Mn(II) ¹⁹ F Electron–Nuclear Double Resonance Spectroscopy as a Structural Tool: Resolution of the Structural Diversity of a Mn(II) Dual ¹⁹ F/ ¹ H MRI Probe

The use of bio-orthogonal 19 F nuclei has an important impact on magnetic resonance. 19 F MRI and 19 F electron–nuclear double-resonance (ENDOR)-based structural measurements are two prominent examples. We demonstrate here the first application of Mn(II) for 19 F ENDOR distance measurements and its potential to reveal otherwise inaccessible structural details in an emerging class of fluorinated Mn(II) MRI agents. We show that Mn(II) 19 F ENDOR spectroscopy can not only provide accurate nominal Mn- 19 F distances but also their distributions using well-established Tikhonov regularization techniques. Even the individual fluorines of an F 3 C group could be resolved. DFT calculations allow the translation of the ENDOR data to molecular structures. The potential of using ab initio molecular dynamics (AIMD) to connect these frozen solution structures to the room-temperature ones relevant to MRI applications is demonstrated. Distance measurements using Mn(II) 19 F ENDOR and Tikhonov analysis represent a promising approach, relevant also to structural biological applications where the use of the redox-stable, nontoxic Mn(II) has an obvious advantage.