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<!?tpct=1pt>Racemic malic acid and trimethoprim [5-(3,4,5-trimethoxy­benz­yl)pyrimidine-2,4-diamine] form a 1:2 salt (monoclinic, P21/c), 2C14H19N4O3+·C4H4O52−, in which the malate component is disordered across a centre of inversion. The crystal structure of the salt consists of protonated trimethoprim residues and a malate dianion. The carboxyl­ate group of the malate ion interacts with the trimethoprim cation in a linear fashion through pairs of N—H...O hydrogen bonds to form a cyclic hydrogen-bonded motif. This is similar to the carboxyl­ate–trimethoprim cation inter­action observed earlier in the complex of dihydro­folate reductase with trimethoprim. The structure of the salt of trimethoprim with racemic DL-malic acid reported here is the first of its kind. The present study investigates the conformations and the hydrogen-bonding inter­actions, which are very important for biological functions. The pyrimidine plane makes a dihedral angle of 78.08 (7)° with the benzene ring of the trimethoprim cation. The cyclic hydrogen-bonded motif observed in this structure is self-organized, leading to novel types of hydrogen-bonding motifs in supra­molecular patterns.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270109000237/gd3265sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270109000237/gd3265Isup2.hkl
Contains datablock I

CCDC reference: 724208

Comment top

Trimethoprim (TMP) is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections. It belongs to the class of chemotherapeutic agents known as dihydrofolate reductase inhibitor. Dihydrofolate reductase (DHFR) is an essential cellular enzyme involved in several biosynthetic processes as well as the target for antifolate drugs such as TMP. Antifolate drugs complexed with DHFR from various sources have been widely studied (Feeney, 2000). TMP has greater affinity towards bacterial DHFR than towards human DHFR. More than a dozen structures of TMP salts have been recorded in the Cambridge Structural Database (Version 5.29; Allen, 2002).

The role of malic acid (2-hydroxy-1,4-butanedioic acid) in supramolecular chemistry has not been widely studied although it is one of the simplest chiral dicarboxylic acids. Studies on the salts formed with primary amines and diamines using L-malic acid (Aakeröy & Nieuwenhuyzen, 1994, 1996) and racemic malic acid (Kaniskas, 1985; Farrell et al., 2002) have been reported. The crystal structures of racemic malic acid adducted with aniline (Perpétuo & Janczak, 2003), melamine (Janczak & Perpétuo, 2003) and piperazine (Wang et al., 2005) have been studied for their aggregation modes and hydrogen-bonding interactions.

The crystal structures of TMP salts formed with racemic compounds have not yet been explored. An earlier report reveals that when both the components of a system are achiral, the adducts generally crystallize in centrosymmetric space groups. This may be due to the occurrence of inversion centres in molecular crystals (Brock & Dunitz, 1994). Even if one component is a racemic mixture of the two enantiomers of a chiral building block, similar considerations apply (Burchell et al., 2000, 2001). The complex of TMP with DL-malic acid, which crystallizes in the centrosymmetric space group P21/c, has been studied in order to investigate the conformations of the components, which is very important in determining the DHFR selectivity and biological functions. The robustness and reliability of the self-complimentary DL-malic acid have also been used for crystal engineering (Pang et al., 1997; Aakeröy et al., 2000). The present study on the salt, (I), of TMP with racemic malic acid is the first to report the synthesis and structure with a view to understanding the conformations and hydrogen-bonding interactions.

The asymmetric unit of (I) (Fig. 1) contains two TMP cations and a malate dianion disordered across a centre of inversion such that half of the sites accommodate molecules of D-configuration and the other half accommodate molecules of L-configuration. If a molecule of D-malic acid occupies any particular site then atom O6 is present and O6$ is absent [the dollar ($) symbol indicates the symmetry operation (- x + 1, -y + 1, -z + 1)]; occupation by L-malic acid means that atom O6$ is present and O6 is absent. This is similar to the 1:1 adduct formed between 1, 2-bis (4'-pyridyl)-ethene and racemic-malic acid (Farrell et al., 2002).

The TMP cations are protonated at atom N4, as confirmed by the increase in the internal angle C1—N4—C2 to 119.80 (18)° from 115.46° found in neutral TMP (Koetzle & Williams, 1976). The bond lengths and angles of the TMP cation are comparable to those of previously reported TMP cations. The C—O—C angles at the methoxy groups differ significantly. This difference has also been observed in the crystal structure of neutral trimethoprim and can be attributed to the close approaches involving the atoms of the three methoxy groups (Koetzle & Williams, 1976). The O atoms of the methoxy groups of the crystal structure of (I) lie in the plane of the benzene ring, as reported previously (Yu et al., 2005).

