An experimental charge-density analysis of pyrazinamide (a first line antitubercular drug) was performed using high-resolution X-ray diffraction data [(sin θ/λ)
max = 1.1 Å
−1] measured at 100 (2) K. The structure was solved by direct methods using
SHELXS97 and refined by
SHELXL97. The total electron density of the pyrazinamide molecule was modeled using the Hansen–Coppens multipole formalism implemented in the
XD software. The topological properties of electron density determined from the experiment were compared with the theoretical results obtained from
CRYSTAL09 at the B3LYP/6-31G** level of theory. The crystal structure was stabilized by N—H
N and N—H
O hydrogen bonds, in which the N3—H3
BN1 and N3—H3
AO1 interactions form two types of dimers in the crystal. Hirshfeld surface analysis was carried out to analyze the intermolecular interactions. The fingerprint plot reveals that the N
H and O
H hydrogen-bonding interactions contribute 26.1 and 18.4%, respectively, of the total Hirshfeld surface. The lattice energy of the molecule was calculated using density functional theory (B3LYP) methods with the 6-31G** basis set. The molecular electrostatic potential of the pyrazinamide molecule exhibits extended electronegative regions around O1, N1 and N2. The existence of a negative electrostatic potential (ESP) region just above the upper and lower surfaces of the pyrazine ring confirm the π-electron cloud.
Supporting information
CCDC reference: 921916
Data collection: KAPPA APEX BRUKER-AXS; cell refinement: SAINTPLUS (BRUKER-AXS); data reduction: SAINTPLUS (BRUKER-AXS); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELX97 (Sheldrick, 2007)
XD2006 (Koritsanszky et al., 2006); molecular graphics: ORTEP (Farrugia, 1997)
PLATON (Spek, 2003)
XD2006 (Koritsanszky et al., 2006); software used to prepare material for publication: XD2006 (Koritsanszky et al., 2006).
Crystal data top
C5H5N3O | Z = 4 |
Mr = 119.09 | Dx = 1.45 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2yn | Cell parameters from 4578 reflections |
a = 3.6173 (3) Å | θ = 2.0–50.1° |
b = 6.7413 (5) Å | µ = 0.11 mm−1 |
c = 22.4625 (16) Å | T = 100 K |
β = 92.395 (4)° | Needle, colourless |
V = 547.28 (1) Å3 | 0.3 × 0.2 × 0.15 mm |
Data collection top
Bruker Kappa APEX II CCD detector diffractometer | 4991 reflections with > 2.0σ(I) |
φ and ω scans | Rint = 0.039 |
Absorption correction: analytical | θmax = 51.1°, θmin = 1.8° |
Tmin = 0.913, Tmax = 0.943 | h = −6→7 |
60977 measured reflections | k = −14→14 |
5880 independent reflections | l = −48→48 |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.038 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.080 | H atoms treated by a mixture of independent and constrained refinement |
S = 2.00 | Weighting scheme based on measured s.u.'s w2 = 1/[s2(Fo2)] |
4486 reflections | (Δ/σ)max = 0.0001 |
221 parameters | Δρmax = 0.29 e Å−3 |
0 restraints | Δρmin = −0.31 e Å−3 |
Special details top
Refinement. Reflections were merged with SORTAV (Blessing, 1995) |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O(1) | 0.04793 (15) | 0.53200 (7) | 0.08373 (2) | 0.017 | |
N(1) | 0.46128 (12) | 1.01005 (6) | 0.089959 (18) | 0.012 | |
N(3) | 0.23007 (16) | 0.73021 (7) | 0.00873 (2) | 0.018 | |
N(2) | 0.43667 (14) | 0.93030 (7) | 0.212208 (19) | 0.016 | |
