Philip A. Gale

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Philip A. Gale
Phil Gale - 2016 - Sydneysider75.jpg
Gale in July 2016
Born1969 (age 5455)
NationalityAustralian/British
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Scientific career
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Philip Alan Gale (born 1969) is an Australian/British chemist, Deputy Dean of Science and Professor of Chemistry at the Faculty of Science, University of Technology Sydney. He is notable for his work on the supramolecular chemistry of anions. [1]

Gale was born in Liverpool and grew up in Woolton attending Gateacre Community Comprehensive School. [2] He moved to Wadham College, Oxford, where he received his B.A. (Hons) degree in 1992 (M.A. Oxon. 1995) then moving in October 1992 to Linacre College where he graduated with a D.Phil. degree in 1995. He then moved to the University of Texas at Austin as a Fulbright Scholar with Prof. Jonathan Sessler. He returned to Oxford in 1997 as a Royal Society University Research Fellow and moved to a lectureship at the University of Southampton in 1999. He was promoted to a personal chair in supramolecular chemistry in 2007 and served as Head of Chemistry at the University of Southampton between 2010 and 2016. He was awarded a Doctor of Science degree by the University of Oxford in 2014. In January 2017 he moved to the University of Sydney where he took up the role of Head of the School of Chemistry [3] and in 2020 Associate Dean (International) in the Faculty of Science. He became interim Dean of the Faculty of Science at the University of Sydney serving from April 2022 to January 2023 and in February 2023 moved to the University of Technology Sydney to take up the role of Deputy Dean of Science.

Gale's research interests are in supramolecular chemistry and in particular the molecular recognition and transmembrane transport of anions. His early work concerned the design of structurally simple anion receptors and elucidating other processes such as proton transfer that often accompany anion complexation. [4] More recent research has focused on transmembrane anion transport. Gale has designed and synthesised a variety of highly effective classes of anion transporters including tren-based tris-ureas and -thioureas, [5] squaramides [6] and ortho-phenylene-based bis ureas. [7] In 2013 Gale and co-workers published a quantitative structure activity relationship study showing that in a series of simple thioureas with one n-hexyl substituent and a phenyl substituent with different groups in the 4-position, the lipophilicity of the receptor is the dominant molecular parameter determining effective transport, with smaller contributions from the receptors’ volume and affinity for chloride. [8]

Very recent work has focused on the design of new assays to measure anion transport [9] and the development of selective transporters. [10] [11] Gale is notable for his work at the interface of supramolecular and medicinal chemistry showing the effect that anionophores developed in his research group have on biological systems. This includes restoring the flux of chloride through epithelial cell membranes (with potential future application as a channel replacement therapy in cystic fibrosis) [12] [13] and causing cell death in cancer cells by triggering apoptosis and interfering with autophagy. [14] [15]

Other aspects of Gale's work on transmembrane transport include the first synthetic chloride pumping system that uses fatty acids as fuels to create a chloride gradient across a lipid bilayer membrane, [16] and the development of anion transporters that can be switched by membrane potential gradients [17] or by the presence of reducing agents found in higher concentrations in tumours than in healthy tissue. [18]

Gale is listed as a Thomson Reuters/Clarivate Analytics Highly Cited Research in Chemistry [19] and has received a number of awards for his research including the RSC Bob Hay Lectureship in 2004, [20] RSC Corday-Morgan Prize in 2005, a 2013 Royal Society Wolfson Research Merit Award, RSC Supramolecular Chemistry Award in 2014 [21] and the International Izatt-Christensen Award in Macrocyclic and Supramolecular Chemistry in 2018. [22] In 2020 he was awarded a University of Sydney Vice-Chancellor’s Excellence Award for Outstanding Research [23] and was highlighted by The Australian newspaper Research supplement (23 September 2020) as an Australian Field Research Leader (Chemistry & Material Sciences (general)) [24] and in the 2024 issue as the field leader in inorganic chemistry. [25]

Gale is the editor-in-chief of Coordination Chemistry Reviews. [26]

Related Research Articles

Supramolecular chemistry refers to the branch of chemistry concerning chemical systems composed of a discrete number of molecules. The strength of the forces responsible for spatial organization of the system range from weak intermolecular forces, electrostatic charge, or hydrogen bonding to strong covalent bonding, provided that the electronic coupling strength remains small relative to the energy parameters of the component. While traditional chemistry concentrates on the covalent bond, supramolecular chemistry examines the weaker and reversible non-covalent interactions between molecules. These forces include hydrogen bonding, metal coordination, hydrophobic forces, van der Waals forces, pi–pi interactions and electrostatic effects.

