Sensing
Many anions are problematic environmental contaminants and are vital to many processes in nature, with anion binding proteins and transport channels implicated in the mechanisms of many disease pathways. This avenue of research is a productive collaboration between the Haley lab and that of UO colleague Darren Johnson to target new organic receptors that selectively bind and sense anions. The project is a union of the synthetic expertise of the Haley group toward the assembly of relatively rigid and inherently fluorescent molecules based on arylethynyl scaffolding with the extensive knowledge of the Johnson lab to design and exhaustively analyze complex supramolecular systems.
The modularity of our design strategy allows for exploration of a variety of recognition motifs for anions, including electrostatic attractions, hydrogen bond interactions and attractions with electron-deficient arenes (anion-π, CH•••X– hydrogen bonds and weak-sigma complexes). This flexibility affords the possibility of selectively binding anions that are challenging to target with traditional approaches. Core and linker substitution provides another approach to tuning the selectivity of the receptors by changing the shape and size of the binding pocket, in addition to modification of the fluorescent behavior through adjustment of the electronics of the conjugated core fluorophore. The functionality of the receptors can also be adjusted to provide water-solubility to the molecules or even cell membrane permeability. These sensors will have long-term applications in sensing, imaging and/or remediating anions, which will impact public health in both discovering and removing environmental contaminants and imaging the role anions play in biological processes.
A serendipitous spin-off of the arylethynyl work is a new, simple synthesis of rarely-reported phosphorous- and nitrogen-containing heterocycles called phosphaquinolines and phosphaquinolinones. In addition to fundamental studies on the scaffold itself, we have appended the heterocycle onto various acenes to make PN-anthracene, PN-phenanthrenes, and PN-pyrenes. We can make the fluorophores rather bright by restricting the degrees of conformational freedom. One of the most exciting results is that a hybrid arylethynyl urea/PN-heterocycle receptor strongly and selectively binds hydrogen sulfate, which is also an environmental pollutant.
Work on the bis(arylethynyl) bisurea based receptor class led to a successful start-up company, SupraSensor Technologies. Co-founded by Haley, Johnson, and former graduate student Dr. Calden Carroll, SupraSensor targets nitrate detection for applications in precision agriculture. Both the basic research from the Haley/Johnson collaboration as well as the applied science from Carroll and his team were highlighted in an NSF-sponsored “Science Nation” video (http://www.nsf.gov/news/special_reports/science_nation/suprasensor.jsp). SupraSensor was acquired in 2016 by The Climate Corporation.
Relevant Publications
Bumpy Roads Lead to Beautiful Places: The Twists and Turns in Developing a New Class of PN-Heterocycles
Bard, J. P.; Johnson, D. W.; Haley, M. M.Synlett 2020, 31, in press.
DOI: 10.1055/s-0040-1707168
Tuning Supramolecular Selectivity for Hydrosulfide: Linear Free Energy Relationships Reveal Preferential C-H Hydrogen Bond Interactions
Fargher, H. A.; Lau, N.; Richardson, H. C.; Cheong, P. H.-Y.; Haley, M. M.; Pluth, M. D.; Johnson, D. W. J. Am. Chem. Soc. 2020, 142, 8243-8251.
DOI: 10.1021/jacs.0c00441
A highly fluorescent PN-heterocycle-fused pyrene derivative with strong self-dimerisation through hydrogen bonding
Bard, J. P.; Mancuso, J. L.; Deng, C.-L.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Supramol. Chem. 2020, 32, 49-55.
DOI: 10.1080/10610278.2019.1687896
Amplification of the Quantum Yields of 2-λ5-Phosphaquinolin-2-ones through Phosphorus Center Modification
Bard, J. P.; Bates, H. J.; Deng, C.-L.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. J. Org. Chem. 2019, 85, 85-91.
DOI: 10.1021/acs.joc.9b02132
PN-Containing Pyrene Derivatives: Synthesis, Structure, and Photophysical Properties
Deng, C.-L.; Bard, J. P.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Org. Lett. 2019, 21, 6427-6431.
