S 1

Synthesis and Biological Activity of Novel Sulfone Derivatives Containing a

[1,2,4]Triazolo[4,3-a]pyridine Moiety

Fang-Zhou Xu 1, Yan-Yan Wang1, #, Yun-Ying Zhu 2, Jia-Hui Shao 3,Gang Yu 1, Wei Xue 1,

Jian Wu 1,*, Hui-Bing Wu1, Jun Shi 1

1 State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key

Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research

and Development Center for Fine Chemicals, Guizhou University, Huaxi District, Guiyang

550025, P.R. China.

2 School of Chemical Engineering, Guizhou Institute of Technology, Yunyan District, Guiyang

550001, P.R. China.

3 College of Life Science, Zaozhuang University, Zaozhuang 277100, P.R. China.

Email: jwu6@126.com

Supplemental Materials

1. The active data of the synthesized compounds

1.1 Antifungal activity

As shown in Table S 1, the inhibition rate of compound 5m against Rhizotonia erealis and

Helminthosporium maydis was up to 78.6% and 76.4%, respectively; Moreover, the antifungal

activities of compounds 5b, 5c, 5d, 5k, 5l, 5m, and 5n were 40.9%, 55.5%, 43.6%, 48.5%, 65%,

67.8%, and 45% respectively; As well as compounds 5d, 5k, 5l, 5m, and 5n displayed

moderated activities against Fusarium graminearum, the compounds 5l, 5m were the best ones,

the inhibition rate of them were 60%, and 61%, respectively. However, the anti-fungal activities

were much low than that of positive control carbendazim, propiconazole. Moreover, The EC50 of

5l and 5m against R. erealis, H. maydis, R. solani were further evaluated (Table S 2), which

indicated that 5l and 5m showed range from 39.3 to 53.6.

S 2

Preliminary SAR analysis indicated that the antifungal activities could be enhanced by

introducing two fluorine atoms to benzene ring (such as compounds 5k, 5l and 5m ). Among

these compounds containing two fluorines (5k, 5m, and 5l), the activity of compound with 2,6-

di-fluorine (5m) was the best one, and the activity of compound with 2,5-di-fluorine (5l) was

slightly higher than that of compound 5k (with 2,4-di-fluorine), which indicated that the position

of fluorine had little impact on their activities. and the replacement of fluorine by other halogen

could reduce their activities (eg: 5k > 5b, 5k > 5n, 5k > 5r, and 5k > 5o). Moreover, the

antifungal activity could be decreased via the introduction of trifluoromethyl (compounds 5h and

5u), as well as the introduction of alkyl group (5e and 5f) and multi-fluoro substituted olefins

(compound 5s)

S 3

Table S 1 Antifungal effects of sulfone derivatives (5a – 5s) in vitro (50 μg/mL)