<span class="mw-page-title-main">Chloride channel</span> Class of transport proteins

Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration in vivo is much higher than other anions. Several families of voltage-gated channels and ligand-gated channels have been characterized in humans.

<span class="mw-page-title-main">Corannulene</span> Chemical compound

Corannulene is a polycyclic aromatic hydrocarbon with chemical formula C20H10. The molecule consists of a cyclopentane ring fused with 5 benzene rings, so another name for it is [5]circulene. It is of scientific interest because it is a geodesic polyarene and can be considered a fragment of buckminsterfullerene. Due to this connection and also its bowl shape, corannulene is also known as a buckybowl. Buckybowls are fragments of buckyballs. Corannulene exhibits a bowl-to-bowl inversion with an inversion barrier of 10.2 kcal/mol (42.7 kJ/mol) at −64 °C.

<span class="mw-page-title-main">Prestin</span> Protein-coding gene in the species Homo sapiens

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In chemistry, a salt bridge is a combination of two non-covalent interactions: hydrogen bonding and ionic bonding. Ion pairing is one of the most important noncovalent forces in chemistry, in biological systems, in different materials and in many applications such as ion pair chromatography. It is a most commonly observed contribution to the stability to the entropically unfavorable folded conformation of proteins. Although non-covalent interactions are known to be relatively weak interactions, small stabilizing interactions can add up to make an important contribution to the overall stability of a conformer. Not only are salt bridges found in proteins, but they can also be found in supramolecular chemistry. The thermodynamics of each are explored through experimental procedures to access the free energy contribution of the salt bridge to the overall free energy of the state.

<span class="mw-page-title-main">Achim Müller</span> German scientist

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<span class="mw-page-title-main">Molecular sensor</span>

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In chemistry, π-effects or π-interactions are a type of non-covalent interaction that involves π systems. Just like in an electrostatic interaction where a region of negative charge interacts with a positive charge, the electron-rich π system can interact with a metal, an anion, another molecule and even another π system. Non-covalent interactions involving π systems are pivotal to biological events such as protein-ligand recognition.

<span class="mw-page-title-main">Squaramide</span> Chemical compound

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<span class="mw-page-title-main">Synthetic ion channels</span>

Synthetic ion channels are de novo chemical compounds that insert into lipid bilayers, form pores, and allow ions to flow from one side to the other. They are man-made analogues of natural ion channels, and are thus also known as artificial ion channels. Compared to biological channels, they usually allow fluxes of similar magnitude but are

  1. minuscule in size,
  2. diverse in molecular architecture, and
  3. may rely on diverse supramolecular interactions to pre-form the active, conducting structures.
<span class="mw-page-title-main">3,4-Dichloroamphetamine</span> Chemical compound

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The anion exchanger family is a member of the large APC superfamily of secondary carriers. Members of the AE family are generally responsible for the transport of anions across cellular barriers, although their functions may vary. All of them exchange bicarbonate. Characterized protein members of the AE family are found in plants, animals, insects and yeast. Uncharacterized AE homologues may be present in bacteria. Animal AE proteins consist of homodimeric complexes of integral membrane proteins that vary in size from about 900 amino acyl residues to about 1250 residues. Their N-terminal hydrophilic domains may interact with cytoskeletal proteins and therefore play a cell structural role. Some of the currently characterized members of the AE family can be found in the Transporter Classification Database.

The sulfate permease (SulP) family is a member of the large APC superfamily of secondary carriers. The SulP family is a large and ubiquitous family of proteins derived from archaea, bacteria, fungi, plants and animals. Many organisms including Bacillus subtilis, Synechocystis sp, Saccharomyces cerevisiae, Arabidopsis thaliana and Caenorhabditis elegans possess multiple SulP family paralogues. Many of these proteins are functionally characterized, and most are inorganic anion uptake transporters or anion:anion exchange transporters. Some transport their substrate(s) with high affinities, while others transport it or them with relatively low affinities. Others may catalyze SO2−
4
:HCO
3
exchange, or more generally, anion:anion antiport. For example, the mouse homologue, SLC26A6, can transport sulfate, formate, oxalate, chloride and bicarbonate, exchanging any one of these anions for another. A cyanobacterial homologue can transport nitrate. Some members can function as channels. SLC26A3 and SLC26A6 can function as carriers or channels, depending on the transported anion. In these porters, mutating a glutamate, also involved in transport in the CIC family, created a channel out of the carrier. It also changed the stoichiometry from 2Cl/HCO
3
to 1Cl/HCO
3
.

The borate bromides are mixed anion compounds that contain borate and bromide anions. They are in the borate halide family of compounds which also includes borate fluorides, borate chlorides, and borate iodides.

