Application of various spectroscopic techniques in investigating the thermodynamics of supramolecular host-guest reactions in solution

Spectrofluorimetry, UV-Vis, and NMR spectroscopy are powerful tools for investigating thermodynamics of host-guest complexation reactions. These fundamental studies help in understanding the factors governing the stability of supramolecular complexes in solution, which is increasingly important, particularly for their pharmaceutical applications. Insights gained from such studies are crucial for stabilizing active pharmaceutical ingredients, increasing their bioavailability, and for aimed drug delivery.
Spectrometric determination of the key thermodynamic quantities relies on performing titrations at various conditions and analysis of thus-obtained spectroscopic data. The significantly higher sensitivity of fluorimetry compared to UV-Vis and NMR provides significant advantage since it enables conducting titrations at much lower concentrations. Besides monitoring scarcely soluble species and using smaller quantities of the materials, this allows for determining up to even 3 orders of magnitude higher equilibrium constants compared to other methods. Although not as sensitive, NMR is a universal method for detailed investigations of the binding processes occurring between a broad array of species. NMR titrations offer additional structural and dynamic information, providing valuable data for unraveling the influence of various structural factors governing complex formation.
Studies performed by our group showcase the application of various spectroscopic techniques in investigating supramolecular host-guest binding processes in solution, enabling determination of thermodynamic parameters such as binding constants, complexation Gibbs energies, enthalpies, and entropies. The results of a few investigations will be presented, highlighting the versatility of various spectroscopic methods and the importance of using them in combination with other experimental and computational methods for gaining a comprehensive insight into the driving forces behind host-guest association.