Chapter 3. Synthetic Receptors for Alkali Metal Cations Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Chapter 3. Synthetic Receptors for Alkali Metal Cations George W. Gokel*a,b,c and Joseph W. Meisela,b aCenter for Nanoscience, bDepartment of Chemistry and Biochemistry, cDepartment of Biology, University of Missouri-St. Louis, 1 University Blvd. Saint Louis, MO 63121 USA *Email: gokelg@umsl.edu

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Chart 3.1 Solid state structure of the polyether ionophore, monensin A, binding Na+.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Chart 3.2 Partial structures of two biological ion channels showing: (A) Two Na+ binding sites in the LeuT Na+-dependent pump (PDB code 2A65). (B) Four K+ binding sites in the KcsA K+ channel (PDB code 1K4C). (Reproduced with permission from Science 2005, 310, 1461, © American Association for the Advancement of Science)

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.1 Coordination compounds and bidentate complexes

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.2 The chemistry leading to the first crown ethers.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.3 Solid state structure of dibenzo-18-crown-6 binding K+ (CSD: BEBFAP).

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.4 Two-armed diaza-18-crown-6 derivatives having three atom sidearms.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Table 3.1 Homogeneous complexation constants and thermodynamic parameters determined in methanola,b.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.5 Binding constants determined in 100% methanol solution for 3n-crown-n compounds where n = 4 – 8.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.6 Solid state structures of uncomplexed 12-crown-4 (CSD: TOXCDP) and K+ ion complexed by 18-crown-6 (CSD: KTHOXD).

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.7 Solid state structures of (12C4)2•Na+ (CSD: BEYHES) and ( Aza-12C4)2•Na+ (CSD: FEHDOL).

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.8 Solvent dependence of 18-crown-6•Na+ binding in methanol and water.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.9 Structures of [2.1.1]cryptand and [3.2.2]cryptand.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.10 Solid state structure of [2.2.2]cryptand complexing KI.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.11 Left: a spherand. Center: a hemispherand. Right a crown-hemispherand.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.12 Macrocyclic compounds formed by acid-catalyzed, multiple condensations.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.13 Calixarene receptor molecules.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.14 K+ complexation by a calix-crown.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.15 Comparison of homogeneous binding and extractions constants with transport rate.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.16 Schematic representation of a liposome and a typical phospholipid.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.17 Redox-switched molecular receptors.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.18 Examples of host molecules that can be photo-switched.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.19 Relative NH4+ binding strengths for 18-membered ring macrocycles.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.20 Crown ether-derived colorimetric sensors: “chromoionophores”.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.21 Fluoroionophores based on crown ethers and calixarenes.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.22 Chemical structure of the cyclic peptide K+ carrier valinomycin.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.23 (Top) Single-armed carbon-pivot and nitrogen pivot lariat ethers. (Bottom) a two-armed or bibracchial nitrogen-pivot lariat ether.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.24 Solid state structure of 4,13-diaza-18-crown-6 having two methoxyethyl side arms attached to nitrogen and binding KI.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Table 2 Sodium and potassium cation binding by lariat ethers expressed as log10 KS.a

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.25 Bibracchial lariat ethers containing π-donor side arms.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.26 Solid state structures of phenyl (CSD: OCABEZ) and pentafluorobenzyl (CSD: OCACIE) side-armed bibracchial lariat ethers binding KI.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.27 Solid state structure of a calixarene•2Cs+ complex (CSD: RADBUT).

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.28 A ditopic receptor binding both Na+ and I- (CSD: IBUKUM).

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.29 An ion-conducting channel based on the cyclodextrin scaffold.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.30 Channel designs reported by Lehn (left) and by Fyles and their coworkers.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.31 The hydraphile channel concept.

© The Royal Society of Chemistry 2015 Supplementary information for Synthetic Receptors for Biomolecules: Design Principles and Applications © The Royal Society of Chemistry 2015 Figure 3.32 An array of synthetic amphiphiles that show channel-like function.