Daniel Whelligan

Dr Daniel Whelligan MSci, PhD


Senior Lecturer in Organic/Medicinal Chemistry

Academic and research departments

School of Chemistry and Chemical Engineering.

About

University roles and responsibilities

  • Departmental Assessments Officer (2019 - present)
  • MSc Drug Discovery Programme Director (2011 - 2015)
  • MRes Chemistry Programme Director (2015 - 2019)

    Research

    Research interests

    Research projects

     

    Research Group and Facilities

    Current PhD Students

    Isobel Beard (3rd year)

    Nermin Ener (3rd year)

    Matthew Burrell (3rd year)

    Applications for PhD Studentships

    Any funded PhD studentships that become available will be advertised on the University of Surrey Chemistry PhD website. Applications from self-funded or overseas government-funded students are welcome. Please email Daniel Whelligan in the first instance.

    Facilities

    All organic synthesis is carried out in the recently refurbished Joseph Kenyon laboratory containing 24 state-of-the-art double fume cupboards, spectroscopy suite and cold room. The lab was shortlisted for the 'Safe, Successful and Sustainable Laboratory Award 2014' and is equipped with all necessary equipment for normal and air-sensitive organic chemistry.

    The Department possesses 500 and 400 MHz NMR spectrometers, an Agilent 6550 QToF LCMS and several LCMS, GCMS, IR and UV-Vis instruments.

    Teaching

    Publications

    Terry R. Willson, Carlos A. Giron Rodriguez, Qiucheng Xu, Jordan Frow, Fabrizia Foglia, Keenan Smith, Ravikumar Ravikumar, Mohanraj Vinothkannan, Najet Mahmoudi, Ihtasham Salam, Arun Prakash Periasamy, Daniel K. Whelligan, Mohamed Mamlouk, Hungyen Lin, Brian Seger, John R. Varcoe (2023)Radiation-grafted anion-exchange membranes for CO 2 electroreduction cells: an unexpected effect of using a lower excess of N -methylpiperidine in their fabrication, In: Journal of materials chemistry. A, Materials for energy and sustainability Royal Society of Chemistry

    Giron Rodriguez et al. [ ACS Sustainable Chem. Eng. , 2023, 11 , 1508] previously showed that radiation-grafted anion-exchange membranes containing N -benzyl- N -methylpiperidinium headgroups (MPIP-RG-AEM) are promising for use in CO 2 electrolysis ( cf. commercial and other RG-AEM types). For a more sustainable synthesis, MPIP-RG-AEMs have now been fabricated using a reduced 1.1 times excess of amine reagent (historically made using >5 times excess). A resulting RG-AEM promisingly had a bulk amination level that was comparable to those made with the traditional large excess. Unexpectedly, however, it had a significantly reduced water content, with two further batches showing that this observation was repeatable (and reproducible via measurements collected on a single batch using different techniques in different labs). The ionic conductivities of the RG-AEM made with a controlled 1.1 excess of amine were also lower, with higher activation energies. Terahertz time-domain spectroscopy measurements showed that the lower water uptake RG-AEMs, made with the 1.1 amine excess, contained smaller amounts of bulk water relative to bound water (a repeatable observation with different counter-anions). This lack of bulk water, yielding reduced water diffusion coefficients, led to a change in the water management when such RG-AEMs were tested in CO 2 electrolysis cells, with significantly affected in situ performances. Small angle scattering data (X-ray and neutron) indicated that MPIP-RG-AEM fabrication with the 1.1 excess of amine reduced the size of the amorphous lamella domains on hydration, and this change is suspected to be the cause of the lower water uptakes and swelling. The finding that chemically similar AEMs can have significantly different hydration properties is potentially important to all ion-exchange membrane users and developers (beyond the CO 2 electrolysis scope of this study).

    Terry R. Willson, Carlos A. Giron Rodriguez, Qiucheng Xu, Jordan Frow, Fabrizia Foglia, Keenan Smith, Ravikumar Ravikumar, Mohanraj Vinothkannan, Najet Mahmoudi, Ihtasham Salam, Arun Prakash Periasamy, Daniel Keith Whelligan, Mohamed Mamlouk, Hungyen Lin, Brian Seger, John Varcoe (2023)Radiation-grafted anion-exchange membranes for CO 2 electroreduction cells: an unexpected effect of using a lower excess of N-methylpiperidine in their fabrication †, In: Journal of Materials Chemistry A: materials for energy and sustainability11pp. 20724-20740 Royal Society of Chemistry