The conformation adopted by the trimethoprim molecule in this structure is described by the two torsion angles C4—C3—C5—C6 and C3—C5—C6—C11. These torsion angles are -81.2 (2) and -166.57 (19)°, respectively, which are comparable with the earlier reported values (Hemamalini et al., 2003). TMP conformation plays an important role in DHFR selectivity (Hitching et al., 1988). The conformation adopted by the methoxy groups C—C—O—C in the trimethoprim molecule is similar to that in the related structure reported by Trilleras et al. (2005). Consistent with these different conformations, the pairs of exocyclic C—C—O angles at C8 and C10 differ widely, while the angles at C9 differ slightly (Table 1). These are typical of the angles found in planar methoxyarenes. An all-trans conformation is observed for the carbon skeleton of the malate anion [C15—C16—C16'—C15' (ψ) = -180.0°; van der Sluis & Kroon, 1985, 1989]. The pyrimidine ring makes a dihedral angle of 78.08 (7)° with the phenyl ring of the TMP cation, which is found to be within the range reported previously (Giuseppetti et al., 1984; Muthiah et al., 2001; Raj, Muthiah et al., 2003; Raj, Sethuraman et al., 2003).

In (I), the carboxylate group of the malate anion forms two nearly parallel N—H···O hydrogen bonds with the amine group and the protonated N4 atom of the TMP cation. This is reminiscent of the carboxylate interaction with the TMP cation in the DHFR–TMP complex (Kuyper, 1990). Similar specific double hydrogen bonds have been formed in almost all the structures of TMP–carboxylate complexes previously reported. This hydrogen-bonded motif formed as a result of the pair of N—H···O hydrogen bonds can be represented by the graph-set notation R22(8) (Etter, 1990; Bernstein et al., 1995). It is one of the 24 recurrent hydrogen-bonded cyclic bimolecular motifs observed in organic crystal structures (Allen et al., 1998). This motif is a well known supramolecular synthon in aminopyrimidine–carboxylate salts (Stanley et al., 2005). It self-organizes in different ways to give different types of hydrogen-bonding patterns (Raj, Stanley et al., 2003). An intermolecular hydrogen bond between the hydroxy group of the anion (O6) and the ring nitrogen (N3) of the cation is observed. The geometries of the hydrogen-bonding interactions of (I) are given in Table 2. The amine groups of each TMP cation form intermolecular hydrogen bonds with the neighbouring carboxylate group of the malate dianion as well as with the methoxy group of the neighbouring TMP cations. Part of the crystal structure of (I), showing the formation of an R22(8) hydrogen-bonded motif is shown in Fig 3. The parallel phenyl rings at (x, y, z) and (-x, 2 - y, 1 - z), which lie in different frameworks, are linked by aromatic ππ stacking interactions. They have an interplanar spacing of 3.427 Å and a centroid separation of 3.56 Å [are s.u. values available?]. The presence of this aromatic ππ interaction along with the C—H···π(arene) interaction (Table 2) is illustrated in Fig. 4. These observed interactions together form an extensive three-dimensional hydrogen-bonded framework.

Related literature top

For related literature, see: Aakeröy & Nieuwenhuyzen (1994, 1996); Aakeröy et al. (2000); Allen (2002); Allen et al. (1998); Bernstein et al. (1995); Brock & Dunitz (1994); Burchell et al. (2000, 2001); Etter (1990); Farrell et al. (2002); Feeney (2000); Giuseppetti et al. (1984); Hemamalini et al. (2003); Hitching et al. (1988); Janczak & Perpétuo (2003); Kaniskas (1985); Koetzle & Williams (1976); Kuyper (1990); Muthiah et al. (2001); Pang et al. (1997); Perpétuo & Janczak (2003); Raj et al. (2003a, 2003b, 2003c); van der Sluis & Kroon (1985, 1989); Stanley et al. (2005); Trilleras et al. (2005); Wang et al. (2005); Yu et al. (2005).

Experimental top

Equimolar quantities of racemic malic acid and trimethoprim were dissolved in water. The solution was stirred well and set aside to crystallize. Colourless crystals of (I), suitable for X-ray diffraction analysis, were obtained from the resulting solution after a week of slow evaporation.

