1

Electronic supplementary information

DNA binding, molecular docking and apoptotic inducing activity of nickel(II), copper(II) and zinc(II) complexes of pyridine-based

5 tetrazolo[1,5-a]pyrimidine ligands A. Haleel, a P. Arthi,a N. Dastagiri Reddy,b V. Veena,c N. Sakthivel,c Y. Arun,d P.T. Perumal,d A. Kalilur Rahiman* a

aPost-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai-600 014, India

10 bDepartment of Chemistry, Pondicherry University, Pondicherry-605 014, IndiacDepartment of Biotechnology, Pondicherry University, Pondicherry-605 014, India

dOrganic Chemistry Division, CSIR-Central Leather Research Institute, Chennai-600 020, India

*Corresponding author. Tel.: +91 44 2835 0297; Fax: +91 44 2835 2883.E-mail address: akrahmanjkr@gmail.com

15

Table of Contents

1. Tables S1-S4: Table S1. Crystal data and structure refinement for ligands L1&2 and complex 6.

20 Table S2. Selected bond lengths (Å) and bond angles (º) for ligand L1.Table S3. Selected interatomic distance (Å) and angles (°) for the ligand L1.Table S4. Selected bond lengths (Å) and bond angles (º) for the ligand L2.Table S5. Selected interatomic distance (Å) and angles (°) for the ligand L2.

25 2. Figures S1-S3: Fig. S1. Crystal packing diagram of ligand L1 projecting along the crystallographic b-axis.Fig. S2. View of crystal lattice packing showing the internuclear hydrogen bonding of ligand L1.Fig. S3. Crystal packing diagram of ligand L2 projecting along the crystallographic c-axis.Fig. S4. View of crystal lattice packing showing the internuclear hydrogen bonding of ligand L2.

30 Fig. S5-S8. FT IR spectrum of ligand L1&2 and complexes 1 and 4.Fig. S9-S16.1H and 13C NMR spectra of ligand L1&2 and complexes 3 and 6.Fig. S17. UV-Vis spectra of the complexes 1 and 2.Fig. S18. X- band EPR spectrum of the complex 2.

35

40

Electronic Supplementary Material (ESI) for RSC Advances.This journal is © The Royal Society of Chemistry 2014

2 |

Table S1 Crystal data and structure refinement for ligands L1&2 and complex 6.

L1 L2 6Empirical Formula C13H14N6O2 CC13H16N6O3 C28H37N12O6.5Cl2ZnFormula Weight 286.30 304.32 781.97Temperature (K) 293(2) 293(2) 293(2) Wavelength (Å) 0.71073 0.71073 0.71073 Crystal system Triclinic Orthorhombic MonoclinicSpace group P-1 Pbca C2/cUnit cell dimensionsa (Å) 8.282(5) 9.3144(3) 10.4600(4) b (Å) 9.501(5) 17.8682(5) 13.5070(5) c (Å) 9.604(5) 18.0638(6) 26.6520(9) α (o) 106.753(5) 90 90β (o) 100.835(5) 90 93.851(2)γ (o) 100.556(5) 90 90Volume (Å3) 687.7(7) 3006.39(16) 3757.0(2) Z 2 8 4Calculated density ( Mg/m-3) 1.383 1.345 1.382Adsorption coefficient ( mm-1) 0.099 0.100 0.853 F(000) 300 1280 1620Crystal size (mm3) 0.30 x 0.20 x 0.20 0.30 x 0.25 x 0.15 0.30 x 0.20 x 0.20Index ranges -9 ≤ h ≤ 9,

-11 ≤ k ≤ 11,-11 ≤ l ≤ 11

-11 ≤ h ≤ 11,-21 ≤ k ≤ 21,-21 ≤ l ≤ 20

-11 ≤ h ≤ 11,-14 ≤ k ≤ 14,-29 ≤ l ≤ 29

Reflections collected 8477 16734 11512Independent reflections 2420[R(int) = 0.0217] 2640 [R(int) = 0.0459] 2751 [R(int) = 0.1363]Refinement method Full-matrix least-squares on F2 Full-matrix least-squares on F2 Full-matrix least-squares on F2

Data/restraints/parameters 2420/0/199 2640/19/232 2751/61/281GOF on F2 1.066 1.054 0.971Final R indices [I<2σ(I)] R1 = 0.0399, wR2 = 0.1091 R1 = 0.0468, wR2 = 0.1142 R1 = 0.0621, wR2 = 0.1518R indexes (all data) R1 = 0.0444, wR2 = 0.1141 R1 = 0.0739, wR2 = 0.1298 R1 = 0.1965, wR2 = 0.1873Largest diff. peak and hole ( e. Å-3)

0.260 and –0.222 0.185 and –0.205 0.468 and –0.306

5

10

15

20

25

30

| 3

Table S2. Selected bond lengths (Å) and bond angles (º) for ligand L1.