    Giron Rodriguez et al. [ACS Sustainable Chem. Eng., 2023, 11, 1508] previously showed that radiation-grafted anion-exchange membranes containing N-benzyl-N-methylpiperidinium headgroups (MPIP-RG-AEM) are promising for use in CO2 electrolysis (cf. commercial and other RG-AEM types). For a more sustainable synthesis, MPIP-RG-AEMs have now been fabricated using a reduced 1.1 times excess of amine reagent (historically made using >5 times excess). A resulting RG-AEM promisingly had a bulk amination level that was comparable to those made with the traditional large excess. Unexpectedly, however, it had a significantly reduced water content, with two further batches showing that this observation was repeatable (and reproducible via measurements collected on a single batch using different techniques in different labs). The ionic conductivities of the RG-AEM made with a controlled 1.1 excess of amine were also lower, with higher activation energies. Terahertz time-domain spectroscopy measurements showed that the lower water uptake RG-AEMs, made with the 1.1 amine excess, contained smaller amounts of bulk water relative to bound water (a repeatable observation with different counter-anions). This lack of bulk water, yielding reduced water diffusion coefficients, led to a change in the water management when such RG-AEMs were tested in CO2 electrolysis cells, with significantly affected in situ performances. Small angle scattering data (X-ray and neutron) indicated that MPIP-RG-AEM fabrication with the 1.1 excess of amine reduced the size of the amorphous lamella domains on hydration, and this change is suspected to be the cause of the lower water uptakes and swelling. The finding that chemically similar AEMs can have significantly different hydration properties is potentially important to all ion-exchange membrane users and developers (beyond the CO2 electrolysis scope of this study).

    John Varcoe, Rachida Bance-Souahli, Arup Chakraborty, Mehdi Choolaei, Carol Crean, Carlos Giron Rodriguez, Bjørt Óladóttir Joensen, Judy Lee, Arun Prakash Periasamy, Ihtasham Salam, Brian Seger, Daniel Whelligan, Terrence Willson (2022)The Latest Developments in Radiation-Grafted Anion-Exchange Polymer Electrolytes for Low Temperature Electrochemical Systems, In: Meeting abstracts (Electrochemical Society)MA2022-01(35)pp. 1443-1443 The Electrochemical Society, Inc
    Wang Jingyi, TERRENCE WILLSON, Sven Brückner, Daniel Keith Whelligan, Chunning Sun, Liang Liang, Xingli Wang, P Strasser, John Varcoe, Wen Ju (2023)Design of NiNC single atom catalyst layers and AEM electrolyzers for stable and efficient CO 2 -to-CO electrolysis: Correlating ionomer and cell performance, In: Electrochimica Acta142613 Elsevier

    Deploying single-site NiNC catalysts in cathode catalyst layers of bipolar electrolyzer cells enables catalytic CO 2 valorization to e-CO at industrially relevant yields and efficiencies. The performance of the cathode layers is controlled by the turnover frequency of the active sites as well as mass transfer to and from the active sites. While the atomic scale structure-reactivity relations of single-site NiNC catalysts have been extensively studied, the mass transfer characteristics of single atom catalyst layers were poorly discussed. In this work, we design, build, and test NiNC catalyst layers using a novel set of distinct ion exchange ionomer materials and correlate the performance of cathode catalyst layers with their reactivity and stability in full single MEA electrolyzer cells. The Sustainion anion exchange ionomer delivered optimal performance, yielding about 90% CO faradaic efficiency up to 300 mA cm 2 and 15 h stable performance at 200 mA cm 2. Our analysis attributes its favorable electrolyzer performance to its balanced conductivity and hydrophobicity, which mitigates electrode flooding while ensuring excellent ion and CO 2 transfer rates even at high current densities.

    Carlos A. Giron Rodriguez, Bjørt Óladottir Joensen, Asger Barkholt Moss, Gastón O Larrazábal, Daniel Keith Whelligan, Brian Seger, John Varcoe, TERRENCE WILLSON (2023)Influence of Headgroups in Ethylene-Tetrafluoroethylene-Based Radiation-Grafted Anion Exchange Membranes for CO 2 Electrolysis, In: ACS sustainable chemistry & engineering

    The performance of zero-gap CO 2 electrolysis (CO 2 E) is significantly influenced by the membrane's chemical structure and physical properties due to its effects on the local reaction environment and water/ion transport. Radiation-grafted anion-exchange membranes (RG-AEM) have demonstrated high ionic conductivity and durability, making them a promising alternative for CO 2 E. These membranes were fabricated using two different thicknesses of ethylene-tetrafluoro-ethylene polymer substrates (25 and 50 μm) and three different headgroup chemistries: benzyl-trimethylammonium, benzyl-N-methyl-pyrrolidinium, and benzyl-N-methylpiperidinium (MPIP). Our membrane characterization and testing in zero-gap cells over Ag electrocatalysts under commercially relevant conditions showed correlations between the water uptake, ionic conductivity, hydration, and cationic-head groups with the CO 2 E efficiency. The thinner 25 μm-based AEM with the MPIP-headgroup (ion-exchange capacities of 2.1 ± 0.1 mmol g −1) provided balanced in situ test characteristics with lower cell potentials, high CO selectivity, reduced liquid product crossover, and enhanced water management while maintaining stable operation compared to the commercial AEMs. The CO 2 electrolyzer with an MPIP-AEM operated for over 200 h at 150 mA cm −2 with CO selectivities up to 80% and low cell potentials (around 3.1 V) while also demonstrating high conductivities and chemical stability during performance at elevated temperatures (above 60 °C).

