Synthesis of different glutathione–sulfur mustard adducts of verified and potential biomarkers

SUPPORTING INFORMATION

Synthesis of Glutathione-Sulfur Mustard Bioadducts

for the Verification of Potential Biomarkers

Andreas Bielmann

[a][b]

_{, Nicolas Sambiagio}

[a][c]

_{, Nathalie Wehr}

[a][b]

_{, Sandrine Gerber}

[c]

_,

Christian G. Bochet

[b]

_{, Christophe Curty*}

[a]

[a]

_{Spiez Laboratory, Austrasse, 3700 Spiez, Switzerland}

[b]

_{University of Fribourg, Departement of Chemistry, Chemin du Musée 9, 1700 Fribourg,}

Switzerland

[c]

_{Ecole Polytechnique Fédéral de Lausanne, Institute of Chemical Sciences and Engineering,}

Station 6, 1015 Lausanne, Switzerland

christophe.curty@babs.admin.ch

Table of Contents

1

_{H NMR and}

13

_{C NMR of 1}

_S2

1

_{H NMR and}

13

_{C NMR of 2}

_S4

1

_{H NMR and}

13

_{C NMR of 3}

_S6

1

_{H NMR and}

13

_{C NMR of 4 by alkylation of GSH}

_S7

1

_{H NMR and}

13

_{C NMR of 5}

_S10

1

_{H NMR and}

13

_{C NMR of 6}

_S12

1

_{H NMR and}

13

_{C NMR of 4 by SPPS}

_S14

1

_{H NMR and}

13

_{C NMR of 7}

_S16

1

_{H NMR and}

13

_{C NMR of 11}

_S18

1

_{H NMR and}

13

_{C NMR of 12}

_S20

1

_{H NMR and}

13

_{C NMR of 8}

_S22

1

_{H NMR and}

13

_{C NMR of 14}

_S24

1

_{H NMR and}

13

_{C NMR of 15}

_S26

1

_{H NMR and}

13

_{C NMR of 9}

_S28

8

7

6

5

4

3

2

1

1.22 2.71 2.73 2.74 2.76 2.78 2.79 2.98 3.00 3.01 3.54 3.55 3.57 3.75 3.76 3.77 3.79 7.27

9.31

2.03

2.05

0.98

2.08

2.09

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

0.00 27.48 32.61 36.45 61.39 62.13 73.63 76.72 77.04 77.35

8

7

6

5

4

3

2

1

1.20 2.68 2.70 2.71 2.91 2.93 2.95 3.53 3.55 3.56 3.65 3.67 3.68 7.27

9.00

2.02

2.13

1.96

2.12

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

0.00 27.52 32.96 34.84 43.20 62.23 73.32 76.71 77.03 77.35

8

7

6

5

4

3

2

1

1.97 1.98 1.99 2.00 2.01 2.01 2.02 2.04 2.44 2.44 2.45 2.46 2.46 2.47 2.47 2.48 2.73 2.74 2.76 2.85 2.87 2.88 2.90 2.91 2.94 3.10 3.12 3.14 3.15 3.45 3.46 3.48 3.63 3.65 3.67 3.72 3.77 3.79 3.83 4.58 4.59 4.60 4.61 4.79

9.12

1.96

1.98

2.05

3.79

2.16

0.95

2.01

2.05

0.97

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

26.59 29.08 31.29 31.52 31.57 31.97 32.92 43.39 53.11 55.01 60.98 75.16 171.92 175.82 176.20 179.24

8

7

6

5

4

3

2

1

2.17 2.18 2.20 2.22 2.24 2.26 2.28 2.30 2.31 2.53 2.55 2.57 2.59 2.61 2.62 2.64 2.66 2.73 2.75 2.76 2.83 2.88 2.90 2.92 2.94 3.06 3.08 3.10 3.11 3.73 3.74 3.76 4.02 4.07 4.08 4.10 4.57 4.58 4.59 4.61 4.79

