Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S160053680704189X/hb2509sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S160053680704189X/hb2509Isup2.hkl |
CCDC reference: 663760
Key indicators
- Single-crystal X-ray study
- T = 293 K
- Mean (C-C) = 0.015 Å
- R factor = 0.064
- wR factor = 0.152
- Data-to-parameter ratio = 6.6
checkCIF/PLATON results
No syntax errors found
Alert level B PLAT026_ALERT_3_B Ratio Observed / Unique Reflections too Low .... 39 Perc. PLAT340_ALERT_3_B Low Bond Precision on C-C Bonds (x 1000) Ang ... 15
Alert level C PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) ..... 6.64 PLAT220_ALERT_2_C Large Non-Solvent C Ueq(max)/Ueq(min) ... 2.95 Ratio PLAT222_ALERT_3_C Large Non-Solvent H Ueq(max)/Ueq(min) ... 3.47 Ratio PLAT242_ALERT_2_C Check Low Ueq as Compared to Neighbors for O1 PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd. # 2 C7 H3 N2 O7
Alert level G REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is correct. If it is not, please give the correct count in the _publ_section_exptl_refinement section of the submitted CIF. From the CIF: _diffrn_reflns_theta_max 70.20 From the CIF: _reflns_number_total 2244 Count of symmetry unique reflns 2278 Completeness (_total/calc) 98.51% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 0 Fraction of Friedel pairs measured 0.000 Are heavy atom types Z>Si present no PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature 293 K PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature . 293 K PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints ....... 1
0 ALERT level A = In general: serious problem 2 ALERT level B = Potentially serious problem 5 ALERT level C = Check and explain 4 ALERT level G = General alerts; check 2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 2 ALERT type 2 Indicator that the structure model may be wrong or deficient 5 ALERT type 3 Indicator that the structure quality may be low 2 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check
For related literature, see: Bernstein et al. (1995); Hemamalini et al. (2005); Hitching et al. (1988); Koetzle & Williams (1976); Kuyper (1990); Panneerselvam et al. (2002).
Hot methanol solutions of trimethoprim (74 mg, obtained as a gift from Shilpa Antibiotics Ltd) and 3,5-dinitrosalicylic acid (57 mg, Merck) were mixed in a 1:1 molar ratio and warmed for half an hour over a water bath. On slow evaporation, yellow prisms of (I) were obtained.
All the hydrogen atoms were placed in idealized locations (C—H = 0.96 Å, O—H = 0.82 Å, N—H = 0.86 Å) and refined as riding with Uiso(H) = 1.2Ueq(carrier) or 1.5Ueq(methyl carrier).
As part of our ongoing studies (Hemamalini et al., 2005) of hydrogen bonding patterns in the molecular salts of protonated trimethoprim [2,4-diamino-5-(3,4,5-trimethoxybenzyl-pyrimidine or TMP], we now report the synthesis and structure of the title compound, (I). [systematic name: 2,4-diamino-5-(3,4,5-trimethoxybenzyl) pyrimidin-1-ium 2-hydroxy-3,5-dinitrobenzoate]. Neutral TMP is a well known antifolate drug and its structure was determined by Koetzle & Williams (1976).
The asymmetric unit of (I) contains a protonated TMP cation and a 3,5-dinitrosalicylate (DNSA) anion (Fig. 1). The trimethoprim molecule is protonated at atom N1 of the pyrimidine moiety, which is evident from the increase in the internal angle at the protonated N1 [C2—N1—C6 = 121.7 (10)°] compared with that at unprotonated atom N3 [C2—N3—C4 = 117.9 (9)°]. The dihedral angle between the pyrimidine and benzene ring planes in (I) is 72.48 (5)°, which falls within the known range of equivalent torsion angles [69.96 (8)–89.5 (2)°] in other TMP structures (Panneerselvam et al., 2002). The conformation of the TMP cation is described by the two torsion angles C4—C5—C7—C8 and C5—C7—C8—C9, which are -176.0 (9)° and 69.9 (13)°, respectively in (I). This TMP conformation plays a very important role in DHFR selectivity (Hitching et al., 1988).
