Abstract
We describe application of theory and kinetic modeling to study transport of basic anions by the small synthetic molecules. The findings should equip researchers in the particular field with a tool necessary to address an essential question: whether a given anion transporter facilitates permeation of F−, CH3COO−, N3 −, and SCN− across biological membrane or it does not. The basic anions undergo hydrolysis and conjugate acids (HAnion) are permeant species. However, because methods to quantitatively account for HAnion transport do not exist, traditionally, the phenomenon is also treated as non-existing. When the relative activities and selectivity of the synthetic anionophores are evaluated, basic and non-basic anions are regarded in the same exact way. Here, we show that HAnion and H+/OH− transport proceed on the same time scale as the anion exchange, nevertheless, comprehensive kinetic study could provide solution to the problems at hands, such as selective transport of HCO3 − or F− anions. We also use theory and modeling to study other questions of particular concern: transport of OH− and H+ ions, facilitated by the small synthetic anionophore, origin of modified anti-Hofmeister selectivity, multi-ion hopping, and anomalous mole-fraction effect in the synthetic ion channels. We do not need to model kinetics in a synthetic channel with multiple ion binding sites. Instead, we “test” the most simple anionophore, a lipophilic electroneutral carrier with Hofmeister-like selectivity, in the classical assays as “presumably, Cl−/OH− antiporter.” The implications of findings to the particular field and beyond are discussed.
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Adriaenssens L, Estarellas C, Vargas Jentzsch A, Martinez Belmonte M, Matile S, Ballester P (2013) Quantification of nitrate–π interactions and selective transport of nitrate using calix[4]pyrroles with two aromatic walls. J Am Chem Soc 135:8324–8330. doi:10.1021/ja4021793
Alvares-Leefmans FJ, Delpire E (2009) Physiology and pathology of chloride transporters and channels in the nervous system. From molecules to diseases. Elsevier-Academic Press, San Diego, CA
Arnaud C (2005) Synthetic sodium transporter. Covalently modified G-quadruplex moves sodium across lipid bilayer. Chem Eng News 2(2006):2010
Arranz-Mascaros P et al (2013) Thermodynamics of anion–pi interactions in aqueous solution. J Am Chem Soc 135:102–105. doi:10.1021/ja311389z
Badr IH, Meyerhoff ME (2005) Highly selective optical fluoride ion sensor with submicromolar detection limit based on aluminum(III) octaethylporphyrin in thin polymeric film. J Am Chem Soc 127:5318–5319. doi:10.1021/ja0500153
Bahmanjah S, Zhang N, Davis JT (2012) Monoacylglycerols as transmembrane Cl− anion transporters. Chem Commun 48:4432–4434. doi:10.1039/c2cc18148g
Baker JL, Sudarsan N, Weinberg Z, Roth A, Stockbridge RB, Breaker RR (2012) Widespread genetic switches and toxicity resistance proteins for fluoride. Science 335:233–235. doi:10.1126/science.1215063
Bemporad D, Luttmann C, Essex JW (2004) Computer simulation of small molecule permeation across a lipid bilayer: dependence on bilayer properties and solute volume, size, and cross-sectional area. Biophys J 87:1–13. doi:10.1529/biophysj.103.030601
Benz R, McLaughlin S (1983) The molecular mechanism of action of the proton ionophore FCCP (carbonylcyanide p-trifluoromethoxyphenylhydrazone). Biophys J 41:381–398. doi:10.1016/s0006-3495(83)84449-x
