Detection of Molecular Transitions with Nitrogen-Vacancy Centers and Electron-Spin Labels*

We present a protocol that detects molecular conformational changes with two nitroxide electron-spin labels and a nitrogen-vacancy (NV) center in diamond. More specifically, we demonstrate that the NV can detect energy shifts induced by the coupling between electron-spin labels. The protocol relies on the judicious application of microwave and radiofrequency pulses in a range of parameters that ensures stable nitroxide resonances. Furthermore, we demonstrate that our scheme is optimized by using nitroxides with distinct nitrogen isotopes. Finally, we use detailed numerical simulations and Bayesian inference techniques to show that our method enables the detection of conformational changes under realistic conditions. In particular, we show that random molecular tumbling can be exploited to extract the associated changes in inter-label distance. In addition, we account for strong NV dephasing rates as a consequence of the diamond surface proximity and for nitroxide decoherence and thermalization mechanisms.