    Lianqin Wang, JJ Brink, Y Liu, AM Herring, J Ponce-González, Daniel Whelligan, John Varcoe (2017)Non-fluorinated pre-irradiation-grafted (peroxidated) LDPE-based anion-exchange membranes with high performance and stability, In: Energy & Environmental Science10pp. 2154-2167 Royal Society of Chemistry

    Radiation-grafted anion-exchange membrane (RG-AEM) research has predominantly focused on the chemical stability of the polymer-bound positively-charged head-groups that enable anion conduction. The effect of the backbone polymer chemistry, of the precursor film, on RG-AEM stability has been studied to a lesser extent and not for RG-AEMs made from pre-irradiation grafting of polymer films in air (peroxidation). The mechanical strength of polymer films is generally weakened by exposure to high radiation doses (e.g. from a high-energy e–-beam) and this is mediated by chemical degradation of the main chains: fluorinated films mechanically weaken at lower absorbed doses compared to nonfluorinated films. This study systematically compares the performance difference between RG-AEMs synthesised from a non-fluorinated polymer film (low-density polyethylene – LDPE) and a partially-fluorinated polymer film (poly(ethylene-cotetrafluoroethylene) – ETFE) using the peroxidation method (pre-irradiation in air using an e–-beam). Both the LDPE and ETFE precursor films used were 25 μm in thickness, which led to RG-AEMs of hydrated thicknesses in the range 52 – 60 μm. The RG-AEMs (designated LDPE-AEM and ETFE-AEM, respectively) all contained identical covalently-bound benzyltrimethylammonium (BTMA) cationic head-groups. An LDPE-AEM achieved a OH– anion conductivity of 145 mS cm-1 at 80 °C in a 95% relative humidity environment and a chloride Cl– anion conductivity of 76 mS cm-1 at 80 °C when fully hydrated. Alkali stability testing showed that the LDPE-AEM mechanically weakened to a much lower extent when treated in aqueous alkaline solution compared to the ETFE-AEM. This LDPE-AEM outperformed the ETFE-AEM in H2/O2 anionexchange membrane fuel cell (AEMFC) tests due to high anion conductivity and enhanced in situ water transport (due to the lower density of the LDPE precursor): a maximum power density of 1.45 W cm-2 at 80 °C was achieved with an LDPE-AEM alongside a Pt-based anode and cathode (cf. 1.21 mW cm-2 for the benchmark ETFE-AEM). The development of more mechanically robust RG-AEMs has, for the first time, led to the ability to routinely test them in fuel cells at 80 °C (cf. 60 °C was the prior maximum temperature that could be routinely used with ETFE-based RG-AEMs). This development facilitates the application of non-Pt catalysts: 931 mW cm-2 was obtained with the use of a Ag/C cathode at 80 °C and a Ag loading of 0.8 mg cm-2 (only 711 mW cm-2 was obtained at 60 °C). This first report on the synthesis of large batch size LDPE-based RGAEMs, using the commercially amenable peroxidation-type radiation-grafting process, concludes that the resulting LDPEAEMs are superior to ETFE-AEMs (for the intended applications).

    Ana Laura Gonçalves Biancolli, Daniel Herranz, Lianqin Wang, Gabriela Stehlíkov, Rachida Bance-Soualhi, Julia Ponce-González, Pilar Ocón, Edson A. Ticianelli, Daniel K. Whelligan, John R. Varcoe, Elisabete I. Santiago (2018)ETFE-based anion-exchange membrane ionomer powders for alkaline membrane fuel cells: a first performance comparison of head-group chemistry, In: Journal of Materials Chemistry A Royal Society of Chemistry

    In the last few years, the development of radiation-grafted powder-form anion-exchange ionomers (AEI), used in combination with anion-exchange membranes (AEM), have led to the assembly of AEM-based fuel cells (AEMFC) that routinely yield power densities ranging between 1 – 2 W cm-2 (with a variety of catalysts). However, to date, only benzyltrimethyammonium-type powder AEIs have been evaluated in AEMFCs. This study presents an initial evaluation of the relative AEMFC power outputs when using a combination of ETFE-based radiation-grafted AEMs and AEIs containing three different head-group chemistries: benzyltrimethylammonium (TMA), benzyl-N-methylpyrrolidinium (MPY), and benzyl-N-methylpiperidinum (MPRD). The results from this study strongly suggest that future research should focus on the development and operando long-term durability testing of AEMs and AEIs containing the MPRD head-group chemistry.