Berezin SK (2009) Catechols as membrane anion transporters. J Am Chem Soc 131(7):2458–2459
Berezin SK (2013) Theoretical modelling of anion transport in liposomes: electrogenic anion exchange as a new paradigm in supramolecular chemistry. Supramol Chem 25:323–334. doi:10.1080/10610278.2013.782099
Berezin SK, Davis JT (2007) Study of anion transport by prodigiosin using novel HPTS-based assay. Unpublished results. University of Maryland Chemistry&Biochemistry Department
Berezin SK, Davis JT (2009) Catechols as membrane anion transporters. J Am Chem Soc 131:2458–2459. doi:10.1021/ja809733c
Berryman OB, Bryantsev VS, Stay DP, Johnson DW, Hay BP (2007) Structural criteria for the design of anion receptors: the interaction of halides with electron-deficient arenes. J Am Chem Soc 129:48–58. doi:10.1021/ja063460m
Bhosale S et al (2006) Photoproduction of proton gradients with pi-stacked fluorophore scaffolds in lipid bilayers. Science 313:84–86. doi:10.1126/science.1126524
Busschaert N et al (2010) Tripodal transmembrane transporters for bicarbonate. Chem Commun 46:6252–6254. doi:10.1039/c0cc01684e
Busschaert N, Wenzel M, Light ME, Iglesias-Hernández P, Pérez-Tomás R, Gale PA (2011) Structure–activity relationships in tripodal transmembrane anion transporters: the effect of fluorination. J Am Chem Soc 133:14136–14148. doi:10.1021/ja205884y
Chifotides HT, Dunbar KR (2013) Anion–pi interactions in supramolecular architectures. Acc Chem Res 46:894–906. doi:10.1021/ar300251k
Davis JT (2010) Supramolecular chemistry: anion transport as easy as pi. Nat Chem 2:516–517. doi:10.1038/nchem.723
Davis AP, Sheppard DN (2012) Synthetic anionophores with therapeutic potential: a coordinated two-centre approach. EPSRC Physical Sciences Chemistry
Davis AP, Sheppard DN, Smith BD (2007) Development of synthetic membrane transporters for anions. Chem Soc Rev 36:348–357. doi:10.1039/b512651g
Davis JT, Gale PA, Okunola OA, Prados P, Iglesias-Sanchez JC, Torroba T, Quesada R (2009) Using small molecules to facilitate exchange of bicarbonate and chloride anions across liposomal membranes. Nat Chem 1:138–144. doi:10.1038/nchem.178
Dawson RE et al (2010) Experimental evidence for the functional relevance of anion–pi interactions. Nat Chem 2:533–538. doi:10.1038/nchem.657
Deamer DW, Nichols JW (1983) Proton-hydroxide permeability of liposomes. Proc Natl Acad Sci USA 80:165–168
Forman SL, Fettinger JC, Pieraccini S, Gottarelli G, Davis JT (2000) Toward artificial ion channels: a lipophilic G-quadruplex. J Am Chem Soc 122:4060–4067. doi:10.1021/ja9925148
Frontera A, Gamez P, Mascal M, Mooibroek TJ, Reedijk J (2011) Putting anion–pi interactions into perspective. Angew Chem 50:9564–9583. doi:10.1002/anie.201100208
Fyles TM (2007) Synthetic ion channels in bilayer membranes. Chem Soc Rev 36:335–347. doi:10.1039/b603256g
Gale PA (2011) From anion receptors to transporters. Acc Chem Res 44:216–226. doi:10.1021/ar100134p
Gale PA (2012) Research Projects. http://www.supramolecularchemistry.net. Accessed 6 June 2012
Gale PA et al (2010) Octafluorocalix[4]pyrrole: a chloride/bicarbonate antiport agent. J Am Chem Soc 132:3240–3241. doi:10.1021/ja9092693
Gale PA, Perez-Tomas R, Quesada R (2013) Anion transporters and biological systems. Acc Chem Res 46:2801–2813. doi:10.1021/ar400019p
Gil-Ramírez G, Escudero-Adán EC, Benet-Buchholz J, Ballester P (2008) Quantitative evaluation of anion–π interactions in solution. Angew Chem 47:4114–4118. doi:10.1002/anie.200800636
