Ion-pairing molecular recognition in water: aggregation at low concentrations that is entropy-driven

Area of Science:

• Supramolecular Chemistry
• Thermodynamics
• Analytical Chemistry

Background:

• Understanding host-guest interactions is crucial in supramolecular chemistry.
• Citrate is a biologically relevant polyanion whose interactions with synthetic hosts are of interest.
• Guanidinium-based hosts are known for their ability to bind anions.

Purpose of the Study:

• To investigate the thermodynamic parameters governing the binding of citrate to a tris-guanidinium host (host 1) in aqueous solution.
• To determine the binding stoichiometry and its dependence on solution conditions.
• To elucidate the driving forces behind the observed binding events.

Main Methods:

• Isothermal Titration Calorimetry (ITC) was employed to quantify binding thermodynamics (K(a), DeltaH°, DeltaS°, DeltaG°).
• Nuclear Magnetic Resonance (NMR) spectroscopy, specifically a Job plot, was used to verify binding stoichiometry.
• Microcalorimetry data was collected across a range of host 1 and citrate concentrations and buffer concentrations (ionic strengths).

Main Results:

• At low ionic strength (low buffer concentration), ITC revealed complexes with greater than 1:1 stoichiometries, with K(1) ranging from 2.0 x 10^3 to 3.0 x 10^3 M⁻¹.
• At high ionic strength (high buffer concentration), only 1:1 binding was detected, with K(1) determined to be 409 M⁻¹.
• The 1:1 binding is characterized by favorable entropy and negative enthalpy, while higher-order complexes are entirely entropy-driven due to desolvation.

Conclusions:

• The binding stoichiometry and thermodynamics between host 1 and citrate are highly dependent on ionic strength.
• Higher-order complex formation at low ionic strength is an entropy-driven process resulting from polyion association in water.
• An unusual observation of higher-order complex formation upon dilution of one component was noted and discussed, likely related to desolvation effects.