Refinement top

The acid component is disordered about a crystallographic center of inversion. Atoms H16A and H16B on atom C16 could not be geometrically constrained for riding-model refinement. This is because one of the C—H directions coincides with the C16—O6 direction (O6 is disordered over two sites). Hence the displacement parameters of these two H atoms were fixed as 1.2Ueq of the carrier C atom taken from the previous refinement. H atoms attached to N atoms were located in difference maps and then refined isotropically. All other H atoms were treated as riding atoms with O—H distances of 0.82 and C—H distances of 0.93–0.97 Å, and with Uiso(H) = kUeq(carrier) (k = 1.2 or 1.5). The distances of atoms H16A and H16B from C16 and the distance of atom H6 from O6 were restrained.

Computing details top

Data collection: APEX2 (Bruker–Nonius, 2004); cell refinement: APEX2 and SAINT (Bruker–Nonius, 2004); data reduction: SAINT and XPREP (Bruker–Nonius, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Macrae et al., 2006); software used to prepare material for publication: PLATON (Spek, 2003).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), showing 40% probability displacement ellipsoids. Both D- and L-malic acid occupy the same site with centrosymmetric disorder. The dollar sign ($) denotes the symmetry operation -x + 1, -y + 1, -z + 1). Atoms O6$, H6$ and H16B are omitted for clarity.
[Figure 2] Fig. 2. The malic acid component in (I), showing 30% probability displacement ellipsoids. It is disordered across a centre of inversion, so that if atom O6 is present (D-malic acid), then O6$ is absent, while if atom O6$ is present (L-malic acid), O6 is absent [the dollar sign ($) denotes the symmetry operation -x + 1, -y + 1, -z + 1)].
[Figure 3] Fig. 3. Part of the crystal structure of (I), showing the formation of an R22(8) hydrogen-bonded motif. For the sake of clarity, only H atoms involved in the hydrogen bonding are shown. Dashed lines represent hydrogen bonds.
[Figure 4] Fig. 4. Part of the crystal structure of (I), showing the aromatic ππ and C—H···π(arene) interactions. Dashed lines represent hydrogen bonds. (Cg2 represents the centroid of the ring C6–C11).
Bis[2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidin-1-ium] DL-malate top
Crystal data top
2C14H19N4O3+·C4H4O52F(000) = 756
Mr = 714.74Dx = 1.343 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 7891 reflections
a = 12.9850 (3) Åθ = 2.5–32.1°
b = 9.3038 (2) ŵ = 0.10 mm1
c = 15.6815 (3) ÅT = 293 K
β = 111.065 (1)°Plate, colourless
V = 1767.88 (7) Å30.30 × 0.20 × 0.20 mm
Z = 2
Data collection top
Bruker Kappa APEXII CCD
diffractometer
3108 independent reflections
Radiation source: fine-focus sealed tube2763 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.020
ω and ϕ scansθmax = 25.0°, θmin = 1.7°
Absorption correction: multi-scan
(SADABS; Bruker, 1999)
h = 1515
Tmin = 0.970, Tmax = 0.980k = 118
