pccp keller etal manuscript july 2016 si r1
TRANSCRIPT
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Supporting information
EPR Characterization of Mn(II) Complexes for Distance Determination
with Pulsed Dipolar Spectroscopy
Katharina Keller,1,a Michal Zalibera,2,3,a Mian Qi,4 Vanessa Koch,4 Julia Wegner,4 Henrik
Hintz,4 Adelheid Godt,4,* Gunnar Jeschke,1 Anton Savitsky,2,* Maxim Yulikov1,*
1) Laboratory of Physical Chemistry, Department of Chemistry and Applied Bioscience,
ETH Zurich, Vladimir Prelog Weg 2, 8093 Zurich, Switzerland 2) Max Planck Institut for Chemical Energy Conversion, Stiftstrasse 34-36, D-45470
Mülheim an der Ruhr, Germany 3) Institute of Physical Chemistry and Chemical Physics, Slovak University of
Technology in Bratislava, Faculty of Chemical and Food Technology, Radlinskeho 9,
81237 Bratislava, Slovak Republic 4) Faculty of Chemistry and Center for Molecular Materials (CM2), Bielefeld University,
Universitätsstraße 25, 33615 Bielefeld, Germany a)these authors contributed equally to the work
* [email protected]; [email protected]; [email protected]
Author contributions: M.Y., A.G. and A.S. designed the research. The compounds were designed and synthesized by the team, M.Q., V.K., J.W., H.H., and A.G. K.K. performed RIDME measurements, and relaxation measurements at Q band. M.Z. performed ED EPR, relaxation, and ENDOR measurements at W band; K.K., M.Y., and G.J. analyzed RIDME and Q-Band relaxation data. M.Z. and A.S. analyzed relaxation data, ENDOR data and fitted ZFS parameters of the Mn(II) complexes. All authors contributed to the writing of the manuscript.
Syntheses of the Mn(II) complexes 1-4 and the Mn-rulers 5n
General
Unless otherwise stated, reactions were performed under ambient atmosphere using solvents and reagents as commercially received, except THF (HPLC grade) which was distilled from sodium/benzophenone prior to use. If inert atmosphere was needed, argon
Electronic Supplementary Material (ESI) for Physical Chemistry Chemical Physics.This journal is © the Owner Societies 2016
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was used that was passed through anhydrous CaCl2 prior to use. The solvents used for extraction and chromatography were of technical grade and were distilled prior to their use. PdCl2(PPh3)2 was synthesized according to the literature,1 however using 2.1 times the given amount of methanol. For the preparation of the aqueous solutions, deionized water was used. The proton-exchange resin (Dowex® 50WX4 hydrogen form, Sigma-Aldrich, 91 g) was subsequently washed with THF (3 × 200 mL), EtOH (2 × 100 mL), H2O (2 × 150 mL), and EtOH (200 mL) and then dried over P4O10 at 0.05 mbar for 5 days to obtain a pure and dry proton-exchange resin (30 g).
Degassed solutions were prepared through applying several freeze-pump-thaw cycles. The temperatures given for the reactions refer to the bath temperature. Solvents were removed at a bath temperature of about 40 oC and reduced pressure. The products were dried at room temperature at ∼0.05 mbar. The pH/pD values of the solutions were determined using pH indicator strips (resolution: 0.3 pH or 0.5 pH).
Column chromatography was carried out on silica gel 60 (0.035− 0.070 mm) applying slight pressure with argon gas. In the procedures reported below, the size of the column is given as diameter × length. The material was loaded onto the column dissolved in a small quantity of the eluent. Thin layer chromatography was performed on silica gel 60 containing fluorescent indicator F254. The solid support for the silica gel layer was aluminum foil. Unless otherwise stated, the spots were detected with UV light of λ = 254 and 366 nm. The compositions of solvent mixtures are given in volume ratios.
A centrifuge with relative centrifugal force of 4000g was used.
NMR spectra were calibrated using the solvent signal as an internal standard [CDCl3: δ (1H) = 7.25, δ (13C) = 77.0; DMSO-d6: δ (1H) = 2.49, δ (13C) = 39.5; CD3OD: δ (1H) = 3.31, δ (13C) = 49.0; D2O: δ (1H) = 4.79]. For 13C NMR experiments in D2O, a drop of MeOH was added as the internal standard [δ (13C)MeOH = 49.5]. Signal assignments are supported by DEPT-135, COSY, HMBC, and HMQC experiments.
ESI MS spectra were recorded using an Esquire 3000 ion trap mass spectrometer (Bruker Daltonik) equipped with a standard ESI source. Unless otherwise stated, the monoisotopic mass of a compound is reported.
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Synthesis of Mn(II)-maleimide-DOTA (1)
The content of the structural motif maleimide-H3DOTA in the purchased [maleimide-H3DOTA • n TFA • m HPF6] (6) was 63.2 wt.%, as was quantified by quantitative 1H NMR spectroscopy.2,3 To [maleimide-H3DOTA • n TFA • m HPF6] (6) (4.204 mg, contains 5.05 µmol of maleimide-DOTA) was added a solution of MnCl2 • 4 H2O in D2O (0.05 M, 95.8 µL, 4.79 µmol). The pH of the solution was adjusted to pH8.2 through the subsequent addition of a solution of NaOD in D2O (0.10 M, 280 µL, 28.0 µmol), a solution of DCl in D2O (0.10 M, 10 µL, 1.0 µmol), a solution of NaOD in D2O (0.10 M, 7 µL, 0.7 µmol), and finally a solution of DCl in D2O (0.10 M, 1 µL, 0.1 µmol). The solution was diluted with D2O (564 µL) to obtain a 5.0 mM solution of Mn(II)-maleimide-DOTA (1) in D2O containing NaCl, NaPF6, NaO2CCF3, and H2O. MS (ESI) m/z = 578.1 [M - Na]-.
Synthesis of Mn(II)-TAHA (2)
Mn(II)-TAHA (2)
N
N
O
OMn
O
O
O
OO
O
O
OO
O
N
(Na+)4
4-
H6TAHA
HO
OH
OHOH
N3
N3
N3
NH2
NH2
NH2
N
NN
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tButBuO2C
N
NN
CO2H
CO2H
CO2H
CO2H
CO2HHO2C
7 8 10 11
12
OTs
OTsTsO
9
n TFA
n TFA (13)
The procedures reported by Viguier et al.4 and by Hellmann et al.5 for the synthesis of 1,1,1-tris(aminomethyl)-1-phenylmethane (11) and the procedures reported by Peters et al. for the syntheses of 1,1,1-tris(aminomethyl)-1-(4-bromo)phenylmethane and TAHA tert-butyl ester with a bromo substituent in para position at the benzene ring6 were the basis for our work. We applied some modifications.
