The Royal Society of Chemistry · Nidhi Sharma,a Sanjeev Kumar,a Indresh K. Maurya,b K. K. Bhasin,a Ajay Verma,c Nishima Wangoo,d Aman K. K. Bhasin,a S. K. Mehta,a Sangit Kumar,c

S1

Synthesis, structural analysis, antimicrobial evaluation and synergistic studies of imidazo[1,2-a]pyrimidine chalcogenides

Nidhi Sharma,a Sanjeev Kumar,a Indresh K. Maurya,b K. K. Bhasin,*a Ajay Verma,c Nishima Wangoo,d Aman K. K. Bhasin,a S. K. Mehta,*a Sangit Kumar,c and Rohit K. Sharma*a

aDepartment of Chemistry and Centre for Advanced Studies in Chemistry, Panjab University, Chandigarh, 160014,

India bDepartment of Microbial Biotechnology, Panjab University, Chandigarh, 160014, India cIndian Institute of Science Education and Research (IISER), Bhopal, India dDepartment of Applied Sciences, University Institute of Engineering and Technology (UIET), Panjab University,

Chandigarh, 160014, India

Table of Contents

S. No. Contents Page no.

1 1H NMR, 13C NMR and mass spectra of compounds 4-11 S2-S13

2 77Se NMR of compound 6 S14

3 HRMS of compound 6 and 7 S15

4 Crystal data and structure refinement for compound 6 S16

5 Selected bond lengths, bond angles and torsional angles for compound 6 S17

6 Calculations of theoretical parameters using density functional theory (DFT) S18 7 Optimized structures of compounds 4-11 S19 8 HOMO-LUMO diagrams of compounds 4-11 S20

9 MIC values of compounds 4-11 against various fungal stains S21

10 MIC values of compounds 4-11 against various bacterial strains S22

Electronic Supplementary Material (ESI) for RSC Advances.This journal is © The Royal Society of Chemistry 2016

