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In the title crystal, trimethoprim perchlorate [2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidin-1-ium perchlorate], C
14H
19N
4O
3+·ClO
4−, the trimethoprim molecule is protonated at N1. The perchlorate ion makes double hydrogen bonds of type N—H
O with the 2-amino group and the protonated N1 atom of the trimethoprim cation, reminiscent of the fork-like interactions of the carboxylate group with the trimethoprim (TMP) cation observed in the dihydrofolate reductase–trimethoprim complex. The pyrimidine moieties of trimethoprim cations are centrosymmetrically paired through a pair of N—H
N hydrogen bonds involving the 4-amino group and the pyrimidinium-N atom. The two pairs of TMP cations are linked by N—H
O hydrogen bonds to form a supramolecular ladder-like structure. The pyrimidine plane makes a dihedral angle of 83.72 (8)° with the phenyl ring in the TMP cation.
Supporting information
CCDC reference: 180547
Key indicators
- Single-crystal X-ray study
- T = 293 K
- Mean (C-C) = 0.002 Å
- R factor = 0.048
- wR factor = 0.168
- Data-to-parameter ratio = 21.4
checkCIF results
No syntax errors found
ADDSYM reports no extra symmetry
General Notes
FORMU_01 There is a discrepancy between the atom counts in the
_chemical_formula_sum and _chemical_formula_moiety. This is
usually due to the moiety formula being in the wrong format.
Atom count from _chemical_formula_sum: C14 H19 Cl1 N4 O7
Atom count from _chemical_formula_moiety:C14 H19 Cl1 N4 O4
Trimethoprim perchlorate was prepared by dissolving trimethoprim (obtained as a
gift from Shilpa Antibiotics Ltd) in hot methanol, followed by addition of
dilute perchloric acid. On cooling, colourless crystals were formed.
After checking their presence in the difference map, the H-atoms were
geometrically fixed and allowed to ride on their parent atoms.
Data collection: AED (Belletti et al., 1993); cell refinement: AED; data reduction: AED; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Farrugia, 1997); software used to prepare material for publication: PLATON (Spek, 1997).
Crystal data top
C14H19N4O3+·ClO41− | Z = 2 |
Mr = 390.78 | F(000) = 408 |
Triclinic, P1 | Dx = 1.498 Mg m−3 |
a = 9.672 (2) Å | Mo Kα radiation, λ = 0.71069 Å |
b = 10.219 (1) Å | Cell parameters from 25 reflections |
c = 9.651 (2) Å | θ = 3.1–30.2° |
α = 91.19 (1)° | µ = 0.27 mm−1 |
β = 107.18 (1)° | T = 293 K |
γ = 72.44 (2)° | Needle, colourless |
V = 866.4 (3) Å3 | 0.3 × 0.3 × 0.2 mm |
Data collection top
Siemens AED diffractometer | θmax = 30.2°, θmin = 3.0° |
ω–2θ scans | h = −13→13 |
5105 measured reflections | k = −14→14 |
5105 independent reflections | l = 0→13 |
3593 reflections with I > 2σ(I) | 4 standard reflections every 60 min |