    Daniel K. Whelligan (2010)ChemInform Abstract: Benzotriazole Linker Units, In: ChemInform41(43)pp. no-no WILEY-VCH Verlag
    Stephane Quideau, Laurent Pouysegu, Anne-Virginie Avellan, Daniel K. Whelligan, Matthew A. Looney (2002)ChemInform Abstract: Hypervalent Iodine(III)-Mediated Oxidative Acetoxylation of 2-Methoxyphenols for Regiocontrolled Nitrogen Benzannulation, In: ChemInform33(3)pp. no-no WILEY-VCH Verlag
    Malcolm B. Berry, Russel J. Griffiths, Mahesh J. Sanganee, Parick G. Steel, Daniel K. Whelligan (2004)Silenes as Novel Synthetic Reagents: Synthesis of Diols and Lactones from Simple Alkyldienes, In: ChemInform35(13)pp. no-no WILEY-VCH Verlag
    RACHIDA BANCE-SOUALHI, MOHAMMADMEHDI CHOOLAEI, SIAN ALICE FRANKLIN, TERRENCE WILLSON, Judy Lee, DANIEL KEITH WHELLIGAN, CAROL CREAN, JOHN VARCOE (2021)Radiation-grafted anion-exchange membranes for reverse electrodialysis: a comparison of N,N,N′,N′-tetramethylhexane-1,6-diamine crosslinking (amination stage) and divinylbenzene crosslinking (grafting stage), In: Dataset The Royal Society of Chemistry

    Radiation-grafted anion-exchange membranes (RG-AEM) are being developed to evaluate a range of chemistries that have relevance to a variety of electrochemical applications including reverse electrodialysis (RED) salinity gradient power. RG-AEMs are typically fabricated using an electron-beam activated (peroxidated) polymer substrate film. These activated films are first grafted with a monomer, such as vinylbenzyl chloride (VBC) and then reacted with a variety of tertiary amines to yield the desired RG-AEMs. The amination process forms covalently bound quaternary ammonium (QA) head-groups that allow the RG-AEMs to conduct anions such as Cl−. RG-AEMs are of interest as they exhibit high conductivities (100 mS cm−1 at elevated temperatures when containing Cl− anions). However, the current generation of RG-AEMs have two main Achilles' heels: (1) they exhibit low permselectivities; and (2) they exhibit a high degree of swelling in water. Introducing covalent crosslinking into ion-exchange membranes is a well-known strategy to overcome these issues but it often comes with a price – a significantly lowered conductivity (raised in situ resistance). Therefore, the level of crosslinking must be carefully optimised. RG-AEMs can be primarily crosslinked using two methods: (1) introduction of a divinyl monomer into the monomer mixture used during grafting; or (2) introduction of a diamine agent into the amination process. This study looks into both methods where either divinylbenzene (DVB) is added into the grafting mixture or N,N,N′,N′-tetramethylhexane-1,6-diamine (TMHDA) is added into the amination mixture. We show that on the balance of two application-relevant properties (resistances in aqueous NaCl (0.5 mol dm−3) solution and permselectivity), the diamine crosslinking method is the most effective for RG-AEMs being used in RED cells.

    Laura Wylie, Paolo Innocenti, Daniel K. Whelligan, Swen Hoelder (2012)ChemInform Abstract: Synthesis of Amino-Substituted Indoles Using the Bartoli Reaction, In: ChemInform43(43)pp. no-no WILEY-VCH Verlag
    Rachida Bance-Soualhi, Carol Crean, Henryk Herman, Saima Islania, Cheuk Ying Lai, Mariya Tencheva, John R. Varcoe, Daniel Whelligan (2020)A Raman Spectroscopic Study of Radiation-Grafted Anion-Exchange Membranes Containing Different Anions, In: Meeting abstracts (Electrochemical Society)MA2020-01(38)pp. 1641-1641

    Anion exchange membranes (AEM) are being developed for use in a variety of electrochemical energy systems, such as alkaline membrane fuel cells, AEM-based electrolysers, reverse electrodialysis (RED), and redox flow batteries (RFB). The AEMs used will contain a variety of anions, depending on the application. For fuel cells and electrolysers (H 2 generating or CO 2 conversion), then alkaline anions such as OH - , CO 3 2- , and HCO 3 - are important. For RED cells and RFBs, non-alkali anions such as Cl - , HSO 4 - , and SO 4 2- are more relevant. If an AEM is synthesised using a methyl iodide reaction, then monitoring the ion-exchange of the resulting "as-synthesised" I - forms to other forms, such as Cl - , is important as it is well known that it can be difficult to completely ion-exchange soft anions such as I - out of AEMs (particularly those containing aromatic cationic groups). This presentation will highlight some initial results obtained from an on-going Raman spectroscopic study of radiation-grafted AEMs (RG-AEM). This study was initiated to see if Raman spectro-microscopy can be used to identify the anion form of a RG-AEM by looking at the shifts and intensity changes of Raman peaks as a function of anion. The RG-AEMs will be made from either the grafting of vinylbenzyl chloride onto ETFE (followed by reaction with amines such as trimethylamine, imidazole and pyridine) or the grafting of alternative monomers such as vinylpyridine onto ETFE (followed by reaction with methyl iodide). The below Figure shows Raman spectra (Renishaw inVia Raman microscope: 785 nm laser, 1800 lines mm -1 grating, and x20 objective giving a Airy spot diameter of ca. 3 μm) of a RG-AEM made from the grafting of vinylpyridine onto ETFE films (with a final methyl iodide reaction) in both the I - and Cl - forms (three spectra each): . Figure 1