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1,1,1-Tris(hydroxymethyl)-1-phenylmethane (8). The procedure of Cho et al.7 and Viguier et al.4 was followed, however with deviation from the reported ways of isolation. Our attempt of isolation of triol 8 through recrystallization in EtOAc, as was reported by Viguier et al.,4 failed.
The experiment was performed in an argon atmosphere. Phenylacetaldehyde (7) (1.0 mL, 8.57 mmol) und Ca(OH)2 (2.54 g, 34.3 mmol) were added to a suspension of paraformaldehyde (1.03 g, 34.4 mmol) in THF (13 mL). The reaction mixture was stirred at 60-65 oC for four days. After cooling to room temperature the reaction mixture was filtered through celite and the celite was rinsed with CH2Cl2 (10 mL). The solvents of the combined filtrates were removed. Chromatography (3.0 cm × 46 cm, first CH2Cl2/MeOH 20:1, then MeOH) of the residual orange oil (1.63 g) gave 1,1,1-tris(hydroxymethyl)-1-phenylmethane (8) (926 mg, 59%) together with a trace of unidentified components as a colorless oil that solidified upon standing. The triol was only eluted after changing the solvent to methanol. 1H NMR (500 MHz, DMSO-d6): δ = 7.40 (m, 2H, H ortho to C(CH2)3), 7.25 (m, 2H, H meta to C(CH2)3), 7.14 (m, 1H, H para to C(CH2)3), 4.43 (br t-like, 3J = 5.0 Hz, 3H, OH), 3.71 (d, 3J = 5.1 Hz, 6H, CH2). 13C NMR (125 MHz, DMSO-d6): δ = 143.0 (CArC), 127.7 (CAr ortho to C(CH2)3), 127.5 (CAr meta to C(CH2)3), 125.4 (CAr para to C(CH2)3), 63.4 (CH2), 49.1 (C(CH2)3). MS (ESI) m/z = 205.0 [M + Na]+, 387.1 [2M + Na]+.
1,1,1-Tris[(4-tolylsulfonyloxy)methyl]-1-phenylmethane (9). The procedure of Viguier et al.4 was applied with deviations. 1,1,1-Tris(hydroxymethyl)-1-phenylmethane (8) was used as obtained in the experiment described above. To a solution of 1,1,1-tris(hydroxymethyl)-1-phenylmethane (8) (882 mg, 4.84 mmol) in pyridine (10 mL), cooled with an ice bath, 4-toluenesulfonyl chloride (4.35 g, 22.8 mmol) was added within one hour. The ice bath was removed. The color of the reaction solution changed to yellow and a colorless precipitate formed. The suspension was stirred at room temperature for two days. All volatiles were removed. The brown residue was suspended in CH2Cl2 (100 mL) and the suspension was filtered. The brown filtrate was washed with water (100 mL). The organic phase was separated and the aqueous phase was extracted with CH2Cl2 (3 × 30 mL). The combined organic phases were washed with brine (50 mL) and the solvents were removed. The residual brown solid (3.41 g) was suspended in EtOH (45 mL), the suspension was stirred vigorously and heated (bath temp. 92 oC). Filtration of the suspension gave 1,1,1-tris[(4-tolylsulfonyloxy)methyl]-1-phenylmethane (9) (2.47 g, 80%) as a colorless solid. 1H NMR (500 MHz, CDCl3): δ = 7.61 and 7.30 (AA'XX' spin system, 6H each, H meta and ortho to CH3), 7.22 (m, H para to C(CH2)3), 7.17 (m, 2H, H meta to C(CH2)3), 6.93 (m, 2H, H ortho to C(CH2)3), 4.17 (s, 6H, CH2), 2.45 (s, 9H, CH3). 13C NMR (125 MHz, CDCl3): δ = 145.3 (CArS), 134.7 (CArC(CH2)3), 131.7 (CArMe), 130.0 (CArH ortho to CH3), 128.8 (CAr meta to C(CH2)3), 128.0 (CAr para to C(CH2)3), 127.9 (CArH meta to CH3), 126.2 (CAr ortho to C(CH2)3)), 68.9 (CH2), 46.0 (C(CH2)3), 21.7 (CH3). MS (ESI) m/z = 667.1 [M + Na]+.
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1,1,1-Tris(azidomethyl)-1-phenylmethane (10). The herein described preparation of triazide 10 is based on the procedure reported for the synthesis of triazide 104 and the procedure published for 1,1,1-tris(azidomethyl)-1-(4-bromophenyl)methane.6 NaN3 (1.86 g, 28.6 mmol) was added to a solution of 1,1,1-tris[(4-tolylsulfonyloxy)methyl]-1-phenylmethane (9) (2.32 g, 3.60 mmol) in dry DMF (35 mL). The orange colored suspension was stirred at 95-100 oC for 2 days. After cooling to room temperature the suspension was poured into ice-water (300 mL). CH2Cl2 (100 mL) were added and the two phases were separated. The aqueous phase was extracted with CH2Cl2 (2 × 100 mL) and then with Et2O (1 × 50 mL). The combined organic phases were washed with water (150 mL) and the aqueous phase was extracted with Et2O (1 × 20 mL). Removal of the solvents of the combined organic phases gave 1,1,1-tris(azidomethyl)-1-phenylmethane (10) (884 mg, 95%) as a yellow oil. 1H NMR (500 MHz, CDCl3): δ = 7.41 (m, 2H, H meta to C(CH2)3), 7.34 (m, 1H, H para to C(CH2)3), 7.29 (m, 2H, H ortho to C(CH2)3), 3.72 (s, 6H, CH2). 13C NMR (125 MHz, CDCl3): δ = 138.4 (CArC), 129.0 (CAr meta to C(CH2)3), 128.0 (CAr para to C(CH2)3), 126.3 (CAr ortho to C(CH2)3), 54.5 (CH2), 47.0 (C(CH2)3).