16178 measured reflectionsl = 1818
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.045H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.115 w = 1/[σ2(Fo2) + (0.0299P)2 + 1.0993P]
where P = (Fo2 + 2Fc2)/3
S = 1.18(Δ/σ)max < 0.001
3108 reflectionsΔρmax = 0.33 e Å3
265 parametersΔρmin = 0.18 e Å3
3 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), FC*=KFC[1+0.001XFC2Λ3/SIN(2Θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0071 (10)
Crystal data top
2C14H19N4O3+·C4H4O52V = 1767.88 (7) Å3
Mr = 714.74Z = 2
Monoclinic, P21/cMo Kα radiation
a = 12.9850 (3) ŵ = 0.10 mm1
b = 9.3038 (2) ÅT = 293 K
c = 15.6815 (3) Å0.30 × 0.20 × 0.20 mm
β = 111.065 (1)°
Data collection top
Bruker Kappa APEXII CCD
diffractometer
3108 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 1999)
2763 reflections with I > 2σ(I)
Tmin = 0.970, Tmax = 0.980Rint = 0.020
16178 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0453 restraints
wR(F2) = 0.115H atoms treated by a mixture of independent and constrained refinement
S = 1.18Δρmax = 0.33 e Å3
3108 reflectionsΔρmin = 0.18 e Å3
265 parameters
Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su'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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
O10.15807 (14)1.2462 (2)0.41545 (14)0.0743 (8)
O20.21086 (12)0.9778 (2)0.35824 (11)0.0624 (6)
O30.06160 (14)0.7989 (2)0.33500 (13)0.0658 (7)
N10.48206 (17)0.8276 (2)0.30313 (14)0.0504 (7)
N20.34759 (16)0.9180 (2)0.52878 (12)0.0469 (7)
N30.41602 (14)0.87465 (19)0.41741 (11)0.0407 (5)
N40.37301 (15)1.0254 (2)0.28944 (12)0.0430 (6)
C10.42365 (16)0.9091 (2)0.33764 (13)0.0382 (6)
C20.31133 (17)1.1114 (2)0.32213 (15)0.0439 (7)
C30.29895 (16)1.0840 (2)0.40228 (14)0.0402 (6)
C40.35477 (15)0.9590 (2)0.45018 (13)0.0384 (6)
C50.22698 (17)1.1764 (2)0.43654 (15)0.0461 (7)
C60.11054 (16)1.1202 (2)0.41540 (13)0.0400 (6)
C70.08111 (17)0.9818 (2)0.38468 (14)0.0437 (7)
C80.02617 (18)0.9337 (3)0.36540 (14)0.0462 (7)
C90.10467 (17)1.0260 (3)0.37653 (14)0.0488 (7)
C100.07485 (17)1.1639 (3)0.40692 (15)0.0492 (7)
C110.03258 (18)1.2117 (3)0.42697 (15)0.0476 (7)
C120.1451 (3)1.3945 (4)0.4203 (3)0.0910 (14)
C130.2836 (2)1.0146 (4)0.26882 (19)0.0768 (10)
C140.0157 (3)0.7033 (3)0.3216 (2)0.0760 (11)
O40.44619 (16)0.65344 (18)0.61581 (11)0.0596 (6)
O50.40311 (14)0.42714 (17)0.62939 (11)0.0552 (6)
O60.3701 (4)0.5719 (5)0.4280 (2)0.0606 (11)0.500
C150.42935 (17)0.5278 (2)0.58784 (13)0.0426 (7)
C160.44079 (18)0.4920 (3)0.49666 (14)0.0462 (7)
H1A0.4751 (19)0.840 (3)0.2441 (18)0.057 (7)*
H1B0.518 (2)0.752 (3)0.3338 (17)0.058 (7)*
H20.276701.191300.288300.0530*
H2A0.383 (2)0.837 (3)0.5547 (18)0.060 (8)*
H2B0.301 (2)0.965 (3)0.5499 (16)0.055 (7)*
H40.379 (2)1.040 (3)0.2361 (18)0.060 (7)*
H5A0.222401.271400.410000.0550*
H5B0.262201.186400.502200.0550*
H70.133500.920300.376800.0520*
H110.052101.304900.448100.0570*
H12A0.086901.419800.476400.1360*
