Monitoring dendrimer conformational transition using ¹⁹ F and ¹ H₂ O NMR

The conformational transition of a fluorinated amphiphilic dendrimer is monitored by the ¹ H signal from water, alongside the ¹⁹ F signal from the dendrimer. High-field NMR data (chemical shift δ, self-diffusion coefficient D, longitudinal relaxation rate R₁ , and transverse relaxation rate R₂ ) for both dendrimer (¹⁹ F) and water (¹ H) match each other in detecting the conformational transition. Among all parameters for both nuclei, the water proton transverse-relaxation rate R₂ (¹ H₂ O) displays the highest relative scale of change upon conformational transition of the dendrimer. Hydrogen/deuterium-exchange mass spectrometry reveals that the compact form of the dendrimer has slower proton exchange with water than the extended form. This result suggests that the sensitivity of R₂ (¹ H₂ O) toward dendrimer conformation originates, at least partially, from the difference in proton exchange efficiency between different dendrimer conformations. Finally, we also demonstrated that this conformational transition could be conveniently monitored using a low-field benchtop NMR spectrometer via R₂ (¹ H₂ O). The ¹ H₂ O signal thus offers a simple way to monitor structural changes of macromolecules using benchtop time-domain NMR.