Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807040731/lw2026sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807040731/lw2026Isup2.hkl |
CCDC reference: 660334
Nevirapine (2.66 g, 0.01 mol) was dissolved in 25 ml of ethanol. Picric acid (2.29 g, 0.01 mol) was dissolved in 10 ml of water. The solutions were mixed and 5 ml of 5M HCl was added to this mixture and stirred for few minutes. The resulting solid was filtered, dried and yellow crystals of (I) were obtained by slow evaporation of an ethanol solution (m.p.: 489–491 K; analysis for C21H17N7O8: Found (calculated): C 50.88 (50.91); H 3.39 (3.46); N 19.71% (19.79%).
The N-bound H atoms were located in difference maps and their positions were freely refined with Uiso(H) = 1.2Ueq(N).
The C-bound H atoms were geometrically placed (C—H = 0.93–0.96 Å) and refined as riding with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C). The methyl group was allowed to rotate, but not to tip, to best fit the electron density.
Nevirapine, C15H14N4O, has several important biological applications: it is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used to treat HIV-1 infection and AIDS (Bartlett, 2005) and it is an inducer of cytochrome P450 isoenzymes CYP3A4 and CYP2B6 (Gazzard, 2005). Nevirapine in triple combination therapy has been shown to suppress viral load effectively when used as initial antiretroviral therapy (Manosuthi et al., 2007).
The crystal structure of nevirapine was described earlier (Mui et al., 1992). In continuation of our work on the structures of pharmaceutical compounds (Harrison, Ashok et al., 2007; Harrison, Bindya et al., 2007), we now report the crystal structure of the title compound, (I), a molecular salt of nevirapine and picric acid.
The structure of (I) (Fig. 1) shows that proton transfer from picric acid (pa) to nevirapine (np) has occurred, and that the N atom of the methyl-substituted pyridine ring has been protonated. The dihedral angle between the C1—C5/N1 and C7—C11/N4 ring planes is 48.27 (8)°, which is substantially different to the equivalent value of 59° (no s.u. stated) for unprotonated nevirapine (Mui et al., 1992). This difference may arise due to the flexibility of the central seven-membered ring. In (I), the bond-angle sum about N2 (350.6°) is ambiguous with respect to the hybridization of the nitrogen atom. The equivalent value for N3 (358.3°) equates to sp2 hybridization, perhaps due to delocalization with the adjacent pyridine ring (Mui et al., 1992).
The significant variation of the C—C bond lengths around the picrate aromatic ring in (I) are normal and can be related to the contributions of various resonance forms involving the nitro groups (Herbstein & Kaftory, 976). The N11/O12/O13 nitro group in (I) is twisted from the benzene ring plane by 46.55 (12)°, whereas the other two nitro groups are close to co-planar with the ring [equivalent dihedral angles for N12/O14/O15 and N13/O16/O17 = 3.03 (11) and 12.2 (2)°, respectively].
The two constituents of (I) interact by a strong, near linear N4—H4N···O11 link (Table 1). Then, centrosymmetric associtions of these ion pairs arise from the N3—HN3···O1i (see Table 1 for symmetry code) bond (Fig. 2). Two short intermolecular C—H···O interactions also occur (Table 1) and a short π-π stacking interaction involving the C1—C5/N1 ring and its inversion-generated partner at (1 - x, 2 - y, -z) with a centroid···centroid separation of 3.5486 (9) Å completes the structure of (I).
For the structure of nevirapine, see: Mui et al. (1992). For related structures, see: Harrison, Ashok et al. (2007); Harrison, Bindya et al. (2007). For background, see: Herbstein & Kaftory (1976); Bartlett (2005); Gazzard (2005); Manosuthi et al. (2007).
Data collection: SMART (Bruker, 1999); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT (Bruker, 1999); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).