The carboxylate group of the DNSA anion in (I) accepts two N—H···O hydrogen bonds (Table 1) from the cation, forming a fork-like interaction. This can be designated by graph-set notation R22(8) (Bernstein et al., 1995). This common motif has been observed in other DHFR-TMP complexes (Kuyper, 1990) A typical intramolecular hydrogen bond occurs in the anion with graph-set notation S(6) (Fig. 2). The TMP cations self assemble via further N—H···O interactions, with the O atom being part of a methoxy or a nitro group. The combination of hydrogen bonds forms a three dimensional network as shown in Fig 3.
For related literature, see: Bernstein et al. (1995); Hemamalini et al. (2005); Hitching et al. (1988); Koetzle & Williams (1976); Kuyper (1990); Panneerselvam et al. (2002).
Data collection: XSCANS (Siemens, 1994); cell refinement: XSCANS (Siemens, 1994); data reduction: XSCANS (Siemens, 1994); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: PLATON (Spek, 2003).
C14H19N4O3+·C7H3N2O7− | F(000) = 1080 |
Mr = 518.45 | Dx = 1.469 Mg m−3 |
Orthorhombic, Pca21 | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: P 2c -2ac | Cell parameters from 26 reflections |
a = 20.928 (3) Å | θ = 4.7–70.2° |
b = 4.898 (2) Å | µ = 1.02 mm−1 |
c = 22.869 (2) Å | T = 293 K |
V = 2344.2 (10) Å3 | Prism, light yellow |
Z = 4 | 0.16 × 0.12 × 0.06 mm |
Siemens AED single-crystal diffractometer | θmax = 70.2°, θmin = 4.7° |
Radiation source: fine- focus sealed tube | h = −25→0 |
Graphite monochromator | k = −5→0 |
ω–2θ scans | l = 0→27 |
2244 measured reflections | 1 standard reflections every 100 reflections |
2244 independent reflections | intensity decay: none |
883 reflections with I > 2σ(I) |
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)] = 0.064 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.152 | H-atom parameters constrained |
S = 0.92 | w = 1/[σ2(Fo2) + (0.0456P)2] where P = (Fo2 + 2Fc2)/3 |
2244 reflections | (Δ/σ)max < 0.001 |
338 parameters | Δρmax = 0.32 e Å−3 |
1 restraint | Δρmin = −0.21 e Å−3 |
C14H19N4O3+·C7H3N2O7− | V = 2344.2 (10) Å3 |
Mr = 518.45 | Z = 4 |
Orthorhombic, Pca21 | Cu Kα radiation |
a = 20.928 (3) Å | µ = 1.02 mm−1 |
b = 4.898 (2) Å | T = 293 K |
c = 22.869 (2) Å | 0.16 × 0.12 × 0.06 mm |
Siemens AED single-crystal diffractometer | 883 reflections with I > 2σ(I) |
2244 measured reflections | 1 standard reflections every 100 reflections |
2244 independent reflections | intensity decay: none |
R[F2 > 2σ(F2)] = 0.064 | 1 restraint |
wR(F2) = 0.152 | H-atom parameters constrained |
S = 0.92 | Δρmax = 0.32 e Å−3 |
2244 reflections | Δρmin = −0.21 e Å−3 |