Bond lengths (Å)

C(1)-N(1) 1.324(2) C(3)-C(11) 1.470(2)C(1)-N(5) 1.352(2) C(4)-C(5) 1.494(2)C(2)-N(1) 1.4630(19) N(1)-N(2) 1.3562(19)C(2)-C(6) 1.522(2) N(2)-N(3) 1.288(2)C(2)-C(3) 1.523(2) N(3)-N(4) 1.367(2)C(3)-C(4) 1.354(2)

Bond angles (º)

N(4)-C(1)-N(5) 129.42(14) C(6)-N(6)-C(7) 117.17(14)N(1)-C(1)-N(5) 120.83(13) C(1)-N(1)-N(2) 108.28(12)N(1)-C(2)-C(6) 108.36(12) C(1)-N(1)-C(2) 125.56(13)C(6)-C(2)-C(3) 113.49(12) N(3)-N(2)-N(1) 105.94(13)C(6)-C(2)-H(2) 109.1(9) N(2)-N(3)-N(4) 111.37(13)C(8)-C(9)-C(10) 119.15(15) C(1)-N(4)-N(3) 104.72(13)N(6)-C(7)-H(7) 118.3 C(1)-N(5)-C(4) 119.50(13)

5

10

15

20

25

30

35

40

45

4 |

Table S3. Selected interatomic distance (Å) and angles (°) for ligand L1.

D-H...A d(D-H) (Å) d(H...A) (Å) d(D...A) (Å) <(DHA) (°)

N(5)-H(5D)...N(4)#1 0.87(2) 2.05(2) 2.906(2) 165.3(18) Symmetry transformations used to generate equivalent atoms: #1 –x, –y, –z+1

5

10

15

20

25

30

35

40

45

50

| 5

Table S4. Selected bond lengths (Å) and bond angles (°) for ligand L2.

. Bond lengths (Å)

C(3)-C(4) 1.457(3) C(6)-N(1) 1.348(3)C(4)-C(5) 1.355(3) C(7)-N(5) 1.463(3)C(4)-C(7) 1.526(3) C(7)-C(8) 1.522(3)C(5)-N(1) 1.377(3) N(2)-N(3) 1.366(3)C(5)-C(13) 1.502(3) N(3)-N(4) 1.291(3)C(6)-N(2) 1.318(3) N(4)-N(5) 1.360(2)C(6)-N(5) 1.323(3)

Bond angles (º)

N(2)-C(6)-N(5) 109.7(2) C(6)-N(1)-C(5) 119.82(19)N(2)-C(6)-N(1) 129.5(2) C(6)-N(2)-N(3) 104.66(19)N(5)-C(6)-N(1) 120.8(2) N(4)-N(3)-N(2) 111.62(18)N(5)-C(7)-C(8) 108.96(15) N(3)-N(4)-N(5) 105.54(18)N(5)-C(7)-C(4) 106.88(16) C(6)-N(5)-N(4) 108.44(17)C(8)-C(7)-C(4) 114.29(16) C(6)-N(5)-C(7) 127.55(18)N(5)-C(7)-H(7) 108.9 N(4)-N(5)-C(7) 123.86(16)

5

10

15

20

25

30

6 |

Table S5. Selected interatomic distance (Å) and angles (°) for ligand L1.

D-H...A d(D-H) (Å) d(H...A) (Å) d(D...A) (Å) <(DHA) (°)

N(1)-H(1)...N(6)#1 0.917 (16) 1.892(17) 2.805(3) 173(2)O(1W)-H(1W)...N(2)#2 0.964(18) 2.077(19) 3.040(3) 176(4)O(1W)-H(2W)...O(2)#3 0.961(19) 2.01(2) 2.931(3) 160(4)

Symmetry transformations used to generate equivalent atoms: #1 –x+3/2,y–1/2,z ; #2 –x+2, –y, –z+1; #3 x+1/2,y, –z+3/2

5

10

15

20

25

30

35

40

| 7

5

10

15

Fig. S1. Crystal packing diagram of ligand L1 projecting along the crystallographic b-axis.

20

25

30

35

40

45

8 |

5

10

15 Fig. S2. View of crystal lattice packing showing the internuclear hydrogen bonding of ligand L1.

20

25

30

35

40

45

50

| 9

5

10

15

Fig. S3. Crystal packing diagram of ligand L2 projecting along the crystallographic c-axis.

20

25

30

35

40

45

10 |

5

10

15

Fig. S4. View of crystal lattice packing showing the internuclear hydrogen bonding of ligand L2.