2.02

2.04

2.18

4.44

2.36

2.32

1.91

1.06

0.90

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

ppm

25.62 30.98 31.11 31.56 32.69 33.31 41.11 52.71 53.10 60.28 111.98 114.87 117.77 120.66 162.47 162.82 163.17 163.52 172.21 172.74 172.93 174.46

8

7

6

5

4

3

2

1

1.15 2.65 2.66 2.68 2.78 2.96 2.97 2.99 3.01 3.05 3.06 3.09 3.10 3.55 3.56 3.58 3.83 3.84 3.85 3.86 4.70

9.17

2.05

4.08

2.10

2.07

1.00

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

26.52 31.14 31.29 31.54 32.00 53.61 60.89 75.16 172.78

8

7

6

5

4

3

2

1

1.17 1.97 2.61 2.63 2.64 2.78 2.91 2.93 2.95 3.05 3.06 3.08 3.09 3.50 3.51 3.53 4.26 4.28 4.30 4.37 4.38 4.38 4.40 4.42 5.47 6.15 6.17 7.35 7.35 7.36 7.37 7.37 7.37 7.39 7.39 7.39 7.43 7.45 7.47 7.70 7.72 7.86 7.88

9.13

3.69

4.76

2.83

2.16

1.08

2.74

0.86

2.02

2.00

2.02

1.99

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

0.28 0.49 0.69 0.84 0.90 1.05 1.10 1.25 1.31 1.52 27.34 32.62 32.72 32.89 33.88 47.55 54.42 54.51 62.33 67.14 73.54 118.11 120.60 125.83 127.77 128.34 141.71 144.60 144.65

8

7

6

5

4

3

2

1

2.08 2.10 2.12 2.14 2.45 2.47 2.48 2.50 2.66 2.67 2.75 2.80 2.83 2.84 2.86 2.99 3.00 3.02 3.04 3.65 3.66 3.68 3.80 3.82 3.83 3.92 4.49 4.50 4.51 4.52 4.70

1.97

2.02

1.92

4.13

2.54

1.94

1.02

2.02

1.04

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

25.88 31.00 31.10 31.57 32.69 33.32 41.26 53.14 53.39 60.30 172.71 173.09 173.14 174.66

8

7

6

5

4

3

2

1

2.14 2.16 2.18 2.20 2.21 2.53 2.54 2.54 2.55 2.56 2.57 2.85 2.89 2.91 2.92 2.94 3.10 3.11 3.13 3.15 3.35 3.77 3.79 3.80 3.81 3.82 4.59 4.60 4.61 4.62 4.79

4.04

4.16

7.65

4.80

2.35

3.67

2.00

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

26.17 30.95 31.37 31.52 32.84 43.03 48.85 53.14 54.07 172.01 173.90 174.87 175.71

8

7

6

5

4

3

2

1

1.44 1.75 1.76 1.79 1.81 1.88 1.90 1.91 1.93 1.94 1.96 2.18 2.20 2.22 2.50 2.89 2.91 2.92 2.95 3.19 3.20 3.22 3.23 3.62 3.66 3.68 3.71 3.72 3.74 3.77 3.78 3.81 3.83 3.84 3.86 3.87 3.88 3.89 3.90 4.46 4.47 4.48 4.49 4.50 4.51 5.75 6.67 6.69 7.03 7.05 8.15 8.17 8.23 8.24 8.26 8.40 8.41

9.58

9.23

1.04

1.06

2.08

2.60

0.38

2.22

1.11

1.08

0.02

0.14

0.85

0.04

1.02

0.99

0.08

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

27.31 28.23 28.68 32.24 33.11 39.35 39.56 39.77 39.98 40.19 40.39 40.60 41.42 52.19 53.56 78.44 85.36 155.95 168.56 170.42 171.38 172.16 174.38