338 parameters |
Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All e.s.d.'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles |
Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2> σ(F2) is used only for calculating -R-factor-obs 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 | ||
O1 | 0.4839 (3) | 0.9192 (16) | −0.0266 (3) | 0.057 (3) | |
O2 | 0.4526 (3) | 0.6666 (16) | −0.1250 (4) | 0.058 (3) | |
O3 | 0.5418 (3) | 0.474 (2) | −0.1986 (4) | 0.067 (3) | |
N1 | 0.7512 (4) | 0.4715 (19) | 0.0459 (4) | 0.046 (3) | |
N2 | 0.8415 (4) | 0.420 (2) | 0.1010 (4) | 0.059 (4) | |
N3 | 0.8398 (4) | 0.7382 (18) | 0.0286 (4) | 0.043 (3) | |
N4 | 0.8399 (4) | 1.0501 (19) | −0.0461 (4) | 0.046 (3) | |
C2 | 0.8108 (4) | 0.546 (3) | 0.0580 (5) | 0.045 (4) | |
C4 | 0.8083 (5) | 0.854 (2) | −0.0162 (5) | 0.037 (3) | |
C5 | 0.7455 (4) | 0.7855 (19) | −0.0311 (5) | 0.040 (4) | |
C6 | 0.7175 (5) | 0.590 (2) | 0.0023 (5) | 0.039 (4) | |
C7 | 0.7130 (5) | 0.917 (2) | −0.0841 (5) | 0.046 (4) | |
C8 | 0.6439 (5) | 0.834 (2) | −0.0912 (5) | 0.045 (4) | |
C9 | 0.5960 (5) | 0.919 (2) | −0.0531 (5) | 0.049 (4) | |
C10 | 0.5337 (5) | 0.849 (2) | −0.0627 (5) | 0.041 (4) | |
C11 | 0.5154 (5) | 0.708 (2) | −0.1126 (5) | 0.041 (3) | |
C12 | 0.5628 (5) | 0.616 (2) | −0.1511 (5) | 0.048 (4) | |
C13 | 0.6270 (4) | 0.683 (2) | −0.1406 (5) | 0.045 (4) | |
C14 | 0.4999 (7) | 1.075 (4) | 0.0227 (6) | 0.109 (8) | |
C15 | 0.4282 (6) | 0.397 (3) | −0.1137 (7) | 0.084 (6) | |
C16 | 0.5889 (7) | 0.331 (3) | −0.2285 (6) | 0.084 (6) | |
O4 | 0.6798 (4) | 0.0705 (17) | 0.0983 (3) | 0.060 (3) | |
O5 | 0.7609 (4) | 0.0101 (16) | 0.1597 (4) | 0.066 (3) | |
O6 | 0.7550 (4) | −0.337 (2) | 0.2374 (5) | 0.077 (4) | |
O7 | 0.7225 (5) | −0.608 (2) | 0.3338 (4) | 0.099 (4) | |
O8 | 0.6653 (4) | −0.961 (2) | 0.3140 (4) | 0.081 (4) | |
O9 | 0.4875 (4) | −0.821 (2) | 0.1826 (4) | 0.094 (4) | |
O10 | 0.4860 (4) | −0.473 (2) | 0.1288 (4) | 0.077 (4) | |
N5 | 0.6863 (5) | −0.730 (2) | 0.3025 (5) | 0.058 (4) | |
N6 | 0.5133 (5) | −0.621 (2) | 0.1634 (4) | 0.056 (3) | |
C17 | 0.6689 (4) | −0.266 (2) | 0.1725 (4) | 0.035 (3) | |
C18 | 0.6985 (5) | −0.400 (2) | 0.2211 (5) | 0.047 (4) | |
C19 | 0.6609 (5) | −0.602 (2) | 0.2491 (4) | 0.040 (4) | |
C20 | 0.6015 (5) | −0.662 (2) | 0.2316 (4) | 0.044 (4) | |
C21 | 0.5760 (5) | −0.542 (2) | 0.1837 (5) | 0.041 (3) | |
C22 | 0.6100 (5) | −0.337 (2) | 0.1543 (5) | 0.047 (4) | |
C23 | 0.7064 (5) | −0.043 (2) | 0.1412 (6) | 0.048 (4) | |
H1 | 0.73350 | 0.34510 | 0.06640 | 0.0560* | |
H2A | 0.88020 | 0.46450 | 0.10930 | 0.0710* | |
H2B | 0.82280 | 0.29290 | 0.12060 | 0.0710* | |
