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The biologically important molecule tricyclic acyclovir, presented here as 3-[(2-hydroxyethoxy)methyl]-6-methyl-3H-imidazolo[1,2-a]purin-9(5H)-one dihydrate, C11H13N5O3·2H2O, shows conformational flexibility, which is observed in the solid state as two symmetrically independent molecules with different side-chain conformations. Additionally, one of these molecules exhibits side-chain disorder, such that there are three different conformations in the crystal. Water molecules found in the crystal form (H2O)8 clusters which are located between molecules of tricyclic acyclovir. The complex hydrogen-bond network formed between water and tricyclic acyclovir in the solid state may be related to the solvation of the molecules in solution.
Supporting information
CCDC reference: 167002
Compound (II) was synthesized as described by Boryski et al. (1988) and
Golankiewicz et al. (1991). Recrystallization from aqueous solution
afforded colourless crystals of (II) suitable for X-ray analysis.
Side-chain disorder in molecule B was observed as a shortening of the O16—C17
bond length, with unusual displacement parameters for these two atoms. At the
same time, residual maxima in the difference electron density maps were
observed. The ratio of 3:1 for conformations B and C was established by
subsequent refinement of site occupancy factors and was kept constant in the
final stages of the refinement. The disorder for the H atoms of the O1W
molecule was found from a difference Fourier synthesis as three maxima with
tetragonal geometry around the O atom. Using a starting model with H1WA and
H1WB only resulted in a very high displacement parameter for H1WB, while the
Uiso of H1WA refined to the expected value of 0.08 Å2. An
additional maximum of approximately 0.4 e Å-3, with tetragonal angles to
the previous two H atoms, was also observed. Additionally, the short distance
[2.816 (3) Å] between atom O1W and its partner related by a centre of
symmetry suggested formation of the O1W···O1W hydrogen bond. Refinement of the
model with three H atoms, two of which (H1WB and H1WC, where H1WC was
introduced in the observed electron-density maximum) had site occupancy
factors of 0.5 and Ueq defined as indicated below, improved the
refinement and the expected hydrogen bond was found as O1W—H1WC···O1W. H
atoms bonded to C were calculated in their ideal positions and refined as
riding, with Uiso = 1.5Ueq of the attached C atom for CH3