DOI: 10.1021/acs.orglett.9b02332
Naphtho[2,1-e]-1,2-azaphosphorine-2-oxide Derivatives: Synthesis, Optoelectronic Properties, and Self-Dimerization Phenomena
Deng, C.-L.; Bard, J. P.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. J. Org. Chem. 2019, 84, 8131-8139.
DOI: 10.1021/acs.joc.9b00994
The road to aryl CH—anion binding was paved with good intentions: fundamental studies, host design, and historical perspectives in CH hydrogen bonding
Eytel, L. M.; Fargher, H. A.; Haley, M. M.; Johnson, D. W. Chem. Commun. 2019, 55, 5195-5206.
DOI: 10.1039/C9CC01460H
Synthesis, photophysical properties, and self-dimerization studies of 2-λ5-phosphaquinolin-2-ones
Bard, J. P.; Deng, C. L.; Richardson, H. C.; Odulio, J. M.; Barker, J. E.; Zakharov, L. N.; Cheong, P. H.-Y.; Johnson, D. W.; Haley, M. M. Org. Chem. Front. 2019, 6, 1257-1265.
DOI: 10.1039/C9QO00199A
Exploiting the Hydrogen Bond Donor/Acceptor Properties of PN-Heterocycles: Selective Anion Receptors for Hydrogen Sulfate
Deng, C.-L.; Bard, J. P.; Lohrman, J. A.; Barker, J. E.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Angew. Chem. 2019, 131, 3974-3978.; Angew. Chem. Int. Ed. 2019, 58, 3934-3938.
DOI: 10.1002/anie.201814431
Methanesulfonyl-Polarized Halogen Bonding Enables Strong Halide Recognition in an Arylethynyl Anion Receptor
Lohrman, J. A.; Deng, C.-L.; Shear, T. A.; Zakharov, L. N.; Haley, M. M.; Johnson, D. W. Chem. Commun. 2019, 55, 1919-1922.
DOI: 10.1039/C8CC09251F
Expanding reversible chalcogenide binding: supremolecular receptors for the hydroselenide (HSe-) anion
Fargher, H. A.; Lau, N.; Zakharov, L. N.; Haley, M. M.; Johnson, D. W.; Pluth, M. D. Chem. Sci. 2019, 10, 67-72.
DOI: 10.1039/C8SC03968B
Conformationally flexible arylethynyl bis-urea receptors bind disparate oxoanions with similar, high affinities
Eytel, L. M.; Brueckner, A. C; Lohrman, J. A.; Haley, M. M.; Cheong, P. H.-Y.; Johnson, D. W. Chem. Commun. 2018, 54, 13208-13211.
DOI: 10.1039/C8CC07301E
Synthesis and Properties of Naphtho[2,3-e]-1,2-azaphosphorine 2-Oxides: PN-Anthracene Analogues
Takaesu, N. A.; Ohta, E.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Organometallics 2017, 36, 2491-2493.
DOI: 10.1021/acs.organomet.7b00281
Computational and Experimental Evidence of Emergent Equilibrium Isotope Effects in Anion Receptor Complexes
Tresca, B. W.; Brueckner, A.C.; Haley, M. M.; Cheong, P. H.-Y.; Johnson, D. W. J. Am. Chem. Soc. 2017, 139, 3962-3965.
DOI: 10.1021/jacs.7b00612
Do CH-Anion and Anion-π Interactions Alter the Mechanism of 2:1 Host-Guest Complexation in Arylethynyl Monourea Anion Receptors?
Eytel, L. M.; Gilbert, A. K.; Gorner, P.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Chem. Eur. J. 2017, 23, 4051-4054.
DOI: 10.1002/chem.201605452
A Synthetic Supramolecular Receptor for the Hydrosulfide Anion”
Hartle, M. D.; Hansen, R. J.; Tresca, B. W.; Prakel, S. S.; Zakharov, L. N.; Haley, M. M.; Pluth, M. D.; Johnson, D. W. Angew. Chem. Int. Ed. 2016, 55, 11480-11484.
