Large 31P-NMR enhancements in liquid state dynamic nuclear polarization through radical/target molecule non-covalent interaction

Dynamic nuclear polarization (DNP) is a method to enhance the low sensitivity of nuclear magnetic resonance (NMR) via spin polarization transfer from electron spins to nuclear spins. In the liquid state, this process is mediated by fast modulations of the electron-nuclear hyperfine coupling and its efficiency depends strongly on the applied magnetic field. A peculiar case study is triphenylphosphine (PPh3) dissolved in benzene and doped with BDPA radical because it gives 31P-NMR signal enhancements of two orders of magnitude up to a magnetic field of 14.1 T. Here we show that the large 31P enhancements of BDPA/PPh3 in benzene at 1.2 T (i) decrease when the moieties are dissolved in other organic solvents, (ii) are strongly reduced when using a nitroxide radical, and (iii) vanish with pentavalent 31P triphenylphosphine oxide. Those experimental observations are rationalized with numerical calculations based on density functional theory that show the tendency of BDPA and PPh3 to form a weak complex via non-covalent interaction that leads to large hyperfine couplings to 31P (ΔAiso ≥ 13 MHz). This mechanism is hampered in other investigated systems. The case study of 31P-DNP in PPh3 is an important example that extends the current understanding of DNP in the liquids state: non-covalent interactions between radical and target can be particularly effective to obtain large NMR signal enhancements.


S1
. Overhauser experiments and parameters 31 P-DNP measurements at 1.2 T were performed on a Bruker ElexSys E580 EPR spectrometer combined with an AVANCE III 1 H 300 MHz NMR console. A Bruker ER-5106QT/W cw resonator was employed. A home built copper coil was wrapped around the Q-Band quartz tube with 4 to 5 turns for NMR detection. This is reducing the Q-value of the resonator but still allows for tuning and matching of the cavity. The MW power was tuned to prevent severe heating of the sample during MW irradiation.
Nuclear � � For the measurements of � 1,dia (i.e. longitudinal nuclear relaxation time of 31 P of phosphorus compounds without radical) larger sample volumes were necessary to detect the NMR signals without DNP. Therefore, we used a setup that can accommodate a larger sample volume, that is 100 µL inside a 3 mm glass tube instead of~4 µL used during the DNP experiments at 1.2 T. The phosphorus compounds were dissolved in the different organic solvents with the respective concentration as in the DNP samples. The solutions were degassed by freeze-pump-thaw cycles (four to six) and afterwards the tube was sealed with a flame. We utilized an EPR resonator with Electron Nuclear Double Resonance (ENDOR) capabilities for NMR detection (Bruker EN4118X-MD-4) tuned at 13.7 MHz, which corresponds to a magnetic field of 0.8 T. � 1,dia of the phosphorus compounds in different solvents were measured with a saturation recovery experiment (with 2 saturation pulses each of duration of ( � 2 ) sat = 6.2 -6.7 μs, � 2 = 6 − 6.5 μs, � RF = 60 W). � 1,dia was obtained by fitting the NMR signals (area) recorded as a function of recovery time with the exponential function � − � ⋅ exp( − �/� 1,dia )) , where A, B, and � 1,dia are fitting parameters. A recovery curve for 31 P of PPh 3 in benzene is shown in Figure S1e with the pulse sequence.
Electronic Supplementary Material (ESI) for Physical Chemistry Chemical Physics. This journal is © the Owner Societies 2022 Enhancement � 31 P-NMR signal enhancements were obtained by the ratio of the area of the NMR signal with and without MW irradiation. Enhanced NMR spectra were obtained with 2 -8 scans, whereas for Boltzmann spectra 150 -900 scans were needed to obtain a moderate signal-to-noise ratio. The recycle delay of the signal averaging was~5 • � 1,n . The signal enhancement � was calculated with: where � DNP and � thermal are the areas of the NMR signal with and without MW irradiation and � DNP and � thermal are the number of scans with and without MW irradiation. DNP enhanced and Boltzmann NMR spectra and pulse sequence are displayed in Figure S1a for 31 P of PPh 3 in benzene doped with BDPA.