H4A | 0.87810 | 1.09470 | −0.03600 | 0.0550* | |
H4B | 0.82180 | 1.13030 | −0.07510 | 0.0550* | |
H6 | 0.67550 | 0.53700 | −0.00490 | 0.0470* | |
H7A | 0.71530 | 1.11400 | −0.08020 | 0.0550* | |
H7B | 0.73630 | 0.86670 | −0.11910 | 0.0550* | |
H9 | 0.60650 | 1.02530 | −0.02070 | 0.0580* | |
H13 | 0.65840 | 0.62720 | −0.16680 | 0.0540* | |
H14A | 0.53340 | 0.98490 | 0.04390 | 0.1630* | |
H14B | 0.46310 | 1.09380 | 0.04730 | 0.1630* | |
H14C | 0.51420 | 1.25200 | 0.01050 | 0.1630* | |
H15A | 0.45520 | 0.26450 | −0.13210 | 0.1250* | |
H15B | 0.38570 | 0.38250 | −0.12910 | 0.1250* | |
H15C | 0.42740 | 0.36540 | −0.07230 | 0.1250* | |
H16A | 0.61990 | 0.45630 | −0.24380 | 0.1260* | |
H16B | 0.56980 | 0.23040 | −0.26000 | 0.1260* | |
H16C | 0.60960 | 0.20610 | −0.20220 | 0.1260* | |
H6A | 0.76040 | −0.17190 | 0.23330 | 0.1160* | |
H20 | 0.57740 | −0.78830 | 0.25250 | 0.0530* | |
H22 | 0.59190 | −0.25010 | 0.12220 | 0.0570* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.035 (4) | 0.076 (6) | 0.060 (5) | 0.002 (4) | 0.000 (4) | 0.000 (5) |
O2 | 0.040 (4) | 0.055 (5) | 0.079 (6) | −0.004 (4) | −0.017 (4) | 0.006 (5) |
O3 | 0.049 (4) | 0.093 (7) | 0.058 (6) | 0.000 (5) | −0.014 (4) | −0.010 (6) |
N1 | 0.044 (5) | 0.037 (5) | 0.058 (6) | −0.002 (5) | 0.008 (4) | 0.007 (5) |
N2 | 0.040 (4) | 0.074 (7) | 0.064 (7) | −0.009 (5) | −0.009 (5) | 0.024 (7) |
N3 | 0.033 (4) | 0.042 (6) | 0.054 (6) | −0.005 (5) | 0.005 (4) | 0.002 (5) |
N4 | 0.028 (4) | 0.060 (7) | 0.050 (6) | −0.003 (5) | 0.002 (4) | 0.009 (6) |
C2 | 0.018 (5) | 0.075 (9) | 0.043 (6) | 0.009 (6) | 0.007 (5) | 0.004 (7) |
C4 | 0.029 (5) | 0.040 (7) | 0.041 (6) | 0.008 (5) | −0.004 (5) | −0.003 (6) |
C5 | 0.030 (5) | 0.027 (6) | 0.062 (8) | 0.000 (5) | 0.011 (5) | −0.005 (6) |
C6 | 0.032 (5) | 0.033 (7) | 0.052 (7) | 0.004 (5) | −0.005 (5) | 0.003 (6) |
C7 | 0.046 (6) | 0.044 (7) | 0.049 (7) | 0.003 (6) | −0.012 (5) | 0.008 (6) |
C8 | 0.042 (6) | 0.038 (7) | 0.054 (7) | −0.010 (5) | 0.015 (5) | 0.011 (6) |
C9 | 0.038 (6) | 0.060 (8) | 0.048 (7) | 0.008 (6) | 0.004 (5) | 0.015 (7) |
C10 | 0.041 (6) | 0.037 (6) | 0.046 (7) | 0.003 (5) | 0.002 (5) | 0.008 (6) |
C11 | 0.038 (5) | 0.032 (6) | 0.054 (7) | −0.003 (5) | −0.016 (6) | 0.004 (6) |
C12 | 0.054 (6) | 0.052 (7) | 0.039 (6) | −0.001 (6) | −0.010 (6) | 0.005 (7) |
C13 | 0.033 (5) | 0.060 (8) | 0.042 (7) | −0.005 (6) | −0.008 (5) | 0.017 (6) |
C14 | 0.077 (10) | 0.186 (19) | 0.064 (9) | 0.046 (12) | 0.004 (8) | −0.006 (12) |
C15 | 0.063 (7) | 0.059 (9) | 0.129 (14) | −0.017 (7) | −0.024 (9) | 0.032 (10) |
C16 | 0.092 (11) | 0.065 (10) | 0.095 (11) | −0.016 (9) | −0.037 (9) | −0.018 (9) |
