General Experimental Methods

Water was purified to ISO3696 Type II specification using an Elga Veolia Purelab Option S7 water purifier. Tetra-N-butylammonium sulfate (TBA2SO4) was purchased as a 50% w/w

aqueous solution and dried in vacuo while cycling between 77 K and room temperature. All

other solvents and chemicals were purchased from commercial sources and used without further purification. Microwave-assisted reactions were carried out in a Biotage Initiator Eight EXP microwave reactor using sealed vials. Thin-layer chromatography (TLC) was carried out using MerckMillipore Kiesegel 60 F254 silica plates and visualised under λex =

254 nm, by staining with an acidified solution of ninhydrinin in ethanol, or by staining in an iodine vapour chamber. Flash chromatography was carried out on a Teledyne Isco CombiFlash Rf 200 UV/Vis automated machine using pre-packed RediSep® cartridges.

Mass-spectrometry was carried out using HPLC grade solvents using electrospray mass spectrometry (ESI). High resolution ESI mass spectra were determined relative to a standard of leucine enkephalin. Infrared spectra were recorded on a Perkin Elmer Spectrum One FTIR spectrometer fitted with a universal ATR sampling accessory. Melting points were determined using an Electrothermal IA9100 digital melting point apparatus. Elemental analysis was either carried out by the UCD School of Chemistry Microanalytical Laboratory, University College Dublin, or by the Department of Chemistry, Maynooth University.

6.1.1 NMR spectroscopy

1_{H NMR spectra were recorded at 400 MHz on a Bruker Avance III 400 NMR or Agilent}

400-MR, or at 600 MHz on a Bruker Avance II 600 NMR. 13_{C NMR spectra were recorded}

at either 100.6 MHz or 150.9 MHz. All 13_{C NMR spectra were decoupled from} 1_H.

Deuterated solvents used for NMR analysis (DMSO-d6, D2O, CDCl3) were purchased from

Apollo Scientific or Sigma Aldrich, and used as received. Chemical shifts are reported in ppm with the residual solvent as internal reference, while 2D spectra were graphically referenced. All NMR spectra were carried out at 25.0 °C unless otherwise stated.

6.1.1.1 1_{H NMR Titration Experiments}

1_{H NMR titration experiments were performed in DMSO-d}

6 at 25.0 °C on a 400 MHz Bruker

Avance III 400 NMR spectrometer. A Norrell 507-HP NMR tube was charged with 0.8 mL

of a solution (7.0 mM or 0.7 mM) in DMSO-d6 of the host being studied and the 1H NMR

spectrum obtained (400 MHz). Sequential additions of a stock solution (0.28 M or 28 mM) in DMSO-d6 of the appropriate TBA+ salt were performed in 2–20 μL aliquots with a Gilson P20 pipette.

6.1.2 Single-crystal X-ray Crystallography

A summary of data collection and refinement parameters is presented in Table 2.7. All diffraction datasets were obtained using graphite-monochromated Mo Kα radiation (λ = 0.71073 Å) using a Bruker APEX-II DUO instrument with CCD detector, with samples mounted on Mitegen micromounts, coated in Paratone immersion oil and held at a temperature of 100K. The diffraction data were reduced and processed using the Bruker

APEX suite of programs.217 _{Multi-scan absorption corrections were applied using}

SADABS.218 _{The data were solved using the Intrinsic Phasing routine in SHELXT and}

refined with full-matrix least squares procedures using SHELXL-2015 within the OLEX-2 GUI.219–221 _{Non-hydrogen atoms were refined with anisotropic displacement parameters,}

while all hydrogen atoms were included in calculated positions with isotropic displacement parameters equal to 1.2 or 1.5 times the isotropic equivalent of their carrier atoms, unless involved in hydrogen bonding, in which case atoms were explicitly located from the Fourier residuals (where possible).

The crystallographic model obtained for compound 96(TBAAcO)2⋅3H2O (CCDC

1840843) included significant disorder and was based on relatively poor quality diffraction data. The tetrabutylammonium cations and urea host molecule were modelled without restraints on position or anisotropic displacement parameters. Both of the two unique acetate anions were modelled at full occupancy, with isotropic approximations and/or rigid group approximations on the ADPs where necessary to prevent the emergence of non-positive definite Uij tensors. Slight positional disorder on one acetate anion was approximated by

modelling one oxygen atom split over two nearby positions at 0.5:0.5 occupancy for each of the two parts O8 and O8A. Water molecules O9 and O10 were modelled at full occupancy with hydrogen atoms refined in riding positions. The remaining lattice water contribution was modelled split over three positions O11, O11A and O11B, with a total occupancy of one. No hydrogen atoms were modelled on these sites due to the low individual occupancies, however these atoms were included in the molecular formula to allow for correct calculation of absorption coefficient, density, etc., in the final refinement.

The asymmetric unit of compound 973(TBA3H3P2O8)⋅0.5CHCl3 (CCDC 1840844)

contained minor disorder as described in the text which was modelled by fixing the lattice chloroform molecule to 0.5 occupancy, and modelling two orientations of the hydrogen atom attached to the central phosphate group, both refined as freely rotating groups (AFIX 147) with distance restraints between each hydrogen atom and corresponding hydrogen bond acceptor to maintain sensible geometries, and values of Uiso fixed at 1.5 times that of the

6.1.3 X-Ray Powder Diffraction

X-ray powder diffraction patterns were recorded using a Bruker D2 Phaser instrument using Cu Kα radiation (1.54178 Å) and a Bruker LynxEye detector. Samples were finely ground and mounted on a silicon single crystal zero-background sample holder, and collected in the 2θ range 5–55° with constant rotation in φ of 1 revolution per minute at room temperature, and matched with simulated patterns calculated from the appropriate single-crystal data.