CompoundsAntifungal effects / %

R. erealis H. maydis R. solani F. graminearum

5a 23.6 ± 1.2 43.6 ± 1.4 16.0 ± 2.9 8.2 ± 2.3

5b 35.5 ± 2.1 35.5 ± 0.9 40.9 ± 2.1 30.9 ± 2.2

5c 53.6 ± 1.1 52.8 ± 3.1 55.5 ± 2.3 35.5 ± 1.3

5d 53.0 ± 2.5 55.5 ± 0.9 43.6 ± 1.1 43.6 ± 1.3

5e 0.0 ± 1.1 3.6 ± 1.4 7.3 ± 0.3 7.3 ± 2.4

5f 0.0 ± 0.5 1.8 ± 1.2 5.5 ± 2.2 5.5 ± 0.9

5g 47.3 ± 2.1 0.0 ± 2.1 3.6 ± 0.9 3.6 ± 2.3

5h 1.8 ± 2.1 3.6 ± 1.2 7.3 ± 1.5 7.3 ± 2.4

5i 33.6 ± 1.7 1.8 ± 0.9 1.8 ± 2.1 1.8 ± 2.1

5j 55.5 ± 1.4 5.5 ± 1.6 5.5 ± 2.2 5.5 ± 1.2

5k 56.4 ± 2.2 52.7 ± 2.4 48.5 ± 1.5 49.0 ± 2.3

5l 68.0 ± 2.5 70.9 ± 2.4 65.0 ± 1.1 60.0 ± 0.9

5m 78.6 ± 2.1 76.4 ± 3.1 67.8 ± 1.3 61.0 ± 3.1

5n 50.2 ± 4.1 50.9 ± 2.1 45.0 ± 2.7 42.0 ± 2.5

5o 56.4 ± 2.2 51.4 ± 1.3 32.0 ± 3.2 27.2 ± 1.3

5p 14.5 ± 2.4 38.2 ± 1.7 0.0 ± 2.5 0.0 ± 1.1

5q 52.0 ± 3.1 54.8 ± 1.2 4.8 ± 2.1 12.7 ± 1.4

5r 2.4 ± 2.7 4.8 ± 0.9 7.3 ± 1.2 12.7 ± 1.2

5s 2.4 ± 0.9 4.8 ± 3.1 4.8 ± 2.4 9.1 ±0.8

carbendazim 100 ± 0.7 100 ± 0.7 100 ± 2.4 100 ± 3.2

propiconazole 100 ± 2.2 100 ± 1.6 100 ± 2.1 100 ± 2.5

S 4

Table S 2 EC50 of 5l and 5m against fungiiFungus Comp. EC50 y = a + bx r

R. erealis5l 41.3 y=1.80+1.98x 0.9843

5m 39.3 y=1.86+1.97x 0.9824

H. maydis5l 42.2 y=1.83+1.95x 0.9856

5m 40.2 y=1.85+1.96x 0.9722

R. solani5l 53.6 y=1.68+1.92x 0.9423

5m 51.9 y=1.69+1.93x 0.9733

1.2 Insecticidal activity

The results listed in Table S 3 indicated that compounds 5d showed > 95% activities at 500 μg

mL-1 and > 65% activities at 100 μg mL-1 against Plutella xylostella; and the activities of

compounds 5d against P. xylostella was 46.7% at 50 μg mL-1. In addition, compound 5j also

showed good insecticidal activities, the mortalities of 5j against P. xylostella at 500 μg mL-1 and

100 μg mL-1 were 76.7% and 53.3%, respectively. Moreover, compounds 5h, 5k and 5r

displayed moderated insecticidal activity against P. xylostella at 500 μg mL-1, the mortalities of

them were 56.7%, 49.6% and 53.3%, respectively. And as presented in Table S 4, the title

compounds displayed weakly to good insecticidal activity against Helicoverpa armigera. The

activity of compound 5d displayed > 90% activities at 500 μg mL-1 and > 70% activities at 200

μg mL-1 against H. armigera, which were slightly better than that of commercial chlorpyrifos,

and the activities of compounds 5d against H. armigera were 53.3% at 100 μg mL-1. Moreover,

compound 5j showed 67.7% activities at 500 μg mbL-1 and > 46.6% activities at 100 μg mL-1

against H. armigera; and the moralities of compounds 5h and 5l at 500 μg mL-1 were 46.7%, and

43.4%, respectively.

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Table S 3 Insecticidal activity of sulfone derivatives (5a – 5s) against P. xylostella

CompoundsInsecticidal activity (%) at different concentrations ( μg mL-1)

500 200 100 50 25

5a 43.7 ± 2.2 16.7± 2.2 / / /

5b 32.7 ± 1.4 13.3 ± 2.2 / / /

5c 38.6 ± 2.7 7.3 ± 1.2 / / /

5d 97.7 ± 3.2 67.7 ± 2.4 46.7 ± 2.4 33.3 ± 2.1 13.7 ± 1.2

5e 24.8 ± 2.2 3.3 ± 0.8 / / /

5f 26.7 ± 1.2 6.7 ± 0.9 / / /

5g 36.7 ± 1.5 16.7 ± 2.2 / / /

5h 56.7 ± 4.2 33.3 ± 1.5 16.7 ± 1.4 / /

5i 26.7 ± 2.2 23.3 ± 2.4 6.7 ± 2.1 / /

5j 76.7 ± 2.7 53.3 ± 2.1 23.3 ± 2.4 / /

5k 49.6 ± 2.3 16.7 ± 2.1 / / /

5l 43.3 ± 2.6 23.3 ± 2.3 6.7 ± 0.7 / /

5m 6.7 ± 2.3 / / / /

5n 16.7 ± 1.2 6.7± 2.2 / / /

5o 13.6 ± 3.2 6.7± 3.2 / / /

5p 26.7 ± 2.2 6.7± 3.1 / / /

5q 16.7 ± 3.1 / / / /

5r 53.7 ± 2.2 33.3 ± 1.7 16.7 ± 2.2 / /

5s 14.0 ± 2.3 9.3 ± 1.2 / / /

chlorpyrifos 100 ± 3.1 100 ± 2.3 100 ± 2.6 90 ± 2.1 83 ± 2.9

chlorantraniliprole 100 ± 2.7 100 ± 2.5 100 ± 3.4 100 ± 2.2 100 ± 3.2

S 6

Table S 4 Insecticidal activity of sulfone derivatives (5a – 5s) against H. armigera