C15H15N4O+·C6H2N3O7− | Z = 2 |
Mr = 495.42 | F(000) = 512 |
Triclinic, P1 | Dx = 1.515 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 9.9921 (5) Å | Cell parameters from 3856 reflections |
b = 10.2126 (5) Å | θ = 2.3–27.5° |
c = 11.5332 (6) Å | µ = 0.12 mm−1 |
α = 70.716 (1)° | T = 291 K |
β = 77.980 (1)° | Block, yellow |
γ = 87.355 (1)° | 0.40 × 0.30 × 0.24 mm |
V = 1086.19 (9) Å3 |
Bruker SMART 1000 CCD diffractometer | 4911 independent reflections |
Radiation source: fine-focus sealed tube | 3575 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.015 |
ω scans | θmax = 27.5°, θmin = 2.1° |
Absorption correction: multi-scan (SADABS; Bruker, 1999) | h = −12→12 |
Tmin = 0.955, Tmax = 0.972 | k = −13→13 |
8228 measured reflections | l = −14→14 |
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)] = 0.042 | Hydrogen site location: difmap (N-H) and geom (C-H) |
wR(F2) = 0.120 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.05 | w = 1/[σ2(Fo2) + (0.0639P)2 + 0.0965P] where P = (Fo2 + 2Fc2)/3 |
4911 reflections | (Δ/σ)max < 0.001 |
333 parameters | Δρmax = 0.25 e Å−3 |
0 restraints | Δρmin = −0.21 e Å−3 |
C15H15N4O+·C6H2N3O7− | γ = 87.355 (1)° |
Mr = 495.42 | V = 1086.19 (9) Å3 |
Triclinic, P1 | Z = 2 |
a = 9.9921 (5) Å | Mo Kα radiation |
b = 10.2126 (5) Å | µ = 0.12 mm−1 |
c = 11.5332 (6) Å | T = 291 K |
α = 70.716 (1)° | 0.40 × 0.30 × 0.24 mm |
β = 77.980 (1)° |
Bruker SMART 1000 CCD diffractometer | 4911 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 1999) | 3575 reflections with I > 2σ(I) |
Tmin = 0.955, Tmax = 0.972 | Rint = 0.015 |
8228 measured reflections |
R[F2 > 2σ(F2)] = 0.042 | 0 restraints |
wR(F2) = 0.120 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.05 | Δρmax = 0.25 e Å−3 |
4911 reflections | Δρmin = −0.21 e Å−3 |
333 parameters |
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.30569 (18) | 1.05420 (17) | 0.08754 (17) | 0.0448 (4) | |
H1 | 0.2861 | 1.1430 | 0.0909 | 0.054* | |
C2 | 0.30848 (17) | 1.03144 (17) | −0.02357 (16) | 0.0426 (4) | |
H2 | 0.2879 | 1.1015 | −0.0925 | 0.051* | |
C3 | 0.34278 (16) | 0.90120 (16) | −0.02970 (15) | 0.0373 (4) | |
H3 | 0.3497 | 0.8833 | −0.1047 | 0.045* | |
C4 | 0.36700 (14) | 0.79642 (14) | 0.07669 (13) | 0.0300 (3) | |
C5 | 0.35655 (14) | 0.83030 (14) | 0.18620 (14) | 0.0306 (3) | |
C6 | 0.41730 (15) | 0.66361 (15) | 0.05906 (14) | 0.0329 (3) | |
C7 | 0.31537 (15) | 0.51453 (14) | 0.27735 (13) | 0.0310 (3) | |
C8 | 0.30914 (15) | 0.60597 (15) | 0.34613 (13) | 0.0313 (3) | |