S2

2-((Butylthio)methyl)imidazo[1,2-a]pyrimidine (4) 1H, 13C, Mass Spectra

S3

WATERS, Q-TOF MICROMASS (LC-MS) SAIF/CIL,PANJAB UNIVERSITY,CHANDIGARH

m/z100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000

%

0

100NIDHI IMP-15 20 (0.224) Cm (11:31) TOF MS ES+

3.07e422230659

1323502

22311206

2237161

2235293

3492022305

16522241362 393

1420

2-((Phenylthio)methyl)imidazo[1,2-a]pyrimidine (5) 1H, 13C, Mass Spectra

S4


m/z100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000

%

0


1.87e4264.3418708

242.3613399

265.092542

381.771418280.34

888505.171001

475.41666

382.28596

S5

2-((Phenylselanyl)methyl)imidazo[1,2-a]pyrimidine (6) 1H, 13C, Mass Spectra

S6


m/z100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000

%

0

100NIDHI NS-II 26 (0.274) Cm (17:41) TOF MS ES+

3.93e4312.039323

310.026446

290.124271

288.111843

133.14468

286.13702

155.11944

312.99869

314.16692

2-((Tolylselanyl)methyl)imidazo[1,2-a]pyrimidine (7) 1H, 13C, Mass Spectra

S7


m/z100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000

%

0


2.27e4304.2722707

302.2813276

300.304142

326.257895

338.31931 382.29

718

S8

2-((Mesitylselanyl)methyl)imidazo[1,2-a]pyrimidine (8) 1H, 13C, Mass Spectra

S9


m/z100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050

%

0


2.16e4332.2721562

330.2913420

328.314778

212.312661

210.311092

354.267280

2-((Pyridylselanyl)methyl)imidazo[1,2-a]pyrimidine (9) 1H, 13C, Mass Spectra

S10


m/z100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000

%

0


3.07e4291.2730674

289.2819143

287.306463

313.2415118

315.261561

S11

Bis(imidazo[1,2-a]pyrimidin-2-ylmethyl)disulfide (10) 1H, 13C, Mass Spectra

S12

WATERS, Q-TOF MICROMASS (ESI-MS) SAIF/CIL,PANJAB UNIVERSITY,CHANDIGARH

m/z60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 420 440 460 480 500

%

0

100NIDHI CH2SH 8 (0.143) Cm (1:8) TOF MS ES+

8.37e3351.28368

329.27319

166.14226

164.1849

167.1400

330.21146331.2686

352.21332

353.2634

Bis(imidazo[1,2-a]pyrimidin-2-ylmethyl)selane (11) 1H, 13C, Mass Spectra

S13


m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000

%

0

100NIDHI IMPSe 16 (0.169) Cm (8:35) TOF MS ES+

2.44e4345.024403

343.013962

341.04594

301.1984

367.07048

S14

2-((Phenylselanyl)methyl)imidazo[1,2-a]pyrimidine (6) 77Se NMR

S15

2-((Phenylselanyl)methyl)imidazo[1,2-a]pyrimidine (6) HRMS


m/z100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 420 440 460 480 500

%

0

100NIDHI IMP-7 6 (0.177) AM (Top,10, Ar,5000.0,556.28,0.70,LS 10); Sm (Mn, 2x3.00); Sb (1,40.00 ); Cm (6:8-16:20) 1: TOF MS ES+

3.85e4289.998138466

288.011329914

133.068318899

132.0759250

94.08255

286.023114720

133.59115026

134.08122970

284.04171507

155.06171259

211.9872217

202.081069 246.1063

48

311.985731534

310.002019397

314.01037009

327.98651053 388.0382

556366.0644

541445.9813

352411.0970

24467.9667

303485.1139

36

2-((Tolylselanyl)methyl)imidazo[1,2-a]pyrimidine (7)


m/z60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 420 440 460 480

%

0

100NIDHI IMP-8 5 (0.153) AM (Top,10, Ar,5000.0,556.28,0.70,LS 10); Sm (Mn, 2x3.00); Sb (1,40.00 ); Cm (5:8-21:28) 1: TOF MS ES+

7.00e4304.003570043

302.020262488

300.034937399

133.070228696

116.09812429100.0980

3178.5300

3

133.59307079

211.98814736134.0831

4301161.1156

2529209.9867

2317

298.04774594

212.15121606

268.0516720

325.994067568

328.019218113

382.10515033

338.07823747 473.5377

3336394.0958

3271 416.06662333

471.53701615

496.01921379

S16

Table S1 Crystal data and structure refinement for 6

Empirical formula C13 H11 N3 Se

Formula weight 288.21

Temperature 296(2) K

Wavelength 0.71073 Å

Crystal system Trigonal

Space group R -3

Unit cell dimensions a = 31.935(2) Å, α= 90°

b = 31.935(2) Å, β= 90°

c = 6.3894(5) Å, γ = 120°

Volume 5643.3(9) Å3

Z 18

Density (calculated) 1.526 g/cm3

Absorption coefficient 2.974 mm-1

F(000) 2592

Theta range for data collection 2.209 to 26.053°

Index ranges -39<=h<=39, -39<=k<=39, -7<=l<=7

Reflections collected 27802

Independent reflections 2467 [R(int) = 0.0928]

Completeness to theta = 25.242° 99.5 %

Absorption correction None

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 2467 / 0 / 154

Goodness-of-fit on F2 1.102

Final R indices [I>2sigma(I)] R1 = 0.0442, wR2 = 0.1088

R indices (all data) R1 = 0.0760, wR2 = 0.1186

Extinction coefficient n/a

Largest diff. peak and hole 0.592 and -0.281 e Å-3

S17

Table S2 Selected bond lengths (Å), bond angles (0) and torsional angles (0) for compound 6

Se1-C8 1.917 C8-C9 1.378

Se1-C1 1.966 C8-C13 1.383

N3-C3 1.371 C6-C5 1.402

N3-C4 1.372 C2-C1-Se1 113.100

N3-C7 1.391 C8-Se1-C1 101.280

N1-C7 1.316 C2-C3-H3 127.100

N1-C2 1.376 N3-C3-H3 127.100

N2-C6 1.318 C1-Se1-C8-C13 37.700

N2-C7 1.346 C1-Se1-C8-C9 -144.600

C2-C3 1.356 Se1-C8-C9-C10 -178.500

C5-C4 1.338 C8-Se1-C1-C2 68.500

C13-C12 1.368 N1-C2-C1-Se1 74.300

C9-C10 1.363 C3-C2-C1-Se1 -104.600

C12-C11 1.376 Se1-C8-C13-C12 178.700

C11-C10 1.384 C3-N3-C7-N1 -0.200

C2-C1 1.477 C3-N3-C7-N2 -179.100

S18

Table S3 Calculations of theoretical parameters using density functional theory (DFT)

Compound

Energy

(a.u.)