Rint = 0.000 | intensity decay: none |
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)] = 0.048 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.168 | H-atom parameters constrained |
S = 1.13 | w = 1/[σ2(Fo2) + (0.1P)2] where P = (Fo2 + 2Fc2)/3 |
5105 reflections | (Δ/σ)max = 0.001 |
238 parameters | Δρmax = 0.50 e Å−3 |
0 restraints | Δρmin = −0.55 e Å−3 |
Crystal data top
C14H19N4O3+·ClO41− | γ = 72.44 (2)° |
Mr = 390.78 | V = 866.4 (3) Å3 |
Triclinic, P1 | Z = 2 |
a = 9.672 (2) Å | Mo Kα radiation |
b = 10.219 (1) Å | µ = 0.27 mm−1 |
c = 9.651 (2) Å | T = 293 K |
α = 91.19 (1)° | 0.3 × 0.3 × 0.2 mm |
β = 107.18 (1)° | |
Data collection top
Siemens AED diffractometer | Rint = 0.000 |
5105 measured reflections | 4 standard reflections every 60 min |
5105 independent reflections | intensity decay: none |
3593 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.048 | 0 restraints |
wR(F2) = 0.168 | H-atom parameters constrained |
S = 1.13 | Δρmax = 0.50 e Å−3 |
5105 reflections | Δρmin = −0.55 e Å−3 |
238 parameters | |
Special details top
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 |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
Cl1 | 0.58921 (5) | 0.22357 (5) | 0.74380 (5) | 0.0417 (2) | |
O1 | 0.5842 (3) | 0.2534 (3) | 0.8818 (2) | 0.1382 (12) | |
O2 | 0.44393 (17) | 0.21975 (16) | 0.65308 (19) | 0.0536 (5) | |
O3 | 0.70113 (19) | 0.09439 (18) | 0.74596 (19) | 0.0680 (6) | |
O4 | 0.6244 (3) | 0.3261 (3) | 0.6778 (4) | 0.1223 (12) | |
O5 | −0.22609 (14) | 0.66522 (13) | 0.88174 (14) | 0.0355 (4) | |
O6 | −0.07301 (16) | 0.78921 (12) | 0.77103 (15) | 0.0408 (4) | |
O7 | 0.14090 (15) | 0.64527 (13) | 0.65037 (16) | 0.0398 (4) | |
N1 | 0.28807 (16) | −0.00692 (14) | 0.54264 (15) | 0.0305 (4) | |
N2 | 0.53292 (18) | −0.15022 (17) | 0.63999 (17) | 0.0436 (5) | |
N3 | 0.40806 (16) | −0.03135 (14) | 0.79476 (14) | 0.0299 (4) | |
N4 | 0.28624 (18) | 0.09237 (17) | 0.94650 (16) | 0.0415 (5) | |
C2 | 0.40918 (18) | −0.06260 (16) | 0.66056 (17) | 0.0281 (4) | |
C4 | 0.28321 (18) | 0.06162 (16) | 0.81173 (17) | 0.0267 (4) | |
C5 | 0.15019 (17) | 0.12401 (15) | 0.69077 (17) | 0.0253 (4) | |
C6 | 0.15972 (18) | 0.08500 (16) | 0.55881 (18) | 0.0288 (4) | |
C7 | 0.00703 (18) | 0.22108 (16) | 0.70981 (19) | 0.0299 (4) | |
C8 | 0.00386 (17) | 0.36849 (16) | 0.73827 (17) | 0.0256 (4) | |
C9 | −0.10110 (18) | 0.44362 (16) | 0.80645 (17) | 0.0273 (4) | |
C10 | −0.12333 (17) | 0.58342 (16) | 0.81887 (17) | 0.0268 (4) | |
C11 | −0.04072 (19) | 0.64888 (16) | 0.76584 (18) | 0.0291 (4) | |
C12 | 0.06679 (19) | 0.57224 (17) | 0.70101 (18) | 0.0292 (4) | |
C13 | 0.08899 (18) | 0.43152 (16) | 0.68792 (18) | 0.0282 (4) | |
C14 | −0.3212 (2) | 0.6021 (2) | 0.9278 (3) | 0.0458 (7) | |
C15 | 0.0414 (3) | 0.8336 (2) | 0.8714 (3) | 0.0524 (7) | |