O4 | 0.071 (5) | 0.061 (6) | 0.048 (5) | −0.008 (5) | 0.005 (4) | 0.016 (5) |
O5 | 0.053 (5) | 0.064 (6) | 0.082 (7) | −0.003 (5) | 0.018 (5) | 0.003 (6) |
O6 | 0.058 (6) | 0.085 (7) | 0.089 (7) | −0.005 (5) | −0.007 (5) | 0.017 (7) |
O7 | 0.151 (9) | 0.083 (7) | 0.063 (7) | −0.012 (7) | −0.050 (7) | 0.009 (6) |
O8 | 0.091 (7) | 0.067 (7) | 0.085 (7) | −0.009 (6) | 0.002 (5) | 0.023 (6) |
O9 | 0.079 (6) | 0.099 (7) | 0.103 (8) | −0.035 (6) | −0.013 (6) | 0.044 (7) |
O10 | 0.072 (6) | 0.080 (7) | 0.078 (7) | −0.017 (6) | −0.028 (5) | 0.009 (6) |
N5 | 0.077 (7) | 0.055 (7) | 0.043 (6) | 0.008 (6) | −0.006 (6) | 0.008 (6) |
N6 | 0.053 (5) | 0.067 (7) | 0.047 (6) | −0.006 (6) | 0.000 (5) | 0.011 (6) |
C17 | 0.038 (5) | 0.037 (7) | 0.030 (6) | 0.013 (5) | 0.005 (5) | −0.005 (5) |
C18 | 0.034 (6) | 0.050 (8) | 0.058 (8) | 0.002 (6) | −0.003 (5) | −0.007 (7) |
C19 | 0.045 (6) | 0.047 (7) | 0.029 (6) | −0.004 (6) | −0.006 (5) | 0.012 (6) |
C20 | 0.046 (6) | 0.049 (7) | 0.038 (6) | 0.005 (6) | 0.002 (5) | −0.001 (6) |
C21 | 0.042 (5) | 0.038 (7) | 0.042 (6) | −0.004 (5) | −0.010 (5) | −0.006 (6) |
C22 | 0.058 (7) | 0.041 (7) | 0.042 (7) | 0.009 (6) | 0.009 (6) | −0.003 (6) |
C23 | 0.039 (6) | 0.031 (7) | 0.073 (9) | −0.015 (5) | 0.019 (6) | −0.015 (7) |
O1—C10 | 1.373 (13) | C7—C8 | 1.511 (15) |
O1—C14 | 1.402 (17) | C8—C13 | 1.396 (15) |
O2—C11 | 1.360 (12) | C8—C9 | 1.392 (15) |
O2—C15 | 1.439 (16) | C9—C10 | 1.366 (15) |
O3—C12 | 1.363 (14) | C10—C11 | 1.388 (16) |
O3—C16 | 1.389 (17) | C11—C12 | 1.401 (15) |
O4—C23 | 1.258 (15) | C12—C13 | 1.404 (14) |
O5—C23 | 1.244 (14) | C6—H6 | 0.9312 |
O6—C18 | 1.278 (14) | C7—H7B | 0.9691 |
O7—N5 | 1.201 (15) | C7—H7A | 0.9702 |
O8—N5 | 1.242 (14) | C9—H9 | 0.9319 |
O9—N6 | 1.202 (14) | C13—H13 | 0.9303 |
O10—N6 | 1.216 (13) | C14—H14C | 0.9586 |
O6—H6A | 0.8219 | C14—H14A | 0.9599 |
N1—C6 | 1.352 (14) | C14—H14B | 0.9582 |
N1—C2 | 1.329 (13) | C15—H15C | 0.9595 |
N2—C2 | 1.327 (15) | C15—H15A | 0.9579 |
N3—C4 | 1.344 (14) | C15—H15B | 0.9593 |
N3—C2 | 1.306 (15) | C16—H16A | 0.9592 |
N4—C4 | 1.352 (14) | C16—H16B | 0.9600 |
N1—H1 | 0.8604 | C16—H16C | 0.9611 |
N2—H2B | 0.8612 | C17—C22 | 1.347 (14) |
N2—H2A | 0.8599 | C17—C23 | 1.524 (14) |
N4—H4A | 0.8603 | C17—C18 | 1.432 (14) |
N4—H4B | 0.8589 | C18—C19 | 1.417 (14) |
N5—C19 | 1.472 (15) | C19—C20 | 1.339 (15) |
N6—C21 | 1.445 (15) | C20—C21 | 1.353 (15) |
C4—C5 | 1.399 (14) | C21—C22 | 1.402 (15) |
C5—C6 | 1.358 (14) | C20—H20 | 0.9303 |
C5—C7 | 1.532 (15) | C22—H22 | 0.9293 |
C10—O1—C14 | 116.0 (9) | C8—C7—H7A | 108.96 |