    Daniel K. Whelligan, Douglas W. Thomson, Dawn Taylor, Swen Hoelder (2010)ChemInform Abstract: Two-Step Synthesis of Aza- and Diazaindoles from Chloroamino-N-heterocycles Using Ethoxyvinylborolane, In: ChemInform41(19)pp. no-no WILEY-VCH Verlag
    Mahesh J. Sanganee, Patrick G. Steel, Daniel K. Whelligan (2003)Novel One-Pot Synthesis of Aryltris(trimethylsilyl)silanes, In: ChemInform34(35)pp. no-no WILEY-VCH Verlag
    J Ponce-González, DK Whelligan, Lianqin Wang, Rachida Bance-Soualhi, Ying Wang, Y Peng, H Peng, DC Apperley, HN Sarode, TP Pandey, AG Divekar, S Seifert, AM Herring, L Zhuang, John Varcoe (2016)High performance aliphatic-heterocyclic benzyl-quaternary ammonium radiation-grafted anion-exchange membranes, In: Energy and Environmental Science9(12)pp. 3724-3735 Royal Society of Chemistry

    Anion-exchange membranes (AEM) containing saturated-heterocyclic benzyl-quaternary ammonium (QA) groups synthesised by radiation-grafting onto poly(ethylene-co-tetrafluoroethylene) (ETFE) films are reported. The relative properties of these AEMs are compared with the benchmark radiation-grafted ETFE-g-poly(vinylbenzyltrimethylammonium) AEM. Two AEMs containing heterocyclic-QA head groups were down-selected with higher relative stabilities in aqueous KOH (1 mol dm-3) at 80°C (compared to the benchmark): these 100 μm thick (fully hydrated) ETFE-g-poly(vinylbenzyl-Nmethylpiperidinium)- and ETFE-g-poly(vinylbenzyl-N-methylpyrrolidinium)-based AEMs had as-synthesised ion-exchange capacities (IEC) of 1.64 and 1.66 mmol g-1, respectively, which reduced to 1.36 mmol dm-3 (ca. 17 – 18% loss of IEC) after alkali ageing (the benchmark AEM showed 30% loss of IEC under the same conditions). These down-selected AEMs exhibited as-synthesised Cl- ion conductivities of 49 and 52 mS cm-1, respectively, at 90°C in a 95% relative humidity atmosphere, while the OH- forms exhibited conductivities of 138 and 159 mS cm-1, respectively, at 80°C in a 95% relative humidity atmosphere. The ETFE-g-poly(vinylbenzyl-N-methylpyrrolidinium)-based AEM produced the highest performances when tested as catalyst coated membranes in H2/O2 alkaline polymer electrolyte fuel cells at 60°C with PtRu/C anodes, Pt/C cathodes, and a polysulfone ionomer: the 100 μm thick variant (synthesised from 50 μm thick ETFE) yielded peak power densities of 800 and 630 mW cm-2 (with and without 0.1 MPa back pressurisation, respectively), while a 52 μm thick variant (synthesised from 25 μm thick ETFE) yielded 980 and 800 mW cm-2 under the same conditions. From these results, we make the recommendation that developers of AEMs, especially pendent benzyl-QA types, should consider the benzyl-Nmethylpyrrolidinium head-group as an improvement to the current de facto benchmark benzyltrimethylammonium headgroup.

    Lianqin Wang, E Magliocca, E Cunningham, W Mustain, S Poynton, R Escudero-Cid, M Nasef, J Ponce-Gonzalez, R Bance-Souahli, Robert Slade, Daniel Whelligan, John Varcoe (2016)An optimised synthesis of high performance radiation-grafted anion-exchange membranes, In: Green Chemistry19pp. 831-843 Royal Society of Cemistry

    High performance benzyltrimethylammonium-type alkaline anion-exchange membranes (AEM), for application in electrochemical devices such as anion-exchange membrane fuel cells (AEMFC), were prepared by the radiation grafting (RG) of vinylbenzyl chloride (VBC) onto 25 μm thick poly(ethylene-co-tetrafluoroethylene) (ETFE) films followed by amination with trimethylamine. Reductions in electron-beam absorbed dose and amount of expensive, potentially hazardous VBC were achieved by using water as a diluent (reduced to 30 – 40 kGy absorbed dose and 5%vol VBC) instead of the prior-art method that used organic propan-2-ol diluent (required 70 kGy dose and 20%vol VBC monomer). Furthermore, the water from the aqueous grafting mixture was easily separated from residual monomer (after cooling) and was reused for a further grafting reaction: the resulting AEM exhibited an ion-exchange capacity of 2.1 mmol g-1 (cf. 2.1 mmol g-1 for the AEM made using fresh grafting mixture). The lower irradiation doses resulted in mechanically stronger RG-AEMs compared to the reference RG-AEM synthesised using the prior-art method. A further positive off-shoot of the optimisation process was the discovery that using water as a diluent resulted in an enhanced (i.e. more uniform) distribution of VBC grafts as proven by Raman microscopy and corroborated using EDX analysis: this led to enhancement in the Cl- anion-conductivities (up to 68 mS cm-1 at 80°C for the optimised fully hydrated RG-AEMs vs. 48 mS cm-1 for the prior-art RG-AEM reference). A down-selected RG-AEM of ion-exchange capacity = 2.0 mmol g-1, that was synthesised using the new greener protocol with 30 kGy electron-beam absorbed dose, led to an exceptional beginning-of-life H2/O2 AEMFC peak power density of 1.16 W cm−2 at 60°C in a benchmark test using industrial standard Pt-based electrocatalysts and unpressurised gas supplies: this was higher than the 0.91 W cm-1 obtained with the reference RG-AEM (IEC = 1.8 mmol g-1) synthesised using the prior-art protocol.

