Re-Entrant Supramolecular Interactions in Inverse Melting α-Cyclodextrin·4-Methylpyridine·Water Mixtures: an NMR Study

Inverse melting is a unique phenomenon describing liquid-to-solid phase transition upon heating. The goal of our research is to understand the microscopic chemical processes that are responsible for this abnormal transition. As a model, we chose the ternary mixture of α-cyclodextrin (αCD), 4-methylpyridine (4MP) and water, which its inverse melting transition was reported in 2004.¹ This mixture was studied using different NMR techniques, focusing on intermolecular interactions and their role in the unusual phase transition process. Temperature dependence ¹H-NMR shows that all peaks that were narrow in the solution state broadened above the liquid-to-gel phase transition. This broadening can be fully averaged out using high-resolution-magic-angle-spinning (HRMAS), spinning at a frequency of only 3 kHz, indicating weak anisotropic interactions in the hot solid phase. Moreover, the spectra have fingerprints indicating hydrogen bond weakening upon heating, supporting the order diminish in the inverse melting. Using NOE measurements, we obtain that upon increasing temperature the intermolecular interactions between 4MP and water and between 4MP and αCD decrease gradually, leaving water as the sole solvent component to support αCD in solution. This water-αCD interaction almost disappears at phase transition temperature, leaving αCD with no interaction with the solvent, so it crystallizes out. Interestingly, the 4MP - water interaction that zeroes at around 280K, re-appears at around the phase transition (~330K), suggesting a non-coincidental relationship between inverse melting and re-entrant phase transitions.

1. M. Plazanet. C. Floare, M. R. Johnson, R. Schweins, and H. P. Trommsdorff, Journal of Chemical Physics, 2004,121,5031-5034.