C16 | 0.2759 (3) | 0.5701 (2) | 0.6172 (3) | 0.0553 (8) | |
H1 | 0.29214 | −0.02961 | 0.45729 | 0.0365* | |
H2A | 0.61174 | −0.18641 | 0.71319 | 0.0523* | |
H2B | 0.53432 | −0.17083 | 0.55346 | 0.0523* | |
H4A | 0.36568 | 0.05333 | 1.01808 | 0.0498* | |
H4B | 0.20877 | 0.15137 | 0.96235 | 0.0498* | |
H6 | 0.07675 | 0.12170 | 0.47695 | 0.0345* | |
H7A | −0.01356 | 0.18298 | 0.79002 | 0.0358* | |
H7B | −0.07598 | 0.22328 | 0.62287 | 0.0358* | |
H9 | −0.15578 | 0.40001 | 0.84333 | 0.0327* | |
H13 | 0.16094 | 0.38061 | 0.64539 | 0.0338* | |
H14A | −0.37606 | 0.56320 | 0.84664 | 0.0687* | |
H14B | −0.39201 | 0.67028 | 0.96417 | 0.0687* | |
H14C | −0.25903 | 0.53080 | 1.00318 | 0.0687* | |
H15A | 0.07538 | 0.78043 | 0.96276 | 0.0786* | |
H15B | 0.00033 | 0.92922 | 0.88535 | 0.0786* | |
H15C | 0.12568 | 0.82131 | 0.83397 | 0.0786* | |
H16A | 0.34555 | 0.51070 | 0.70040 | 0.0829* | |
H16B | 0.32234 | 0.63317 | 0.59198 | 0.0829* | |
H16C | 0.25078 | 0.51582 | 0.53671 | 0.0829* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
Cl1 | 0.0327 (2) | 0.0445 (3) | 0.0473 (3) | −0.0095 (2) | 0.0150 (2) | −0.0205 (2) |
O1 | 0.0950 (17) | 0.201 (3) | 0.0562 (13) | 0.0274 (18) | 0.0101 (12) | −0.0673 (16) |
O2 | 0.0370 (8) | 0.0556 (9) | 0.0673 (10) | −0.0171 (7) | 0.0120 (7) | −0.0114 (8) |
O3 | 0.0522 (10) | 0.0651 (11) | 0.0622 (10) | 0.0149 (8) | 0.0161 (8) | −0.0181 (9) |
O4 | 0.0676 (14) | 0.0830 (16) | 0.224 (3) | −0.0383 (13) | 0.0374 (17) | 0.0263 (18) |
O5 | 0.0327 (6) | 0.0309 (6) | 0.0397 (7) | 0.0009 (5) | 0.0178 (5) | −0.0106 (5) |
O6 | 0.0450 (8) | 0.0204 (6) | 0.0487 (8) | −0.0011 (5) | 0.0116 (6) | −0.0053 (5) |
O7 | 0.0388 (7) | 0.0276 (6) | 0.0561 (8) | −0.0065 (5) | 0.0226 (6) | 0.0007 (5) |
N1 | 0.0314 (7) | 0.0321 (7) | 0.0235 (7) | −0.0028 (6) | 0.0094 (5) | −0.0068 (5) |
N2 | 0.0358 (8) | 0.0488 (10) | 0.0313 (8) | 0.0101 (7) | 0.0126 (6) | −0.0078 (7) |
N3 | 0.0290 (7) | 0.0282 (7) | 0.0250 (7) | 0.0030 (5) | 0.0094 (5) | −0.0025 (5) |
N4 | 0.0366 (8) | 0.0466 (9) | 0.0271 (7) | 0.0070 (7) | 0.0094 (6) | −0.0087 (6) |
C2 | 0.0296 (8) | 0.0244 (7) | 0.0272 (8) | −0.0020 (6) | 0.0106 (6) | −0.0045 (6) |
C4 | 0.0276 (8) | 0.0222 (7) | 0.0277 (8) | −0.0023 (6) | 0.0101 (6) | −0.0045 (6) |
C5 | 0.0231 (7) | 0.0189 (7) | 0.0310 (8) | −0.0027 (5) | 0.0081 (6) | −0.0040 (6) |
C6 | 0.0246 (7) | 0.0263 (7) | 0.0286 (8) | −0.0022 (6) | 0.0039 (6) | −0.0022 (6) |
C7 | 0.0235 (7) | 0.0229 (7) | 0.0409 (9) | −0.0029 (6) | 0.0109 (7) | −0.0049 (7) |
C8 | 0.0209 (7) | 0.0223 (7) | 0.0280 (8) | −0.0008 (5) | 0.0053 (6) | −0.0032 (6) |
C9 | 0.0235 (7) | 0.0247 (7) | 0.0305 (8) | −0.0022 (6) | 0.0089 (6) | −0.0034 (6) |
C10 | 0.0220 (7) | 0.0251 (7) | 0.0255 (7) | 0.0022 (6) | 0.0059 (6) | −0.0051 (6) |