C11—O2—C15 | 116.3 (9) | C5—C7—H7A | 108.87 |
C12—O3—C16 | 114.9 (9) | C5—C7—H7B | 108.86 |
C18—O6—H6A | 109.37 | H7A—C7—H7B | 107.69 |
C2—N1—C6 | 121.7 (10) | C10—C9—H9 | 119.55 |
C2—N3—C4 | 117.9 (9) | C8—C9—H9 | 119.67 |
C6—N1—H1 | 119.08 | C8—C13—H13 | 119.86 |
C2—N1—H1 | 119.23 | C12—C13—H13 | 119.82 |
C2—N2—H2A | 120.11 | O1—C14—H14C | 109.44 |
H2A—N2—H2B | 119.76 | O1—C14—H14B | 109.42 |
C2—N2—H2B | 120.13 | H14A—C14—H14C | 109.56 |
C4—N4—H4A | 119.95 | O1—C14—H14A | 109.29 |
H4A—N4—H4B | 120.07 | H14A—C14—H14B | 109.55 |
C4—N4—H4B | 119.99 | H14B—C14—H14C | 109.57 |
O7—N5—C19 | 120.7 (10) | H15A—C15—H15B | 109.60 |
O7—N5—O8 | 123.4 (11) | O2—C15—H15A | 109.48 |
O8—N5—C19 | 115.8 (10) | O2—C15—H15B | 109.33 |
O9—N6—O10 | 120.8 (10) | O2—C15—H15C | 109.35 |
O10—N6—C21 | 118.4 (9) | H15B—C15—H15C | 109.52 |
O9—N6—C21 | 120.6 (9) | H15A—C15—H15C | 109.54 |
N1—C2—N2 | 118.8 (11) | H16B—C16—H16C | 109.30 |
N2—C2—N3 | 119.4 (9) | O3—C16—H16B | 109.43 |
N1—C2—N3 | 121.8 (10) | O3—C16—H16C | 109.44 |
N3—C4—C5 | 123.1 (10) | H16A—C16—H16B | 109.65 |
N3—C4—N4 | 116.5 (9) | H16A—C16—H16C | 109.31 |
N4—C4—C5 | 120.5 (10) | O3—C16—H16A | 109.69 |
C6—C5—C7 | 123.4 (9) | C18—C17—C22 | 121.2 (9) |
C4—C5—C6 | 116.0 (10) | C18—C17—C23 | 118.1 (8) |
C4—C5—C7 | 120.6 (9) | C22—C17—C23 | 120.8 (9) |
N1—C6—C5 | 119.5 (9) | O6—C18—C19 | 123.4 (10) |
C5—C7—C8 | 113.4 (9) | C17—C18—C19 | 115.5 (9) |
C7—C8—C13 | 118.2 (9) | O6—C18—C17 | 121.1 (10) |
C7—C8—C9 | 122.8 (10) | N5—C19—C18 | 118.1 (9) |
C9—C8—C13 | 118.9 (9) | C18—C19—C20 | 122.3 (9) |
C8—C9—C10 | 120.8 (10) | N5—C19—C20 | 119.3 (9) |
O1—C10—C11 | 114.2 (9) | C19—C20—C21 | 120.9 (9) |
C9—C10—C11 | 121.4 (10) | N6—C21—C22 | 119.9 (10) |
O1—C10—C9 | 124.4 (10) | C20—C21—C22 | 119.9 (10) |
O2—C11—C12 | 120.4 (10) | N6—C21—C20 | 120.1 (9) |
C10—C11—C12 | 118.8 (10) | C17—C22—C21 | 120.1 (10) |
O2—C11—C10 | 120.8 (10) | O4—C23—C17 | 117.1 (9) |
C11—C12—C13 | 119.7 (10) | O5—C23—C17 | 117.5 (10) |
O3—C12—C11 | 115.9 (9) | O4—C23—O5 | 125.4 (10) |
O3—C12—C13 | 124.4 (10) | C19—C20—H20 | 119.73 |
C8—C13—C12 | 120.3 (9) | C21—C20—H20 | 119.41 |
C5—C6—H6 | 120.30 | C17—C22—H22 | 119.93 |
N1—C6—H6 | 120.20 | C21—C22—H22 | 119.99 |
C8—C7—H7B | 108.93 | ||
C14—O1—C10—C9 | 0.5 (16) | C9—C8—C13—C12 | −0.7 (15) |
C14—O1—C10—C11 | −176.6 (11) | C8—C9—C10—C11 | −4.6 (16) |
C15—O2—C11—C12 | 78.5 (14) | C8—C9—C10—O1 | 178.5 (10) |
C15—O2—C11—C10 | −103.5 (12) | O1—C10—C11—C12 | −177.2 (9) |
C16—O3—C12—C13 | 17.4 (16) | C9—C10—C11—C12 | 5.6 (15) |
C16—O3—C12—C11 | −165.6 (10) | O1—C10—C11—O2 | 4.8 (14) |
C6—N1—C2—N3 | 0.3 (18) | C9—C10—C11—O2 | −172.4 (10) |