8

7

6

5

4

3

2

1

2.15 2.17 2.19 2.20 2.31 2.33 2.36 2.37 2.38 2.40 2.42 2.43 2.76 2.77 2.79 2.79 2.81 2.82 2.83 2.84 2.97 3.15 3.17 3.18 3.20 3.26 3.27 3.30 3.31 3.76 3.77 3.78 3.94 3.95 3.98 3.99 4.10 4.11 4.13 4.14 4.16 4.27 4.29 4.30 4.31 4.33 4.35 4.36 4.37 4.39 4.64 4.65 4.66 4.67 4.68 4.69 5.38 5.40 6.97 6.99 7.23 7.25 7.27

9.50

9.34

1.56

1.98

2.14

9.07

1.12

2.19

4.10

2.53

5.17

1.09

1.06

1.03

2.16

0.06

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

0.00 28.16 28.33 30.30 30.46 31.92 35.35 35.38 41.45 53.84 60.98 61.03 64.64 64.73 76.71 77.03 77.23 77.35 85.92 169.41 170.44 172.35 172.75

8

7

6

5

4

3

2

1

2.23 2.25 2.27 2.28 2.30 2.32 2.34 2.60 2.62 2.64 2.66 2.68 2.70 2.77 2.77 2.78 2.79 2.80 2.80 2.87 2.89 2.90 2.92 2.94 2.96 2.97 3.75 3.76 3.78 4.03 4.07 4.09 4.13 4.22 4.24 4.25 4.34 4.36 4.37 4.44 4.46 4.47 4.56 4.57 4.59 4.79

2.09

2.20

4.25

2.33

3.76

4.21

2.03

1.03

2.15

2.05

0.96

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

25.31 25.41 29.66 29.69 30.64 33.54 33.62 41.31 52.15 55.53 60.29 64.70 65.30 169.49 171.03 172.49 174.09

8

7

6

5

4

3

2

1

1.17 1.44 1.86 1.87 1.89 1.90 1.91 1.93 1.95 2.09 2.11 2.12 2.14 2.16 2.46 2.48 2.50 2.63 2.64 2.66 2.79 2.80 2.82 3.50 3.52 3.54 4.16 4.18 4.20 4.24 4.26 4.27 4.27 4.29 4.30 4.31 4.36 4.37 4.86 7.28 7.30 7.32 7.36 7.38 7.40 7.59 7.61 7.76 7.78

8.98

9.13

2.02

2.01

2.11

2.01

2.07

1.83

2.09

1.98

2.02

2.04

2.06

2.04

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

26.42 26.49 26.53 27.41 29.91 30.44 32.32 34.50 46.63 47.04 47.25 47.47 47.60 47.68 47.81 47.89 48.02 48.10 48.23 48.32 52.98 61.31 61.91 64.15 66.18 73.12 79.32 119.68 124.76 126.87 127.52 141.18 143.78 156.55 172.21 172.76

8

7

6

5

4

3

2

1

1.24 1.44 1.85 1.87 1.88 1.89 1.90 1.92 1.94 2.01 2.08 2.10 2.11 2.13 2.15 2.16 2.39 2.41 2.43 2.67 2.68 2.70 2.81 2.83 2.85 3.31 3.55 3.57 3.59 4.07 4.09 4.11 4.12 4.14 4.15 4.16 4.18 4.25 4.27 4.29 4.31 4.32 4.86 6.99 7.01

8.54

1.31

9.21

2.90

1.96

1.99

2.00

2.00

0.66

0.84

2.01

0.10

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

26.44 27.31 29.73 30.34 32.28 53.12 61.93 64.12 73.13 79.25 156.66 172.38 174.90

8

7

6

5

4

3

2

1

2.16 2.18 2.19 2.19 2.21 2.21 2.23 2.54 2.55 2.56 2.57 2.58 2.59 2.68 2.69 2.71 2.83 2.84 2.86 2.88 3.66 3.67 3.69 3.79 4.12 4.14 4.15 4.35 4.36 4.38 4.47 4.48 4.48 4.50 4.70

2.07

2.10

2.05

3.85

2.07

2.06

1.02

2.05

1.02

200

190

180

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

p

p

m

25.30 25.44 29.61 30.72 33.50 42.40 52.11 55.54 60.25 65.26 169.47 171.82 174.15 174.84