H12B0.212701.438800.418300.1360*
H12C0.126701.427400.369500.1360*
H13A0.292601.117100.264200.1150*
H13B0.354000.970000.257100.1150*
H13C0.253300.981600.224800.1150*
H14A0.040000.740400.274900.1140*
H14B0.018200.611100.303200.1140*
H14C0.077900.693400.377600.1140*
H60.393600.654300.431200.0550*0.500
H16A0.4118 (18)0.4019 (11)0.4752 (15)0.0550*
H16B0.394 (5)0.553 (2)0.452 (3)0.0550*0.500
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0495 (10)0.0830 (14)0.1055 (15)0.0107 (9)0.0461 (10)0.0052 (11)
O20.0360 (8)0.0949 (14)0.0589 (10)0.0087 (8)0.0201 (7)0.0076 (9)
O30.0604 (11)0.0655 (11)0.0753 (12)0.0180 (9)0.0290 (9)0.0147 (9)
N10.0622 (12)0.0566 (12)0.0431 (11)0.0125 (10)0.0318 (10)0.0056 (9)
N20.0465 (11)0.0626 (13)0.0399 (10)0.0061 (10)0.0255 (9)0.0046 (9)
N30.0398 (9)0.0508 (10)0.0366 (9)0.0038 (8)0.0198 (7)0.0034 (8)
N40.0482 (10)0.0488 (11)0.0405 (9)0.0014 (8)0.0263 (8)0.0060 (8)
C10.0363 (10)0.0455 (11)0.0365 (10)0.0040 (9)0.0177 (8)0.0011 (9)
C20.0419 (11)0.0441 (12)0.0507 (12)0.0008 (9)0.0228 (10)0.0053 (10)
C30.0340 (10)0.0451 (12)0.0461 (11)0.0052 (9)0.0200 (9)0.0029 (9)
C40.0321 (10)0.0498 (12)0.0369 (10)0.0052 (9)0.0166 (8)0.0020 (9)
C50.0414 (11)0.0486 (12)0.0544 (13)0.0032 (10)0.0246 (10)0.0063 (10)
C60.0368 (10)0.0508 (12)0.0365 (10)0.0012 (9)0.0180 (9)0.0017 (9)
C70.0396 (11)0.0522 (13)0.0429 (11)0.0021 (10)0.0192 (9)0.0011 (10)
C80.0450 (12)0.0557 (14)0.0400 (11)0.0086 (10)0.0178 (9)0.0011 (10)
C90.0368 (11)0.0708 (16)0.0426 (11)0.0038 (11)0.0189 (9)0.0055 (11)
C100.0388 (11)0.0666 (15)0.0491 (12)0.0069 (11)0.0242 (10)0.0041 (11)
C110.0462 (12)0.0515 (13)0.0526 (12)0.0009 (10)0.0268 (10)0.0029 (10)
C120.0671 (19)0.083 (2)0.132 (3)0.0266 (17)0.047 (2)0.001 (2)
C130.0496 (15)0.103 (2)0.0670 (17)0.0117 (15)0.0080 (13)0.0024 (16)
C140.087 (2)0.0653 (18)0.0759 (18)0.0148 (16)0.0295 (16)0.0236 (15)
O40.0944 (13)0.0522 (10)0.0437 (9)0.0079 (9)0.0387 (9)0.0023 (7)
O50.0735 (11)0.0547 (10)0.0557 (9)0.0074 (8)0.0453 (9)0.0043 (8)
O60.057 (2)0.081 (2)0.0383 (19)0.0021 (18)0.0105 (15)0.0021 (17)
C150.0426 (11)0.0548 (14)0.0360 (10)0.0087 (10)0.0211 (9)0.0022 (10)
C160.0454 (13)0.0636 (15)0.0327 (10)0.0027 (11)0.0179 (9)0.0034 (10)
Geometric parameters (Å, º) top
O1—C101.370 (3)C5—C61.520 (3)
O1—C121.389 (4)C6—C71.380 (3)
O2—C91.379 (3)C6—C111.384 (3)
O2—C131.423 (3)C7—C81.389 (3)
O3—C81.362 (3)C8—C91.391 (4)
O3—C141.412 (4)C9—C101.375 (4)
O4—C151.240 (3)C10—C111.388 (3)
O5—C151.256 (3)C2—H20.9300
O6—C161.358 (5)C5—H5A0.9700
O6—H60.8200C5—H5B0.9700
N1—C11.318 (3)C7—H70.9300
N2—C41.325 (3)C11—H110.9300
N3—C41.344 (3)C12—H12A0.9600
N3—C11.329 (3)C12—H12C0.9600
N4—C21.356 (3)C12—H12B0.9600
N4—C11.348 (3)C13—H13C0.9600
N1—H1B0.89 (3)C13—H13A0.9600
N1—H1A0.91 (3)C13—H13B0.9600
N2—H2A0.90 (3)C14—H14A0.9600
N2—H2B0.90 (3)C14—H14C0.9600
N4—H40.88 (3)C14—H14B0.9600
C2—C31.348 (3)C15—C161.527 (3)
C3—C51.504 (3)C16—C16i1.511 (3)
C3—C41.432 (3)C16—H16A0.931 (14)