C11 | 0.0297 (8) | 0.0204 (7) | 0.0302 (8) | −0.0009 (6) | 0.0061 (6) | −0.0029 (6) |
C12 | 0.0272 (8) | 0.0248 (7) | 0.0309 (8) | −0.0026 (6) | 0.0075 (6) | 0.0000 (6) |
C13 | 0.0237 (7) | 0.0233 (7) | 0.0340 (8) | −0.0006 (6) | 0.0106 (6) | −0.0044 (6) |
C14 | 0.0434 (11) | 0.0443 (11) | 0.0539 (12) | −0.0062 (9) | 0.0289 (10) | −0.0109 (9) |
C15 | 0.0716 (16) | 0.0361 (10) | 0.0509 (12) | −0.0245 (10) | 0.0133 (11) | −0.0121 (9) |
C16 | 0.0375 (11) | 0.0499 (12) | 0.0804 (17) | −0.0062 (9) | 0.0274 (11) | 0.0094 (11) |
Geometric parameters (Å, º) top
Cl1—O1 | 1.372 (2) | C5—C6 | 1.347 (2) |
Cl1—O2 | 1.4309 (19) | C7—C8 | 1.518 (2) |
Cl1—O3 | 1.4284 (19) | C8—C9 | 1.399 (2) |
Cl1—O4 | 1.411 (3) | C8—C13 | 1.378 (3) |
O5—C10 | 1.374 (2) | C9—C10 | 1.387 (2) |
O5—C14 | 1.439 (3) | C10—C11 | 1.388 (3) |
O6—C11 | 1.376 (2) | C11—C12 | 1.400 (3) |
O6—C15 | 1.421 (3) | C12—C13 | 1.397 (2) |
O7—C12 | 1.362 (2) | C6—H6 | 0.93 |
O7—C16 | 1.424 (3) | C7—H7A | 0.97 |
N1—C2 | 1.352 (2) | C7—H7B | 0.97 |
N1—C6 | 1.361 (2) | C9—H9 | 0.93 |
N2—C2 | 1.327 (3) | C13—H13 | 0.93 |
N3—C2 | 1.330 (2) | C14—H14A | 0.96 |
N3—C4 | 1.344 (2) | C14—H14B | 0.96 |
N4—C4 | 1.326 (2) | C14—H14C | 0.96 |
N1—H1 | 0.86 | C15—H15A | 0.96 |
N2—H2A | 0.86 | C15—H15B | 0.96 |
N2—H2B | 0.86 | C15—H15C | 0.96 |
N4—H4B | 0.86 | C16—H16A | 0.96 |
N4—H4A | 0.86 | C16—H16B | 0.96 |
C4—C5 | 1.440 (2) | C16—H16C | 0.96 |
C5—C7 | 1.500 (2) | | |
| | | |
Cl1···H16A | 3.1039 | C10···H2Aiv | 2.8386 |
Cl1···H1i | 2.9657 | C12···H14Cv | 2.9196 |
Cl1···H2Bi | 2.8719 | C12···H15C | 2.9592 |
O2···C2 | 3.009 (2) | C13···H16C | 2.7450 |
O2···N1 | 3.135 (2) | C13···H16A | 2.8032 |
O2···N3 | 3.088 (2) | C13···H14Cv | 3.0296 |
O2···C6 | 3.322 (3) | C14···H2Aiv | 2.8157 |
O2···C4 | 3.224 (3) | C14···H4Bv | 3.0845 |
O2···C5 | 3.386 (3) | C14···H9 | 2.4892 |
O2···N2i | 2.958 (2) | C16···H13 | 2.5612 |
O3···N1i | 2.929 (2) | C16···H7Bvi | 2.9425 |
O3···O6ii | 3.188 (2) | H1···H2B | 2.2721 |
O4···C9iii | 3.154 (4) | H1···Cl1i | 2.9657 |
O5···N2iv | 2.958 (2) | H1···O3i | 2.0702 |
O5···N4v | 2.958 (2) | H2A···O5ii | 2.1367 |
O5···O6 | 2.657 (2) | H2A···O6ii | 2.8658 |
O6···O7 | 2.705 (2) | H2A···C10ii | 2.8386 |
O6···O3iv | 3.188 (2) | H2A···C14ii | 2.8157 |
O6···O5 | 2.657 (2) | H2B···H1 | 2.2721 |
O6···C6vi | 3.230 (2) | H2B···Cl1i | 2.8719 |
O7···O6 | 2.705 (2) | H2B···O2i | 2.1001 |
O7···C15 | 3.017 (3) | H4A···N3viii | 2.3425 |
O1···H14Bv | 2.6425 | H4B···C7 | 2.5844 |
O2···H2Bi | 2.1001 | H4B···C8 | 2.9226 |
O2···H13 | 2.7147 | H4B···H7A | 2.2327 |
O2···H16A | 2.9064 | H4B···O5v | 2.3934 |
O3···H1i | 2.0702 | H4B···C14v | 3.0845 |
O3···H15Bii | 2.8072 | H6···H7B | 2.3422 |
O4···H16A | 2.8532 | H6···O6vi | 2.5646 |
O4···H16Bvii | 2.8608 | H6···O7vi | 2.6797 |
