Organic Polyradicals as Redox Mediators: Effect of Intramolecular Radical Interactions on Their Efficiency

The spin–spin interactions between unpaired electrons in organic (poly)radicals, especially nitroxides, are largely investigated and are of crucial importance for their applications in areas such as organic magnetism, molecular charge transfer, or multiple spin labeling in structural biology. Recently, 2,2,6,6-tetramethylpiperidinyloxyl and polymers functionalized with nitroxides have been described as successful redox mediators in several electrochemical applications; however, the study of spin–spin interaction effect in such an area is absent. This communication reports the preparation of a novel family of discrete polynitroxide molecules, with the same number of radical units but different arrangements to study the effect of intramolecular spin–spin interactions on their electrochemical potential and their use as oxidation redox mediators in a Li–oxygen battery. We find that the intensity of interactions, as measured by the d1/d electron paramagnetic resonance parameter, progressively lowers the reduction potential. This allows us to tune the charging potential of the battery, optimizing its energy efficiency.


Materials and methods
Chemicals and dry solvents were purchased from Sigma Aldrich and used without further purification. Where "degassed" solvents or solutions are noted, degassing was carried out by three freeze-pump-thaw cycles. Flash chromatography (FC) was performed as described in literature 1 using Macherey-Nagel silica gel 60 (0.04-0.063 mm, 230-400 mesh). TLC analyses: Macherey-Nagel POLYGRAM ® SIL G/UV 254 ; detection by UV/VIS and by treatment with PMA staining reagent made from a solution of phosphomolibdic acid (H 3 PMo 12 O 40, 10 g) in 100 mL ethanol. 1 H and 13 C{ 1 H}-NMR spectra were recorded at 301K on Bruker AC-200, 300 MHz instruments. Chemical shifts (δ) have been reported in parts per million (ppm) relative to the residual undeuterated solvent as an internal reference. The following abbreviations have been used to explain the multiplicities: s = singlet, d = doublet, t = triplet, dd = doublet, doublet, m = multiplet, br = broad. 13 C{ 1 H}-NMR spectra have been recorded with complete proton decoupling. ESI-MS spectra have been obtained on: i) a LC/MS Agilent series 1100 spectrometer in both positive and negative modes using acetonitrile/formic acid 0.1% as mobile phase, with ESI-ion trap mass detector or a ii) ESI-TOF Mariner TM Biospectrometry TM Workstation of Applied Biosystems by flow injection, using acetonitrile or methanol/formic acid 0.1% as mobile phase, was used. Analytical gas chromatography with mass spectrometry detector (GC-MS) has been carried out on an Agilent 6850 spectrometer equipped with a split mode capillary injector and electron impact mass detector. Injector temperature has been set to 250 °C, detector temperature has been set to 280 °C and the carrier gas is He (1 mL/min) with a HP-5MS column. Melting points are uncorrected and have been determined with a Leitz-Laboroux 12. IR spectra have been recorded on a Nicolet 5700 FT-IR, with range 4000-400 cm -1 and resolution 4 cm -1 , using KBr pellets or NaCl plates. EPR spectra were obtained with an X-Band Bruker ELEXSYS E-500 spectrometer equipped with a TE102 microwave cavity, a Bruker variable temperature unit, a field frequency lock system Bruker ER 033 M and a NMR Gaussmeter Bruker ER 035 M. The modulation amplitude was kept well below the line width, and the microwave power was well below saturation. All samples were previously degassed with Ar. The same concentration was used in each pair. For 5a and 5b, 1 mM, and for 6a and 6b, either 1 mM or 2 mM, obtaining the same trend in both cases.
The CV measurements were done with a potentiostat Autolab/PGSTAT204 Metrohm in a standard 3 electrodes cell. Compounds were dissolved in 0.1 M of TBAHFP as electrolyte in DMF and using a glassy carbon electrode as the working electrode, a Ag/AgCl reference electrode and a platinum wire as the auxiliary electrode. The same concentration was used in each pair. For 5a and 5b, 1 mM, and for 6a and 6b, either 1 mM or 2 mM, obtaining the same trend in both cases.
Li-O 2 batteries were 2-compartment cells, separated by a lithium-ion conducting glass-ceramics (LICGC TM AG-01, Ohara Corporation) soldered on a polypropylene support. The cathode consisted of carbon black (Super P, Timcal) supported on a 0.79 cm 2 carbon paper (Toray TGP-H-060). It was prepared by mixing 90% Super P with 10 wt% of polyvinylidene difluoride in Nmethylpyrrolidone. The slurry obtained was used to impregnate the carbon paper surface on both sides, which was finally dried at 100 °C for 12 h and punched in disks of 10 mm diameter. The electrolyte was a solution of 1M lithium trifluoromethanesulfonate (99.9%, vacuum-dried overnight) in anhydrous diethylene glycol dimethyl ether (DEGDME, ≥99 %). For the cathode side TEMPO redox species were added to the same solution in order to obtain the specified concentrations and stored protected from light. The same concentration was used in each pair, and in addition, the same concentration per radical unit among them. 1 mM for 5a and 5b and 2 mM for 6a and 6b. The final electrolyte water content resulted of <30 ppm as determined by a Coulometric Karl Fischer titrator (Metrohm KFC 899).
The battery casing consisted of a homemade teflon design based on the cell described by Bender et al. 2 assembled in an Ar-filled glove box with < 1 ppm moisture. The inner cylinder was filled with several layers: 0.1 mm Nickel foil (99% purity, ADVENT Research Materials), 10 mm diameter as current collector; two layers of lithium metal foil as anode (Rockwood Lithium, 0.3 mm tick); two disks made by glass microfiber filter (90 mm thick, Prat Dumas), soaked with 100 mL of additive-free electrolyte; the glass-ceramic separator; two glass microfiber disks soaked with 100 mL of mediator electrolyte; the carbon cathode, and finally two stainless steel meshes (AISI 316, 180 mesh per inch, ADVENT Research Material Ltd). To replace Ar with O 2 the cell was purged with pure oxygen for a few minutes. capacity of 40 A/cm 2 by using a MTI BST8 multichannel potentiostat. Synthesis of Tris-(2-hydroxy-3-benzyl-5-formylbenzyl)amine (1a). A nitrogen purged Schlenk tube was charged with ortho substituted Tris-(2-hydroxy-3-benzyl)amine (2.16 g, 4.03 mmol) and hexamethylenetetramine (3.39 g, 24.2 mmol) and diluted with TFA (3 mL/mmol sub.) and the mixtures were stirred at 90°C for 12h. The crude mixtures were evaporated to dryness and HCl aq 4N (36 mL) was added and the mixture was stirred for 3 h at 90 °C. The precipitate was filtered off, washed with NaHCO 3 and extracted with CH 2 Cl 2 . The organic phase was dried over anhydrous Na 2 SO 4 and evaporated to dryness. The final product was obtained by crystallization in acetonitrile as a yellow solid (94%). 1