Gokel GW (2000) Hydraphiles: design, synthesis and analysis of a family of synthetic, cation-conducting channels. Chem Commun 1–9. doi:10.1039/A903825F
Gokel GW, Carasel IA (2007) Biologically active, synthetic ion transporters. Chem Soc Rev 36:378–389. doi:10.1039/b605910b
Gokel GW, Daschbach MM (2008) Coordination and transport of alkali metal cations through phospholipid bilayer membranes by hydraphile channels. Coord Chem Rev 252:886–902. doi:10.1016/j.ccr.2007.07.026
Gokel GW, Mukhopadhyay A (2001) Synthetic models of cation-conducting channels. Chem Soc Rev 30:274–286. doi:10.1039/B008667N
Gorteau V, Bollot G, Mareda J, Perez-Velasco A, Matile S (2006) Rigid oligonaphthalenediimide rods as transmembrane anion–π slides. J Am Chem Soc 128:14788–14789. doi:10.1021/ja0665747
Gorteau V, Bollot G, Mareda J, Matile S (2007) Rigid-rod anion–[small pi] slides for multi-ion hopping across lipid bilayers. Org Biomol Chem 5:3000–3012. doi:10.1039/B708337H
Guha S, Saha S (2010) Fluoride ion sensing by an anion–pi interaction. J Am Chem Soc 132:17674–17677. doi:10.1021/ja107382x
Guha S, Goodson FS, Roy S, Corson LJ, Gravenmier CA, Saha S (2011) Electronically regulated thermally and light-gated electron transfer from anions to naphthalenediimides. J Am Chem Soc 133:15256–15259. doi:10.1021/ja2055726
Guha S, Goodson FS, Corson LJ, Saha S (2012) Boundaries of anion/naphthalenediimide interactions: from anion–pi interactions to anion-induced charge-transfer and electron-transfer phenomena. J Am Chem Soc 134:13679–13691. doi:10.1021/ja303173n
Gutknecht J, Walter A (1981) Transport of protons and hydrochloric acid through lipid bilayer membranes. Biochim Biophys Acta 641:183–188
Harrell WA Jr, Bergmeyer ML, Zavalij PY, Davis JT (2010) Ceramide-mediated transport of chloride and bicarbonate across phospholipid membranes. Chem Commun 46:3950–3952. doi:10.1039/c0cc00493f
Hennig A, Fischer L, Guichard G, Matile S (2009) Anion–macrodipole interactions: self-assembling oligourea/amide macrocycles as anion transporters that respond to membrane polarization. J Am Chem Soc 131:16889–16895. doi:10.1021/ja9067518
Hille B (2001) Ionic channels of excitable membranes, 3rd edn. Sinauer Associates Inc, Sunderland, MA
Hille B, Schwarz W (1978) Potassium channels as multi-ion single-file pores. J Gen Physiol 72:409–442
Hiscock JR, Caltagirone C, Light ME, Hursthouse MB, Gale PA (2009) Fluorescent carbazolylurea anion receptors. Org Biomol Chem 7:1781–1783. doi:10.1039/B900178F
Hussain S, Brotherhood PR, Judd LW, Davis AP (2011) Diaxial diureido decalins as compact, efficient, and tunable anion transporters. J Am Chem Soc 133:1614–1617. doi:10.1021/ja1076102
Iqbal KS, Allen MC, Fucassi F, Cragg PJ (2007) Artificial transmembrane ion channels from commercial surfactants. Chem Commun 3951–3953. doi:10.1039/b707194a
Izzo I, Licen S, Maulucci N, Autore G, Marzocco S, Tecilla P, De Riccardis F (2008) Cationic calix[4]arenes as anion-selective ionophores. Chem Commun 2986–2988 doi:10.1039/B719482J
Jentzsch AV et al (2012) Transmembrane anion transport mediated by halogen-bond donors. Nat Commun 3:905. doi:10.1038/ncomms1902
Jentzsch VA, Hennig A, Mareda J, Matile S (2013) Synthetic ion transporters that work with anion–π interactions halogen bonds, and anion–macrodipole interactions. Acc Chem Res 46:2791–2800. doi:10.1021/ar400014r
Karlish SJ, Shavit N, Avron M (1969) On the mechanism of uncoupling in chloroplasts by ion-permeability inducing agents. Eur J Biochem 9:291–298