O4···H9iii | 2.5603 | H7A···N4 | 2.7198 |
O4···H14Aiii | 2.8913 | H7A···H4B | 2.2327 |
O5···H4Bv | 2.3934 | H7A···H9 | 2.3676 |
O5···H2Aiv | 2.1367 | H7B···H6 | 2.3422 |
O6···H6vi | 2.5646 | H7B···O7vi | 2.7951 |
O6···H2Aiv | 2.8658 | H7B···C16vi | 2.9425 |
O7···H15C | 2.5019 | H9···O4ix | 2.5603 |
O7···H6vi | 2.6797 | H9···C14 | 2.4892 |
O7···H7Bvi | 2.7951 | H9···H7A | 2.3676 |
N1···O2 | 3.135 (2) | H9···H14A | 2.2837 |
N1···O3i | 2.929 (2) | H9···H14C | 2.2765 |
N2···O5ii | 2.958 (2) | H9···H15Av | 2.4342 |
N2···O2i | 2.958 (2) | H13···O2 | 2.7147 |
N3···O2 | 3.088 (2) | H13···C5 | 2.7051 |
N3···N4viii | 3.155 (2) | H13···C16 | 2.5612 |
N4···O5v | 2.958 (2) | H13···H16A | 2.4658 |
N4···C8 | 3.436 (2) | H13···H16C | 2.2555 |
N4···C14v | 3.402 (3) | H14A···O4ix | 2.8913 |
N4···N3viii | 3.155 (2) | H14A···C9 | 2.7102 |
N3···H4Aviii | 2.3425 | H14A···H9 | 2.2837 |
N4···H7A | 2.7198 | H14B···O1v | 2.6425 |
N4···H14Bv | 2.9261 | H14B···N4v | 2.9261 |
C2···O2 | 3.009 (2) | H14C···C9 | 2.7484 |
C4···O2 | 3.224 (3) | H14C···H9 | 2.2765 |
C5···O2 | 3.386 (3) | H14C···C12v | 2.9196 |
C6···O2 | 3.322 (3) | H14C···C13v | 3.0296 |
C6···O6vi | 3.230 (2) | H15A···H9v | 2.4342 |
C8···N4 | 3.436 (2) | H15B···O3iv | 2.8072 |
C9···O4ix | 3.154 (4) | H15C···O7 | 2.5019 |
C9···C10v | 3.593 (2) | H15C···C12 | 2.9592 |
C10···C9v | 3.593 (2) | H16A···Cl1 | 3.1039 |
C14···N4v | 3.402 (3) | H16A···O2 | 2.9064 |
C15···O7 | 3.017 (3) | H16A···O4 | 2.8532 |
C5···H13 | 2.7051 | H16A···C13 | 2.8032 |
C7···H4B | 2.5844 | H16A···H13 | 2.4658 |
C8···H16Cvi | 3.0031 | H16B···O4vii | 2.8608 |
C8···H4B | 2.9226 | H16C···C13 | 2.7450 |
C9···H14C | 2.7484 | H16C···H13 | 2.2555 |
C9···H14A | 2.7102 | H16C···C8vi | 3.0031 |
| | | |
O1—Cl1—O2 | 110.64 (15) | O6—C11—C12 | 121.61 (17) |
O1—Cl1—O3 | 110.85 (14) | C10—C11—C12 | 119.40 (15) |
O1—Cl1—O4 | 111.12 (19) | O6—C11—C10 | 118.89 (16) |
O2—Cl1—O3 | 109.32 (11) | O7—C12—C11 | 115.34 (15) |
O2—Cl1—O4 | 106.33 (16) | C11—C12—C13 | 120.23 (17) |
O3—Cl1—O4 | 108.45 (15) | O7—C12—C13 | 124.40 (17) |
C10—O5—C14 | 117.13 (14) | C8—C13—C12 | 119.74 (16) |
C11—O6—C15 | 115.22 (15) | N1—C6—H6 | 119.27 |
C12—O7—C16 | 117.66 (15) | C5—C6—H6 | 119.27 |
C2—N1—C6 | 120.10 (14) | C5—C7—H7A | 107.93 |
C2—N3—C4 | 118.22 (14) | C5—C7—H7B | 107.93 |
C2—N1—H1 | 119.95 | C8—C7—H7A | 107.93 |
C6—N1—H1 | 119.94 | C8—C7—H7B | 107.93 |
C2—N2—H2A | 120.00 | H7A—C7—H7B | 107.21 |
H2A—N2—H2B | 120.00 | C8—C9—H9 | 120.12 |
C2—N2—H2B | 120.00 | C10—C9—H9 | 120.12 |
H4A—N4—H4B | 120.00 | C8—C13—H13 | 120.14 |
C4—N4—H4A | 120.00 | C12—C13—H13 | 120.13 |
C4—N4—H4B | 120.00 | O5—C14—H14A | 109.44 |
N2—C2—N3 | 119.58 (16) | O5—C14—H14B | 109.45 |
N1—C2—N2 | 118.24 (15) | O5—C14—H14C | 109.48 |
N1—C2—N3 | 122.18 (16) | H14A—C14—H14B | 109.46 |