C9 | 0.16245 (17) | 0.44673 (17) | 0.51808 (15) | 0.0413 (4) | |
H9 | 0.1121 | 0.4249 | 0.5998 | 0.050* | |
C10 | 0.16491 (17) | 0.35632 (16) | 0.45418 (15) | 0.0409 (4) | |
H10 | 0.1151 | 0.2730 | 0.4916 | 0.049* | |
C11 | 0.24218 (16) | 0.38812 (15) | 0.33232 (14) | 0.0354 (3) | |
C12 | 0.2488 (2) | 0.28451 (18) | 0.26464 (17) | 0.0516 (5) | |
H12A | 0.2239 | 0.3280 | 0.1848 | 0.077* | |
H12B | 0.1865 | 0.2082 | 0.3138 | 0.077* | |
H12C | 0.3402 | 0.2510 | 0.2520 | 0.077* | |
C13 | 0.40744 (19) | 0.79138 (17) | 0.39300 (15) | 0.0436 (4) | |
H13 | 0.3329 | 0.8414 | 0.4286 | 0.052* | |
C14 | 0.4982 (2) | 0.7114 (2) | 0.47783 (19) | 0.0604 (5) | |
H14A | 0.5339 | 0.6250 | 0.4675 | 0.072* | |
H14B | 0.4787 | 0.7122 | 0.5636 | 0.072* | |
C15 | 0.5491 (2) | 0.8434 (3) | 0.3756 (2) | 0.0744 (7) | |
H15A | 0.5606 | 0.9242 | 0.3995 | 0.089* | |
H15B | 0.6157 | 0.8370 | 0.3034 | 0.089* | |
N1 | 0.32925 (14) | 0.95717 (13) | 0.19133 (13) | 0.0408 (3) | |
N2 | 0.38048 (13) | 0.73279 (12) | 0.30040 (11) | 0.0342 (3) | |
N3 | 0.40003 (14) | 0.54343 (13) | 0.15722 (12) | 0.0355 (3) | |
H3N | 0.4310 (18) | 0.4702 (19) | 0.1367 (16) | 0.043* | |
N4 | 0.23304 (13) | 0.56827 (14) | 0.46307 (12) | 0.0362 (3) | |
H4N | 0.2240 (18) | 0.6221 (19) | 0.5097 (17) | 0.043* | |
O1 | 0.47388 (13) | 0.66345 (12) | −0.04642 (10) | 0.0478 (3) | |
C21 | 0.14876 (16) | 0.71482 (16) | 0.73045 (14) | 0.0356 (3) | |
C22 | 0.09458 (16) | 0.83633 (15) | 0.76164 (14) | 0.0354 (3) | |
C23 | 0.05246 (16) | 0.84102 (16) | 0.88013 (15) | 0.0373 (4) | |
H23 | 0.0128 | 0.9201 | 0.8940 | 0.045* | |
C24 | 0.07029 (16) | 0.72442 (16) | 0.98010 (14) | 0.0361 (3) | |
C25 | 0.13314 (16) | 0.60842 (16) | 0.95952 (15) | 0.0356 (3) | |
H25 | 0.1474 | 0.5326 | 1.0271 | 0.043* | |
C26 | 0.17471 (15) | 0.60485 (15) | 0.83888 (15) | 0.0346 (3) | |
N11 | 0.08437 (17) | 0.96236 (14) | 0.65664 (14) | 0.0460 (4) | |
N12 | 0.02625 (15) | 0.72525 (16) | 1.10704 (14) | 0.0450 (3) | |
N13 | 0.24590 (15) | 0.48166 (14) | 0.82482 (14) | 0.0432 (3) | |
O11 | 0.16134 (14) | 0.71111 (13) | 0.62164 (11) | 0.0528 (3) | |
O12 | 0.18419 (18) | 0.99914 (15) | 0.57137 (15) | 0.0781 (5) | |
O13 | −0.02037 (18) | 1.02612 (18) | 0.65992 (16) | 0.0875 (6) | |
O14 | 0.04083 (15) | 0.61899 (16) | 1.19367 (11) | 0.0602 (4) | |
O15 | −0.02505 (17) | 0.83064 (15) | 1.12454 (13) | 0.0670 (4) | |
O16 | 0.24491 (16) | 0.38042 (13) | 0.91924 (13) | 0.0620 (4) | |
O17 | 0.30523 (17) | 0.48267 (15) | 0.72064 (13) | 0.0704 (4) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0555 (10) | 0.0274 (8) | 0.0513 (10) | 0.0056 (7) | −0.0086 (8) | −0.0145 (7) |