The borate iodides are mixed anion compounds that contain both borate and iodide anions. They are in the borate halide family of compounds which also includes borate fluorides, borate chlorides, and borate bromides.

A Phosphide chloride is a mixed anion compound containing both phosphide (P3−) and chloride (Cl) ions.

Arsenide chlorides or chloride arsenides are compounds containing anions composed of chloride (Cl) and arsenide (As3−). They can be considered as mixed anion compounds. They are in the category of pnictidehalides. Related compounds include the arsenide bromides, arsenide iodides, phosphide chlorides, and antimonide chlorides.

References

  1. Gale, Philip A.; Howe, Ethan N.W.; Wu, Xin (September 2016). "Anion Receptor Chemistry". Chem. 1 (3): 351–422. doi: 10.1016/j.chempr.2016.08.004 .
  2. Busschaert, Nathalie; Caltagirone, Claudia; Van Rossom, Wim; Gale, Philip A. (12 August 2015). "Applications of Supramolecular Anion Recognition". Chemical Reviews. 115 (15): 8038–8155. doi: 10.1021/acs.chemrev.5b00099 . PMID   25996028.
  3. "P.A. Gale". www.journals.elsevier.com.
  4. Gale, Philip A. (1 July 2006). "Structural and Molecular Recognition Studies with Acyclic Anion Receptors". Accounts of Chemical Research. 39 (7): 465–475. doi:10.1021/ar040237q. PMID   16846210.
  5. Busschaert, Nathalie; Wenzel, Marco; Light, Mark E.; Iglesias-Hernández, Paulina; Pérez-Tomás, Ricardo; Gale, Philip A. (7 September 2011). "Structure–Activity Relationships in Tripodal Transmembrane Anion Transporters: The Effect of Fluorination". Journal of the American Chemical Society. 133 (35): 14136–14148. doi:10.1021/ja205884y. PMC   3436094 . PMID   21846096.
  6. Busschaert, Nathalie; Kirby, Isabelle L.; Young, Sarah; Coles, Simon J.; Horton, Peter N.; Light, Mark E.; Gale, Philip A. (27 April 2012). "Squaramides as Potent Transmembrane Anion Transporters". Angewandte Chemie International Edition. 51 (18): 4426–4430. doi:10.1002/anie.201200729. PMID   22461434. S2CID   34164978.
  7. Karagiannidis, Louise E.; Haynes, Cally J. E.; Holder, Katie J.; Kirby, Isabelle L.; Moore, Stephen J.; Wells, Neil J.; Gale, Philip A. (16 September 2014). "Highly effective yet simple transmembrane anion transporters based upon ortho-phenylenediamine bis-ureas". Chemical Communications. 50 (81): 12050–12053. doi: 10.1039/C4CC05519E . PMID   25178589.
  8. Busschaert, Nathalie; Bradberry, Samuel J.; Wenzel, Marco; Haynes, Cally J. E.; Hiscock, Jennifer R.; Kirby, Isabelle L.; Karagiannidis, Louise E.; Moore, Stephen J.; Wells, Neil J.; Herniman, Julie; Langley, G. John; Horton, Peter N.; Light, Mark E.; Marques, Igor; Costa, Paulo J.; Félix, Vítor; Frey, Jeremy G.; Gale, Philip A. (2 July 2013). "Towards predictable transmembrane transport: QSAR analysis of anion binding and transport". Chemical Science. 4 (8): 3036–3045. doi:10.1039/C3SC51023A. hdl: 10773/19223 . S2CID   95013961.
  9. Wu, Xin; Howe, Ethan N. W.; Gale, Philip A. (21 August 2018). "Supramolecular Transmembrane Anion Transport: New Assays and Insights". Accounts of Chemical Research. 51 (8): 1870–1879. doi:10.1021/acs.accounts.8b00264. hdl: 2123/24729 . PMID   30063324. S2CID   51890600.
  10. Wu, Xin; Gale, Philip A. (2021). "Measuring anion transport selectivity: a cautionary tale". Chemical Communications. 57 (33): 3979–3982. doi:10.1039/D1CC01038G. hdl: 2123/27334 . PMID   33885701. S2CID   233349341.