1,1,1-Tris(aminomethyl)-1-phenylmethane (11). The published procedure4 was followed making slight changes. Under an argon atmosphere 10% Pd/C (311 mg) was added to a solution of 1,1,1-tris(azidomethyl)-1-phenylmethane (10) (801 mg, 3.11 mmol) in anhydrous EtOH (17 mL) in a round-bottom flask (100 mL). The atmosphere in the flask was exchanged for argon through evacuation and filling of the flask with argon for two times. Then, the round-bottom flask with the suspension was evacuated once more and filled with H2 (1 atm). The suspension was stirred at room temperature for 20 h. Then it was filtered through celite and the celite was rinsed with EtOH (50 mL) and the solvent was removed. The 1H NMR spectrum of the residue revealed an incomplete conversion. To the residue 10% Pd/C (360 mg) and ethanol (16 mL) were added. This suspension was treated as described above. Removal of the solvent from the filtrate gave a colorless oily residue (445 mg) that consisted mainly of 1,1,1-tris(aminomethyl)-1-phenylmethane (11) (about 80% yield) and other, unidentified components in minor amounts. 1H NMR (500 MHz, CDCl3): δ = 7.37 (m, H meta to C(CH2)3), 7.32 (m, 2H, H ortho to C(CH2)3), 7.24 (m, 1H, H para to C(CH2)3), 3.04 (s, 6H, CH2). 13C NMR (125 MHz, CDCl3): δ = 142.0 (CArC), 128.8 (CAr meta to C(CH2)3), 126.9 (CAr ortho to C(CH2)3), 126.4 (CAr para to C(CH2)3), 48.5 (C(CH2)3), 45.5 (CH2). MS (ESI) m/z = 180.0 [M + H]+.
TAHA tert-butyl ester (12). The procedure published for the TAHA tert-butyl ester with a bromo substituent in para position at the benzene ring6 was used making some changes. The reaction was performed in an argon atmosphere. iPr2NEt (1.12 mL, 6.59 mmol) and tert-butyl bromoacetate (0.74 mL, 5.08 mmol) were added successively to a degassed suspension of 1,1,1-tris(aminomethyl)-1-phenylmethane (11) (101 mg, 0.56 mmol) in anhydrous acetonitrile (14 mL). The suspension was heated to reflux (bath temperature 83 oC) for 68 h. Shortly after heating, the suspension turned into a brown
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solution. After cooling to room temperature, EtOAc (40 mL) and then water (60 mL) were added. The organic phase was separated, washed with diluted citric acid aqueous solution (2 × 50 mL) and water (60 mL), dried over MgSO4, filtered, and the solvents were removed. Column chromatography (3.0 cm × 46 cm, EtOAc/n-hexane 1:4; The material was loaded onto the silica gel column as a solution in EtOAc.) of the residual brown oil (512 mg) gave (313 mg; Rf = 0.33) consisting mainly of TAHA tert-butyl ester (12) (ca. 65% yield) and small amounts of unidentified components. 1H NMR (500 MHz, CDCl3): δ = 7.37 (m, 2H, H ortho to C(CH2)3), 7.22 (m, 2H, H meta to C(CH2)3), 7.12 (m, 1H, H para to C(CH2)3), 3.25 (s, 6H, C(CH2N)3), 3.20 (s, 12H, CH2CO2
tBu), 1.40 (s, 54 H, tBu). 13C NMR (125 MHz, CDCl3): δ = 171.2 (CO), 144.7 (CArC), 128.5 (CAr meta to C(CH2)3), 126.6 (CAr ortho to C(CH2)3), 125.8 (CAr para to C(CH2)3), 80.4 (CMe3), 59.3 (C(CH2N)3), 56.5 (CH2CO2
tBu), 48.5 (C(CH2N)3), 28.2 (CH3). MS (ESI) m/z = 864.5 [M + H]+, 886.5 [M + Na]+.
H6TAHA • n TFA (13). TAHA tert-butyl ester (12) (261 mg, 300 µmol) was dissolved in trifluoroacetic acid (TFA, 4 mL) and the solution was stirred at room temperature for 1 h. The volatile components were removed at room temperature lowering the pressure down to 10 mbar. This procedure was applied a second time. Then Et2O (5 mL) was added to the residual yellow oil, whereupon a colorless solid precipitated. The precipitate was isolated via centrifugation (1000 rpm, 1 min) and washed with Et2O (2 × 5 mL). The 1H NMR spectrum of the precipitate revealed an incomplete reaction. The precipitate was dissolved in TFA (4 mL) and the solution was stirred at room temperature for 2 h. The volatile components were removed at room temperature lowering the pressure down to 10 mbar. Et2O (6 mL) was added to the residual yellow oil, whereupon a colorless solid precipitated. The precipitate was separated via centrifugation (1000 rpm, 1 min), washed with Et2O (2 × 5 mL), and dried at reduced pressure. H6TAHA • n TFA (13) was obtained (148 mg, 74%) in mixture with a trace of unidentified component as a colorless solid. The content of the structural motif H6TAHA was determined by quantitative 1H NMR spectroscopy2,3 to be 82 wt.%. 1H NMR (500 MHz, CD3OD): δ = 7.66 (d, 3J = 7.8 Hz, 2H, H ortho to C(CH2)3), 7.41 (t like, 3J = 7.8 Hz, 3J = 7.2 Hz, 2H, H meta to C(CH2)3), 7.34 (t, 3J = 7.2 Hz, 2H, H para to C(CH2)3), 3.68 (s, 6H, C(CH2N)3), 3.59 (s, 12H, CH2CO2H). 13C NMR (125 MHz, CD3OD): δ = 172.9 (CO), 141.3 (CArC), 130.3 (CAr meta to C(CH2)3), 128.8 (CAr para to C(CH2)3), 127.9 (CAr ortho to C(CH2)3), 62.2 (C(CH2N)3), 56.8 (CH2CO2H), 48.0 (C(CH2N)3). MS (ESI) m/z = 528.2 [M + H]+, 550.1 [M + Na]+.
Mn(II)-TAHA (2). H6TAHA • n TFA (13) (10.053 mg, contains 15.63 µmol of the structural motif H6TAHA) was dissolved in D2O (600 µL). A part of the obtained solution (100 µL, contains 2.60 µmol of the structural motif H6TAHA) was mixed with a solution of MnCl2 • 4 H2O in D2O (0.05 M, 49 µL, 2.45 µmol). A solution of NaOD in D2O (0.10 M, 150 µL, 15 µmol) was added to rise the pH of the solution to pH7. The solution was diluted with D2O
7
(up to a total volume of 520 µL) to obtain a 5.0 mM solution of Mn(II)-TAHA (2) in D2O containing Na(O2CCF3).
