13471.
- 14 Bioinspired organic chemistry. Annual Reports on the Progress of Chemistry - Section B, 101, 352-373.
- Amino-functionalized DNA: the properties of C5-amino-alkyl substituted 2'-deoxyuridines and their application in DNA triplex formation.. Nucleic Acids Res, 33(4), 1362-1371.
- Altered mechanisms of reactions of phosphate esters bridging a dinuclear metal center. J AM CHEM SOC, 126(38), 11864-11869.
- Bioinspired Organic Chemistry. ChemInform, 35(39).
- Mononuclear Co(III)-complex promoted phosphate diester hydrolysis: dependence of reactivity on the leaving group. J PHYS ORG CHEM, 17(6-7), 472-477.
- Models for biological phosphoryl transfer.. Biochim Biophys Acta, 1697(1-2), 279-287.
- Copper-mediated LDL oxidation by homocysteine and related compounds depends largely on copper ligation.. Biochim Biophys Acta, 1688(1), 33-42.
- Anti-inflammatory and cytoprotective action of novel synthetic MSH peptides in human skin keratinocytes. Transactions - 7th World Biomaterials Congress, 1067.
- Bioinspired organic chemistry. Annual Reports on the Progress of Chemistry - Section B, 100, 407-434.
- Comment on "The pentacovalent phosphorus intermediate of a phosphoryl transfer reaction".. Science, 301(5637), 1184.
- The rate of hydrolysis of phosphomonoester dianions and the exceptional catalytic proficiencies of protein and inositol phosphatases.. Proc Natl Acad Sci U S A, 100(10), 5607-5610.
- Oligonucleotide based artificial nuclease (OBAN) systems. Bulge size dependence and positioning of catalytic group in cleavage of RNA-bulges. ORG BIOMOL CHEM, 1(9), 1461-1465.
- Cooperative binding at lipid bilayer membrane surfaces.. J Am Chem Soc, 125(15), 4593-4599.
- Bioinspired organic chemistry. Annual Reports on the Progress of Chemistry - Section B, 99, 447-473.
- An altered mechanism of hydrolysis for a metal-complexed phosphate diester. J AM CHEM SOC, 124(50), 14860-14861.
- Transmembrane Signalling. Angewandte Chemie, 114(20), 4034-4037.
- Models for biological phosphoryl transfer: From very, very slow to very fast.. ABSTR PAP AM CHEM S, 223, C24-C24.
- Mimicking metallophosphatases: revealing a role for an OH group with no libido.. Angew Chem Int Ed Engl, 41(5), 849-852.
- Transmembrane signalling. ANGEW CHEM INT EDIT, 41(20), 3878-3881.
- Phosphate diester hydrolysis within a highly reactive dinuclear cobalt(III) complex. Ligand effect on reactivity, transition state and dissociation. J CHEM SOC PERK T 2(11), 2068-2073.
- Mechanism of reaction of phosphate esters coordinated to a model of dinuclear metallophosphatases.. ABSTR PAP AM CHEM S, 222, U154-U154.
- Base catalysed phosphate diester hydrolysis. CHEM COMMUN(14), 1268-1269.
- Magnesium ion catalyzed ATP hydrolysis. J AM CHEM SOC, 122(48), 12023-12024.
- A structural and functional model of dinuclear metallophosphatases. J AM CHEM SOC, 121(14), 3341-3348.
- Structure and nuclease activity of simple dinuclear metal complexes: Quantitative dissection of the role of metal ions. Accounts of Chemical Research, 32(6), 485-493.
- A novel solid support for synthesis of 2 ',3 '-cyclic phosphate terminated oligonucleotides. TETRAHEDRON LETT, 39(43), 7975-7978.
- Reactivity of phosphate diesters doubly coordinated to a dinuclear cobalt(III) complex: Dependence of the reactivity on the basicity of the leaving group. J AM CHEM SOC, 120(32), 8079-8087.
- Metal-ion catalysed phosphate diester transesterification: Quantifying double Lewis-acid activation. Chemical Communications(2), 131-132.
- EFFICIENT INTRAMOLECULAR GENERAL ACID CATALYSIS OF ENOL ETHER HYDROLYSIS - HYDROGEN-BONDING STABILIZATION OF THE TRANSITION-STATE FOR PROTON-TRANSFER TO CARBON. JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2(4), 643-648.
- THE ANOMERIC EFFECTS OF ARYLOXY GROUPS. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS(18), 1286-1287.
- ELECTRONIC EFFECTS ON CONFORMATIONAL PREFERENCES - A-VALUES FOR ARYLOXY GROUPS. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS(18), 1285-1286.
- EFFICIENT INTRAMOLECULAR GENERAL ACID CATALYSIS OF VINYL ETHER HYDROLYSIS BY THE NEIGHBORING CARBOXYLIC-ACID GROUP. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS(22), 1643-1644.
- THERE IS NO EVIDENCE FOR ELECTROSTATIC CATALYSIS OF VINYL ETHER HYDROLYSIS IN WATER. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS(22), 1644-1645.
- Adhesion between oppositely charged polyelectrolytes in salt solution. Journal of Applied Polymer Science, 49130-49130.
- Computer simulations of the catalytic mechanism of wild-type and mutant β-phosphoglucomutase. Organic & Biomolecular Chemistry, 16(12), 2060-2073. View this article in WRRO
- DNA Hydrolysis: Mechanism and Reactivity, Artificial Nucleases (pp. 3-17). Springer Berlin Heidelberg
- Anomeric and Gauche Effects, The Anomeric Effect and Associated Stereoelectronic Effects (pp. 55-69).
Conference proceedings papers
- A Simple Arg to Lys Mutant of Protein Phosphatase 1 Exhibits Catalytic Efficiencies toward Monoanionic Substrates Superior to Wild Type. FASEB JOURNAL, Vol. 26
- Mechanistic study of phosphoryl transfer reactions catalyzed by protein phosphatase-1. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 239
- Alteration of the mechanisms of phosphate ester hydrolysis by complexation to a dinuclear metal cneter.. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 226 (pp U747-U748)
- ANOMERIC AND GAUCHE EFFECTS - SOME BASIC STEREOELECTRONICS. ANOMERIC EFFECT AND ASSOCIATED STEREOELECTRONIC EFFECTS, Vol. 539 (pp 55-69)
- ANOMERIC AND GAUCHE EFFECTS - SOME BASIC STEREOELECTRONICS. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 204 (pp 91-CARB)
- Cover Feature: Coordination‐Cage‐Catalysed Hydrolysis of Organophosphates: Cavity‐ or Surface‐Based? (Chem. Eur. J. 14/2020). Chemistry – A European Journal, 26(14), 2981-2981.
- Teaching interests
Organic Chemistry; Biological Chemistry
- Teaching activities
Undergraduate and postgraduate taught modules
- Stereochemistry (Level 2)
This course discusses stereochemistry and conformation in organic chemistry.
- Mechanistic Organic Chemistry (Level 3)
This module discusses how to investigate organic reaction mechanisms.
- Stereoelectronics, Mechanism and Reactivity in Organic Chemistry (Level 4)
This lecture course develops and unites your understanding of the factors that contribute to the reactivity and mechanisms of organic compounds, and particularly the role of stereoelectronic effects in influencing the outcome of ionic, pericyclic and radical reactions.
- Level 3 Literature Review
- Level 4 Research Project
- Stereochemistry (Level 2)