groups and 1.2Ueq for other C atoms. H atoms bonded to non-water O or
N atoms were found in difference electron density maps and refined
geometrically, with Uiso = 1.2Ueq for those attached to N
and 1.5Ueq for those attached to O. The H atoms of the water
molecules were found in difference electron density maps and refined as
riding, with Uiso = 1.5Ueq of the parent O atom.
Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: SDP (Frenz, 1985); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976) and ATOMS (Dowty, 1998); software used to prepare material for publication: SHELXL97.
3-[(2-hydroxyethoxy)methyl]-6-methyl-3
H-imidazol[1,2-
a]purin-9(5
H)-one
top
Crystal data top
C11H13N5O3.2H2O | Z = 4 |
Mr = 299.30 | F(000) = 632 |
Triclinic, P1 | Dx = 1.434 Mg m−3 |
a = 8.450 (1) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 11.665 (2) Å | Cell parameters from 25 reflections |
c = 14.930 (3) Å | θ = 5–12° |
α = 75.44 (2)° | µ = 0.12 mm−1 |
β = 76.65 (2)° | T = 293 K |
γ = 86.44 (2)° | Block, colourless |
V = 1385.9 (4) Å3 | 0.32 × 0.28 × 0.22 mm |
Data collection top
Enraf-Nonius CAD4 diffractometer | Rint = 0.023 |
Radiation source: fine-focus sealed tube | θmax = 30.0°, θmin = 2.0° |
Graphite monochromator | h = −11→11 |
ω/2θ scans | k = 0→16 |
8414 measured reflections | l = −20→20 |
8047 independent reflections | 3 standard reflections every 60 min |
4182 reflections with I > 2σ(I) | intensity decay: 0.3% |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.062 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.155 | w = 1/[σ2(Fo2) + (0.0709P)2] where P = (Fo2 + 2Fc2)/3 |
S = 1.02 | (Δ/σ)max = 0.016 |
8047 reflections | Δρmax = 0.26 e Å−3 |
389 parameters | Δρmin = −0.20 e Å−3 |
0 restraints | Extinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0050 (13) |
Crystal data top
C11H13N5O3.2H2O | γ = 86.44 (2)° |
Mr = 299.30 | V = 1385.9 (4) Å3 |
Triclinic, P1 | Z = 4 |
a = 8.450 (1) Å | Mo Kα radiation |
b = 11.665 (2) Å | µ = 0.12 mm−1 |
c = 14.930 (3) Å | T = 293 K |
α = 75.44 (2)° | 0.32 × 0.28 × 0.22 mm |
β = 76.65 (2)° | |
Data collection top
Enraf-Nonius CAD4 diffractometer | Rint = 0.023 |
8414 measured reflections | 3 standard reflections every 60 min |
8047 independent reflections | intensity decay: 0.3% |
4182 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.062 | 0 restraints |
wR(F2) = 0.155 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.02 | Δρmax = 0.26 e Å−3 |
8047 reflections | Δρmin = −0.20 e Å−3 |