O1···O22.659 (3)C13···H2Bii2.94 (2)
O1···C133.145 (4)C14···H72.4900
O2···O32.677 (3)C15···H4iii2.71 (3)
O2···N2ii3.081 (3)C15···H13Bx3.1000
O2···O12.659 (3)C15···H1Aiii2.61 (3)
O3···C133.356 (4)C15···H2A2.95 (3)
O3···O22.677 (3)C15···H1Bi2.86 (3)
O4···O62.852 (3)C15···H6i2.9600
O4···N1iii2.810 (3)C15···H12Bii2.8000
O4···N22.882 (3)H1A···H42.22 (4)
O5···N1i2.798 (3)H1A···H13Bvii2.4700
O5···N4iii2.712 (2)H1A···O5v2.76 (3)
O6···C13iv2.929 (4)H1A···C15v2.61 (3)
O6···O42.852 (3)H1A···O4v1.91 (3)
O6···N32.896 (5)H1B···O5i1.93 (3)
O1···H2Bii2.89 (3)H1B···C15i2.86 (3)
O1···H13A2.6700H2···H5A2.3800
O2···H2Bii2.22 (3)H2A···O41.99 (3)
O4···H16Ai2.76 (2)H2A···C152.95 (3)
O4···H62.7300H2B···C52.59 (3)
O4···H2A1.99 (3)H2B···C62.98 (3)
O4···H1Aiii1.91 (3)H2B···C73.09 (3)
O5···H12Bii2.6300H2B···H5B2.1900
O5···H4iii1.84 (3)H2B···O1ii2.89 (3)
O5···H1Aiii2.76 (3)H2B···O2ii2.22 (3)
O5···H1Bi1.93 (3)H2B···C13ii2.94 (2)
O6···H13Aiv2.8400H4···C15v2.71 (3)
O6···H13Civ2.4800H4···O5v1.84 (3)
N1···O5i2.798 (3)H4···H1A2.22 (4)
N1···O4v2.810 (3)H5A···H22.3800
N2···C73.437 (3)H5A···H112.5100
N2···O42.882 (3)H5B···H2B2.1900
N2···O2ii3.081 (3)H5B···N22.7000
N2···C1vi3.365 (3)H6···C15i2.9600
N3···C4vi3.335 (3)H6···H16Ai2.4800
N3···O62.896 (5)H6···C42.9100
N4···O5v2.712 (2)H6···O42.7300
N1···H13Bvii2.8100H6···N32.0900
N2···H72.9400H6···C12.8900
N2···H5B2.7000H7···C42.7100
N3···H62.0900H7···N22.9400
C1···N2vi3.365 (3)H7···C32.5500
C4···N3vi3.335 (3)H7···C142.4900
C4···C73.332 (3)H7···H14A2.3300
C6···C9ii3.561 (3)H7···H14C2.2300
C6···C14viii3.566 (3)H11···C122.5800
C7···C43.332 (3)H11···H5A2.5100
C7···N23.437 (3)H11···H12A2.2700
C7···C10ii3.566 (3)H11···H12C2.4800
C8···C11ii3.554 (3)H12A···C112.7600
C8···C10ii3.453 (3)H12A···H112.2700
C9···C6ii3.561 (3)H12A···H12Axi2.5800
C10···C7ii3.566 (3)H12A···H14Cii2.4800
C10···C8ii3.453 (3)H12B···O5ii2.6300
C11···C8ii3.554 (3)H12B···C15ii2.8000
C13···O33.356 (4)H12C···C112.7900
C13···O6viii2.929 (4)H12C···H112.4800
C13···O13.145 (4)H13A···O12.6700
C14···C6iv3.566 (3)H13A···C102.9400
C1···H62.8900H13A···O6viii2.8400
C3···H72.5500H13B···N1xii2.8100
C4···H72.7100H13B···H1Axii2.4700
C4···H62.9100H13B···C15xiii3.1000
C5···H2B2.59 (3)H13C···C83.0100
C5···H16Aix3.08 (2)H13C···O6viii2.4800
C6···H2B2.98 (3)H14A···C72.7600
C7···H14A2.7600H14A···H72.3300
C7···H14Bviii3.0100H14A···C11iv2.9700
C7···H2B3.09 (3)H14B···C7iv3.0100
C7···H14C2.6900H14C···C72.6900
C8···H13C3.0100H14C···H72.2300
C10···H13A2.9400H14C···C12ii3.0800
C11···H12C2.7900H14C···H12Aii2.4800
C11···H14Aviii2.9700H16A···C5xiv3.08 (2)
C11···H12A2.7600H16A···O4i2.76 (2)
C12···H14Cii3.0800H16A···H6i2.4800
C12···H112.5800
C10—O1—C12118.5 (3)N4—C2—H2119.00
C9—O2—C13112.76 (19)C3—C2—H2119.00
C8—O3—C14117.6 (2)C3—C5—H5A109.00
C16—O6—H6109.00C3—C5—H5B109.00
C1—N3—C4118.27 (17)H5A—C5—H5B108.00
C1—N4—C2119.80 (18)C6—C5—H5B109.00
C1—N1—H1B120.2 (17)C6—C5—H5A109.00
C1—N1—H1A119.1 (17)C6—C7—H7120.00
H1A—N1—H1B120 (2)C8—C7—H7120.00