Synthesis of Mn(II)-4-MOMethynyl-PyMTA (3)
4-MOMethynyl-PyMTA ethyl ester (15). The procedure reported for a structurally closely related compound8 was applied. The reaction was performed in dried glassware under argon using the Schlenk technique. To a solution of 4-iodo-PyMTA ethyl ester (14)2 (301 mg, 496 µmol) and 3-methoxyprop-1-yne (63.3 µL, 741 µmol) in THF (6 mL) and iPr2NH (3.5 mL) was added PdCl2(PPh3)2 (4.4 mg, 6.3 µmol) and CuI (2.1 mg, 11.0 µmol). Shortly after the addition of the catalysts a colorless precipitate formed. The yellow suspension was stirred at room temperature for 23 h. All volatiles were evaporated, strictly keeping the reaction mixture in argon. The residue was suspended in degassed anhydrous CH2Cl2 (10 mL) and metal scavenger QuadraPure TU (36 mg) was added. The suspension was stirred at room temperature for 19 h. Metal scavenger QuadraPure BzA (5 mg) was added, and the suspension was stirred for another 4 h at room temperature. The metal scavenger QuadraPure BzA did not change its color, which indicated that there had been no free Cu(I/II) left in the solution. The suspension was filtered through a syringe filter (PTFE membrane, 13 mm, w/0.45 μm), the filter cake was washed with CH2Cl2 (3 x 15 mL), and the solvent of the combined filtrates was removed. Column chromatography (2.0 cm × 38 cm, CH2Cl2/Et2O 10:4) of the residual yellow solid gave 4-MOMethynyl-PyMTA ethyl ester (15) (240 mg, 88%; Rf = 0.2) as a yellow oil. 1H NMR (500 MHz, CDCl3): δ = 7.48 (s, 2H, ArH), 4.28 (s, 2H, MeOCH2), 4.13 (q, 3J = 7.2 Hz, 8H, CH2CH3), 3.97 (s, 4H, ArCH2), 3.56 (s, 8H, CH2CO), 3.41 (s, 3H, MeO), 1.23 (t, 3J = 7.2 Hz, 12H, CH2CH3). 13C NMR (125 MHz, CDCl3): 171.0 (CO), 158.6 (CAr meta to C≡C), 131.9 (CArC≡C), 123.3 (CArH), 89.1 (CArC≡C), 84.4 (CArC≡C), 60.5 (CH2CH3), 60.1 (MeOCH2), 59.6 (ArCH2), 57.8 (MeO), 54.9 (CH2CO), 14.2 (CH2CH3). MS (ESI) m/z = 572.3 [M + Na]+, 550.3 [M + H]+.
{[4-MOMethynyl-H4PyMTA - 4H]4- • n H+ • m Na+} (16). 4-MOMethynyl-PyMTA ethyl ester (15) (132 mg, 240 μmol) was dissolved in EtOH (5 mL). A solution of NaOH in H2O (2.0 M, 1.2 mL, 240 mmol) was added whereupon a mixture of two liquid phases formed, which turned into one brownish yellow phase within the next 15 min of stirring. This solution was stirred at room temperature for 18 h. Then, proton-exchange resin was
8
added as much as was needed to reduce the pH of the solution to pH 3. The solution was separated from the proton-exchange resin through filtration through a syringe filter (PDVF membrane, 13 mm, w/0.45 μm) and the proton-exchange resin was washed with water (3 × 5 mL) and a 1:1 mixture of EtOH and H2O (5 × 2 mL). The solvents of the combined filtrates were removed. {[4-MOMethynyl-H4PyMTA - 4 H+]4- • n H+ • m Na+} (16) was obtained (66 mg, 56%) as a slightly brown solid. The content of the structural motif [4-MOMethynyl-H4PyMTA - 4 H+]4- was determined by elemental analysis to be 88 wt.%. 1H NMR (500 MHz, CD3OD): δ = 7.45 (s, 2H, ArH), 4.36 (s, 2H, MeOCH2), 4.28 (s, 4H, ArCH2), 3.66 (s, 8H, CH2CO), 3.43 (s, 2H, MeO). 13C NMR (125 MHz, CD3OD): 173.1 (CO), 156.4 (CAr meta to C≡C), 134.6 (CArC≡C), 126.3 (CArH), 92.7 (CArC≡C), 84.1 (CArC≡C), 60.8 (MeOCH2), 59.9 (ArCH2), 58.1 (MeO), 57.6 (CH2CO). MS (ESI) m/z = 436.0 [M - H]-, 217.4 [M – 2 H]2-. Elemental analysis calcd (%) for {[4-MOMethynyl-H4PyMTA - 4 H+]4- • n H+ • m Na+} with 88 wt.% of [4-MOMethynyl-H4PyMTA - 4 H+]4- (C19H19N3O9): C, 46.34; H, 3.89; N, 8.54. Found C, 46.59; H, 5.09*; N, 8.39. *H comes from [4-MOMethynyl-H4PyMTA - 4 H+]4- as well as from "• n H+".
Mn(II)-4-MOMethynyl-PyMTA (3). {[4-MOMethynyl-H4PyMTA - 4 H+]4- • n H+ • m Na+} (16) (2.566 mg, contains 5.27 µmol of the structural motif [4-MOMethynyl-H4PyMTA - 4 H+]4-) was dissolved in D2O (500 µL). A solution of MnCl2 • 4 H2O in D2O (0.05 M, 100.2 µL, 5.01 µmol) was added and then a solution of NaOD in D2O (0.10 M, 150 µL, 15 µmol) was added to rise the pH of the solution to pH8.2. The solution was diluted with D2O (304.8 µL) to obtain a 5.0 mM solution of Mn(II)-4-MOMethynyl-PyMTA (3) in D2O containing NaCl. MS (ESI) m/z = 243.9 [M - 2Na]2-.
Synthesis of Mn(II)-NO3Py (4)
The synthesis of the ligand NO3Py (19; also called also called tptcn) has been described9,10 as well as that of Mn(II)-NO3Py, which was isolated as the perchlorate salt.10 We used a slightly different procedure for the preparation of NO3Py (19) which is based on the report of Roger et al.11
NO3Py (19). To a suspension of 1,4,7-triazacyclononane trihydrochloride (17) (100 mg, 0.42 mmol) and K2CO3 (701 mg, 5.07 mmol) in acetonitrile (30 ml) was added a solution of 2-(chloromethyl)pyridine hydrochloride (18) (207 mg, 1.26 mmol) in acetonitrile (5 mL).
9
The suspension was heated under reflux for 21.5 h. After cooling to room temperature the beige suspension was filtered and the solvents of the filtrate were removed under vacuum. The residual orange viscous oil (164 mg) was dissolved in CH2Cl2 (20 mL) and the solution was washed with water (20 mL). The organic phase was separated and the aqueous phase was extracted with CH2Cl2 (2 × 10 mL). The combined organic phases were washed with water (2 × 10 mL), dried over Na2SO4, filtered and the solvents were removed. NO3Py (19) was obtained as a yellow oil (150 mg, 89%). 1H NMR (500 MHz, CDCl3): δ = 8.49 (d like, 3J = 4.8 Hz, 3H, H ortho to N), 7.63 (apparent dt, 3J = 7.7 Hz, 4J = 1.7 Hz, 3H, H para to N), 7.49 (d, 3J = 7.7 Hz, 3H, H ortho to CH2), 7.12 (dd like, 3J = 7.7 Hz, 3J = 4.8 Hz, 3H, H para to CH2), 3.81 (s, 6H, ArCH2), 2.87 (s, 12H, NCH2CH2N). 13C NMR (500 MHz, CDCl3): δ = 160.4 (CArCH2), 148.9 (CAr ortho to N), 136.3 (CAr para to N), 123.2 (CAr ortho to CH2), 121.8 (CAr para to CH2), 64.4 (ArCH2), 55.7 (NCH2CH2N). MS (ESI) m/z = 425.2 [M + Na]+, 403.2 [M + H]+.