C2 | 0.0482 (9) | 0.0314 (8) | 0.0428 (9) | 0.0041 (7) | −0.0092 (7) | −0.0057 (7) |
C3 | 0.0422 (8) | 0.0363 (8) | 0.0331 (8) | −0.0014 (6) | −0.0067 (7) | −0.0114 (7) |
C4 | 0.0326 (7) | 0.0267 (7) | 0.0297 (7) | −0.0021 (5) | −0.0026 (6) | −0.0100 (6) |
C5 | 0.0312 (7) | 0.0278 (7) | 0.0327 (8) | −0.0010 (5) | −0.0037 (6) | −0.0112 (6) |
C6 | 0.0379 (8) | 0.0298 (7) | 0.0309 (8) | 0.0009 (6) | −0.0038 (6) | −0.0117 (6) |
C7 | 0.0381 (8) | 0.0268 (7) | 0.0288 (7) | 0.0045 (6) | −0.0078 (6) | −0.0098 (6) |
C8 | 0.0363 (7) | 0.0288 (7) | 0.0294 (7) | 0.0038 (6) | −0.0078 (6) | −0.0103 (6) |
C9 | 0.0469 (9) | 0.0410 (9) | 0.0300 (8) | −0.0010 (7) | −0.0010 (7) | −0.0074 (7) |
C10 | 0.0488 (9) | 0.0312 (8) | 0.0372 (9) | −0.0027 (7) | −0.0045 (7) | −0.0063 (7) |
C11 | 0.0442 (8) | 0.0278 (7) | 0.0345 (8) | 0.0023 (6) | −0.0101 (7) | −0.0094 (6) |
C12 | 0.0739 (12) | 0.0345 (9) | 0.0462 (10) | −0.0101 (8) | −0.0026 (9) | −0.0174 (8) |
C13 | 0.0577 (10) | 0.0426 (9) | 0.0363 (9) | −0.0056 (7) | −0.0103 (8) | −0.0192 (7) |
C14 | 0.0669 (13) | 0.0731 (14) | 0.0477 (11) | −0.0071 (10) | −0.0223 (10) | −0.0210 (10) |
C15 | 0.0817 (15) | 0.0929 (17) | 0.0526 (12) | −0.0393 (13) | −0.0131 (11) | −0.0242 (12) |
N1 | 0.0524 (8) | 0.0301 (7) | 0.0415 (8) | 0.0026 (6) | −0.0071 (6) | −0.0154 (6) |
N2 | 0.0445 (7) | 0.0297 (6) | 0.0304 (7) | −0.0012 (5) | −0.0082 (5) | −0.0121 (5) |
N3 | 0.0476 (7) | 0.0256 (6) | 0.0321 (7) | 0.0034 (5) | −0.0009 (6) | −0.0127 (5) |
N4 | 0.0456 (7) | 0.0342 (7) | 0.0297 (7) | 0.0019 (6) | −0.0036 (6) | −0.0142 (6) |
O1 | 0.0695 (8) | 0.0366 (6) | 0.0324 (6) | 0.0056 (5) | 0.0036 (6) | −0.0139 (5) |
C21 | 0.0413 (8) | 0.0334 (8) | 0.0318 (8) | 0.0001 (6) | −0.0045 (6) | −0.0122 (6) |
C22 | 0.0437 (8) | 0.0275 (7) | 0.0341 (8) | −0.0004 (6) | −0.0097 (7) | −0.0078 (6) |
C23 | 0.0430 (8) | 0.0322 (8) | 0.0405 (9) | 0.0028 (6) | −0.0090 (7) | −0.0169 (7) |
C24 | 0.0402 (8) | 0.0380 (8) | 0.0313 (8) | −0.0019 (6) | −0.0060 (6) | −0.0134 (7) |
C25 | 0.0395 (8) | 0.0335 (8) | 0.0323 (8) | −0.0013 (6) | −0.0091 (6) | −0.0077 (6) |
C26 | 0.0391 (8) | 0.0296 (7) | 0.0354 (8) | 0.0020 (6) | −0.0074 (6) | −0.0114 (6) |
N11 | 0.0612 (9) | 0.0333 (7) | 0.0423 (8) | 0.0015 (7) | −0.0130 (7) | −0.0095 (6) |
N12 | 0.0475 (8) | 0.0534 (9) | 0.0376 (8) | 0.0016 (7) | −0.0078 (6) | −0.0203 (7) |
N13 | 0.0508 (8) | 0.0354 (7) | 0.0445 (8) | 0.0080 (6) | −0.0110 (7) | −0.0148 (6) |