    Silenes generated through a silyl-modified Peterson olefination procedure can be trapped with a range of alkyl butadienes via a [4 + 2] cycloaddition pathway to afford silacycles accompanied by variable amounts of competing ene, [2 + 2] and silene dimer by-products. The silacycles are formed with good chemo- and stereo-selectivity and provide access to diols and lactones via a phenyl-triggered Fleming-Tamao oxidation.

    MB Berry, RJ Griffiths, MJ Sanganee, PG Steel, DK Whelligan (2004)Silenes as novel synthetic reagents: identification of a practical method for silene generation and trapping., In: Org Biomol Chem2(16)pp. 2381-2392

    The elucidation of a robust and reliable sequence for the generation of highly reactive transient silenes from simple aldehydes is described. The key step involves a silyl-modified Peterson olefination which critically depends on the presence of a sub-stoichiometric amount of soluble lithium salts (LiBr).

    DK Whelligan (2009)Benzotriazole Linker Units, In: PJH Scott (eds.), Linker Strategies in Solid-Phase Organic Synthesis(11) Wiley

    Syntheses of polymer-supported benzotriazoles Polymer-supported benzotriazole linked reactions

    J Ponce-González, I Ouachan, John Varcoe, Daniel Whelligan (2017)Radiation-induced grafting of a butyl-spacer styrenic monomer onto ETFE: the synthesis of the most alkali stable radiationgrafted anion-exchange membrane to date, In: JOURNAL OF MATERIALS CHEMISTRY A6(3)pp. 823-827 The Royal Society of Chemistry

    An ETFE-(poly(ethylene-co-tetrafluoroethylene))-based radiationgrafted anion-exchange membrane (AEM) containing a butylspacer between the benzene and the methylpyrrolidinium groups (C4-AEM) had double the ex-situ alkali stability at 80 °C compared to a methylene benchmark (C1-AEM). H2/O2 fuel cells containing the C4-AEM still achieved a peak power density of > 1 W cm-2.

    J Ponce-González, John Varcoe, Daniel Whelligan (2018)Commercial monomer availability leading to missed opportunities? Anion-exchange membranes made from meta-vinylbenzyl chloride exhibit an alkali stability enhancement, In: ACS Applied Energy Materials1(5)pp. 1883-1887 American Chemical Society

    Benzyltrimethylammonium-type anion-exchange polymers are common in alkali membrane fuel cells and water electrolysers but they suffer from degradation under alkaline conditions. Radiationgrafted anion-exchange membranes exhibit an alkali stability enhancement when made using non-commercial meta-only vinylbenzyl chloride (VBC) monomer, compared to the use of commercially available para-only or meta/para-mixed VBC isomers. We hypothesize a mechanism on why the use of meta-VBC eliminates AEM degradation via chain scission.

    DK Whelligan, S Solanki, D Taylor, DW Thomson, KMJ Cheung, K Boxall, C Mas-Droux, C Barillari, S Burns, CG Grummitt, I Collins, RLM van Montfort, GW Aherne, R Bayliss, S Hoelder (2010)Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization, In: J Med Chem53(21)pp. 7682-7698

    We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.

    DK Whelligan, DW Thomson, D Taylor, S Hoelder (2010)Two-Step Synthesis of Aza- and Diazaindoles from Chloroamino-N-heterocycles Using Ethoxyvinylborolane, In: J Org Chem75(1)pp. 11-15

    An efficient two-step route to a broad range of aza- and diazaindoles was established, starting from chloroamino-N-heterocycles, without the need for protecting groups. The method involves an optimized Suzuki-Miyaura coupling with (2-ethoxyvinyl)borolane followed by acetic acid-catalyzed cyclization.

    Samuel F. Gérard, Belinda S. Hall, Afroditi M. Zaki, Katherine A. Corfield, Peter U. Mayerhofer, Catia Costa, Daniel K. Whelligan, Philip C. Biggin, Rachel E. Simmonds, Matthew K. Higgins (2020)Structure of the Inhibited State of the Sec Translocon, In: Molecular Cell79(3)pp. 406-415.e7 Cell Press

    Protein secretion in eukaryotes and prokaryotes involves a universally conserved protein translocation chan-nel formed by the Sec61 complex. Unrelated small-molecule natural products and synthetic compoundsinhibit Sec61 with differential effects for different substrates or for Sec61 from different organisms, makingthis a promising target for therapeutic intervention. To understand the mode of inhibition and provide insightinto the molecular mechanism of this dynamic translocon, we determined the structure of mammalian Sec61inhibited by theMycobacterium ulceransexotoxin mycolactone via electron cryo-microscopy. Unexpect-edly, the conformation of inhibited Sec61 is optimal for substrate engagement, with mycolactone wedgingopen the cytosolic side of the lateral gate. The inability of mycolactone-inhibited Sec61 to effectively trans-port substrate proteins implies that signal peptides and transmembrane domains pass through the site occu-pied by mycolactone. This provides a foundation for understanding the molecular mechanism of Sec61 inhib-itors and reveals novel features of translocon function and dynamics.