Band gap

(eV)

Se1/S1-C8 Bond

length (Å)

Se1-C1 Bond

length (Å)

C8-Se1-C1

Bond angle (0)

C8-Se1-C1-C2

Dihedral angle (0)

4 -990.6457 4.1676 1.840 1.850 100.53 -73.31

5 -1064.4399 3.9608 1.793 1.858 103.76 -99.03

6 -3065.6345 3.9197 1.920 2.000 99.70 -101.40

7 -3104.9527 3.8906 1.925 2.000 99.74 -101.13

8 -3183.5905 3.9017 1.930 2.000 99.63 -109.90

9 -3081.6726 4.2019 1.920 1.972 101.30 -70.19

10 -3268.5440 3.5740 1.940 1.940 109.40 -60.00

11 -1665.5157 3.5541 1.780 1.780 - -

S19

Table S4 Optimized structures of compounds 4-11 with DFT

Compound Optimized structure

4

5

6

7

8

9

10

11

S20

Fig. S1 HOMO-LUMO diagrams of compounds 4-11

4

∆E = 4.16 eV

5

∆E = 3.96 eV

6

∆E = 3.91 eV

7

∆E = 3.89 eV

8

∆E = 3.90 eV

9

∆E = 4.20 eV

10

∆E = 3.55 eV

11

∆E = 3.57 eV

S21

Table S5 MIC values of compounds 4-11 and standard antifungal agent (Amp B) against various fungal stains (in ug/ml)a

Compound Candida

albicans

Candida

glabrata

Candida

tropicals

Candida

krusei

Candida

parapsolisis

Candida

kyfer

Cryptococcus

neoformans

Aspergillus

niger

Neurospora

crassa

4 >27.62 >27.62 >27.62 >27.62 >27.62 >27.62 >27.62 NT NT

5 >30.12 >30.12 >30.12 >30.12 >30.12 >30.12 >30.12 NT NT

6 36.00 >36.00 >36.00 >36.00 >36.00 >36.00 >36.00 >36.00 18

7 >37.75 >37.75 >37.75 >37.75 >37.75 18.87 >37.75 37.75 18.87

8 >41.25 NT NT NT NT >41.25 >41.25 >41.25 20.62

9 >36.12 NT NT NT NT >36.12 >36.12 >36.12 18.06

10 >42.87 NT NT NT NT >42.87 >42.87 >42.87 >42.87

11 NT NT NT NT NT NT NT NT NT

Amp B 0.78 - - - - 12.50 0.20 0.39 0.39

aNT = Not Tested

S22

Table S6 MIC values of compounds 4-11 and standard antibacterial agent (RIF) against various bacterial strains (in

µg/ml)

Compounds Escherichia coli Staphylococcus

aureus

Vibrio cholera Enterococcus

faecalis

Listeria

monocytogens

4 >27.62 >27.62 >27.62 >27.62 >27.62

5 >30.12 >30.12 >30.12 >30.12 >30.12

6 >36.00 >36.00 >36.00 >36.00 >36.00

7 18.87 >37.75 >37.75 37.75 >37.75

8 >41.25 >41.25 >41.25 >41.25 >41.25

9 >36.12 >36.12 >36.12 >36.12 >36.12

10 >42.87 >42.87 >42.87 >42.87 42.87

11 NT NT NT NT NT

RIF 4.00 - - 12.50 78.80

Documents

The Royal Society of Chemistry · Nidhi Sharma,a Sanjeev Kumar,a Indresh K. Maurya,b K. K. Bhasin,*a Ajay Verma,c Nishima Wangoo,d Aman K. K. Bhasin,a S. K. Mehta,*a Sangit Kumar,c

The Royal Society of Chemistry · Nidhi Sharma,a Sanjeev Kumar,a Indresh K. Maurya,b K. K. Bhasin,a Ajay Verma,c Nishima Wangoo,d Aman K. K. Bhasin,a S. K. Mehta,a Sangit Kumar,c