H2A—N2—H2B123 (2)C6—C11—H11120.00
C4—N2—H2B118.9 (16)C10—C11—H11120.00
C4—N2—H2A117.8 (17)O1—C12—H12A109.00
C1—N4—H4117.8 (18)O1—C12—H12B109.00
C2—N4—H4122.4 (18)H12B—C12—H12C109.00
N3—C1—N4122.34 (19)O1—C12—H12C109.00
N1—C1—N3119.75 (18)H12A—C12—H12B110.00
N1—C1—N4117.91 (19)H12A—C12—H12C109.00
N4—C2—C3121.71 (19)O2—C13—H13A109.00
C4—C3—C5122.63 (18)O2—C13—H13B110.00
C2—C3—C5121.52 (18)O2—C13—H13C109.00
C2—C3—C4115.81 (19)H13B—C13—H13C109.00
N2—C4—N3115.89 (18)H13A—C13—H13B109.00
N3—C4—C3122.08 (18)H13A—C13—H13C109.00
N2—C4—C3122.01 (19)O3—C14—H14B110.00
C3—C5—C6115.00 (16)H14A—C14—H14C109.00
C5—C6—C7121.76 (19)O3—C14—H14C109.00
C5—C6—C11118.50 (18)H14A—C14—H14B109.00
C7—C6—C11119.7 (2)O3—C14—H14A109.00
C6—C7—C8120.5 (2)H14B—C14—H14C109.00
C7—C8—C9119.8 (2)O5—C15—C16117.33 (18)
O3—C8—C7124.0 (2)O4—C15—O5124.5 (2)
O3—C8—C9116.2 (2)O4—C15—C16118.2 (2)
O2—C9—C10120.8 (2)O6—C16—C15111.0 (3)
C8—C9—C10119.5 (2)O6—C16—C16i112.5 (3)
O2—C9—C8119.8 (2)C15—C16—C16i110.66 (18)
O1—C10—C9114.9 (2)O6—C16—H16A97.8 (13)
O1—C10—C11124.2 (2)C15—C16—H16A111.9 (14)
C9—C10—C11120.8 (2)C16i—C16—H16A112.5 (15)
C6—C11—C10119.8 (2)
C12—O1—C10—C9162.1 (3)C11—C6—C7—C80.1 (3)
C12—O1—C10—C1118.1 (4)C7—C6—C11—C100.5 (3)
C13—O2—C9—C1084.5 (3)C5—C6—C7—C8179.62 (19)
C13—O2—C9—C896.4 (3)C6—C7—C8—C90.5 (3)
C14—O3—C8—C9179.0 (2)C6—C7—C8—O3179.9 (2)
C14—O3—C8—C70.6 (3)O3—C8—C9—O21.0 (3)
C1—N3—C4—N2178.38 (19)O3—C8—C9—C10179.9 (2)
C4—N3—C1—N1179.2 (2)C7—C8—C9—C100.3 (3)
C4—N3—C1—N40.5 (3)C7—C8—C9—O2179.37 (19)
C1—N3—C4—C30.5 (3)O2—C9—C10—O11.0 (3)
C2—N4—C1—N30.3 (3)C8—C9—C10—C110.3 (3)
C2—N4—C1—N1179.4 (2)O2—C9—C10—C11178.8 (2)
C1—N4—C2—C30.0 (3)C8—C9—C10—O1179.9 (2)
N4—C2—C3—C40.0 (3)O1—C10—C11—C6179.5 (2)
N4—C2—C3—C5177.6 (2)C9—C10—C11—C60.7 (3)
C4—C3—C5—C681.2 (2)O4—C15—C16—O659.2 (4)
C5—C3—C4—N3177.82 (19)O4—C15—C16—C16i66.4 (3)
C2—C3—C5—C696.2 (2)O5—C15—C16—O6120.7 (3)
C2—C3—C4—N2178.5 (2)O5—C15—C16—C16i113.8 (3)
C2—C3—C4—N30.3 (3)O6—C16—C16i—O6i180.0 (3)
C5—C3—C4—N21.0 (3)O6—C16—C16i—C15i55.3 (3)
C3—C5—C6—C713.0 (3)C15—C16—C16i—O6i55.3 (3)
C3—C5—C6—C11166.57 (19)C15—C16—C16i—C15i180.0 (2)
C5—C6—C11—C10179.1 (2)
Symmetry codes: (i) x+1, y+1, z+1; (ii) x, y+2, z+1; (iii) x, y+3/2, z+1/2; (iv) x, y1/2, z+1/2; (v) x, y+3/2, z1/2; (vi) x+1, y+2, z+1; (vii) x+1, y, z; (viii) x, y+1/2, z+1/2; (ix) x, y+1, z; (x) x+1, y+3/2, z+1/2; (xi) x, y+3, z+1; (xii) x1, y, z; (xiii) x1, y+3/2, z1/2; (xiv) x, y1, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O4v0.91 (3)1.91 (3)2.810 (3)173 (3)
N1—H1B···O5i0.89 (3)1.93 (3)2.798 (3)165 (2)
N2—H2A···O40.90 (3)1.99 (3)2.882 (3)173 (3)
N2—H2B···O2ii0.90 (3)2.22 (3)3.081 (3)159 (2)
N4—H4···O5v0.88 (3)1.84 (3)2.712 (2)176 (3)
O6—H6···N30.82002.09002.896 (5)166.00
C13—H13C···O6viii0.962.482.929 (4)109
C14—H14A···Cg2iv0.962.973.546 (3)119
Symmetry codes: (i) x+1, y+1, z+1; (ii) x, y+2, z+1; (iv) x, y1/2, z+1/2; (v) x, y+3/2, z1/2; (viii) x, y+1/2, z+1/2.

