Isodesmic Supramolecular Assembly of Phenylethynylene Bis-Urea Macrocycles

In this study, we report a soluble phenylethynylene bis-urea macrocycle with a supramolecular assembly mechanism distinct from previously studied bis-urea macrocycles. The macrocycle was synthesized via a dynamic covalent synthesis approach with two exterior n-dodecyloxy groups to enhance solubility in organic and mixed aqueous media. Temperature-dependent UV-Visible and fluorescence spectroscopy in 45% H₂O/THF are well described by an isodesmic mechanism, characterized by a clear isosbestic point, strong enthalpic stabilization (ΔH ∼ -133 kJ mol^-1), and a degree of polymerization of ∼4 at 284 K. Fourier-transform infrared (FTIR) spectroscopy confirms hydrogen-bond-driven association. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) detects primarily dimers, likely due to dissociation during ionization. Dynamic light scattering (DLS) and atomic force microscopy (AFM) showed the formation of nanoscale aggregates and fibrillar supramolecular structures. Additives capable of engaging the urea NH units, including a phosphate-functionalized quarterphenyl guest, reduced both the enthalpy and degree of polymerization, demonstrating tunable control of chain length. Overall, these findings identify this phenylethynylene bis-urea macrocycle as a rare example of an isodesmic, hydrogen-bonded supramolecular polymer in polar media and highlight design principles for controlling assembly length and developing solution-phase host-guest frameworks.