389 parameters | |
Special details top
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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | Occ. (<1) |
C1A | −0.5280 (3) | 0.1796 (2) | 0.32358 (16) | 0.0510 (6) | |
H1A1 | −0.6394 | 0.1684 | 0.3231 | 0.077* | |
H1A2 | −0.4679 | 0.1077 | 0.3195 | 0.077* | |
H1A3 | −0.4817 | 0.2424 | 0.2703 | 0.077* | |
C2A | −0.5201 (2) | 0.21074 (18) | 0.41287 (15) | 0.0389 (5) | |
N3A | −0.5959 (2) | 0.14063 (15) | 0.49989 (12) | 0.0397 (4) | |
H3A | −0.672 (3) | 0.075 (2) | 0.5153 (15) | 0.048* | |
C4A | −0.5713 (2) | 0.18402 (16) | 0.57063 (14) | 0.0341 (4) | |
N5A | −0.47555 (19) | 0.28419 (14) | 0.52842 (11) | 0.0344 (4) | |
C6A | −0.4467 (2) | 0.29944 (19) | 0.42965 (15) | 0.0400 (5) | |
H6A | −0.3872 | 0.3603 | 0.3839 | 0.048* | |
N7A | −0.6284 (2) | 0.14185 (14) | 0.66214 (12) | 0.0375 (4) | |
C8A | −0.5781 (2) | 0.20899 (17) | 0.71061 (14) | 0.0357 (4) | |
C9A | −0.4780 (2) | 0.30844 (18) | 0.67727 (15) | 0.0378 (5) | |
C10A | −0.4177 (2) | 0.35330 (17) | 0.57896 (15) | 0.0374 (5) | |
O11A | −0.32736 (18) | 0.43793 (13) | 0.53515 (11) | 0.0501 (4) | |
N12A | −0.4558 (2) | 0.34980 (17) | 0.75291 (13) | 0.0479 (5) | |
C13A | −0.5403 (3) | 0.2783 (2) | 0.82742 (17) | 0.0502 (6) | |
H13A | −0.5474 | 0.2858 | 0.8888 | 0.060* | |
N14A | −0.6181 (2) | 0.19102 (16) | 0.80790 (12) | 0.0430 (4) | |
C15A | −0.7248 (3) | 0.0979 (2) | 0.87221 (17) | 0.0552 (6) | |
H15A | −0.6990 | 0.0247 | 0.8522 | 0.066* | |
H15B | −0.7055 | 0.0854 | 0.9356 | 0.066* | |
O16A | −0.8903 (2) | 0.12564 (16) | 0.87489 (12) | 0.0612 (5) | |
C17A | −0.9599 (4) | 0.1917 (3) | 0.9417 (2) | 0.0784 (9) | |
H17A | −0.8923 | 0.2597 | 0.9328 | 0.094* | |
H17B | −0.9665 | 0.1431 | 1.0055 | 0.094* | |
C18A | −1.1254 (4) | 0.2322 (3) | 0.9291 (2) | 0.0767 (9) | |
H18A | −1.1653 | 0.2876 | 0.9680 | 0.092* | |
H18B | −1.1184 | 0.2742 | 0.8633 | 0.092* | |
O19A | −1.2377 (2) | 0.13951 (18) | 0.95317 (14) | 0.0718 (5) | |
H19A | −1.250 (4) | 0.096 (3) | 0.903 (2) | 0.108* | |
C1B | −0.1148 (3) | 0.5774 (2) | 0.32975 (16) | 0.0458 (5) | |
H1B1 | −0.2291 | 0.5614 | 0.3520 | 0.069* | |
H1B2 | −0.0553 | 0.5041 | 0.3363 | 0.069* | |
H1B3 | −0.0930 | 0.6198 | 0.2642 | 0.069* | |
C2B | −0.0639 (2) | 0.64977 (18) | 0.38643 (14) | 0.0369 (5) | |
N3B | −0.1188 (2) | 0.62648 (15) | 0.48459 (12) | 0.0356 (4) | |
H3B | −0.185 (3) | 0.572 (2) | 0.5218 (15) | 0.043* | |
C4B | −0.0537 (2) | 0.70418 (16) | 0.51935 (14) | 0.0313 (4) | |