O11 | 0.0816 (9) | 0.0462 (7) | 0.0326 (6) | 0.0143 (6) | −0.0118 (6) | −0.0172 (5) |
O12 | 0.0899 (11) | 0.0531 (9) | 0.0639 (10) | −0.0085 (8) | 0.0036 (8) | 0.0066 (7) |
O13 | 0.0858 (12) | 0.0721 (11) | 0.0801 (12) | 0.0331 (9) | −0.0187 (9) | 0.0045 (9) |
O14 | 0.0723 (9) | 0.0698 (9) | 0.0320 (7) | 0.0122 (7) | −0.0091 (6) | −0.0107 (6) |
O15 | 0.0913 (11) | 0.0638 (9) | 0.0536 (8) | 0.0143 (8) | −0.0067 (8) | −0.0359 (7) |
O16 | 0.0835 (10) | 0.0364 (7) | 0.0571 (8) | 0.0168 (6) | −0.0146 (7) | −0.0054 (6) |
O17 | 0.0959 (11) | 0.0658 (9) | 0.0487 (8) | 0.0363 (8) | −0.0084 (8) | −0.0262 (7) |
C1—N1 | 1.335 (2) | C13—C15 | 1.486 (3) |
C1—C2 | 1.370 (2) | C13—C14 | 1.490 (3) |
C1—H1 | 0.9300 | C13—H13 | 0.9800 |
C2—C3 | 1.379 (2) | C14—C15 | 1.493 (3) |
C2—H2 | 0.9300 | C14—H14A | 0.9700 |
C3—C4 | 1.393 (2) | C14—H14B | 0.9700 |
C3—H3 | 0.9300 | C15—H15A | 0.9700 |
C4—C5 | 1.399 (2) | C15—H15B | 0.9700 |
C4—C6 | 1.4867 (19) | N3—H3N | 0.881 (19) |
C5—N1 | 1.3296 (18) | N4—H4N | 0.878 (19) |
C5—N2 | 1.4236 (19) | C21—O11 | 1.2480 (18) |
C6—O1 | 1.2305 (17) | C21—C26 | 1.440 (2) |
C6—N3 | 1.3559 (19) | C21—C22 | 1.454 (2) |
C7—C11 | 1.399 (2) | C22—C23 | 1.360 (2) |
C7—C8 | 1.4030 (19) | C22—N11 | 1.464 (2) |
C7—N3 | 1.4097 (18) | C23—C24 | 1.392 (2) |
C8—N4 | 1.3425 (19) | C23—H23 | 0.9300 |
C8—N2 | 1.3933 (18) | C24—C25 | 1.382 (2) |
C9—N4 | 1.347 (2) | C24—N12 | 1.441 (2) |
C9—C10 | 1.355 (2) | C25—C26 | 1.379 (2) |
C9—H9 | 0.9300 | C25—H25 | 0.9300 |
C10—C11 | 1.395 (2) | C26—N13 | 1.4557 (19) |
C10—H10 | 0.9300 | N11—O13 | 1.207 (2) |
C11—C12 | 1.500 (2) | N11—O12 | 1.219 (2) |
C12—H12A | 0.9600 | N12—O15 | 1.2294 (19) |
C12—H12B | 0.9600 | N12—O14 | 1.2357 (19) |
C12—H12C | 0.9600 | N13—O17 | 1.2211 (18) |
C13—N2 | 1.4587 (19) | N13—O16 | 1.2278 (18) |
N1—C1—C2 | 124.23 (14) | C15—C14—H14A | 117.8 |
N1—C1—H1 | 117.9 | C13—C14—H14B | 117.8 |
C2—C1—H1 | 117.9 | C15—C14—H14B | 117.8 |
C1—C2—C3 | 117.77 (16) | H14A—C14—H14B | 114.9 |
C1—C2—H2 | 121.1 | C13—C15—C14 | 60.03 (13) |
C3—C2—H2 | 121.1 | C13—C15—H15A | 117.8 |
C2—C3—C4 | 119.89 (15) | C14—C15—H15A | 117.8 |
C2—C3—H3 | 120.1 | C13—C15—H15B | 117.8 |
C4—C3—H3 | 120.1 | C14—C15—H15B | 117.8 |
C3—C4—C5 | 117.31 (13) | H15A—C15—H15B | 114.9 |
C3—C4—C6 | 116.49 (13) | C5—N1—C1 | 117.62 (14) |
C5—C4—C6 | 125.80 (14) | C8—N2—C5 | 117.84 (12) |
N1—C5—C4 | 123.08 (14) | C8—N2—C13 | 116.95 (12) |
N1—C5—N2 | 114.28 (13) | C5—N2—C13 | 115.85 (12) |
C4—C5—N2 | 122.58 (12) | C6—N3—C7 | 129.12 (13) |
O1—C6—N3 | 120.04 (13) | C6—N3—H3N | 113.9 (11) |