C(2) | 0.33506 (11) | 0.83736 (5) | 0.110271 (17) | 0.010 | |
C(5) | 0.19390 (12) | 0.68607 (6) | 0.065867 (18) | 0.012 | |
C(3) | 0.32544 (12) | 0.79671 (6) | 0.171033 (18) | 0.013 | |
C(4) | 0.55574 (13) | 1.10413 (6) | 0.191690 (19) | 0.015 | |
C(1) | 0.57000 (12) | 1.14395 (6) | 0.130926 (19) | 0.014 | |
H(3A) | 0.358146 | 0.857514 | −0.002022 | 0.028 | |
H(3) | 0.222536 | 0.655094 | 0.186097 | 0.024 | |
H(1) | 0.673524 | 1.285428 | 0.116119 | 0.021 | |
H(4) | 0.638611 | 1.215593 | 0.224292 | 0.026 | |
H(3B) | 0.144508 | 0.630528 | −0.022376 | 0.034 | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O(1) | 0.02489 (19) | 0.01328 (14) | 0.01325 (14) | −0.01034 (14) | 0.00178 (14) | 0.00013 (12) |
N(1) | 0.01611 (15) | 0.01028 (12) | 0.01089 (13) | −0.00431 (11) | 0.00107 (11) | −0.00003 (10) |
N(3) | 0.0284 (2) | 0.01550 (15) | 0.01040 (14) | −0.01173 (15) | 0.00102 (14) | −0.00024 (12) |
N(2) | 0.02147 (18) | 0.01514 (15) | 0.01045 (14) | −0.00331 (14) | −0.00012 (13) | −0.00021 (12) |
C(2) | 0.01223 (14) | 0.00943 (11) | 0.00984 (12) | −0.00265 (10) | 0.00083 (10) | 0.00013 (10) |
C(5) | 0.01543 (15) | 0.01026 (12) | 0.01062 (13) | −0.00478 (11) | 0.00102 (11) | −0.00005 (10) |
C(3) | 0.01691 (16) | 0.01156 (12) | 0.01079 (13) | −0.00282 (11) | 0.00071 (11) | 0.00097 (10) |
C(4) | 0.01758 (17) | 0.01359 (14) | 0.01233 (14) | −0.00327 (12) | 0.00016 (12) | −0.00243 (11) |
C(1) | 0.01715 (16) | 0.01057 (12) | 0.01303 (14) | −0.00431 (11) | 0.00102 (12) | −0.00100 (11) |
Geometric parameters (Å, º) top
O(1)—C(5) | 1.2395 (5) | N(2)—C(4) | 1.3370 (6) |
N(1)—C(2) | 1.3377 (5) | C(2)—C(5) | 1.5011 (5) |
N(1)—C(1) | 1.3364 (5) | C(2)—C(3) | 1.3940 (5) |
N(3)—C(5) | 1.3293 (6) | C(3)—H(3) | 1.0840 (4) |
N(3)—H(3A) | 1.0094 (4) | C(4)—C(1) | 1.3941 (6) |
N(3)—H(3B) | 1.0087 (4) | C(4)—H(4) | 1.0828 (4) |
N(2)—C(3) | 1.3406 (6) | C(1)—H(1) | 1.0821 (4) |
| | | |
C(2)—N(1)—C(1) | 116.60 (4) | N(3)—C(5)—C(2) | 116.42 (4) |
C(5)—N(3)—H(3A) | 119.08 (4) | N(2)—C(3)—C(2) | 121.63 (4) |
C(5)—N(3)—H(3B) | 118.68 (4) | N(2)—C(3)—H(3) | 118.25 (4) |
H(3A)—N(3)—H(3B) | 122.10 (4) | C(2)—C(3)—H(3) | 120.11 (4) |
C(3)—N(2)—C(4) | 116.27 (4) | N(2)—C(4)—C(1) | 122.13 (4) |
N(1)—C(2)—C(5) | 118.44 (3) | N(2)—C(4)—H(4) | 117.33 (4) |
N(1)—C(2)—C(3) | 121.86 (4) | C(1)—C(4)—H(4) | 120.53 (4) |
C(5)—C(2)—C(3) | 119.69 (3) | N(1)—C(1)—C(4) | 121.48 (4) |
O(1)—C(5)—N(3) | 124.10 (4) | N(1)—C(1)—H(1) | 118.64 (4) |
O(1)—C(5)—C(2) | 119.47 (4) | C(4)—C(1)—H(1) | 119.87 (4) |
| | | |
C(1)—N(1)—C(2)—C(5) | 177.28 (6) | N(1)—C(2)—C(5)—O(1) | −174.12 (6) |
C(1)—N(1)—C(2)—C(3) | −1.52 (4) | N(1)—C(2)—C(5)—N(3) | 4.72 (4) |
C(2)—N(1)—C(1)—C(4) | 0.67 (4) | N(1)—C(2)—C(3)—N(2) | 1.14 (4) |
C(2)—N(1)—C(1)—H(1) | −179.95 (6) | N(1)—C(2)—C(3)—H(3) | −179.76 (6) |
H(3A)—N(3)—C(5)—O(1) | −178.53 (8) | C(3)—C(2)—C(5)—O(1) | 4.71 (4) |
H(3A)—N(3)—C(5)—C(2) | 2.69 (4) | C(3)—C(2)—C(5)—N(3) | −176.45 (6) |
H(3B)—N(3)—C(5)—O(1) | −2.81 (5) | C(5)—C(2)—C(3)—N(2) | −177.64 (6) |
H(3B)—N(3)—C(5)—C(2) | 178.41 (7) | C(5)—C(2)—C(3)—H(3) | 1.45 (4) |
C(4)—N(2)—C(3)—C(2) | 0.19 (4) | N(2)—C(4)—C(1)—N(1) | 0.65 (4) |
C(3)—N(2)—C(4)—C(1) | −1.05 (4) | N(2)—C(4)—C(1)—H(1) | −178.72 (7) |
C(4)—N(2)—C(3)—H(3) | −178.92 (6) | H(4)—C(4)—C(1)—N(1) | −178.50 (7) |
C(3)—N(2)—C(4)—H(4) | 178.13 (7) | H(4)—C(4)—C(1)—H(1) | 2.13 (4) |