Mn(II)-NO3Py (4). NO3Py (19) (9.473 mg, 23.53 µmol) was dissolved in CD3OD (600.8 µL). A part of this solution (100 µL, contains 3.92 µmol NO3Py (19)) was mixed with a solution of MnCl2 • 4 H2O in D2O (0.05 M, 71.6 µL, 3.58 µmol). The solution was diluted with D2O to a total volume of 754 µL to obtain a 5.0 mM solution of Mn(II)-NO3Py (4). The solution had a pH 6.5. MS (ESI) m/z = 228.5 [M - 2Cl]2-.
Synthesis of the Mn-rulers 5n
O
O
N
NO
O
O
O
NO
O
O
OMn
NN
N
NN
N
OO
O
O
O
O
O
O
O O
O
O
O
O
O
O
N
NO
O
O
O
NO
O
O
OMn
4-
n(Na+)4
O
O
NN
N
NN
N
OO
O
O
O
O
O
O
O O
O
O
O
O
O
O
n
HO2C
HO2C
HO2C
HO2C
N
N
N N
N
N
CO2H
CO2H
CO2H
CO2H
H4PyMTA-spacer-H4PyMTA 20n Mn-ruler 5n
10
Mn-ruler 53. H4PyMTA-spacer-H4PyMTA 2038 (1.681 mg, 0.428 µmol) was dissolved in
D2O (750 µL). A solution of MnCl2 • 4 H2O in D2O (0.05 M, 16.70 µL, 0.835 µmol) was added and then a solution of NaOD in D2O (0.10 M, 25 µL, 2.5 µmol) was added to rise the pH of the solution to pH 8.2. The solution was diluted with D2O (278.5 µL) to obtain a 400 µM solution of Mn-ruler 53 in D2O. MS (ESI): because of the high molecular weight of this compound and therefore the broad isotopic distribution, the most abundant mass is reported instead of the monoisotopic mass; m/z = 1007.0 [M - 4Na]4-, 1343.0 [M - 4Na + H]3-, 1350.3 [M - 3Na]3-, 2015.1 [M - 4Na + 2H]2-, 2026.1 [M - 3Na + H]2-, 2037.1 [M - 2Na]2-.
Mn-ruler 55. H4PyMTA-spacer-H4PyMTA 2058 (2.481 mg, 0.411 µmol) was dissolved in
D2O (750 µL). A solution of MnCl2 • 4 H2O in D2O (0.05 M, 16.03 µL, 0.801 µmol) was added and then a solution of NaOD in D2O (0.10 M, 30 µL, 3.0 µmol) was added to rise the pH of the solution to pH 8.2. The solution was diluted with D2O (231.5 µL) to obtain a 400 µM solution of Mn-ruler 55. MS (ESI): because of the high molecular weight of this compound and therefore the broad isotopic distribution, the most abundant mass is reported instead of the monoisotopic mass; m/z = 2046.7 [M - 4Na + H]3-.
RIDME data analysis
For better comparison of the form factors obtained for different mixing times and temperatures Figure S1 shows a modulation depth scaled representation. Careful investigation shows that the form factors are indeed almost identical at various mixing times, though with changing temperature small deviations can be observed. This suggests the use of different overtone coefficients for analysis. Nevertheless, the deviation of the coefficient is within 5% and an overall analysis using the same coefficients still leads to the anticipated mean distance with a relatively low level of artefacts.
11
0 0.5 1 1.5 2 2.5 3 3.5 4
10 K 12 sμ30 K 24 sμ
10 K 24 sμ
10 K 48 sμ20 K 12 sμ
20 K 24 sμ
20 K 48 sμ
30 K 12 sμ30 K 24 sμ
0 0.5 1 1.5 2
10 K 12 sμ30 K 48 sμ
10 K 24 sμ10 K 48 sμ
10 K 72 sμ20 K 12 sμ
20 K 24 sμ20 K 48 sμ
20 K 72 sμ
30 K 12 sμ30 K 24 sμ
F(t
)/F
(t=
0)
F(t
)/F
(t=
0)
t [ s]μ t [ s]μ
0 0.5 1 1.5 2 0 0.5 1 1.5 2 2.5 3 3.5 4
(a) (b)
(c) (d)
Figure SI1. Modulation depth scaled RIDME form factors acquired at W-band (94GHz) forMn-rulers 53 and 55 in frozen solution of 1:1 D2O/glycerol-D8 at different temperatures. (a), (b) Complete data set for Mn-rulers 53 and 55, respectively. (c), (d) showing the time traces with largest deviation for Mn-rulers 53 and 55. The strongest differences are observed between different temperatures.
The influence of the harmonic overtone coefficients is shown in Figure SI2 –Figure SI7. In most cases the cleanest distance distribution does not correspond to the best fit of time and frequency domain data. For Mn-ruler 53 it is seen that with growing higher harmonics the form factor fit quality improves at the cost of intensification of the artefact at approx. 4 nm. E.g. at 10 K time and frequency domain are best fitted with P2=0.50 and P3=0.07 or 0.09, while the lowest artefact level is obtained for P2=0.46 and P3= 0.06. Yet higher coefficients do not improve the fitting, but clearly enlarge the artefact. Furthermore, precise determination of P1, P2, P3 values is hampered by minor deviations in fit quality upon modification of the coefficients. For the 4.7 nm model compound the picture appears to be reversed. Cleaner distance distributions are obtained for coefficients that overfit the P2 contribution in frequency domain. The coefficients for best fitted form factors intensify the artefact around 4 nm. The best set of coefficients P1=0.41, P2=0.50 and P3=0.09 indicates nearly the same contribution of the main dipolar frequency and its first overtone (double frequency) to the dipolar evolution data. The contribution of the triple frequency is relatively small (P3=0.09) but cannot be neglected.
It is important to note that the artefact appearance is sensitive to background correction and a very “clean” distance distribution can also be obtained with a clearly incorrect background fit that results in a very poor fit of the form factors. Besides the background
12
correction, artefacts are also caused by noise or sample imperfections and thus cannot be suppressed by overtone correction. Nevertheless, these additional imperfections might be difficult to identify when they appear at the same distances as the overtone artefacts.