N5B | 0.04373 (19) | 0.77785 (13) | 0.44167 (11) | 0.0332 (4) | |
C6B | 0.0355 (3) | 0.74324 (18) | 0.36010 (15) | 0.0393 (5) | |
H6B | 0.0893 | 0.7787 | 0.2984 | 0.047* | |
N7B | −0.07732 (19) | 0.70939 (14) | 0.60838 (11) | 0.0334 (4) | |
C8B | 0.0083 (2) | 0.80027 (16) | 0.61521 (13) | 0.0319 (4) | |
C9B | 0.1093 (2) | 0.87946 (16) | 0.54216 (14) | 0.0333 (4) | |
C10B | 0.1348 (2) | 0.87290 (17) | 0.44696 (14) | 0.0348 (4) | |
O11B | 0.21984 (18) | 0.93470 (13) | 0.37512 (10) | 0.0476 (4) | |
N12B | 0.1735 (2) | 0.95958 (14) | 0.57846 (12) | 0.0393 (4) | |
C13B | 0.1130 (3) | 0.92974 (18) | 0.66937 (15) | 0.0399 (5) | |
H13B | 0.1357 | 0.9696 | 0.7116 | 0.048* | |
N14B | 0.0115 (2) | 0.83283 (15) | 0.69687 (11) | 0.0369 (4) | |
C15B | −0.0669 (3) | 0.7764 (2) | 0.79438 (15) | 0.0429 (5) | |
H15C | −0.1228 | 0.8362 | 0.8251 | 0.052* | |
H15D | −0.1477 | 0.7210 | 0.7941 | 0.052* | |
O16B | 0.0437 (3) | 0.71609 (18) | 0.84654 (13) | 0.0442 (5) | 0.75 |
C17B | 0.1091 (5) | 0.6150 (3) | 0.8140 (2) | 0.0504 (8) | 0.75 |
H17C | 0.1618 | 0.6392 | 0.7472 | 0.061* | 0.75 |
H17D | 0.0218 | 0.5611 | 0.8208 | 0.061* | 0.75 |
O16C | 0.0020 (8) | 0.6593 (6) | 0.8223 (4) | 0.0407 (13)* | 0.25 |
C17C | 0.1673 (13) | 0.6693 (10) | 0.8267 (7) | 0.051 (2)* | 0.25 |
H17E | 0.1748 | 0.7243 | 0.8647 | 0.061* | 0.25 |
H17F | 0.2328 | 0.6997 | 0.7633 | 0.061* | 0.25 |
C18B | 0.2286 (3) | 0.5536 (3) | 0.86870 (18) | 0.0649 (7) | |
H18C | 0.2931 | 0.4998 | 0.8345 | 0.078* | |
H18D | 0.3017 | 0.6118 | 0.8732 | 0.078* | |
O19B | 0.1569 (3) | 0.4902 (2) | 0.95949 (14) | 0.0943 (8) | |
H19B | 0.0846 | 0.5302 | 0.9839 | 0.141* | |
O1W | 0.38838 (12) | 0.41397 (8) | 0.05977 (6) | 0.0563 (4) | |
H1WA | 0.3618 | 0.4275 | 0.1253 | 0.085* | |
H1WB | 0.3004 | 0.4376 | 0.0373 | 0.085* | 0.50 |
H1WC | 0.4582 | 0.4614 | 0.0263 | 0.085* | 0.50 |
O2W | 0.28759 (12) | 0.45991 (8) | 0.23102 (6) | 0.0795 (6) | |
H2WA | 0.3363 | 0.5166 | 0.2383 | 0.119* | |
H2WB | 0.2345 | 0.4190 | 0.2762 | 0.119* | |
O3W | 0.28203 (12) | −0.02140 (8) | 0.17551 (6) | 0.0824 (6) | |
H3WA | 0.3487 | 0.0345 | 0.1541 | 0.124* | |
H3WB | 0.2664 | −0.0369 | 0.2442 | 0.124* | |
O4W | 0.47373 (12) | 0.17077 (8) | 0.07327 (6) | 0.0972 (7) | |
H4WA | 0.4524 | 0.2370 | 0.0581 | 0.146* | |
H4WB | 0.5717 | 0.1748 | 0.0504 | 0.146* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1A | 0.0547 (14) | 0.0528 (14) | 0.0482 (13) | −0.0047 (11) | −0.0108 (11) | −0.0167 (11) |
C2A | 0.0347 (10) | 0.0351 (11) | 0.0449 (12) | −0.0040 (9) | −0.0069 (9) | −0.0071 (9) |