C6—N1—C2—N2 | −179.4 (10) | O2—C11—C12—C13 | 173.9 (9) |
C2—N1—C6—C5 | 1.7 (16) | C10—C11—C12—C13 | −4.1 (15) |
C2—N3—C4—C5 | 2.5 (16) | O2—C11—C12—O3 | −3.3 (15) |
C2—N3—C4—N4 | −179.3 (10) | C10—C11—C12—O3 | 178.7 (9) |
C4—N3—C2—N2 | 177.3 (10) | C11—C12—C13—C8 | 1.8 (15) |
C4—N3—C2—N1 | −2.3 (17) | O3—C12—C13—C8 | 178.7 (10) |
O8—N5—C19—C18 | −155.6 (10) | C23—C17—C18—O6 | −0.8 (15) |
O8—N5—C19—C20 | 30.1 (14) | C23—C17—C18—C19 | 178.9 (9) |
O7—N5—C19—C20 | −146.2 (11) | C18—C17—C22—C21 | 1.2 (15) |
O7—N5—C19—C18 | 28.1 (15) | C23—C17—C22—C21 | −179.8 (10) |
O10—N6—C21—C22 | −14.5 (15) | C18—C17—C23—O4 | 179.4 (10) |
O10—N6—C21—C20 | 164.4 (10) | C22—C17—C18—O6 | 178.3 (10) |
O9—N6—C21—C22 | 169.3 (10) | C22—C17—C18—C19 | −2.0 (14) |
O9—N6—C21—C20 | −11.9 (16) | C22—C17—C23—O5 | −179.0 (10) |
N3—C4—C5—C7 | −177.7 (9) | C22—C17—C23—O4 | 0.3 (15) |
N4—C4—C5—C6 | −178.7 (10) | C18—C17—C23—O5 | 0.1 (15) |
N4—C4—C5—C7 | 4.2 (15) | O6—C18—C19—C20 | 179.2 (11) |
N3—C4—C5—C6 | −0.6 (15) | O6—C18—C19—N5 | 5.0 (16) |
C4—C5—C6—N1 | −1.4 (15) | C17—C18—C19—N5 | −174.7 (9) |
C6—C5—C7—C8 | 7.2 (14) | C17—C18—C19—C20 | −0.5 (15) |
C4—C5—C7—C8 | −176.0 (9) | N5—C19—C20—C21 | 178.1 (9) |
C7—C5—C6—N1 | 175.5 (9) | C18—C19—C20—C21 | 4.0 (16) |
C5—C7—C8—C13 | −115.1 (11) | C19—C20—C21—C22 | −4.9 (16) |
C5—C7—C8—C9 | 69.9 (13) | C19—C20—C21—N6 | 176.3 (9) |
C7—C8—C13—C12 | −175.9 (9) | N6—C21—C22—C17 | −178.9 (10) |
C13—C8—C9—C10 | 2.1 (15) | C20—C21—C22—C17 | 2.3 (16) |
C7—C8—C9—C10 | 177.0 (10) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O4 | 0.86 | 1.90 | 2.743 (12) | 167 |
N2—H2A···O10i | 0.86 | 2.26 | 3.101 (12) | 166 |
N2—H2B···O5 | 0.86 | 2.10 | 2.946 (12) | 169 |
N4—H4A···O1ii | 0.86 | 2.23 | 3.050 (11) | 160 |
N4—H4B···O8iii | 0.86 | 2.59 | 3.202 (13) | 129 |
O6—H6A···O5 | 0.82 | 1.90 | 2.462 (14) | 124 |
C15—H15A···O3 | 0.96 | 2.58 | 3.093 (16) | 114 |
Symmetry codes: (i) x+1/2, −y, z; (ii) x+1/2, −y+2, z; (iii) −x+3/2, y+2, z−1/2. |
Experimental details
Crystal data | |
Chemical formula | C14H19N4O3+·C7H3N2O7− |
Mr | 518.45 |
Crystal system, space group | Orthorhombic, Pca21 |
Temperature (K) | 293 |
a, b, c (Å) | 20.928 (3), 4.898 (2), 22.869 (2) |
V (Å3) | 2344.2 (10) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 1.02 |
Crystal size (mm) | 0.16 × 0.12 × 0.06 |
Data collection | |
Diffractometer | Siemens AED single-crystal |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2244, 2244, 883 |
Rint | ? |
(sin θ/λ)max (Å−1) | 0.610 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.064, 0.152, 0.92 |
No. of reflections | 2244 |