In the following set of fitted RIDME data one can see that for Mn-ruler 53 there seems to be a small trend towards lower overtone coefficients with increasing temperature.
Figure SI2. Variation of overtone coefficients for Mn-ruler 53 with increasing mixing times from top to bottom acquired at W-band (94GHz) forMn-ruler 53 in frozen solution of 1:1 D2O/glycerol-D8 at 10K. Left to right: Primary data together with background fits, background corrected form factors and their corresponding form factor fit resulting from Tikhonov regularization, corresponding frequency domain spectra and extracted distance distributions. It is seen that the cleanest distance distribution (P2=0.46 P3=0.06) does not correspond to the best fit. With increasing higher harmonics, the fit quality improves however the artefact at approx. 4 nm is increased as well. Time and frequency domain are best fitted with P2=0.50 and P3=0.07 or 0.09. Yet higher coefficients do not improve the fitting, but clearly increase the artefact level.
13
Figure SI3. Variation of overtone coefficients for t Mn-ruler 53 with increasing mixing times (from top to bottom) acquired at W-band (94GHz) for Mn-ruler 53 in frozen solution of 1:1 D2O/glycerol-D8 at 20 K. Left to right: Primary data together with background fits, background corrected form factors and their corresponding form factor fit resulting from Tikhonov regularization, corresponding frequency domain spectra and extracted distance distributions. It is seen that the cleanest distance distribution (P2=0.46 P3=0.06) does not correspond to the best fit. With increasing higher harmonics, the fit quality improves however the artefact at approx. 4 nm is increased as well. Time and frequency domain are best fitted with P2=0.50 and P3=0.07 or 0.05. Yet higher coefficients do not improve the fitting, but clearly increase the artefact level.
14
Figure SI4. From top to bottom variation of overtone coefficients for Mn-ruler 53 acquired at W-band (94GHz) for Mn-ruler 53 in frozen solution of 1:1 D2O/glycerol-D8 at 30 K. Left to right: Primary data together with background fits, background corrected form factors and their corresponding form factor fit resulting from Tikhonov regularization, corresponding frequency domain spectra and extracted distance distributions. It is seen that the cleanest distance distribution (P2=0.46 P3=0.06) does not correspond to the best fit. Time and frequency domain are best fitted with P2=0.48 and P3=0.07 or 0.05. Yet higher coefficients do not improve the fitting, but clearly increase the artefact level.
15
Figure SI5. Variation of overtone coefficients for the Mn-ruler 55 with increasing mixing times (from top to bottom) acquired at W-band (94GHz) forMn-ruler 55 in frozen solution of 1:1 D2O/glycerol-D8 at 10K. Left to right: Primary data together with background fits, background corrected form factors and their corresponding form factor fit resulting from Tikhonov regularization, corresponding frequency domain spectra and extracted distance distributions. It is seen that the cleanest distance distribution (P2=0.52 P3=0.09) does not correspond to the best fit (P2=0.50 P3=0.09).
16
Figure SI6. Variation of overtone coefficients for Mn-ruler 55 with increasing mixing times (from top to bottom) acquired at W-band (94GHz) for Mn-ruler 55 in frozen solution of 1:1 D2O/glycerol-D8 at 20K. Left to right: Primary data together with background fits, background corrected form factors and their corresponding form factor fit resulting from Tikhonov regularization, corresponding frequency domain spectra and extracted distance distributions. It is seen that the cleanest distance distribution (P2=0.52 P3=0.09) does not correspond to the best fit (P2=0.50 P3=0.07 or even P2=0.48 P3=0.09).
17
Figure SI7. Variation of overtone coefficients for Mn-ruler 55 with increasing mixing times (from top to bottom) acquired at W-band (94GHz) forMn-ruler 55 in frozen solution of 1:1 D2O/glycerol-D8 at 20K. Left to right: Primary data together with background fits, background corrected form factors and their corresponding form factor fit resulting from Tikhonov regularization, corresponding frequency domain spectra and extracted distance distributions. It is seen that the cleanest distance distribution (P2=0.52 P3=0.09) does not correspond to the best fit (P2=0.50 P3=0.07 or even P2=0.48 P3=0.09).
ED field sweep and line shape analysis
Figure SI8. a) Q-band and b) W-band ED EPR spectra of the four studied Mn(II) complexes 1-4 at 10 K.
18
Figure SI9. Experimental (blue lines) W-band (94 GHz) field swept ED–EPR spectra of the studied Mn(II) complexes 1-4 and the simulated spectra (green line), calculated with spin Hamiltonian parameters from Table 1 (main text).
Thermal spin polarization – determination of the sign of D
The reduction of the temperature results in a progressive depopulation of the higher energy mS levels (mS= +5/2,+3/2,+1/2 ,−1/2 , for a S=5/2 spin system) and consequently reduces the contribution of the corresponding transitions (|mS = +3/2 |+5/2, |mS =
+1/2 |+3/2) in the EPR spectrum. Due to the larger Zeeman splitting the effect is more pronounced in the high field EPR and is detectable at W-band at temperatures approaching the Boltzman temperature of 4.5 K. Depending on the sign of D the thermal polarization will result in the drop of the signal intensity either in the high-field or low-field part of the spectrum (with respect to the central transition) as schematically illustrated in Fig. SI10 for a S=5/2 system.
19
Figure SI10. Schematic illustration of the thermal spin polarization effect of a powder (glass) sample of an S=5/2 spin system
Figure SI11 compares the ESE EPR spectra of Mn-TAHA (2), Mn-4-MOMethynyl-PyMTA (3), and Mn-NO3Py (4) at 10 K and 5 K. The decrease of the spectral intensity in the low field part of the spectrum upon cooling is consistent with the negative sign of the D parameter for all three complexes.
20
Figure SI11. Comparison of the normalized ED EPR spectra of Mn-TAHA (2), Mn-4-MOMethynyl-PyMTA (3), and Mn-NO3Py (4) at 10 K or 20 K and 5 K.
Relaxation properties
Table SI1. Relaxation parameters of 100 µM solutions of Mn(II) complexes 1-4 in D2O/glycerol-D8 at Q-Band (34 GHz) and 10 K.
complex Tm/µs a x a Tm(1/e)/ µs b Tm
*/μs c T1 d x d
T1(1/e)/ µs e
T1*/µs f
(1) (1)*
26.6 3.8
0.91 1.67
27.0 3.9
66.6 6.0
999 797
0.63 0.60
1008 810
3816 3240
(2) 10.8 0.69 10.4 36.8 503 0.68 497 1817 (3) 14.7 1.15 15.0 30.2 546 0.69 546 1842 (4) 11.3 0.78 10.8 34.8 257 0.62 260 940
*in H2O/glycerol glass
a Tm phase memory time extracted from the fit of the decay with the stretched exponential model , R2 > 0.99 in all cases ; b Tm(1/e) time required for the decay of Hahn-echo to 1/e of the initial intensity; c Tm
*
time required for the decay of the echo 10% of the initial intensity; d T1 relaxation time extracted from the
fit of the echo recovery with the stretched exponential model 1 , R2 > 0.99 in all cases; e T1(1/e)
time required for recovery of 1–1/e of the initial echo intensity; f T1*
time required for recovery of 90% initial echo intensity.
