Polyglycerol‐Tagged Molecular Clips as Receptors in Protic Solvents

Abstract

Four charge‐neutral molecular clips modified with polyglycerol (PG) dendrons of first and second generation and with hyperbranched polyglycerols (HPG) in the central unit as solubilizing units were synthesized. Their use as supramolecular hosts for the complexation of several guest molecules such as caffeine, N‐methylnicotinamide iodide, and Kosower salt was studied in methanol and water. Association constants and Gibbs enthalpies of association were determined by 1H NMR titration experiments. The obtained results were compared to the association behavior of molecular clips that carry anionic substituents. These results offer remarkable insights into the contribution of the substituents to host–guest binding and enable a strategy for improved substituent design.

The Hydrophobic Effect Revisited—Studies with Supramolecular Complexes Imply High‐Energy Water as a Noncovalent Driving Force

“…The affinity of ClipP for cationic aromatic guest molecules is high; it reaches, for example, 9⋅10 4 M −1 in D 2 O and 2⋅10 4 M −1 in MeOD for N ‐methyl nicotinamide (NMNA; Figure 9 c). 67a Polyglycerol‐tagged clips exhibit lower affinities for organic cations by 1–2 orders of magnitude as compared to anion‐bearing clips 67e. Remarkably, the affinity is higher in water than in methanol, although the electrostatic attraction between the electron‐rich inside of the concave clips and the electron‐poor guest, and the ion pairing between the methanephosphonate groups and the positively charged NMNA guest are weaker in the more polar medium.…”

Experimental Binding Energies in Supramolecular Complexes

“…Large hydrophobic binding contributions can also occur in the absence of closed cavities, as can be seen for some molecular clips and tweezers. ,,,− For instance, the affinity of a negatively charged clip (Figure a) for the cationic aromatic guest N -methyl nicotinamide (NMNA) is higher in water ( K = 9 × 10 4 M –1 ) than in methanol (1700 M –1 ), although the electrostatic attraction between oppositely charged species is weaker in the more polar medium. For NAD + as a guest ( K = 8800 M –1 ), Δ H = −30.5 kJ/mol and –T Δ S = 8.0 kJ/mol were obtained in water, which is consistent with the high-energy water release model.…”

Neues zum hydrophoben Effekt – Studien mit supramolekularen Komplexen zeigen hochenergetisches Wasser als nichtkovalente Bindungstriebkraft

“…B. für N ‐Methylnicotinamid (NMNA) mit K a =9×10 4 M −1 in D 2 O und K a =2×10 4 M −1 in MeOD (Abbildung 9 c). 67a Polyglycerol‐funktionalisierte Klammermoleküle zeigen für kationische Gäste um ungefähr eine Größenordnung kleinere Affinitäten als die anionischen Klammern 67e. Interessanterweise ist die Komplexbindungsstärke in Wasser größer als die in Methanol, obwohl elektrostatische Wechselwirkungen zwischen der elektronenreichen Kavitätsinnenwand der Klammermoleküle und dem elektronenarmen Gast sowie auch die ionische Anziehung zwischen den negativ geladenen Methanphosphonatgruppen R und dem positiv geladenen NMNA‐Gast im polareren Lösungsmittel schwächer sind.…”