Professor Richard Henderson
Professor of Inorganic Chemistry

  • Email: richard.henderson@ncl.ac.uk
  • Telephone: +44 (0) 191 222 6636
  • Fax: +44 (0) 191 222 6929
  • Address: Chemistry, School of Natural Sciences,
    University of Newcastle,
    Newcastle upon Tyne,
    NE1 7RU

Background

1976-1977: Postdoctoral Fellow (UCL)
1977-1979: Postdoctoral Fellow (Leeds)
1979-1999: Project Leader at BBSRC Nitrogen Fixation Laboratory

Roles and Responsibilities

Professor of Inorganic Chemistry
Degree Programme Director for most UG Chemistry programmes

Qualifications

1973 B.Sc. (Hons) Chemistry, University College London
1976 Ph.D. Chemistry, University College London

Previous Positions

1976 - 1977 Postdoctoral Fellow with A G Davies FRS, University College London
1977- 1979 Postdoctoral Fellow with A G Sykes FRS, University of Leeds
1979-1999 Project Leader, BBSRC Nitrogen Fixation Laboratory
1999 – present Professor of Inorganic Chemistry, University of Newcastle

Memberships

Fellow of the Royal Society of Chemistry

Honours and Awards

1985 - 1995 Honorary Lecturer, University of Sussex
1995 – 1999 Honorary Lecturer, University of East Anglia
1993 RSC Award in Inorganic Reaction Mechanisms
1999 Fellow Royal Society of Chemistry

Research Interests

My research focuses on all aspects of inorganic reaction mechanisms. A broad spectrum of areas are encompassed ranging from bioinorganic chemistry (working on both model compounds for metalloenzymes and the iron, molybdenum cofactor from nitrogenase) through to organometallic chemistry ( reactivity of eg hydride, isonitrile and hydrocarbon complexes).

My main interest is in the area of MECHANISTIC INORGANIC CHEMISTRY. In particular the binding and activation of small molecules at transition metal sites. This is a broad topic which is relevant to areas as diverse as BIOINORGANIC and ORGANOMETALLIC chemistry.

My current research interests can be accessed through the following links.
Techniques Used
Synthetic Fe-S-Based Clusters
Extracted FeMo-cofactor
Protonation of Coordinated Small Molecules
Summaries of these research areas can be found in the following reviews.

Catalysis by Nitrogenases and Synthetic Analogs.
David J Evans, Richard A Henderson and Barry E Smith.
Bioinorganic Catalysis (ed. J Reedijk and E Bouwman), Marcel Dekker, New York, 1999, pp153.

Protonation of Unsaturated Hydrocarbon Ligands: Regioselectivity, Stereoselectivity and Product Specificity.
Richard A Henderson. Angewandte Chemie, 1996, 35, 946.
Techniques Used
All of my research involves air- and moisture-sensitive compounds and the laboratory is fully equipped to prepare, handle and study such materials. Compounds are usually prepared using Schlenk and vacuum line techniques. In addition, a glove box (which operates at less than 1ppm oxygen), is available for extremely sensitive materials.

Our primary technique for studying mechanisms of reactions is stopped-flow spectrophotometery. This apparatus is capable of mixing reagents in less than 2milliseconds and monitoring the subsequent reaction time-course. In addition it is also capable of sequentially mixing three reactants for the study of compounds which are very short-lived. Since we are not interested in mathematics, only the chemistry it defines, the kinetics are invariably studied under pseudo first-order conditions (ie where one reactant is present in a large excess). This makes the analysis of the data very straight forward.

In addition to kinetics, we also use detailed product analysis (using NMR, IR and UV-visible spectroscopies, GLC and Mass Spectrometry), and isotope experiments to help define the mechanism in more detail.

NMR spectroscopy plays a major role in all of this research, primarily to establish the identity of the reactants and products. We have also developed an approach to detecting intermediates using this technique. Stopped-flow apparatus can be used to detect intermediates, but our apparatus is only capable of measuring the UV-visible spectrum of such intermediates. Unfortunately this spectroscopy is not diagnostic of structure. In contrast, NMR spectroscopy can often give unambiguous structural information. With reactions which show evidence of short-lived intermediates at ambient temperatures, we also study the reaction under analogous concentrations but at -700C in the probe of an NMR spectrometer. Under these conditions the intermediate has a sufficiently long life-time that we can measure its 1H, 31P and 13C NMR spectra.

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Synthetic Fe-S-Based Clusters
Iron-sulfur-based clusters are found in a variety of metalloenzymes where they play roles as diverse as: electron-transfer mediators; iron sensors, and the substrate binding site in redox and non-redox enzymic reactions.

