crystal structures of pyrazinamide- p-amino benzoic acid
TRANSCRIPT
S1
Crystal structures of pyrazinamide-p-amino benzoic acid cocrystal and their transamidation reaction product, 4-(pyrazine-2-carboxamido)benzoic acid in molten state
Shridhar H. Thorat, Sanjay kumar Sahu and Rajesh G Gonnade*
Center for Materials Characterization, CSIR-National Chemical Laboratory, Pune - 411008, India.
Correspondence e-mail: [email protected]
Entry Content Page
1 Figure S1. 1H NMR spectrum of cocrystals 1 in DMSO-d6 S2
2 Figure S2. 1H NMR of 4-(pyrazine-2-carboxamido) benzoic acid (2) in
DMSO-d6
S3
3 Figure S3. 1H NMR of 4-(pyrazine-2-carboxamido) benzoic acid (2) in
DMSO-d6 with D2O exchange
S4
4 Figure S4. IR spectra S5
5 Figure S5. DSC profile of cocrystal 1 and carboxamide 2 S6
6 Figure S6. DSC profile of carboxamide 2 S7
7 Figure S7. Overlay of the PXRD patterns of cocrystal 1 (experimental and
simulated)
S8
8 Figure S8. Overlay of PXRD patterns of cocrystal 1, carboxamide 2 with,
cocrystal components PZA and pABA.
S9
9 Figure S9. PXRD patterns of cocrystal 1 prepared by different grinding
methods.
S10
7 Figure S10. TGA plot of cocrystal 1 S11
Figure S11. TGA plot of carboxamide 2 S12
8 Figure S12. Photomicrographs of the cocrystal (1) grabbed HSM studies. S13
S2
Figure S1. 1H NMR of pyrazinamide (PZA) and p-amino benzoic acid (pABA) cocrystal (1) recorded at 200 MHz in DMSO-d6.
Thu2av2#134.001.001.1r.esp
10 9 8 7 6 5 4 3 2 1 0
2.12
2.23
2.21
0.95
0.88
1.10
1.07
1.00
9.19
9.18
8.85
8.72
8.71
8.71
8.27
7.87
7.63 7.58 6.
556.
51
5.87
3.34
2.52
2.51
2.50
2.49
-0.0
1
N
N O
NH2
Pyrazinamide (PZA)
O
HO
NH2
p-Amino Benzoic Acid (pABA)
S3
Figure S2. 1H NMR of 4-(pyrazine-2-carboxamido) benzoic acid (2) recorded at 200 MHz in DMSO-d6.
Thu1av2#133.001.001.1r.esp
16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)
2.001.900.930.900.860.930.71
TMS
DMSO
Water
2.10
7.94
7.99
8.05
8.098.
868.
878.
978.
989.33
9.34
11.0
5
12.8
212
.83
12.8
412
.85
NH
O
OHO
N
N
S4
Figure S3. 1H NMR of 4-(pyrazine-2-carboxamido) benzoic acid (2) recorded at 200 MHz in DMSO-d6 with D2O.
NH
O
OHO
N
N
Mon2av2#049.001.001.1r.esp
11 10 9 8 7 6 5 4 3 2 1 0 -1
4.49
1.10
1.09
1.00
DMSO
Water
9.31
9.30
8.94 8.93
8.83
8.83
8.82
8.01
7.97
7.93
-0.0
1
S5
IR Analysis
Figure S4. Infrared spectra of the PZA-p-ABA cocrystal (1, blue), their molten product (2, green), pyrazinamide (PZA, black) and p-amino benzoic acid (p-ABA, red).
S6
DSC analysis
Figure S5. DSC profile of PZA – p-ABA cocrystal 1.
S7
Figure S6. DSC profile of carboxamide 2.
S8
PXRD analysis
Figure S7. Overlay of PXRD patterns of cocrystal 1, experimental (black) and simulated from
single crystal diffraction data (red).
S9
Figure S8. Overlay of PXRD patterns of cocrystal 1 (blue), carboxamide 2 (green), PZA (black),
pABA (red).
S10
Figure S9. PXRD patterns of cocrystal 1 prepared by dry grinding (blue), liquid assisted
grinding (green) and their comparison with PXRD patterns of cocrystals 1 produced from
solution crystallization (magenta), PZA (black) and pABA (red).
S11
TGA Study
Figure S10. TGA plot of cocrystal 1 showing slight weight loss around melting attributed to the release of ammonia molecules as the byproduct of transamidation reaction in molten state.
S12
Figure S11. TGA plot of carboxamide 2.
S13
HSM Analysis
Figure S12. Photomicrographs of the cocrystal 1 grabbed during heating experiment showing thermal response at different temperatures.