    C Beemelmanns, R Husmann, DK Whelligan, S Özçubukçu, C Bolm (2012)Planar-Chiral Bis-silanols and Diols as H-Bonding Asymmetric Organocatalysts, In: Eur J Org Chempp. 3373-3376
    AL Ong, Daniel Whelligan, ML Fox, John Varcoe (2013)Impact of 1 mmol dm(-3) concentrations of small molecules containing nitrogen-based cationic groups on the oxygen reduction reaction on polycrystalline platinum in aqueous KOH (1 mol dm(-3)), In: PHYSICAL CHEMISTRY CHEMICAL PHYSICS15(43)pp. 18992-19000 ROYAL SOC CHEMISTRY

    Alkaline anion-exchange membranes (AAEMs) containing cationic head-groups (e.g. involving quaternary ammonium and imidazolium groups) are of interest with regard to application in alkaline polymer electrolyte fuel cells (APEFCs). This initial ex situ study evaluated the effect of 1 mmol dm concentrations of model molecules containing (AAEM-relevant) cationic groups on the oxygen reduction reaction on a polycrystalline platinum disk (Pt) electrode in aqueous KOH (1 mol dm(-3)). The cationic molecules studied were tetramethylammonium (TMA), benzyltrimethylammonium (BTMA), 1-benzyl-3-methylimidazolium (BMI), 1-benzyl-4-aza-1-azoniabicyclo[2.2.2]octane (BAABCO) and 6-(benzyloxy)-N,N,N-trimethylhexan-1-aminium (BOTMHA). Both cyclic and hydrodynamic linear sweep rotating disk electrode voltammetry techniques were used. The resulting voltammograms, derived estimates of apparent electrochemically active surface areas, Tafel slopes, apparent exchange-current densities and the number of electrons transferred (per O molecule) were compared. The results strongly suggest that 1 mmol dm(-3) concentrations of BTMA, BAABCO, and (especially) BMI seriously inhibit the catalytic activities of Pt in an aqueous KOH electrolyte at 25 °C. The negative influence of (benzene-ring-free) TMA and Cl anions (KCl control experiment) appeared to be less severe. The separation of the trimethylammonium group from the benzene ring via a hexyloxy spacer chain (in BOTMHA) also produced a milder negative effect.

    AL Ong, KK Inglis, DK Whelligan, S Murphy, JR Varcoe (2015)Effect of cationic molecules on the oxygen reduction reaction on fuel cell grade Pt/C (20 wt%) catalyst in potassium hydroxide (aq, 1 mol dm(-3)), In: PHYSICAL CHEMISTRY CHEMICAL PHYSICS17(18)pp. 12135-12145 ROYAL SOC CHEMISTRY

    Synthetic routes to pseudo-geminal, pseudo-ortho and ortho hydroxy-oxazolinyl-[2.2]paracyclophanes (and the diastereoisomers of each) for use as N,O ligands in asymmetric catalysis have been devised. The substitution pattern was found to have a strong effect on the rate and enantioselectivity of the formed catalyst in the addition of diethylzinc to benzaldehyde.

    L Wylie, P Innocenti, DK Whelligan, S Hoelder (2012)Synthesis of amino-substituted indoles using the Bartoli reaction, In: Org Biomol Chem10(22)pp. 4441-4447

    We report herein the concise preparation of a range of functionalised aminoindoles via a new application of the Bartoli reaction. Scope and limitations of the methodology have been extensively studied to reveal the importance of protecting groups and substitution patterns. The use of amino substituted nitroanilines for the Bartoli reaction is to our knowledge unprecedented. Our work thus represents a novel entry into substituted aminoindoles which are relevant building blocks for both the fine chemical and pharmaceutical industry.

    Syntheses of three regioisomers of aromatic-substituted phosphinyl-oxazolinyl-[2.2]paracyclophanes, pseudo-geminal, pseudo-ortho, and ortho, have been carried out or, in the latter two cases, newly developed. It has, therefore, been demonstrated that all aromatic-substituted isomers relevant for use as chelating ligands for asymmetric catalysis are accessible. These P,N-ligands, along with their diastereoisomers, were shown to exhibit widely differing activity and enantioselectivity (up to 89% ee) in the Pd-catalyzed asymmetric allylic alkylation reaction.

    MB Berry, RJ Griffiths, MJ Sanganee, PG Steel, DK Whelligan (2003)Silenes as novel synthetic reagents: synthesis of diols and lactones from simple alkyldienes, In: Tetrahedron Lett44(51)pp. 9135-9138

    Aryl substituted silenes can be generated by a modified Peterson olefination reaction and trapped in situ to afford silacycles with high diastereoselectivity. These silacycles can be elaborated by 'Fleming-Tamao' type oxidation to provide access to functionalized diols and lactones. (C) 2003 Elsevier Ltd. All rights reserved.