N3A | 0.0385 (9) | 0.0325 (9) | 0.0473 (11) | −0.0112 (8) | −0.0065 (8) | −0.0087 (8) |
C4A | 0.0276 (9) | 0.0278 (10) | 0.0452 (12) | −0.0073 (8) | −0.0045 (8) | −0.0074 (9) |
N5A | 0.0323 (8) | 0.0286 (8) | 0.0397 (9) | −0.0104 (7) | −0.0039 (7) | −0.0049 (7) |
C6A | 0.0371 (11) | 0.0392 (11) | 0.0388 (11) | −0.0096 (9) | −0.0009 (9) | −0.0055 (9) |
N7A | 0.0378 (9) | 0.0304 (8) | 0.0414 (10) | −0.0104 (7) | −0.0040 (7) | −0.0055 (7) |
C8A | 0.0326 (10) | 0.0312 (10) | 0.0401 (11) | −0.0031 (8) | −0.0045 (8) | −0.0053 (9) |
C9A | 0.0345 (10) | 0.0327 (10) | 0.0473 (12) | −0.0058 (9) | −0.0069 (9) | −0.0122 (9) |
C10A | 0.0319 (10) | 0.0315 (10) | 0.0487 (12) | −0.0066 (8) | −0.0065 (9) | −0.0105 (9) |
O11A | 0.0519 (9) | 0.0408 (8) | 0.0544 (10) | −0.0257 (7) | −0.0049 (7) | −0.0062 (7) |
N12A | 0.0488 (11) | 0.0487 (11) | 0.0481 (11) | −0.0130 (9) | −0.0096 (9) | −0.0133 (9) |
C13A | 0.0545 (14) | 0.0531 (14) | 0.0451 (13) | −0.0083 (11) | −0.0101 (11) | −0.0146 (11) |
N14A | 0.0444 (10) | 0.0402 (10) | 0.0414 (10) | −0.0077 (8) | −0.0070 (8) | −0.0050 (8) |
C15A | 0.0602 (15) | 0.0507 (14) | 0.0449 (13) | −0.0152 (12) | −0.0014 (11) | 0.0000 (11) |
O16A | 0.0553 (10) | 0.0770 (12) | 0.0496 (10) | −0.0192 (9) | 0.0031 (8) | −0.0214 (9) |
C17A | 0.0706 (19) | 0.095 (2) | 0.0738 (19) | −0.0234 (17) | 0.0056 (15) | −0.0417 (18) |
C18A | 0.072 (2) | 0.0676 (19) | 0.079 (2) | −0.0145 (16) | 0.0108 (16) | −0.0195 (16) |
O19A | 0.0630 (11) | 0.0745 (13) | 0.0716 (13) | −0.0191 (10) | 0.0036 (10) | −0.0191 (10) |
C1B | 0.0515 (13) | 0.0434 (12) | 0.0458 (13) | −0.0058 (10) | −0.0119 (10) | −0.0144 (10) |
C2B | 0.0363 (10) | 0.0346 (11) | 0.0384 (11) | −0.0020 (9) | −0.0063 (9) | −0.0077 (9) |
N3B | 0.0364 (9) | 0.0296 (9) | 0.0385 (10) | −0.0112 (7) | −0.0038 (7) | −0.0055 (7) |
C4B | 0.0279 (9) | 0.0241 (9) | 0.0379 (11) | −0.0047 (7) | −0.0039 (8) | −0.0025 (8) |
N5B | 0.0335 (8) | 0.0278 (8) | 0.0345 (9) | −0.0071 (7) | −0.0028 (7) | −0.0036 (7) |
C6B | 0.0419 (11) | 0.0390 (11) | 0.0343 (11) | −0.0075 (9) | −0.0032 (9) | −0.0071 (9) |
N7B | 0.0348 (8) | 0.0296 (8) | 0.0333 (9) | −0.0096 (7) | −0.0048 (7) | −0.0034 (7) |
C8B | 0.0299 (9) | 0.0285 (9) | 0.0366 (10) | −0.0008 (8) | −0.0085 (8) | −0.0056 (8) |
C9B | 0.0304 (10) | 0.0268 (9) | 0.0413 (11) | −0.0064 (8) | −0.0094 (8) | −0.0030 (8) |
C10B | 0.0286 (9) | 0.0283 (10) | 0.0436 (12) | −0.0054 (8) | −0.0055 (8) | −0.0028 (8) |
