LnDOTA‐d8, a versatile chemical‐shift thermometer for 2H solid‐state NMR

2H solid‐state nuclear magnetic resonance (NMR) is a method for examining the mobility and orientation of molecules in the field of biophysics. In studies on lipid bilayer membranes, 2H NMR is often adopted to detect a phase transition from the gel to the liquid‐crystal phase, which is observed as a change in spectral shape, and to evaluate the ordering of lipid alkyl chains using quadrupole coupling values. Because the mobility of membrane lipids is highly temperature dependent, precise temperature control is a prerequisite for evaluating the physical properties of membranes. Generally, NMR instruments monitor the temperature of the variable temperature (VT) gas. The temperature inside the sample tube and the VT gas match only when the heat generated by the radio frequency (rf) pulse emitted from the coil or magic angle spinning is significantly lower than the cooling capacity of the VT gas. In other words, the sample temperature inside the tube depends on the measurement method. Therefore, in this study, we took advantage of temperature‐dependent changes in the chemical shift of a paramagnetic metal–ligand complex. We designed and synthesized a deuterated ligand complex and evaluated its temperature dependence as a thermometer for 2H solid‐state NMR spectroscopy. We chose Tb, Dy, Ho, and Er as the paramagnetic central metals. We then measured the 2H NMR spectrum of each metal complex and confirmed the 2H chemical shift to be temperature dependent. Furthermore, with the use of the thermometer molecule with Er, we succeeded in accurately evaluating the segmental melting of an alkyl chain in lipid bilayers with 0.1°C accuracy. To determine an accurate sample temperature in broadband solid‐state 2H NMR measurements, the temperature dependence of the 2H chemical shift of 2H‐labeled LnDOTAs was evaluated. The results showed that all the metal complexes exhibited a large temperature dependence suitable for 2H NMR measurement, and ErDOTA‐d8 had less overlap with lipid‐derived signals. Using this molecule as a temperature indicator, the depth‐dependent melting of a lipid bilayer was examined.