20

25

30

35

40

45

| 11

5

10

15

20

25

Fig. S5. FT IR spectrum of ligand L1

30

35

40

45

50

55

Fig. S6. FT IR spectrum of ligand L2

H

N

NEtOOC

H3C

N

NN

N

L1

Wavenumber (cm-1)

N

NEtOOC

H3C

N

NN

N

L2

H

Wavenumber (cm-1)

12 |

5

10

15

20

25

Fig. S7. FT IR spectrum of Complex 1

30

35

40

45

50

55

Fig. S8. FT IR spectrum of complex 4

NiN

N

H

NN

NO

O

Cl

Cl

1

Wavenumber (cm-1)

NN

N

NN

N

NiH

Cl

Cl

N NN

O

H

O

NN

NO

O

4

Wavenumber (cm-1)

| 13

5

10

15

20

25

Fig. S9. 1H NMR spectrum of ligand L1

30

35

40

45

Fig. S10. 13C NMR spectrum of ligand L1

H

N

NEtOOC

H3C

N

NN

N

L1

H

N

NEtOOC

H3C

N

NN

N

L1

14 |

5

10

15

Fig. S11. 1H NMR spectrum of ligand L2

20

25

30

35

Fig. S12. 13C NMR spectrum of ligand L2

N

NEtOOC

H3C

N

NN

N

L2

H

N

NEtOOC

H3C

N

NN

N

L2

H

| 15

5

10

15

Fig. S13. 1H NMR spectrum of complex 3

20

25

30

35

Fig. S14. 13C NMR spectrum of complex 3

12 11 10 9 8 7 6 5 4 3 2 1 ppm

1.075

1.092

2.410

2.497

2.501

2.506

3.938

3.948

3.956

3.966

3.973

3.984

3.995

4.003

4.013

4.021

4.030

6.691

7.236

7.238

7.248

7.250

7.255

7.257

7.267

7.269

7.513

7.533

7.739

7.744

7.759

7.763

7.778

7.782

8.169

8.393

8.394

8.404

8.406

11.161

3.03

0.24

3.06

2.06

1.00

1.02

1.04

1.03

0.12

1.00

0.99

Current Data ParametersNAME KB-AH-ZN-3EXPNO 1PROCNO 1

F2 - Acquisition ParametersDate_ 20120626Time 15.51INSTRUM spectPROBHD 5 mm DUL 13C-1PULPROG zg30TD 65536SOLVENT DMSONS 16DS 2SWH 8223.685 HzFIDRES 0.125483 HzAQ 3.9846387 secRG 128DW 60.800 usecDE 6.00 usecTE 298.0 KD1 1.00000000 secTD0 1

======== CHANNEL f1 ========NUC1 1HP1 11.42 usecPL1 -3.00 dBSFO1 400.1324710 MHz

F2 - Processing parametersSI 32768SF 400.1299918 MHzWDW EMSSB 0LB 0.30 HzGB 0PC 1.00

200 180 160 140 120 100 80 60 40 20 ppm

13.85

18.54

38.91

39.12

39.33

39.53

39.74

39.95

40.16

59.59

78.44

78.77

79.10

96.98

122.30

123.43

136.61

147.19

149.20

149.54

158.21

164.47

Current Data ParametersNAME KB-AH-ZN-3EXPNO 2PROCNO 1

F2 - Acquisition ParametersDate_ 20120626Time 16.04INSTRUM spectPROBHD 5 mm DUL 13C-1PULPROG zgpg30TD 65536SOLVENT DMSONS 512DS 4SWH 24038.461 HzFIDRES 0.366798 HzAQ 1.3631988 secRG 50.8DW 20.800 usecDE 6.00 usecTE 298.8 KD1 2.00000000 secd11 0.03000000 secDELTA 1.89999998 secTD0 1

======== CHANNEL f1 ========NUC1 13CP1 9.15 usecPL1 0.00 dBSFO1 100.6228298 MHz

======== CHANNEL f2 ========CPDPRG2 waltz16NUC2 1HPCPD2 90.00 usecPL12 14.90 dBPL13 14.90 dBPL2 -3.00 dBSFO2 400.1316005 MHz

F2 - Processing parametersSI 32768SF 100.6128123 MHzWDW EMSSB 0LB 1.00 HzGB 0PC 1.40

C13CPD DMSO {D:\NDR} KOPAL 1

ZnN

N

H

NN

NO

O

Cl

Cl

3

ZnN

N

H

NN

NO

O

Cl

Cl

3

16 |

5

10

15

Fig. S15. 1H NMR spectrum of complex 6

20

25

30

35

40

Fig. S16. 13C NMR spectrum of complex 6

45

NN

N

NN

N

ZnH

Cl

Cl

N NN

O

H

O

NN

NO

O

6

NN

N

NN

N

ZnH

Cl

Cl

N NN

O

H

O

NN

NO

O

6

| 17

5

10

15

Fig. S17. UV-Vis spectra of complexes 1 & 2

20

25

30

35

40

45

200 300 400 500 600 700-0.2

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

Abso

rban

ce

Wavelength (nm)

1 2

18 |

5

10

15

Fig. S18. X- band EPR spectrum of complex 2

20

25

30

35

40

2000 2500 3000 3500 4000 4500-30

-20

-10

0

10

20

Relat

ive I

nten

sity

Magnetic Field (G)