O11B | 0.0478 (9) | 0.0448 (9) | 0.0412 (8) | −0.0210 (7) | 0.0039 (7) | −0.0021 (7) |
N12B | 0.0396 (9) | 0.0334 (9) | 0.0462 (11) | −0.0101 (8) | −0.0143 (8) | −0.0056 (8) |
C13B | 0.0429 (11) | 0.0344 (11) | 0.0451 (12) | −0.0075 (9) | −0.0155 (10) | −0.0077 (9) |
N14B | 0.0391 (9) | 0.0352 (9) | 0.0358 (9) | −0.0068 (7) | −0.0101 (7) | −0.0046 (7) |
C15B | 0.0422 (12) | 0.0452 (12) | 0.0375 (11) | −0.0013 (10) | −0.0056 (9) | −0.0059 (9) |
O16B | 0.0584 (13) | 0.0446 (11) | 0.0342 (10) | 0.0026 (10) | −0.0152 (9) | −0.0140 (9) |
C17B | 0.072 (2) | 0.0464 (18) | 0.0338 (16) | 0.0080 (18) | −0.0125 (15) | −0.0123 (14) |
C18B | 0.0581 (16) | 0.0706 (18) | 0.0560 (16) | 0.0097 (14) | −0.0106 (13) | −0.0017 (13) |
O19B | 0.0819 (16) | 0.1127 (18) | 0.0631 (13) | 0.0055 (13) | −0.0194 (11) | 0.0260 (12) |
O1W | 0.0553 (10) | 0.0639 (11) | 0.0449 (9) | −0.0107 (8) | −0.0060 (7) | −0.0067 (8) |
O2W | 0.1103 (16) | 0.0781 (13) | 0.0481 (10) | −0.0566 (12) | 0.0067 (10) | −0.0208 (9) |
O3W | 0.1037 (16) | 0.0766 (13) | 0.0606 (12) | −0.0119 (12) | −0.0022 (11) | −0.0176 (10) |
O4W | 0.0932 (16) | 0.0727 (14) | 0.1014 (17) | −0.0029 (12) | 0.0232 (13) | −0.0173 (12) |
Geometric parameters (Å, º) top
C1A—C2A | 1.484 (3) | C2B—N3B | 1.392 (3) |
C2A—C6A | 1.342 (3) | N3B—C4B | 1.350 (2) |
C2A—N3A | 1.383 (3) | C4B—N7B | 1.314 (2) |
N3A—C4A | 1.341 (3) | C4B—N5B | 1.381 (2) |
C4A—N7A | 1.315 (3) | N5B—C6B | 1.393 (3) |
C4A—N5A | 1.389 (2) | N5B—C10B | 1.416 (2) |
N5A—C6A | 1.405 (3) | N7B—C8B | 1.357 (2) |
N5A—C10A | 1.408 (3) | C8B—N14B | 1.372 (3) |
N7A—C8A | 1.336 (3) | C8B—C9B | 1.390 (3) |
C8A—N14A | 1.377 (3) | C9B—N12B | 1.384 (2) |
C8A—C9A | 1.395 (3) | C9B—C10B | 1.408 (3) |
C9A—N12A | 1.388 (3) | C10B—O11B | 1.227 (2) |
C9A—C10A | 1.410 (3) | N12B—C13B | 1.300 (3) |
C10A—O11A | 1.234 (2) | C13B—N14B | 1.381 (3) |
N12A—C13A | 1.297 (3) | N14B—C15B | 1.456 (3) |
C13A—N14A | 1.370 (3) | C15B—O16B | 1.398 (3) |
N14A—C15A | 1.453 (3) | C15B—O16C | 1.452 (7) |
C15A—O16A | 1.410 (3) | O16B—C17B | 1.419 (4) |
O16A—C17A | 1.412 (3) | C17B—C18B | 1.483 (4) |
C17A—C18A | 1.486 (4) | O16C—C17C | 1.427 (12) |
C18A—O19A | 1.405 (3) | C17C—C18B | 1.456 (11) |
C1B—C2B | 1.478 (3) | C18B—O19B | 1.387 (3) |
C2B—C6B | 1.339 (3) | | |
| | | |
C6A—C2A—N3A | 107.40 (19) | C4B—N3B—C2B | 110.32 (16) |
C6A—C2A—C1A | 132.1 (2) | N7B—C4B—N3B | 127.55 (17) |
N3A—C2A—C1A | 120.51 (18) | N7B—C4B—N5B | 126.74 (17) |
C4A—N3A—C2A | 110.48 (17) | N3B—C4B—N5B | 105.70 (17) |