DOI: 10.1002/anie.201605757
Harnessing solid-state packing for selective detection of chloride in a macrocyclic anionophore
Vonnegut, C. L.; Shonkwiler, A. M.; Zakharov, L. N.; Haley, M. M.; Johnson, D. W. Chem. Commun. 2016, 52, 9506-9509.
DOI: 10.1039/C6CC03795J
Anion-directed self-assembly of a 2,6-bis(2-anilinoethynyl)pyridine bis(amide) scaffold
Tresca, B. W.; Berryman, O. B.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Supramol. Chem. 2016, 28, 37-44.
DOI: 10.1080/10610278.2015.1072199
Substituent Effects in CH Hydrogen Bond Interactions: Linear Free Energy Relationships and Influence of Anions
Tresca, B. W.; Hansen, R. J.; Chau, C. V.; Hay, B. P.; Zakharov, L. N.; Haley, M. M.; Johnson, D. W. J. Am. Chem. Soc. 2015, 137, 14959-14967.
DOI: 10.1021/jacs.5b08767
Facile Synthesis and Properties of 2-λ5-Phosphaquinolines and 2-λ5-Phosphaquinolinones
Vonnegut, C. L.; Shonkwiler, A. M.; Khalifa, M. K.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Angew. Chem. Int. Ed. 2015, 54, 13318-13322.
DOI: 10.1002/anie.201507696
‘Off-On’ Aggregation-Based Fluorescent Sensor for the Detection of Chloride in Water
Watt, M. M.; Engle, J. M.; Fairley, K. C.; Robitshek, T. E.; Haley, M. M.; Johnson, D. W. Org. Biomol. Chem. 2015, 13, 4266-4270.
DOI: 10.1039/C4OB02409E
Solid-State Examination of Conformationally Diverse Sulfonamide Receptors Based on Bis(2-anilinoethynyl)pyridine, -Bipyridine, and -Thiophene
Berryman, O. B.; Johnson, C. A.; Vonnegut, C. L.; Fajardo, K. A.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Cryst. Growth Des. 2015, 15, 1502-1511.
DOI: 10.1021/cg5018856
Ion and Molecular Recognition Using Aryl–Ethynyl Scaffolding
Vonnegut, C. L.; Tresca, B. W.; Johnson, D. W.; Haley, M. M. Chem. Asian J. 2015, 10, 522-535.
DOI: 10.1002/asia.201403212
Cover art:
Exploring anion-induced conformational flexibility and molecular switching in a series of heteroaryl-urea receptors
Gavette, J. V.; Evoniuk, C. J.; Zakharov, L. N.; Carnes, M. E.; Haley, M. M.; Johnson, D. W. Chem. Sci. 2014, 5, 2899–2905.
DOI: 10.1039/C4SC00950A
Intramolecular N–H•••Cl hydrogen bonds in the outer coordination sphere of a bipyridyl bisurea-based ligand stabilize a tetrahedral FeLCl2 complex
Gavette, J. V.; Klug, C. M.; Zakharov, L. N.; Shores, M. P.; Haley, M. M.; Johnson, D. W. Chem. Commun. 2014, 50, 7173–7175.
DOI: 10.1039/C4CC02297A
Synthesis and solid-state structures of a macrocyclic receptor based on the 2,6-bis(2-anilinoethynyl)pyridine scaffold
J. M. Engle, P. S. Singh, C. L. Vonnegut, L. N. Zakharov, D. W. Johnson and M. M. Haley CrystEngComm 2014, 16, 3703-3706.
DOI: 10.1039/C3CE42307G
Selective Nitrate Binding in Competitive Hydrogen Bonding Solvents: Do Anion–π Interactions Facilitate Nitrate Selectivity?
Watt, M. M.; Zakharov, L. N.; Haley, M. M.; Johnson, D. W. Angew. Chem. Int. Ed. 2013, 52, 10275–10280.
