NMR method for simultaneous host-guest binding constant measurement.

Area of Science:

• Supramolecular Chemistry
• Analytical Chemistry
• Chemical Sensing

Background:

• Determining relative binding affinities is crucial for designing selective host-guest systems.
• Existing methods can be time-consuming or require high concentrations.
• Nuclear Magnetic Resonance (NMR) spectroscopy offers a sensitive tool for molecular recognition studies.

Purpose of the Study:

• To develop a novel NMR-based method for measuring relative binding affinities (ΔlogK(ass)) of synthetic receptors.
• To enable simultaneous determination of multiple ΔlogK(ass) values in a single experimental run.
• To validate the method's accuracy and compare it with existing techniques.

Main Methods:

• Utilized NMR spectroscopy in DMSO-d6/H2O (99.5%:0.5% m/m) to measure binding affinity differences.
• Applied the method to a series of indolocarbazole- and urea-based synthetic receptors interacting with acetate ions.
• Simultaneously determined multiple ΔlogK(ass) values in a single NMR acquisition.

Main Results:

• Successfully created a binding affinity scale for 33 receptors, spanning 2.32 log units.
• Achieved excellent self-consistency with a standard deviation of 0.01 log units.
• Demonstrated high accuracy through excellent agreement with UV-Vis spectrophotometry results, indicating interchangeability of techniques.

Conclusions:

• The developed NMR-based method provides an accurate and efficient way to measure relative binding affinities.
• The technique allows for high-throughput screening of receptor-guest interactions.
• A correlation was observed between acetate binding affinity and the (15)N chemical shift for symmetrical receptors, offering insights into binding mechanisms.