O1—C6—C4 | 119.18 (13) | C7—N3—H3N | 115.4 (11) |
N3—C6—C4 | 120.77 (13) | C8—N4—C9 | 123.33 (13) |
C11—C7—C8 | 119.18 (13) | C8—N4—H4N | 122.4 (12) |
C11—C7—N3 | 119.24 (12) | C9—N4—H4N | 114.3 (12) |
C8—C7—N3 | 121.48 (13) | O11—C21—C26 | 127.20 (14) |
N4—C8—N2 | 118.15 (12) | O11—C21—C22 | 120.70 (15) |
N4—C8—C7 | 118.47 (13) | C26—C21—C22 | 111.99 (13) |
N2—C8—C7 | 123.36 (13) | C23—C22—C21 | 125.00 (14) |
N4—C9—C10 | 119.90 (14) | C23—C22—N11 | 118.07 (14) |
N4—C9—H9 | 120.1 | C21—C22—N11 | 116.93 (13) |
C10—C9—H9 | 120.1 | C22—C23—C24 | 118.30 (14) |
C9—C10—C11 | 120.04 (14) | C22—C23—H23 | 120.9 |
C9—C10—H10 | 120.0 | C24—C23—H23 | 120.9 |
C11—C10—H10 | 120.0 | C25—C24—C23 | 120.94 (14) |
C10—C11—C7 | 119.08 (14) | C25—C24—N12 | 119.15 (15) |
C10—C11—C12 | 119.49 (14) | C23—C24—N12 | 119.89 (14) |
C7—C11—C12 | 121.41 (14) | C26—C25—C24 | 120.10 (15) |
C11—C12—H12A | 109.5 | C26—C25—H25 | 120.0 |
C11—C12—H12B | 109.5 | C24—C25—H25 | 120.0 |
H12A—C12—H12B | 109.5 | C25—C26—C21 | 122.93 (14) |
C11—C12—H12C | 109.5 | C25—C26—N13 | 116.69 (14) |
H12A—C12—H12C | 109.5 | C21—C26—N13 | 120.37 (13) |
H12B—C12—H12C | 109.5 | O13—N11—O12 | 123.37 (17) |
N2—C13—C15 | 116.94 (15) | O13—N11—C22 | 118.84 (15) |
N2—C13—C14 | 116.71 (15) | O12—N11—C22 | 117.77 (16) |
C15—C13—C14 | 60.23 (14) | O15—N12—O14 | 122.93 (15) |
N2—C13—H13 | 117.0 | O15—N12—C24 | 118.83 (15) |
C15—C13—H13 | 117.0 | O14—N12—C24 | 118.24 (14) |
C14—C13—H13 | 117.0 | O17—N13—O16 | 122.36 (14) |
C13—C14—C15 | 59.74 (14) | O17—N13—C26 | 119.31 (14) |
C13—C14—H14A | 117.8 | O16—N13—C26 | 118.33 (14) |
N1—C1—C2—C3 | −2.5 (3) | C15—C13—N2—C5 | −81.3 (2) |
C1—C2—C3—C4 | 2.9 (2) | C14—C13—N2—C5 | −149.74 (15) |
C2—C3—C4—C5 | −0.8 (2) | O1—C6—N3—C7 | −165.46 (15) |
C2—C3—C4—C6 | −173.88 (14) | C4—C6—N3—C7 | 13.8 (2) |
C3—C4—C5—N1 | −2.2 (2) | C11—C7—N3—C6 | 138.44 (16) |
C6—C4—C5—N1 | 170.24 (14) | C8—C7—N3—C6 | −45.4 (2) |
C3—C4—C5—N2 | −179.24 (13) | N2—C8—N4—C9 | −178.36 (15) |
C6—C4—C5—N2 | −6.8 (2) | C7—C8—N4—C9 | 0.2 (2) |
C3—C4—C6—O1 | 22.0 (2) | C10—C9—N4—C8 | −0.8 (3) |
C5—C4—C6—O1 | −150.49 (15) | O11—C21—C22—C23 | 166.67 (16) |
C3—C4—C6—N3 | −157.26 (14) | C26—C21—C22—C23 | −9.7 (2) |
C5—C4—C6—N3 | 30.3 (2) | O11—C21—C22—N11 | −13.0 (2) |
C11—C7—C8—N4 | 0.2 (2) | C26—C21—C22—N11 | 170.67 (13) |
N3—C7—C8—N4 | −175.92 (14) | C21—C22—C23—C24 | 4.5 (2) |
C11—C7—C8—N2 | 178.69 (14) | N11—C22—C23—C24 | −175.84 (14) |
N3—C7—C8—N2 | 2.5 (2) | C22—C23—C24—C25 | 2.1 (2) |
N4—C9—C10—C11 | 1.0 (3) | C22—C23—C24—N12 | −179.67 (14) |