N3—C4—C5 | 122.30 (14) | H14A—C14—H14C | 109.49 |
N4—C4—C5 | 120.80 (16) | H14B—C14—H14C | 109.50 |
N3—C4—N4 | 116.90 (15) | O6—C15—H15A | 109.49 |
C4—C5—C6 | 115.70 (15) | O6—C15—H15B | 109.45 |
C6—C5—C7 | 121.68 (15) | O6—C15—H15C | 109.51 |
C4—C5—C7 | 122.56 (14) | H15A—C15—H15B | 109.43 |
N1—C6—C5 | 121.47 (16) | H15A—C15—H15C | 109.49 |
C5—C7—C8 | 117.50 (15) | H15B—C15—H15C | 109.45 |
C7—C8—C9 | 116.97 (15) | O7—C16—H16A | 109.50 |
C7—C8—C13 | 122.37 (15) | O7—C16—H16B | 109.47 |
C9—C8—C13 | 120.37 (15) | O7—C16—H16C | 109.47 |
C8—C9—C10 | 119.75 (16) | H16A—C16—H16B | 109.48 |
O5—C10—C9 | 123.48 (16) | H16A—C16—H16C | 109.48 |
O5—C10—C11 | 116.05 (14) | H16B—C16—H16C | 109.43 |
C9—C10—C11 | 120.47 (16) | | |
| | | |
C14—O5—C10—C9 | −4.1 (2) | C6—C5—C7—C8 | −104.57 (19) |
C14—O5—C10—C11 | 175.49 (17) | C5—C7—C8—C13 | 28.5 (2) |
C15—O6—C11—C10 | 110.6 (2) | C5—C7—C8—C9 | −157.51 (15) |
C15—O6—C11—C12 | −73.2 (2) | C13—C8—C9—C10 | 2.2 (2) |
C16—O7—C12—C11 | 164.60 (18) | C7—C8—C13—C12 | 171.72 (16) |
C16—O7—C12—C13 | −17.3 (3) | C7—C8—C9—C10 | −171.83 (15) |
C6—N1—C2—N3 | 0.4 (3) | C9—C8—C13—C12 | −2.0 (3) |
C6—N1—C2—N2 | −179.02 (16) | C8—C9—C10—C11 | −0.9 (2) |
C2—N1—C6—C5 | 0.8 (3) | C8—C9—C10—O5 | 178.75 (15) |
C4—N3—C2—N1 | −1.9 (3) | C9—C10—C11—O6 | 175.61 (15) |
C4—N3—C2—N2 | 177.54 (17) | O5—C10—C11—C12 | 179.64 (15) |
C2—N3—C4—N4 | −178.96 (16) | O5—C10—C11—O6 | −4.0 (2) |
C2—N3—C4—C5 | 2.2 (3) | C9—C10—C11—C12 | −0.7 (3) |
N4—C4—C5—C6 | −179.88 (17) | O6—C11—C12—O7 | 2.9 (2) |
N3—C4—C5—C7 | 176.07 (16) | O6—C11—C12—C13 | −175.28 (16) |
N3—C4—C5—C6 | −1.1 (2) | C10—C11—C12—O7 | 179.14 (16) |
N4—C4—C5—C7 | −2.7 (3) | C10—C11—C12—C13 | 1.0 (3) |
C7—C5—C6—N1 | −177.62 (16) | O7—C12—C13—C8 | −177.59 (16) |
C4—C5—C6—N1 | −0.4 (2) | C11—C12—C13—C8 | 0.4 (3) |
C4—C5—C7—C8 | 78.4 (2) | | |
Symmetry codes: (i) −x+1, −y, −z+1; (ii) x+1, y−1, z; (iii) x+1, y, z; (iv) x−1, y+1, z; (v) −x, −y+1, −z+2; (vi) −x, −y+1, −z+1; (vii) −x+1, −y+1, −z+1; (viii) −x+1, −y, −z+2; (ix) x−1, y, z. |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O3i | 0.86 | 2.07 | 2.929 (2) | 176.7 |
N2—H2A···O5ii | 0.86 | 2.14 | 2.958 (2) | 159.7 |
N2—H2B···O2i | 0.86 | 2.10 | 2.958 (2) | 175.2 |
N4—H4A···N3viii | 0.86 | 2.34 | 3.155 (2) | 157.8 |
N4—H4B···O5v | 0.86 | 2.39 | 2.958 (2) | 123.7 |
C6—H6···O6vi | 0.93 | 2.56 | 3.230 (2) | 128.8 |
C9—H9···O4ix | 0.93 | 2.56 | 3.154 (4) | 122.1 |
C15—H15C···O7 | 0.96 | 2.50 | 3.017 (3) | 113.6 |
Symmetry codes: (i) −x+1, −y, −z+1; (ii) x+1, y−1, z; (v) −x, −y+1, −z+2; (vi) −x, −y+1, −z+1; (viii) −x+1, −y, −z+2; (ix) x−1, y, z. |
Experimental details
Crystal data |
Chemical formula | C14H19N4O3+·ClO41− |
Mr | 390.78 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 293 |
a, b, c (Å) | 9.672 (2), 10.219 (1), 9.651 (2) |