In order to understand how the clusters operate in enzymic reactions it is necessary to define their fundamental chemistry outside the polypeptide matrix. Many of the clusters in these metalloenzymes can be synthesised in the laboratory from simple reagents.

Our initial studies on synthetic Fe-S-based clusters involved simple substitution reactions of the terminal thiolate and halido-ligands, and the protonation and binding of small molecules and ions (eg L = halide, CO, N2O, N3-, CN-). The binding of protons and small molecules are not associated with an appreciable change in the electronic spectrum of the cluster and so we have to study these reactions indirectly; effectively by measuring the effect that these species have on the rate of the substitution reactions of these cluster, as illustrated in the Figure. The binding of these molecules and ions to Fe-S-based clusters is important since several of these species are substrates for enzymes containing Fe-S-based clusters. Studying a variety of clusters allows us to reasonably suggest the identity of the cluster binding sites for these molecules and ions.

Most recently we have started to look at the mechanisms by which these clusters are assembled from mononuclear complexes.

Enforced Slow Protonation of [Fe4S4Cl4]2- and the Maximum Rate of Protonation of the Cluster Core.Richard A Henderson and Kay E Oglieve.
J Chem Soc, Dalton Trans, 1999, 3927.
Combined versus Individual Labilising Effects of H+, Na+ and Nucleophile on Catalysed Substitution Reactions: Studies on [Fe4S4X4]2- (X = Cl or PhS).
Richard A Henderson.
J Chem Soc, Dalton Trans, 1999, 119.

A Unified Mechanism for the Stoichiometric Reduction of H+ and C2H2 by [Fe4S4(SPh)4]3- in MeCN.
Karin L C Grönberg, Richard A Henderson and Kay E Oglieve. J Chem Soc, Dalton Trans, 1998, 3093.
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Extracted FeMo-cofactor
Nitrogenase is a multi-component metalloenzyme which converts molecular nitrogen into ammonia by a sequence of coupled electron- and proton-transfer reactions. The crystal structures of all the component proteins have been determined and shown in Figure 4 is a portion of the structure showing the clusters involved: an Fe4S4 cube (electron transfer mediator); a unique Fe8S7 cluster (P-cluster, electron storage) and a unique MoFe7S9 cluster (FeMo-cofactor, substrate binding site).

This cluster is bound to the polypeptide matrix via a cysteinate to the unique tetrahedral Fe (all other Fe's are three coordinate), and a histidine to the Mo atom. The Mo atom is six coordinate and the remainder of the coordination sphere is made up from a R-homocitrate molecule acting as a bidentate ligand. The skeleton structure of FeMo-cofactor is shown in the Figure.

FeMo-cofactor can be removed, intact, from the protein and extracted into N-methylformamide (NMF). This extraction must involve cleavage of the Fe-cysteinate and Mo-histidine bonds, and what we reasonably assume is that in the extract these positions are occupied by NMF.

The approach we have developed to investigate the reactivity of this cluster is adapted from our studies with the synthetic Fe-S-based clusters (above). The reaction of extracted FeMo-cofactor with PhS- occurs exclusively at the unique tetrahedral Fe site as shown in the Figure. By measuring how the rate of this reaction is affected by binding of molecules and ions to the cofactor we can "map out" where these species bind on the cluster, and how changing the polycarboxylate affects the reactivity.

Currently, we are also looking at the analogous cofactor from the V-based enzyme, FeV-cofactor.

A New Approach to Identifying Substrate Binding Sites on Isolated FeMo-cofactor of Nitrogenase.
Karin L C Grönberg, Barry E Smith and Richard A Henderson.
J Chem Soc, Chem Comm, 1997, 713.

Why R-Homocitrate is Essential to the Reactivity of FeMo-cofactor of Nitrogenase: Studies on NifV--Extracted FeMo-cofactor.
Karin L C Grönberg, Carol A Gormal, Marcus C Durrant, Barry E Smith and Richard A Henderson.
J Am Chem Soc, 1998, 120, 10613.

Protonation and Substitution Reactions of Fe-S 'Basket' Clusters including Extracted FeMo-cofactor of Nitrogenase.
Valentim R Almeida, Carol A Gormal, Karin L C Grönberg, Richard A Henderson, Kay E Oglieve and Barry E Smith.
Inorganica Chimica Acta, 1999, 291, 212
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Regio-, Stereo- and Product-Specific Protonation
For some time we have been investigating the protonation of small molecules coordinated to electron-rich transition metal sites such as {M(Ph2PCH2CH2PPh2)2} (M = Fe, Ru, Os, Mo, W, Re). The ligands which have been of particular interest include: N2, RNC, RCN, alkynes, alkenes, unsaturated hydrocarbon residues and hydrides.