  11. Wu, Xin; Judd, Luke W.; Howe, Ethan N.W.; Withecombe, Anne M.; Soto-Cerrato, Vanessa; Li, Hongyu; Busschaert, Nathalie; Valkenier, Hennie; Pérez-Tomás, Ricardo; Sheppard, David N.; Jiang, Yun-Bao; Davis, Anthony P.; Gale, Philip A. (July 2016). "Nonprotonophoric Electrogenic Cl − Transport Mediated by Valinomycin-like Carriers". Chem. 1 (1): 127–146. doi: 10.1016/j.chempr.2016.04.002 . hdl: 1983/e011b659-e323-496b-942f-048a49fbc7b4 .
  12. Spooner, Michael J.; Li, Hongyu; Marques, Igor; Costa, Pedro M. R.; Wu, Xin; Howe, Ethan N. W.; Busschaert, Nathalie; Moore, Stephen J.; Light, Mark E.; Sheppard, David N.; Félix, Vítor; Gale, Philip A. (2019). "Fluorinated synthetic anion carriers: experimental and computational insights into transmembrane chloride transport". Chemical Science. 10 (7): 1976–1985. doi:10.1039/C8SC05155K. PMC   6381411 . PMID   30881627.
  13. Li, Hongyu; Valkenier, Hennie; Thorne, Abigail G.; Dias, Christopher M.; Cooper, James A.; Kieffer, Marion; Busschaert, Nathalie; Gale, Philip A.; Sheppard, David N.; Davis, Anthony P. (2019). "Anion carriers as potential treatments for cystic fibrosis: transport in cystic fibrosis cells, and additivity to channel-targeting drugs". Chemical Science. 10 (42): 9663–9672. doi:10.1039/C9SC04242C. PMC   6984391 . PMID   32055336.
  14. Busschaert, Nathalie; Park, Seong-Hyun; Baek, Kyung-Hwa; Choi, Yoon Pyo; Park, Jinhong; Howe, Ethan N. W.; Hiscock, Jennifer R.; Karagiannidis, Louise E.; Marques, Igor; Félix, Vítor; Namkung, Wan; Sessler, Jonathan L.; Gale, Philip A.; Shin, Injae (July 2017). "A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations". Nature Chemistry. 9 (7): 667–675. Bibcode:2017NatCh...9..667B. doi:10.1038/nchem.2706. PMC   5648535 . PMID   28644464.
  15. Park, Sang-Hyun; Park, Seong-Hyun; Howe, Ethan N.W.; Hyun, Ji Young; Chen, Li-Jun; Hwang, Inhong; Vargas-Zuñiga, Gabriela; Busschaert, Nathalie; Gale, Philip A.; Sessler, Jonathan L.; Shin, Injae (August 2019). "Determinants of Ion-Transporter Cancer Cell Death". Chem. 5 (8): 2079–2098. doi:10.1016/j.chempr.2019.05.001. PMC   8009298 . PMID   33791443.
  16. Howe, Ethan N. W.; Gale, Philip A. (10 July 2019). "Fatty Acid Fueled Transmembrane Chloride Transport". Journal of the American Chemical Society. 141 (27): 10654–10660. doi:10.1021/jacs.9b02116. PMID   31244178. S2CID   195695655.
  17. Wu, Xin; Small, Jennifer R.; Cataldo, Alessio; Withecombe, Anne M.; Turner, Peter; Gale, Philip A. (14 October 2019). "Voltage-Switchable HCl Transport Enabled by Lipid Headgroup–Transporter Interactions". Angewandte Chemie International Edition. 58 (42): 15142–15147. doi:10.1002/anie.201907466. PMID   31400024. S2CID   199519085.
  18. Fares, Mohamed; Wu, Xin; Ramesh, Deepthi; Lewis, William; Keller, Paul A.; Howe, Ethan N. W.; Pérez-Tomás, Ricardo; Gale, Philip A. (28 September 2020). "Stimuli-Responsive Cycloaurated 'OFF-ON' Switchable Anion Transporters". Angewandte Chemie International Edition. 59 (40): 17614–17621. doi:10.1002/anie.202006392. hdl: 2123/23683 . PMID   32583552. S2CID   220059631.
  19. "Clarivate Analytics Highly Cited Researchers 2018". clarivate.com. Archived from the original on 2019-02-20. Retrieved 2020-05-05.
  20. "The Bob Hay Lectureship". www.rsc.org.
  21. "Supramolecular Chemistry Award 2014 Winner". www.rsc.org.
  22. "Ryoji Noyori ACES Award: M. G. Banwell / Liebig Memorial Medal: W. Schnick / Izatt-Christensen Award: P. A. Gale / Cram Lehn Pedersen Prize: R. Klajn". Angewandte Chemie International Edition. 57 (38): 12210. 17 September 2018. doi:10.1002/anie.201809044. S2CID   52018834.
  23. "Staff Profile".
  24. "Research September 2020". Research September 2020. Retrieved 2021-07-13.
  25. "Research September 2024".
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