Synthesis of 3-iodo-2-(methoxymethoxy)benzaldehyde (S2):
To a stirred solution of 2-hydroxy-3iodobenzaldehyde (S1) (88.7 mmol, 22.0 g) in dry DMF (60 mL) were added K 2 CO 3 (88.7 mmol, 12.2 g) and MOMCl (88.7 mmol, 6.9 mL) under a N 2 atmosphere. The color change from yellowish brown to yellow instantaneously occurs. After 16 h at room temperature the mixture was diluted with water (150 mL), extracted with EtOAc, and washed with brine. The organic phase was dried over Na 2 SO 4 and concentrated under vacuum. The crude product was purified by distillation using Kuegelrohr apparatus affording the final product as a yellow oil (81 %). 1

Synthesis of Tris-(2-hydroxy-3-(3'-formylbenzyl)-benzyl)amine (1b). Tris-(2-(methoxymethoxy)-
3-(3'-formylbenzyl)-benzyl)amine S4 (2.8 mmol, 2.5 g) was dissolved in THF (84 mL) and then HCl 1.25 M in methanol (16.8 mL) was added. The reaction mixture was heated at 50 °C for 18 h. A solution of HCl aq 1M was added and the reaction was vigorously stirred for 3 h. Then NaHCO 3aq sat. was added till pH = 8 was reached. The residue was extracted with EtOAc. The organic phases were dried over anhydrous Na 2 SO 4 and concentrated under vacuum. The product, a brownish foam, was used without any further purification (92%). 1    General synthesis of Ti(IV) TPA µ-oxo complexes 4a, 4b. To the above in situ prepared mononuclear complex 3a, 3b solutions water (0.25 ml for 0.7 mmol of complex) was added and the mixture was stirred at r.t. for 1-2 h. The suspension was concentrated under pressure and the yellow solid, precipitated with diethyl ether or n-hexane, was recovered by filtration or centrifugation (98 %).

Quantitative EPR study
The full functionalization with radicals of all compounds was quantitatively determined by EPR spectroscopy. The intensity (double integral) of the EPR signal of all compounds was measured, in the same conditions. TEMPO-derived compounds presented an experimental number of radicals very close to the theoretical value and in agreement within the ±10% tolerance of EPR measurements, showing the complete functionalization of all compounds (see Table S1).

EPR study of monoradical TEMPO
TEMPO free radical was studied at different concentrations (1, 3, 6 and 12 mM). As expected, it did not present half-field transition band. Only in the most concentrated solutions (6 and 12 mM) a little band was observed but, in this case, due to intermolecular interactions favoured at very high concentration (see Table S2). This band was much smaller than those in the polyradical species because of the lack of intramolecular radical interactions. The same effect was also reflected in the d 1 /d ratio, which slightly increased from 0.51 to 0.54 with the increase of concentration due to the closer distance between molecules (Table S2).

X-ray crystallography
Single crystal X-ray data for 5b were collected at 123 K with Agilent Super-Nova dual source wavelength diffractometer with an Atlas CCD detector using multilayer optics monochromatized Mo-Kα (λ = 1.54184 Å) radiation. The data collection and reduction were performed using the program CrysAlisPro, 3 the intensities are corrected for absorption with empirical method. The structure was solved with SHELXT 4 and refined by full-matrix least squares on F 2 using the OLEX2, 5 which utilizes the SHELXL-2015 module. 6 Anisotropic displacement parameters were assigned to non-H atoms. All the hydrogen atoms were refined using riding models with Ueq(H) of 1.5Ueq(parent) for terminal methyl groups, and 1.2 Ueq(parent) for other groups. One of the TEMPO groups in the asymmetric unit is disordered over three positions. They were split according to the difference Fourier maps, and their occupancies were first freely refined and then fixed to 0.40, 0.32 and 0.28, respectively. Geometric restraints (DFIX and SADI), as well as the ADP restraints (SIMU) were used to treat the disordered groups. For the disordered atom attached with the imine-N were very close, for whom, EADP command was utilized to force them with the same thermal displacement parameters. Badly disordered solvent molecules were found in the lattice and were treated using the "SQUEEZE" protocol within PLATON. 7 Crystal Data for 5b