C9—C10—C11—C7 | −0.6 (3) | C23—C24—C25—C26 | −2.4 (2) |
C9—C10—C11—C12 | 177.43 (17) | N12—C24—C25—C26 | 179.29 (14) |
C8—C7—C11—C10 | 0.0 (2) | C24—C25—C26—C21 | −3.8 (2) |
N3—C7—C11—C10 | 176.22 (15) | C24—C25—C26—N13 | 177.17 (13) |
C8—C7—C11—C12 | −178.01 (16) | O11—C21—C26—C25 | −166.96 (16) |
N3—C7—C11—C12 | −1.8 (2) | C22—C21—C26—C25 | 9.1 (2) |
N2—C13—C14—C15 | 107.25 (18) | O11—C21—C26—N13 | 12.1 (3) |
N2—C13—C15—C14 | −106.86 (18) | C22—C21—C26—N13 | −171.83 (13) |
C4—C5—N1—C1 | 2.7 (2) | C23—C22—N11—O13 | −46.4 (2) |
N2—C5—N1—C1 | 180.00 (14) | C21—C22—N11—O13 | 133.22 (18) |
C2—C1—N1—C5 | −0.3 (3) | C23—C22—N11—O12 | 131.86 (18) |
N4—C8—N2—C5 | −124.09 (15) | C21—C22—N11—O12 | −48.5 (2) |
C7—C8—N2—C5 | 57.4 (2) | C25—C24—N12—O15 | 177.36 (15) |
N4—C8—N2—C13 | 21.2 (2) | C23—C24—N12—O15 | −0.9 (2) |
C7—C8—N2—C13 | −157.30 (15) | C25—C24—N12—O14 | −3.3 (2) |
N1—C5—N2—C8 | 130.07 (13) | C23—C24—N12—O14 | 178.44 (15) |
C4—C5—N2—C8 | −52.61 (19) | C25—C26—N13—O17 | −167.53 (16) |
N1—C5—N2—C13 | −15.56 (19) | C21—C26—N13—O17 | 13.4 (2) |
C4—C5—N2—C13 | 161.75 (14) | C25—C26—N13—O16 | 11.8 (2) |
C15—C13—N2—C8 | 132.73 (18) | C21—C26—N13—O16 | −167.29 (15) |
C14—C13—N2—C8 | 64.3 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3N···O1i | 0.881 (19) | 2.063 (19) | 2.9242 (17) | 165.4 (16) |
N4—H4N···O11 | 0.878 (19) | 1.808 (19) | 2.6656 (17) | 164.9 (17) |
C9—H9···O14ii | 0.93 | 2.46 | 3.386 (2) | 174 |
C23—H23···O15iii | 0.93 | 2.49 | 3.335 (2) | 151 |
Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x, −y+1, −z+2; (iii) −x, −y+2, −z+2. |
Experimental details
Crystal data | |
Chemical formula | C15H15N4O+·C6H2N3O7− |
Mr | 495.42 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 291 |
a, b, c (Å) | 9.9921 (5), 10.2126 (5), 11.5332 (6) |
α, β, γ (°) | 70.716 (1), 77.980 (1), 87.355 (1) |
V (Å3) | 1086.19 (9) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.12 |
Crystal size (mm) | 0.40 × 0.30 × 0.24 |
Data collection | |
Diffractometer | Bruker SMART 1000 CCD |
Absorption correction | Multi-scan (SADABS; Bruker, 1999) |
Tmin, Tmax | 0.955, 0.972 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 8228, 4911, 3575 |
Rint | 0.015 |
(sin θ/λ)max (Å−1) | 0.650 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.042, 0.120, 1.05 |
No. of reflections | 4911 |
No. of parameters | 333 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.25, −0.21 |
Computer programs: SMART (Bruker, 1999), SAINT (Bruker, 1999), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEP-3 (Farrugia, 1997).