DOI: 10.1002/anie.201303881
An Anion-Modulated Three-Way Supramolecular Switch that Selectively Binds Dihydrogen Phosphate, H2PO4−
Gavette, J. V.; Mills, N. S.; Zakharov, L. N.; Johnson, C. A.; Johnson, D. W.; Haley, M. M. Angew. Chem. Int. Ed 2013, 52, 10460–10464.
DOI: 10.1002/anie.201302929
Aryl C–H•••Cl− hydrogen bonding in a fluorescent anion sensor
Tresca, B. W.; Zakharov, L. N.; Carroll, C. N.; Johnson, D. W.; Haley, M. M. Chem. Commun. 2013, 49, 7240-7242.
DOI: 10.1039/C3CC44574G
Lithium-selective phosphine oxide-based ditopic receptors show enhanced halide binding upon alkali metal ion coordination
Gavette, J. V.; Lara, J.; Reling, L. L.; Haley, M. M.; Johnson, D. W. Chem. Sci. 2013, 4, 585-590.
DOI: 10.1039/C2SC21501B
Synthesis and optoelectronic properties of 2,6-bis(2-anilinoethynyl)pyridine scaffolds
Engle, J. M.; Carroll, C. N.; Johnson, D. W.; Haley, M. M. Chem. Sci. 2012, 3, 1105-1110.
DOI: 10.1039/C2SC00975G
Molecular Self-Assembly: Solvent Guests Tune the Conformation of a series of 2,6-Bis(2-anilinoethynyl)pyridine-Based Ureas
Engle, J. M.; Lakshminarayanan, P. S.; Carroll, C. N.; Zakharov, L. N.; Haley, M. M.; Johnson, D. W. Cryst. Growth Des. 2011, 11, 5144-5152.
DOI: 10.1021/cg201074v
Lithium cation enhances anion binding in a tripodal phosphine oxide-based ditopic receptor
Gavette, J. V.; Lara, J.; Berryman, O. B.; Zakharov, L. N.; Haley, M. M.; Johnson, D. W. Chem. Commun. 2011, 47, 7653-7655.
DOI: 10.1039/C1CC12475G
Anion-dependent fluorescence in bis(anilinoethynyl)pyridine derivatives: switchable ON–OFF and OFF–ON responses
Carroll, C. N.; Coombs, B. A.; McClintock, S. P.; Johnson II, C. A.; Berryman, O. B.; Johnson, D. W.; Haley, M. M. Chem. Commun. 2011, 47, 5539-5541.
DOI: 10.1039/C1CC10947B
Arylethynyl receptors for neutral molecules and anions: emerging applications in cellular imaging
Carroll, C. N.; Naleway, J. J.; Haley, M. M.; Johnson, D. W. Chem. Soc. Rev. 2010, 39, 3875–3888.
DOI: 10.1039/B926231H
Anion Binding Induces Helicity in a Hydrogen-Bonding Receptor: Crystal Structure of a 2,6-Bis(anilinoethynyl)pyridinium Chloride
Johnson, C. A.; Berryman, O. B.; Sather, A. C.; Zakharov, L. N.; Haley, M. M.; Johnson , D. W. Cryst. Growth Des., 2009, 9, 4247–4249.
DOI: 10.1021/cg900674p
Protonation activates anion binding and alters binding selectivity in new inherently fluorescent 2,6-bis(2-anilinoethynyl)pyridine bisureas
Carroll, C. N.; Berryman, O. B.; Johnson, C. A.; Zakharov, L. N.; Haley, M. M.; Johnson, D. W. Chem. Commun. 2009, 18, 2520–2522.
DOI: 10.1039/B901643K
Water and Hydrogen Halides Serve the Same Structural Role in a Series of 2+2 Hydrogen-Bonded Dimers Based on 2,6-Bis(2-anilinoethynyl)pyridine Sulfonamide Receptors
Berryman, O. B.; Johnson, C. A.; Zakharov, L. N.; Haley, M. M.; Johnson D. W. Angew. Chem. Int. Ed. 2008, 47, 117-120.
DOI: 10.1002/anie.200703971