Kaucher MS, Davis JT (2006). http://www.nanocenter.umd.edu/nanoday/2006/posters/Kaucher-bioscience-poster-05f-273-04-21-06.pdf
Kaucher MS, Harrell WA Jr, Davis JT (2006) A unimolecular G-quadruplex that functions as a synthetic transmembrane Na+ transporter. J Am Chem Soc 128:38–39. doi:10.1021/ja056888e
Ke IS, Myahkostupov M, Castellano FN, Gabbai FP (2012) Stibonium ions for the fluorescence turn-on sensing of F− in drinking water at parts per million concentrations. J Am Chem Soc 134:15309–15311. doi:10.1021/ja308194w
Langecker M et al (2012) Synthetic lipid membrane channels formed by designed DNA nanostructures. Science 338:932–936. doi:10.1126/science.1225624
Leevy WM, Donato GM, Ferdani R, Goldman WE, Schlesinger PH, Gokel GW (2002) Synthetic hydraphile channels of appropriate length kill Escherichia coli. J Am Chem Soc 124:9022–9023
Li X, Shen B, Yao XQ, Yang D (2009) Synthetic chloride channel regulates cell membrane potentials and voltage-gated calcium channels. J Am Chem Soc 131:13676–13680. doi:10.1021/ja902352g
Madhavan N, Robert EC, Gin MS (2005) A highly active anion-selective aminocyclodextrin ion channel. Angew Chem 44:7584–7587. doi:10.1002/anie.200501625
Mareda J, Matile S (2009) Anion–pi slides for transmembrane transport. Chemistry 15:28–37. doi:10.1002/chem.200801643
Mascal M, Yakovlev I, Nikitin EB, Fettinger JC (2007) Fluoride-selective host based on anion–pi interactions, ion pairing, and hydrogen bonding: synthesis and fluoride-ion sandwich complex. Angew Chem 46:8782–8784. doi:10.1002/anie.200704005
Matile S, Sakai N (2007) The characterization of synthetic ion channels and pores. In: Schalley C (ed) Analytical methods in supramolecular chemistry. Wiley, Weinheim, pp 391–418. doi:10.1002/9783527610273
Matile S, Sakai N (2012) The characterization of synthetic ion channels and pores. In: Schalley CA (ed) Analytical methods in supramolecular chemistry. 2nd edn. Wiley, Weinheim, pp 711–742. doi:10.1002/9783527644131
Miller C (1984) Ion channels in liposomes. Annu Rev Physiol 46:549–558. doi:10.1146/annurev.ph.46.030184.003001
Miller C (1999) Ionic hopping defended. J Gen Physiol 113:783–787
Missner A, Pohl P (2009) 110 years of the Meyer-Overton rule: predicting membrane permeability of gases and other small compounds. Chemphyschem 10:1405–1414. doi:10.1002/cphc.200900270
Muraoka T et al (2012) Ion permeation by a folded multiblock amphiphilic oligomer achieved by hierarchical construction of self-assembled nanopores. J Am Chem Soc 134:19788–19794. doi:10.1021/ja308342g
Nozaki Y, Tanford C (1981) Proton and hydroxide ion permeability of phospholipid vesicles. Proc Natl Acad Sci USA 78:4324–4328
Otis F, Racine-Berthiaume C, Voyer N (2011) How far can a sodium ion travel within a lipid bilayer? J Am Chem Soc 133:6481–6483. doi:10.1021/ja110336s
Otis F, Auger M, Voyer N (2013) Exploiting peptide nanostructures to construct functional artificial ion channels. Acc Chem Res 46:2934–2943. doi:10.1021/ar400044k
Ovchinnikov YA, Ivanov VD, Shkrob AM (1974) Membrane active chelators. Nauka, Moscow
Paula S, Volkov AG, Deamer DW (1998) Permeation of halide anions through phospholipid bilayers occurs by the solubility–diffusion mechanism. Biophys J 74:319–327. doi:10.1016/s0006-3495(98)77789-6
Perez-Velasco A, Gorteau V, Matile S (2008) Rigid oligoperylenediimide rods: anion–pi slides with photosynthetic activity. Angew Chem 47:921–923. doi:10.1002/anie.200703749
Saha S, Guha S (2013) Colorimetric and fluorimetric fluoride sensing. Google Patents.