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3N···O1i | 0.881 (19) | 2.063 (19) | 2.9242 (17) | 165.4 (16) |
N4—H4N···O11 | 0.878 (19) | 1.808 (19) | 2.6656 (17) | 164.9 (17) |
C9—H9···O14ii | 0.93 | 2.46 | 3.386 (2) | 174 |
C23—H23···O15iii | 0.93 | 2.49 | 3.335 (2) | 151 |
Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x, −y+1, −z+2; (iii) −x, −y+2, −z+2. |
Nevirapine, C15H14N4O, has several important biological applications: it is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used to treat HIV-1 infection and AIDS (Bartlett, 2005) and it is an inducer of cytochrome P450 isoenzymes CYP3A4 and CYP2B6 (Gazzard, 2005). Nevirapine in triple combination therapy has been shown to suppress viral load effectively when used as initial antiretroviral therapy (Manosuthi et al., 2007).
The crystal structure of nevirapine was described earlier (Mui et al., 1992). In continuation of our work on the structures of pharmaceutical compounds (Harrison, Ashok et al., 2007; Harrison, Bindya et al., 2007), we now report the crystal structure of the title compound, (I), a molecular salt of nevirapine and picric acid.
The structure of (I) (Fig. 1) shows that proton transfer from picric acid (pa) to nevirapine (np) has occurred, and that the N atom of the methyl-substituted pyridine ring has been protonated. The dihedral angle between the C1—C5/N1 and C7—C11/N4 ring planes is 48.27 (8)°, which is substantially different to the equivalent value of 59° (no s.u. stated) for unprotonated nevirapine (Mui et al., 1992). This difference may arise due to the flexibility of the central seven-membered ring. In (I), the bond-angle sum about N2 (350.6°) is ambiguous with respect to the hybridization of the nitrogen atom. The equivalent value for N3 (358.3°) equates to sp2 hybridization, perhaps due to delocalization with the adjacent pyridine ring (Mui et al., 1992).
The significant variation of the C—C bond lengths around the picrate aromatic ring in (I) are normal and can be related to the contributions of various resonance forms involving the nitro groups (Herbstein & Kaftory, 976). The N11/O12/O13 nitro group in (I) is twisted from the benzene ring plane by 46.55 (12)°, whereas the other two nitro groups are close to co-planar with the ring [equivalent dihedral angles for N12/O14/O15 and N13/O16/O17 = 3.03 (11) and 12.2 (2)°, respectively].
The two constituents of (I) interact by a strong, near linear N4—H4N···O11 link (Table 1). Then, centrosymmetric associtions of these ion pairs arise from the N3—HN3···O1i (see Table 1 for symmetry code) bond (Fig. 2). Two short intermolecular C—H···O interactions also occur (Table 1) and a short π-π stacking interaction involving the C1—C5/N1 ring and its inversion-generated partner at (1 - x, 2 - y, -z) with a centroid···centroid separation of 3.5486 (9) Å completes the structure of (I).