No. of parameters | 338 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.32, −0.21 |
Computer programs: XSCANS (Siemens, 1994), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003).
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O4 | 0.86 | 1.90 | 2.743 (12) | 167 |
N2—H2A···O10i | 0.86 | 2.26 | 3.101 (12) | 166 |
N2—H2B···O5 | 0.86 | 2.10 | 2.946 (12) | 169 |
N4—H4A···O1ii | 0.86 | 2.23 | 3.050 (11) | 160 |
N4—H4B···O8iii | 0.86 | 2.59 | 3.202 (13) | 129 |
O6—H6A···O5 | 0.82 | 1.90 | 2.462 (14) | 124 |
C15—H15A···O3 | 0.96 | 2.58 | 3.093 (16) | 114 |
Symmetry codes: (i) x+1/2, −y, z; (ii) x+1/2, −y+2, z; (iii) −x+3/2, y+2, z−1/2. |
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As part of our ongoing studies (Hemamalini et al., 2005) of hydrogen bonding patterns in the molecular salts of protonated trimethoprim [2,4-diamino-5-(3,4,5-trimethoxybenzyl-pyrimidine or TMP], we now report the synthesis and structure of the title compound, (I). [systematic name: 2,4-diamino-5-(3,4,5-trimethoxybenzyl) pyrimidin-1-ium 2-hydroxy-3,5-dinitrobenzoate]. Neutral TMP is a well known antifolate drug and its structure was determined by Koetzle & Williams (1976).
The asymmetric unit of (I) contains a protonated TMP cation and a 3,5-dinitrosalicylate (DNSA) anion (Fig. 1). The trimethoprim molecule is protonated at atom N1 of the pyrimidine moiety, which is evident from the increase in the internal angle at the protonated N1 [C2—N1—C6 = 121.7 (10)°] compared with that at unprotonated atom N3 [C2—N3—C4 = 117.9 (9)°]. The dihedral angle between the pyrimidine and benzene ring planes in (I) is 72.48 (5)°, which falls within the known range of equivalent torsion angles [69.96 (8)–89.5 (2)°] in other TMP structures (Panneerselvam et al., 2002). The conformation of the TMP cation is described by the two torsion angles C4—C5—C7—C8 and C5—C7—C8—C9, which are -176.0 (9)° and 69.9 (13)°, respectively in (I). This TMP conformation plays a very important role in DHFR selectivity (Hitching et al., 1988).
The carboxylate group of the DNSA anion in (I) accepts two N—H···O hydrogen bonds (Table 1) from the cation, forming a fork-like interaction. This can be designated by graph-set notation R22(8) (Bernstein et al., 1995). This common motif has been observed in other DHFR-TMP complexes (Kuyper, 1990) A typical intramolecular hydrogen bond occurs in the anion with graph-set notation S(6) (Fig. 2). The TMP cations self assemble via further N—H···O interactions, with the O atom being part of a methoxy or a nitro group. The combination of hydrogen bonds forms a three dimensional network as shown in Fig 3.