Sakai N, Matile S (2006) The determination of the ion selectivity of synthetic ion channels and pores in vesicles. J Phys Org Chem 19:452–460. doi:10.1002/poc.1047
Satake A, Yamamura M, Oda M, Kobuke Y (2008) Transmembrane nanopores from porphyrin supramolecules. J Am Chem Soc 130:6314–6315. doi:10.1021/ja801129a
Schweigert N, Zehnder AJ, Eggen RI (2001) Chemical properties of catechols and their molecular modes of toxic action in cells, from microorganisms to mammals. Environ Microbiol 3:81–91
Selwin MJ (1976) Triorganotin compounds as ionophores and inhibitors of ion translocating ATPases. In: Zuckerman JJ (ed) Organotin compounds: new chemistry and applications, vol 157. Advances in Chemistry, Washington, DC, pp 204–226
Smith SS, Steinle ED, Meyerhoff ME, Dawson DC (1999) Cystic fibrosis transmembrane conductance regulator. Physical basis for lyotropic anion selectivity patterns. J Gen Physiol 114:799–818
Stockbridge RB, Lim HH, Otten R, Williams C, Shane T, Weinberg Z, Miller C (2012) Fluoride resistance and transport by riboswitch-controlled CLC antiporters. Proc Natl Acad Sci USA 109:15289–15294. doi:10.1073/pnas.1210896109
Tabcharani JA, Rommens JM, Hou YX, Chang XB, Tsui LC, Riordan JR, Hanrahan JW (1993) Multi-ion pore behaviour in the CFTR chloride channel. Nature 366:79–82. doi:10.1038/366079a0
Tong CC, Quesada R, Sessler JL, Gale PA (2008) Meso-octamethylcalix[4]pyrrole: an old yet new transmembrane ion-pair transporter. Chem Commun 6321–6323 doi:10.1039/b814988g
Tsikolia M et al (2009) Synthesis and characterization of a redox-active ion channel supporting cation flux in lipid bilayers. Org Biomol Chem 7:3862–3870. doi:10.1039/b907350g
Valkenier H, Davis AP (2013) Making a match for valinomycin: steroidal scaffolds in the design of electroneutral electrogenic anion carriers. Acc Chem Res 46:2898–2909. doi:10.1021/ar4000345
Vargas Jentzsch A, Matile S (2013) Transmembrane halogen-bonding cascades. J Am Chem Soc 135:5302–5303. doi:10.1021/ja4013276
Wade CR, Ke IS, Gabbai FP (2012) Sensing of aqueous fluoride anions by cationic stibine–palladium complexes. Angew Chem 51:478–481. doi:10.1002/anie.201106242
Walter A, Gutknecht J (1986) Permeability of small nonelectrolytes through lipid bilayer membranes. J Membr Biol 90:207–217
Wang DX, Wang MX (2013) Anion–pi interactions: generality, binding strength, and structure. J Am Chem Soc 135:892–897. doi:10.1021/ja310834w
Weiss LA, Sakai N, Ghebremariam B, Ni C, Matile S (1997) Rigid rod-shaped polyols: functional nonpeptide models for transmembrane proton channels. J Am Chem Soc 119:12142–12149. doi:10.1021/ja973126d
Woods CJ et al (2002) Fluoride-selective binding in a new deep cavity calix[4]pyrrole: experiment and theory. J Am Chem Soc 124:8644–8652
Yamnitz CR, Negin S, Carasel IA, Winter RK, Gokel GW (2010) Dianilides of dipicolinic acid function as synthetic chloride channels. Chem Commun 46:2838–2840. doi:10.1039/b924812a
Acknowledgments
This work is dedicated to my former colleagues and friends who conducted graduate and postdoctoral research in the field of supramolecular ion transport. We thank all the experts who reviewed the original draft. Financial support for the study is kindly provided by Dr. Peter Berezin.
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Berezin, S.K. Synthetic Anionophores for Basic Anions as “Presumably, OH−/Cl− Antiporters”: From the Synthetic Ion Channels to Multi-ion Hopping, Anti-Hofmeister Selectivity, and Strong Positive AMFE. J Membrane Biol 247, 651–665 (2014). https://doi.org/10.1007/s00232-014-9683-7
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DOI: https://doi.org/10.1007/s00232-014-9683-7