α, β, γ (°) | 91.19 (1), 107.18 (1), 72.44 (2) |
V (Å3) | 866.4 (3) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.27 |
Crystal size (mm) | 0.3 × 0.3 × 0.2 |
|
Data collection |
Diffractometer | Siemens AED diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 5105, 5105, 3593 |
Rint | 0.000 |
(sin θ/λ)max (Å−1) | 0.707 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.048, 0.168, 1.13 |
No. of reflections | 5105 |
No. of parameters | 238 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.50, −0.55 |
Selected geometric parameters (Å, º) topCl1—O1 | 1.372 (2) | O7—C12 | 1.362 (2) |
Cl1—O2 | 1.4309 (19) | O7—C16 | 1.424 (3) |
Cl1—O3 | 1.4284 (19) | N1—C2 | 1.352 (2) |
Cl1—O4 | 1.411 (3) | N1—C6 | 1.361 (2) |
O5—C10 | 1.374 (2) | N2—C2 | 1.327 (3) |
O5—C14 | 1.439 (3) | N3—C2 | 1.330 (2) |
O6—C11 | 1.376 (2) | N3—C4 | 1.344 (2) |
O6—C15 | 1.421 (3) | N4—C4 | 1.326 (2) |
| | | |
O1—Cl1—O2 | 110.64 (15) | N1—C2—N2 | 118.24 (15) |
O1—Cl1—O3 | 110.85 (14) | N1—C2—N3 | 122.18 (16) |
O1—Cl1—O4 | 111.12 (19) | N3—C4—C5 | 122.30 (14) |
O2—Cl1—O3 | 109.32 (11) | N4—C4—C5 | 120.80 (16) |
O2—Cl1—O4 | 106.33 (16) | N3—C4—N4 | 116.90 (15) |
O3—Cl1—O4 | 108.45 (15) | N1—C6—C5 | 121.47 (16) |
C10—O5—C14 | 117.13 (14) | O5—C10—C9 | 123.48 (16) |
C11—O6—C15 | 115.22 (15) | O5—C10—C11 | 116.05 (14) |
C12—O7—C16 | 117.66 (15) | O6—C11—C12 | 121.61 (17) |
C2—N1—C6 | 120.10 (14) | O6—C11—C10 | 118.89 (16) |
C2—N3—C4 | 118.22 (14) | O7—C12—C11 | 115.34 (15) |
N2—C2—N3 | 119.58 (16) | O7—C12—C13 | 124.40 (17) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O3i | 0.86 | 2.07 | 2.929 (2) | 176.7 |
N2—H2A···O5ii | 0.86 | 2.14 | 2.958 (2) | 159.7 |
N2—H2B···O2i | 0.86 | 2.10 | 2.958 (2) | 175.2 |
N4—H4A···N3iii | 0.86 | 2.34 | 3.155 (2) | 157.8 |
N4—H4B···O5iv | 0.86 | 2.39 | 2.958 (2) | 123.7 |
C6—H6···O6v | 0.93 | 2.56 | 3.230 (2) | 128.8 |
C9—H9···O4vi | 0.93 | 2.56 | 3.154 (4) | 122.1 |
C15—H15C···O7 | 0.96 | 2.50 | 3.017 (3) | 113.6 |
Symmetry codes: (i) −x+1, −y, −z+1; (ii) x+1, y−1, z; (iii) −x+1, −y, −z+2; (iv) −x, −y+1, −z+2; (v) −x, −y+1, −z+1; (vi) x−1, y, z. |
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Trimethoprim (TMP) is a well known antifolate drug, which selectively inhibits the bacterial species of the enzyme dihydrofolate reductase (DHFR) (Hitching et al., 1988). This enzyme is found in bacteria and mammals. TMP and other antifolate drugs complexed with DHFR from various sources have been widely studied and are of current interest (Feeney, 2000). The N1-protonated diaminopyrimidine ring of TMP binds deep inside the enzyme cleft through several hydrogen bonds. The crystal structures of TMP and its complexes have been reported in the literature (Koetzle & Williams, 1976; Giuseppetti