Experimental details

Crystal data
Chemical formula2C14H19N4O3+·C4H4O52
Mr714.74
Crystal system, space groupMonoclinic, P21/c
Temperature (K)293
a, b, c (Å)12.9850 (3), 9.3038 (2), 15.6815 (3)
β (°) 111.065 (1)
V3)1767.88 (7)
Z2
Radiation typeMo Kα
µ (mm1)0.10
Crystal size (mm)0.30 × 0.20 × 0.20
Data collection
DiffractometerBruker Kappa APEXII CCD
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 1999)
Tmin, Tmax0.970, 0.980
No. of measured, independent and
observed [I > 2σ(I)] reflections
16178, 3108, 2763
Rint0.020
(sin θ/λ)max1)0.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.045, 0.115, 1.18
No. of reflections3108
No. of parameters265
No. of restraints3
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.33, 0.18

Computer programs: APEX2 (Bruker–Nonius, 2004), APEX2 and SAINT (Bruker–Nonius, 2004), SAINT and XPREP (Bruker–Nonius, 2004), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Macrae et al., 2006), PLATON (Spek, 2003).

Selected bond and torsion angles (º) top
C10—O1—C12118.5 (3)O3—C8—C9116.2 (2)
C9—O2—C13112.76 (19)O2—C9—C10120.8 (2)
C8—O3—C14117.6 (2)O2—C9—C8119.8 (2)
C1—N4—C2119.80 (18)O1—C10—C9114.9 (2)
O3—C8—C7124.0 (2)O1—C10—C11124.2 (2)
C12—O1—C10—C1118.1 (4)C14—O3—C8—C70.6 (3)
C13—O2—C9—C896.4 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O4i0.91 (3)1.91 (3)2.810 (3)173 (3)
N1—H1B···O5ii0.89 (3)1.93 (3)2.798 (3)165 (2)
N2—H2A···O40.90 (3)1.99 (3)2.882 (3)173 (3)
N2—H2B···O2iii0.90 (3)2.22 (3)3.081 (3)159 (2)
N4—H4···O5i0.88 (3)1.84 (3)2.712 (2)176 (3)
O6—H6···N30.82002.09002.896 (5)166.00
C13—H13C···O6iv0.96002.48002.929 (4)109.00
C14—H14A···Cg2v0.96002.97003.546 (3)119.00
Symmetry codes: (i) x, y+3/2, z1/2; (ii) x+1, y+1, z+1; (iii) x, y+2, z+1; (iv) x, y+1/2, z+1/2; (v) x, y1/2, z+1/2.
 

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