Saturation factor � 퐞��
Effective saturation factors were obtained by performing an ELDOR (Electron Nuclear Double Resonance) experiment. There, a long saturation pulse (5 μs) is swept through the EPR spectrum, while the EPR signal is detected on one of the EPR transitions. If the ELDOR pulse is on resonance with either one of the EPR lines, a drop in signal intensity is observed. The saturation factors � � can be obtained from these signal drops. The effective saturation factor � eff can then be calculated for a �-line system with the following equation [1]: In Figure S1b, an ELDOR spectrum is shown for BDPA in benzene with PPh 3 and the ELDOR pulse sequence in the inset.

Leakage factor �
The leakage factor � was calculated as: where � 1,n and � 1,dia are the nuclear relaxation times with and without the presence of the paramagnetic species. Due to the low sensitivity, � 1,n was measured with a polarization decay experiment, where a short pre-polarization MW pulse (2 -6 s) was applied before NMR detection. The delay time between pre-pulse and detection was incremented and the decay of the NMR signal (area) was fitted with the exponential function � ⋅ exp( − �/� 1,n ) where A and � 1,n are fitting parameters. The build-up times � Buildup were measured by increasing the MW irradiation time and � Buildup were again obtained by fitting the NMR signals (area) with the exponential function � − � ⋅ (1 − exp( − �/� Buildup )), where A, B, and � Buildup are fitting parameters. � Buildup and � 1,n curves for 31 P of PPh3 in benzene doped with BDPA are shown in Figure S1c,d with their respective pulse sequences.

S2. Quantum chemistry calculations
Geometry optimization Geometry optimizations of the polarizing agent structures, target molecule structures, and complexes have been computed with Orca 5.0.2 [2]. The calculations were performed at B3LYP level of theory and the def2-TZVPP basis set was used. Resolution-of-the-identity, chains-of-spheres approximations (RIJCOSX with def2/J auxiliary basis set) and the dispersion correction (D3BJ) were also employed. The optimization procedure (TIGHTOPT) was used and for the SCF very tight convergence criteria (VERYTIGHTSCF). For each complex, different orientations of the PA with respect to the target molecule were chosen as starting point for the geometry optimization ( Figure S3). The optimizations were computed in vacuum, benzene, and chloroform using the same starting structures [3]. Afterwards, the isotropic hyperfine coupling to 31 P was calculated for each optimized geometry using EPR-III basis set [4] for H, C, N, and O atoms and IGLO-II [5] for P atom.

Interaction energy
Interaction energies were computed as described by Boys and Bernardi in Ref. [6]. Interaction energies for each complex are: where the index R stands for 'radical', and T stands for 'target molecule'. The terms are:  Figure S4 shows the hyperfine coupling � iso calculated for each optimized structure in vacuum, benzene, and chloroform and plotted as a function of the distance between 31 P and the electron spin density on the radical. The interaction energy � int is shown as color map. Figure S5 shows the interaction energy of each of the optimized complex radical/PPh 3 as a function of the distance between 31 P and the site where the electron spin density is localized. Figure S4. a) Hyperfine coupling � iso calculated for each of the optimized structures vacuum, benzene, and chloroform plotted as a function of the distance between 31 P and the allyl group of the BDPA. The distance is the mean of the distances between 31 P and the two closest carbons of the ally group of BPDA. b) Same calculations for the complex TN/PPh3; In this case, we considered the mean distance between 31 P and the NO group of TN radical. Figure S5. a) Interaction energy of the optimized complexes BDPA/PPh3 as a function of the mean distance between 31 P and the two closest atoms of the allyl group of BDPA. b) Interaction energy of TN/PPh3 as a function of the mean distance between 31 P and the NO group.
Additional series of geometry optimization calculations were run with fixed distances between 31 P and the radical site with the largest spin density ( Figure S6). For BPDA, we fixed the distance between 31 P and the C atom at the center of the allyl group, while for TN we consider the distance between 31 P and the oxygen atom of the NO group. Figure S6 shows the interaction energies (in vacuum) of the compounds and the tendency of BDPA/PPh 3 to for a complex.