et al., 1984; Bryan et al., 1987; Bettinetti & Sardone, 1997). As part of structural investigations on drugs and their complexes in a variety of molecular environments carried out in our laboratory, we have reported the structures of trimethoprim formate (Umadevi & Muthiah, 1994), trimethoprim salicylate monohydrate (Murugesan & Muthiah, 1996), trimethoprim nitrate (Murugesan & Muthiah, 1997), trimethoprim hydrogen maleate (Prabakaran et al., 2001), trimethoprim glutarate (Robert et al., 2001) and trimethoprim sulfate trihydrate (Muthiah et al., 2001). The present study has been aimed at understanding the conformation and hydrogen bonding interactions in trimethoprim perchlorate, (I).
In the crystal structure of trimethoprim perchlorate (TMPP), the perchlorate ion is tetrahedral in shape as expected, with Cl—O distances ranging from 1.372 (2) to 1.431 (2) Å (Yokota et al., 1999). Small deviations from ideal values can be attributed to the relatively high temperature factors of the atoms in the perchlorate anion. The TMP is protonated at N1, as reported in various crystal structures containing TMP cations (Prabakaran et al., 2001). This is evident from the increase in the ring angle at the site of protonation, namely N1. The internal angle at N1, C2—N1—C6 has increased to 120.10 (14)°, as compared with 115.46° in neutral TMP (Koetzle & Williams, 1976). The conformation of the TMP molecule is described by two torsion angles, i.e. C4—C5—C7—C8 of 78.4 (2) and C5—C7—C8—C9 of -157.51 (1)°. These values are in the range reported for TMP sulfate trihydrate (Muthiah et al., 2001). The pyrimidine ring makes a dihedral angle of 83.72 (8)° with the phenyl ring, which is close to the value of 85.5 (2)° observed for trimethoprim sulfate trihydrate (Muthiah et al., 2001). An ORTEPIII (Farrugia, 1997) diagram of the molecule with the atom-labelling scheme is shown in Fig. 1.
The TMP cation and the perchlorate anion are linked by hydrogen bonds N1—H···O2 (of perchlorate ion) and N2—H···O3 (of the same perchlorate ion). This is reminiscent of the fork-like interaction of the carboxylate group (of Asp27 of the enzyme) with the TMP cation (Kuyper, 1990). The pyrimidine moieties of the trimethoprim cations are centrosymmetrically paired through a pair of N—H···N hydrogen bonds involving the 4-amino group and the pyrimidinium N3 atom. This type of pairing has also been reported in trimethoprim hydrogen maleate (Prabakaran et al., 2001) and trimethoprim sulfate trihydrate (Muthiah et al., 2001). The two pairs of TMP cations are linked by N2—H···O5 and N4—H···O5 hydrogen bonds to form a supramolecular ladder-like structure. These interactions are shown in Fig. 2. In addition, C—H···O hydrogen bonds also stabilize the crystal structure.