21
Table SI2. Relaxation parameters of Mn-maleimide-DOTA (1) in D2O/glycerol-D8 and H2O/glycerol-d8 glasses.
D2O/glycerol-D8
Temp./K c/μM Tm/μs
a x a Tm(1/e)/μs
b Tm
*/μs c
T1 d x d
T1(1/e)/ μs e
T1*/μs f
T1*/Tm
*
10 50 29.1 1.2 28.1 43.6 210 0.6 228 900 20.6 100 29.6 1.2 29.1 44.8 210 0.6 228 864 19.3 300 22.3 1.2 22.2 32.6 159 0.6 174 666 20.4 500 19.9 1.3 19.8 28.4 153 0.6 162 624 22.0 15 50 26.8 1.2 26.0 40.4 124 0.6 132 504 12.5 100 26.9 1.2 26.5 40.4 119 0.6 128 484 12.0 300 18.8 1.3 18.5 26.7 104 0.6 112 412 15.4 500 16.1 1.4 16.1 22.4 92 0.6 100 384 17.1 20 25 22.9 1.2 22.0 50 24.1 1.2 22.9 36.8 79 0.7 82 286 7.8 100 23.2 1.2 22.5 35.5 78 0.7 82 286 8.1 300 15.7 1.3 15.6 22.1 66 0.7 70 246 11.1 500 13.2 1.4 13.1 18.5 61 0.7 64 226 12.2 30 50 17.5 1.1 16.8 28.8 36 0.7 36 116 4.0 100 16.5 1.1 16.2 27.1 35 0.7 36 116 4.3 300 10.8 1.3 10.6 15.7 31 0.7 32 100 6.4 500 9.0 1.3 9.0 13.0 31 0.7 32 104 8.0 H2O/glycerol-
D8
10 50 6.4 2.1 6.2 9.4 229 0.6 246 924 98.3 100 6.3 2.0 6.2 9.3 211 0.6 228 852 91.6 300 6.3 2.0 5.9 9.0 198 0.6 210 774 86.0 500 6.0 2.0 5.8 8.9 181 0.7 188 684 76.9 15 50 6.3 2.1 6.2 9.2 135 0.6 144 532 57.8 100 6.3 2.2 6.2 9.2 124 0.6 132 488 53.0 300 6.3 2.2 6.0 8.9 109 0.6 116 440 49.4 500 5.9 2.0 5.8 8.7 120 0.7 125 443 50.9 20 50 6.1 2.0 6.0 9.0 84 0.7 88 304 33.8 100 6.1 2.1 6.0 9.0 78 0.7 82 284 31.6 300 6.1 2.1 5.8 8.6 70 0.7 74 260 30.2 500 5.6 2.0 5.5 8.3 76 0.8 77 237 28.6 30 50 5.7 1.9 5.6 8.6 37 0.7 38 120 14.0 100 5.6 1.9 5.4 8.4 36 0.7 37 116 13.8 300 5.6 1.9 5.1 8.0 34 0.7 35 110 13.8 500 4.8 1.8 4.8 7.5 36 0.7 37 112 14.9
a Tm phase memory time extracted from the fit of the decay with the stretched exponential model , R2 > 0.99 in all cases ; b Tm(1/e) time required for the decay of Hahn-echo to 1/e of the initial intensity; c Tm
*
22
time required for the decay of the echo 10% of the initial intensity; d T1 relaxation time extracted from the
fit of the echo recovery with the stretched exponential model 1 , R2 > 0.99 in all cases; e T1(1/e)
time required for recovery of 1–1/e of the initial echo intensity; f T1*
time required for recovery of 90% initial echo intensity.
ENDOR-based determination of the local surrounding of Mn(II) ions
Figure SI12. Davies 55Mn ENDOR spectra of Mn-maleimide-DOTA (1) and Mn-4-MOMethynyl-PyMTA (3) recorded at 10K (blue lines) together with the spectra simulated using the parameters from Table 1 (main text) (black lines).
23
Figure SI13. Davies 1H ENDOR spectra of Mn-maleimide-DOTA (1) and Mn-4-MOMethynyl-PyMTA (3) recorded at 10K (blue lines) together with the spectra simulated using the parameters from Table SI3 (black lines).
Figure SI14. Mn-H distance distribution obtained from the crystal structure of Mn-H2DOTA.8
24
Figure SI15. Mims 14N ENDOR spectra spectrum of Mn-maleimide-DOTA (1) and Mn-4-MOMethynyl-PyMTA (3) recorded at 20 K (blue line) together with the simulation (black line) using parameters from Table SI4. Contributions from NMR transitions within the mS = ±1/2 and mS = ±3/2 spin manifolds are shown as red and green line, respectively.
Table SI3. Spin Hamiltonian parameters used in the simulation of the 1H Davies and 14N Mims ENDOR spectra
complex nucleus Aiso /MHz T /MHz e2Qq/h /MHz γ
Mn-maleimide-DOTA (1) 14N 2.05 0.52 4.59 0
Mn-4-MOMethynyl-PyMTA (3) 2.00 0.25 5.01 0
Mn-maleimide-DOTA (1) 1H 0 1.75
0.28 1.01
Mn-4-MOMethynyl-PyMTA (3) 1H 0 1.72
0.11 1.08
2. The average Mn-N distance in Mn-H2DOTA is 0.2364 nm12
corresponding to T = 0.43 MHz.
25
Comparison of EPR properties of Mn-maleimide-DOTA (1) and Gd-DOTA
Table SI4. Relaxation properties of Mn-maleimide-DOTA (1) and Gd-DOTA (W band; 0.1 mM in 1:1 (v/v) D2O/glycerol-d8).
T / K Tm/μs a x a Tm(1/e)/μs b Tm*/μs c T1
d x dT1(1/e)/ μs
e T1
*/μs f T1
*/ Tm*
10 Mn 29.6 1.2
29.1 44.8 210 0.6
228 864 19.3
Gd 19.6 1 19.6 44.9 69 0.6
76 257 5.7
15 Mn 26.9 1.
2 26.5 40.4 119 0.
