Multiple quantum 19 F electron-nuclear double resonance (ENDOR) for distance measurements with multifluorinated spin probes

Mims electron–nuclear double resonance (ENDOR) spectroscopy with 19 F spin labels is emerging as a powerful tool to access molecular distances in the 5 to 20 Å range. A time domain (TD) version of the experiment allows to manipulate nuclear spin coherences, similarly to NMR, and thus to increase distance resolution. Nevertheless, Mims ENDOR sensitivity strongly decays with the inter spin distance r , and measurements of longer distances benefit from labels with multiple 19 F nuclei, such as CF 3 probes. Here, we demonstrate that TD Mims ENDOR with two or three 19 F nuclei reveals multiple-quantum effects and homonuclear dipolar couplings. We present a general theoretical framework for TD Mims ENDOR with multiple like nuclei (i.e., 19 F), enabling analysis of spin evolution and the controlled experimental generation of single- and multiple-quantum nuclear coherences. Our results directly report not only on electron-nuclear distances but also on measurements and correlation of internuclear distances. Overall, TD ENDOR potentially offers a toolbox for molecular structure investigations.