By studying the mechanisms with a variety of different, but analogous, complexes we can build up a detailed picture of: (i) all the possible ways in which the ligand is transformed by protonation; (ii) which are the most favoured sites of protonation (metal versus different sites on the ligand) and (iii) how controlling the system (variation of ancillary ligands or the concentration of acid) can favour one pathway over another. For example, our studies on alkene complexes have shown how simply altering the concentration of acid can result in the production of either alkanes, isomerised alkenes or even alkynes, as summarised in the Figure.

Recently we have started to study the protonation of ligands bound to NiII-phosphine sites; in particular looking at the reactivity of hydride and alkyl ligands.

New Insights into the Mechanism of Methane Formation in the Protonation of Methyl Complexes. Richard A Henderson and Kay E Oglieve.
J Chem Soc, Chem Comm, 1999, 2271.

Reaction of [Ni(Ph2PCH2CH2PPh2)2] with DCl: Controlling the Formation of HD and D2.
Sian C Davies, Richard A Henderson, David L Hughes and Kay E Oglieve.
J Chem Soc, Dalton Trans, 1998, 425.

Metal Hydrides as Intermediates in the Reactions of Coordinated Unsaturated Hydrocarbons:
Formation of Propyne by Protonation of trans-[WH(h 3-C3H5)(Ph2PCH2CH2PPh2)2].
Richard A Henderson, David L Hughes, Colin J Macdonald and Kay E Oglieve.
Inorganica Chimica Acta, 1997, 259, 107.

Postgraduate Supervision

Adrian Dunford 1999-2002
Lin Ping 2000-2005
Valerie Autissier 2000-2004
Brendan Garrett 2003-present
Katie Bates 2004-present
Rizwana Tariq 2006-present

Esteem Indicators

1. Invitations to give section/keynote lectures at International Meetings including: ICCC36, Mexico; Reaction Mechanisms VII, Dublin; GRC Nitrogen Fixation Meeting 2002, USA; Inorganic Mechanisms Meeting, Greece, 2004; RSC Annual Conference, Birmingham 2001; RSC Education Meeting 2007

2. Invitations to Contribute Chapters to Books and Articles in Special editions of Journals including: Recent Advances in Hydride Chemistry (ed. M. Peruzzini and R. Poli), Elsevier, 2001, “Metal Hydride Intermediates in Hydrogenases and Nitrogenases”, p463-505; Nitrogen Fixation at the Millenium (ed. G. J. Leigh), Elsevier, 2002, “Advances Towards the Mechanism of Nitrogenases”, p223-261; “Kinetic Studies on the Reactions of HCl with trans-[MoL(CNPh)(Ph2PCH2CH2PPh2)2] (L = N2, H2 or CO), M.-C. Rosenblat and R. A. Henderson, Inorganica Chimica Acta, 2002, 331, 270-278 (Special Issue for A. G. Sykes); “Mechanistic Studies on Synthetic Fe-S-Based Clusters and their Relevance to the Action of the Nitrogenases”, R. A. Henderson*, Chemical Reviews, 2005, 105, 2365-2438 (Special Issue on Inorganic Mechanisms); “Proton Transfer to Synthetic Fe-S-Based Clusters”, R. A. Henderson*, Coord. Chem. Rev., 2005, in press (Special Issue for ICCC Keynote Lecturers).

3. Chairman of the Royal Society of Chemistry Inorganic Mechanisms Discussion Group (1999-2003).

4. Organising Committee of conferences including: IRMDG Galway, Eire, 2001; Dalton Discussion No. 4, Kloster Banz, Germany, 2002; Inorganic Mechanisms Meeting, Newcastle, UK, 2003.

5. Chemistry Education: External Examiner for University of Malaysia (2004-2007); Reviewer of new edition of Shriver and Atkins.

6. Invitations to give departmental seminars including: University of Birmingham; University of Edinburgh; University of St Andrews; University of Warwick.

7. External Examiner for PhD including: University of St Andrews; Royal College of Surgeons, Dublin; University of East Anglia; Universite de Brest, France

Undergraduate Teaching

CHY135 Inorganic and Structural Chemistry
CHY180 Data Handling in Chemistry
CHY274 Landmarks in Chemistry
CHY277 Topics in Chemistry
CHY300 Problem Solving
CHY301 problem Solving 2
CHY382 Chemical Biology