6 128 484 12.0
Gd 14.1 1 14.1 32.8 42.7
0.7
47 156 4.8
20 Mn 23.2 1.
2 22.5 35.5 78 0.
7 82 286 8.1
Gd 11.0 1 19.6 24.7 28 0.7
30 97 3.9
30 Mn 16.5 1.
1 16.2 27.1 35 0.
7 36 116 4.3
Gd 7.6 0.9
6.7 16.4 14 0.7
14.9 44 2.7
Note: The Tm*= 44.9 µs value of Gd-DOTA at 10 K is close to the value of 37.8 µs previously reported for Gd-DOTA.13 The somewhat different value in this study might be accounted for by a higher level of solvent deuteration as well as by the experimental uncertainty.
Figure SI16. Temperature dependence of (a) Tm* and (b) T1* relaxation times of 0.1 mM solution of Mn-
maleimide-DOTA (1) and Gd-DOTA in 1:1 (v/v) D2O/glycerol-D8 at W-band.
26
Figure SI17. Temperature dependence of Tm*/T1* ratio of 0.1 mM solution of Mn-maleimide-DOTA (1) and
Gd-DOTA in 1:1 (v/v) D2O/glycerol-D8 at W-band. The optimum Tm*/T1* ratio of 0.2 is found at 14 K for Gd-DOTA and 27 K for Mn-maleimide-DOTA (1).
Figure SI18. (a) W-band field-swept echo-detected EPR spectra for 0.1 mM solution of Mn-maleimide-DOTA (1) (green) and of Gd-DOTA (blue) in 1:1 (v/v) D2O/glycerol-D8 recorded at 10K. (b) Integral normalized central Gd EPR and 3rd Mn EPR line. Note that the B1/2 = 1.3 mT value agrees with preciously reported values of 1.30 mT 13and 1.36 mT.8,14 The echo intensity ratio Gd(III)/Mn(II) is 2.8, instead of 6, due to the difference in EPR linewidth.
27
Figure SI19. Temperature dependence of the population difference between 1/2 and +1/2 electron spin energy levels calculated for 3.35 T resonance field.
Table SI5. Comparison of the performance of Mn-maleimide-DOTA (1) and Gd-DOTA for Mn(II)-Mn(II) or Gd(III)-Gd(III) RIDME.
Mn-maleimide-DOTA (1) at 27 K Gd-DOTA at 17K Tm /µs 29.2 29.2 T1 /µs 160 130 Tm/T1 0.18 0.22
Polarization |-1/2>|1/2> 0.027 0.028 Signal loss due to the
hyperfine splitting 1/6 1
Linewidth signal win 2.1 1 EPR signal intensity 0.35 1
The disadvantage of Mn(II) spin labels in comparison to Gd(III) spin labels is a somewhat lower EPR signal intensity.
28
Fig
ure
SI2
0. 1 H
NM
R s
pect
rum
of 1
,1,1
-tris
(hyd
roxy
met
hyl)-
1-ph
enyl
met
hane
(8)
.
29
Fig
ure
SI2
1.1 H
NM
R s
pect
rum
of 1
,1,1
-tris
[(4-
toly
lsul
fony
loxy
)met
hyl]-
1-ph
enyl
met
hane
(9)
.
30
Fig
ure
SI2
2. 1 H
NM
R s
pect
rum
of 1
,1,1
-tris
(azi
dom
ethy
l)-1-
phen
ylm
etha
ne (
10).
31
Fig
ure
SI2
3. 1 H
NM
R s
pect
rum
of 1
,1,1
-tris
(am
inom
ethy
l)-1-
phen
ylm
etha
ne (
11).
32
Fig
ure
SI2
4. 1 H
NM
R s
pect
rum
of T
AH
A te
rt-b
utyl
est
er (
12).
33
Fig
ure
SI2
5. 1 H
NM
R s
pect
rum
of H
6TA
HA
• n
TF
A (
13)
cont
aini
ng E
t 2O
.
H6T
AH
A
N NN
CO
2H
CO
2H
CO
2H
CO
2H
CO
2HH
O2C
n T
FA
n T
FA
(13)
34
Fig
ure
SI2
6. 1 H
NM
R s
pect
rum
of 4
-MO
Met
hyny
l-PyM
TA
eth
yl e
ster
(15
).
35
Fig
ure
SI2
7. 1 H
NM
R s
pect
rum
of {
[4-M
OM
ethy
nyl-P
yMT
A -
4H
]4- •
n H
+ •
m N
a+}
(16)
.
36
Fig
ure
SI2
8. 1 H
NM
R s
pect
rum
of N
O3P
y (1
9).
37
References
1 R. F. Heck, Palladium reagents in organic syntheses, Academic Press, London, 1985, p18.
2 M. Qi, M. Hülsmann and A. Godt, Synthesis, 2016, DOI: 10.1055/s-0035-1561660.
3 S. K. Bharti and R. Roy, TrAC Trends Anal. Chem., 2012, 35, 5–26. 4 R. Viguier, G. Serratrice, A. Dupraz and C. Dupuy, Eur. J. Inorg. Chem., 2001,
2001, 1789–1795. 5 K. W. Hellmann, S. Friedrich, L. H. Gade, W.-S. Li and M. McPartlin, Chem.
Ber., 1995, 128, 29–34. 6 F. Peters, M. Maestre-Martinez, A. Leonov, L. Kovacic, S. Becker, R. Boelens
and C. Griesinger, J. Biomol. NMR, 2011, 51, 329–337. 7 S. D. Cho, I. D. Kim, J. H. Jo and J. S. Chung, J. Korean Chem. Soc., 1990,
34, 501–502. 8 M. Qi, M. Hülsmann and A. Godt, J. Org. Chem., 2016, 81, 2549–2571. 9 L. Christiansen, D. N. Hendrickson, H. Toftlund, S. R. Wilson and C. L. Xie,
Inorg. Chem., 1986, 25, 2813–2818. 10 K. Wieghardt, E. Schoeffmann, B. Nuber and J. Weiss, Inorg. Chem., 1986, 25,
4877–4883. 11 M. Roger, L. M. P. Lima, M. Frindel, C. Platas-Iglesias, J.-F. Gestin, R.
Delgado, V. Patinec and R. Tripier, Inorg. Chem., 2013, 52, 5246–5259. 12 S. Wang and T. D. Westmoreland, Inorg. Chem., 2009, 48, 719–727. 13 A. Collauto, A. Feintuch, M. Qi, A. Godt, T. Meade and D. Goldfarb, J. Magn.
Reson., 2016, 263, 156–163. 14 R. B. Clarkson, A. I. Smirnov, T. I. Smirnova, H. Kang, R. L. Belford, K. Earle
and J. H. Freed, Mol. Phys., 1998, 95, 1325–1332.