    Eduard Mas Claret, Balqees Al Yahyaei, Shuyu Chu, Ruan M. Elliott, Manuel Imperato, Arnaud Lopez, LISIANE BORGES MEIRA, Brendan J. Howlin, Daniel K. Whelligan (2020)An aza-nucleoside, fragment-like inhibitor of the DNA repair enzyme alkyladenine glycosylase (AAG), In: Bioorganic & Medicinal Chemistry28(11)115507 Elsevier

    The DNA repair enzyme AAG has been shown in mice to promote tissue necrosis in response to ischaemic reperfusion or treatment with alkylating agents. A chemical probe inhibitor is required for investigations of the biological mechanism causing this phenomenon and as a lead for drugs that are potentially protective against tissue damage from organ failure and transplantation, and alkylative chemotherapy. Herein, we describe the rationale behind the choice of arylmethylpyrrolidines as appropriate aza-nucleoside mimics for an inhibitor followed by their synthesis and the first use of a microplate-based assay for quantification of their inhibition of AAG. We finally report the discovery of an imidazol-4-ylmethylpyrrolidine as a fragment-sized, weak inhibitor of AAG.

    MJ Sanganee, PG Steel, DK Whelligan (2003)Novel one-pot synthesis of aryltris(trimethylsilyl)silanes., In: J Org Chem68(8)pp. 3337-3339

    The simple combination of tris(trimethylsilyl)potassium, ArMgBr, and ArBr provides a novel "one-pot" synthesis of aryl(tristrimethylsilyl)silanes. A mechanistic rationale for this conversion is proposed.

    Arup Chakraborty, Ihtasham Salam, Mehdi Choolaei, Judy Yu-Ting Lee, Carol Crean, Daniel Keith Whelligan, Rachida Bance-Soualhi, John Varcoe (2023)Changes in permselectivity of radiation-grafted anion-exchange membranes with different cationic headgroup chemistries are primarily due to water content differences †, In: Materials Advances4pp. 2099-2105 Royal Society of Chemistry

    In a prior paper [Bance-Soualhi et al., J. Mater. Chem. A, 2021, 9, 22025], we showed that the crosslinking of radiation-grafted anion-exchange membranes (RG-AEM) was necessary to obtain high enough apparent permselectivities for use in applications such as (reverse)electrodialysis. However, a separate result in this prior study suggested that comparable AEMs (similar ion-exchange capacity, IEC, and backbone chemistry) with different cationic headgroups may yield different balances between permselectivity and conductivity. This short follow-up study compares the permselectivities and Cl À conductivities of a series of non-crosslinked RG-AEMs with either aliphatic quaternary ammonium headgroups (N-benzyl-N-methylpiperidinium, MPIP, and benzyltrimethylammonium, TMA) or aromatic cationic headgroups (N-benzylpyridinium, PYR, or 1-benzyl-2,3-dimethylimidazolium, DMI). We show that a change in the headgroup chemistry modified the permselectivity-conductivity balance of the RG-AEM, but this was primarily due to the different headgroups inducing varying intrinsic water contents: higher water content RG-AEMs yield lower permselectivites. As also expected from this water content observation, higher IEC variants yielded RG-AEMs with lower permselectivities. The addition of N,N,N 0 ,N 0-tetramethylhexane-1,6-diamine-(TMHDA)-based ionic crosslinking to a DMI-based RG-AEM also raised permselectivity, confirming the observation of the prior study also applies to aromatic headgroup RG-AEMs. In summary, high IEC AEMs containing imidazolium-type headgroups along with an optimal amount of ionic crosslinking could be promising and warrant more study (i.e. a comparison of RG-AEMs with cheaper, more scalable non-RG-analogues that contain these attributes).

    PG Steel, DK Whelligan (2002)Silenes: Novel reagents for alkene functionalisation., In: ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY224pp. U161-U161 AMER CHEMICAL SOC
    S Quideau, L Pouysegu, AV Avellan, DK Whelligan (2001)Synthetic studies on Amaryllidaceae lycorine-type alkaloids., In: ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY221pp. U199-U199 AMER CHEMICAL SOC
    S Quideau, L Pouysegu, AV Avellan, DK Whelligan, MA Looney (2001)Hypervalent iodine(III)-mediated oxidative acetoxylation of 2-methoxyphenols for regiocontrolled nitrogen benzannulation, In: Tetrahedron Lett42(42)pp. 7393-7396

    Nitrogen-tethered 2-methoxyphenols are conveniently dearomatized into synthetically useful orthoquinol acetates by treatment with phenyliodine(III) diacetate in methylene chloride at low temperature. Subsequent fluoride- or base-induce intramolecular nucleophilic addition reactions furnish indole and quinoline derivatives. The potential of this methodology for the synthesis or a functionalized lycorine-type alkaloid skeleton is introduced here. (C) 2001 Elsevier Science Ltd. All rights reserved.