CompoundsInsecticidal activity (%) at different concentrations ( μg mL-1)

500 200 100 50 25

5a 33.6 ± 2.1 13.3 ± 1.3 / / /

5b 33.6 ± 2.3 6.7 ± 1.2 / / /

5c 26.7 ± 0.8 / / / /

5d 93.3 ± 3.2 73.7 ± 3.1 53.3 ± 2.5 36.7 ± 1.7 16.7 ± 1.3

5e 26.7 ± 1.1 6.7 ± 0.6 / / /

5f 23.3 ± 0.9 13.3 ± 0.9 / / /

5g 33.3 ± 1.1 23.3 ± 1.2 / / /

5h 46.7 ± 2.1 26.7 ± 1.8 13.3 ± 0.8 / /

5i 16.7 ± 0.9 / / / /

5j 67.7 ± 2.5 46.7 ± 2.1 23.3 ± 1.6 6.7± 0.9 /

5k 14.8 ± 1.4 3.5 ± 2.2 / / /

5l 43.3 ± 1.3 26.7 ± 1.4 13.3 ± 1.3 / /

5m 16.7 ± 1.1 / / / /

5n 13.3 ± 1.1 / / / /

5o 10.6 ± 2.4 / / / /

5p 6.7 ± 0.7 / / / /

5q 18.6 ± 1.4 7.3 ± 2.3 / / /

5r 33.7 ± 2.1 16.7 ± 2.4 / / /

5s 14.0 ± 1.3 11.2 ± 0.8 / / /

chlorpyrifos 83.3 ± 2.9 60 ± 2.3 56.7 ± 3.1 30 ± 2.1 20 ± 0.8

chlorantraniliprole 100 ± 3.2 100 ± 2.1 100 ± 3.3 100 ± 3.4 100 ± 2.1

S 7

Figure S 1. 1H NMR of compound 5a

Figure S 2. 13C NMR of compound 5a

S 8

Figure S 3. 1H NMR of compound 5b

Figure S 4. 13C NMR of compound 5b

S 9

Figure S 5. 1H NMR of compound 5c

Figure S 6. 13C NMR of compound 5c

S 10

Figure S 7. 1H NMR of compound 5d

S 11

Figure S 8. 13C NMR of compound 5d

Figure S 9. 1H NMR of compound 5e

S 12

Figure S 10. 13C NMR of compound 5e

Figure S 11. 1H NMR of compound 5f

S 13

Figure S 12. 13C NMR of compound 5f

S 14

Figure S 13. 1H NMR of compound 5g

Figure S 14. 13C NMR of compound 5g

S 15

Figure S 15. 1H NMR of compound 5h

Figure S 16. 13C NMR of compound 5h

S 16

Figure S 17. 1H NMR of compound 5i

Figure S 18. 13C NMR of compound 5i

S 17

Figure S 19. 1H NMR of compound 5j

Figure S 20. 13C NMR of compound 5j

S 18

Figure S 21. 1H NMR of compound 5k

Figure S 22. 13C NMR of compound 5k

S 19

Figure S 23. 1H NMR of compound 5l

Figure S 24. 13C NMR of compound 5l

S 20

Figure S 25. 1H NMR of compound 5m

Figure S 26. 13C NMR of compound 5m

S 21

Figure S 27. 1H NMR of compound 5n

Figure S 28. 13C NMR of compound 5n

S 22

Figure S 29. 1H NMR of compound 5o

Figure S 30. 13C NMR of compound 5o

S 23

Figure S 31. 1H NMR of compound 5p

Figure S 32. 13C NMR of compound 5p

S 24

Figure S 33. 1H NMR of compound 5q

Figure S 34. 13C NMR of compound 5q

S 25

Figure S 35. 1H NMR of compound 5r

Figure S 36. 13C NMR of compound 5r

S 26

Figure S 37. 1H NMR of compound 5s

Figure S 38. 13C NMR of compound 5s