N7A—C4A—N3A | 127.11 (17) | C4B—N5B—C6B | 108.96 (16) |
N7A—C4A—N5A | 126.29 (18) | C4B—N5B—C10B | 124.06 (17) |
N3A—C4A—N5A | 106.59 (17) | C6B—N5B—C10B | 126.97 (16) |
C4A—N5A—C6A | 107.55 (16) | C2B—C6B—N5B | 107.78 (18) |
C4A—N5A—C10A | 124.29 (17) | C4B—N7B—C8B | 110.29 (16) |
C6A—N5A—C10A | 128.14 (16) | N7B—C8B—N14B | 126.41 (17) |
C2A—C6A—N5A | 107.97 (18) | N7B—C8B—C9B | 127.73 (18) |
C4A—N7A—C8A | 109.80 (16) | N14B—C8B—C9B | 105.86 (16) |
N7A—C8A—N14A | 124.99 (17) | N12B—C9B—C8B | 109.94 (17) |
N7A—C8A—C9A | 129.47 (19) | N12B—C9B—C10B | 128.40 (17) |
N14A—C8A—C9A | 105.54 (18) | C8B—C9B—C10B | 121.66 (18) |
N12A—C9A—C8A | 110.03 (18) | O11B—C10B—C9B | 129.70 (19) |
N12A—C9A—C10A | 129.62 (18) | O11B—C10B—N5B | 120.78 (18) |
C8A—C9A—C10A | 120.34 (19) | C9B—C10B—N5B | 109.52 (16) |
O11A—C10A—N5A | 119.56 (19) | C13B—N12B—C9B | 105.11 (16) |
O11A—C10A—C9A | 130.72 (19) | N12B—C13B—N14B | 113.13 (18) |
N5A—C10A—C9A | 109.72 (16) | C8B—N14B—C13B | 105.96 (16) |
C13A—N12A—C9A | 104.44 (18) | C8B—N14B—C15B | 128.76 (17) |
N12A—C13A—N14A | 114.2 (2) | C13B—N14B—C15B | 125.22 (18) |
C13A—N14A—C8A | 105.76 (17) | O16B—C15B—O16C | 38.9 (2) |
C13A—N14A—C15A | 129.6 (2) | O16B—C15B—N14B | 112.45 (18) |
C8A—N14A—C15A | 124.60 (19) | O16C—C15B—N14B | 109.8 (3) |
O16A—C15A—N14A | 112.15 (19) | C15B—O16B—C17B | 111.4 (2) |
C15A—O16A—C17A | 113.6 (2) | O16B—C17B—C18B | 110.7 (3) |
O16A—C17A—C18A | 109.5 (2) | C17C—O16C—C15B | 109.8 (6) |
O19A—C18A—C17A | 113.5 (3) | O16C—C17C—C18B | 109.7 (8) |
C6B—C2B—N3B | 107.23 (18) | O19B—C18B—C17C | 121.6 (5) |
C6B—C2B—C1B | 130.9 (2) | O19B—C18B—C17B | 113.3 (2) |
N3B—C2B—C1B | 121.91 (18) | C17C—C18B—C17B | 35.9 (4) |
| | | |
C6A—C2A—N3A—C4A | 0.1 (2) | N3B—C4B—N5B—C6B | 0.2 (2) |
C1A—C2A—N3A—C4A | 179.08 (18) | N7B—C4B—N5B—C10B | −0.2 (3) |
C2A—N3A—C4A—N7A | 178.30 (19) | N3B—C4B—N5B—C10B | 179.83 (17) |
C2A—N3A—C4A—N5A | −0.7 (2) | N3B—C2B—C6B—N5B | 0.4 (2) |
N7A—C4A—N5A—C6A | −178.00 (19) | C1B—C2B—C6B—N5B | −179.4 (2) |
N3A—C4A—N5A—C6A | 1.0 (2) | C4B—N5B—C6B—C2B | −0.4 (2) |
N7A—C4A—N5A—C10A | 3.4 (3) | C10B—N5B—C6B—C2B | 179.97 (18) |
N3A—C4A—N5A—C10A | −177.65 (17) | N3B—C4B—N7B—C8B | −179.57 (18) |
N3A—C2A—C6A—N5A | 0.5 (2) | N5B—C4B—N7B—C8B | 0.4 (3) |
C1A—C2A—C6A—N5A | −178.3 (2) | C4B—N7B—C8B—N14B | 179.33 (17) |
C4A—N5A—C6A—C2A | −0.9 (2) | C4B—N7B—C8B—C9B | −0.4 (3) |
C10A—N5A—C6A—C2A | 177.61 (18) | N7B—C8B—C9B—N12B | 179.69 (18) |
N3A—C4A—N7A—C8A | −179.87 (19) | N14B—C8B—C9B—N12B | −0.1 (2) |
N5A—C4A—N7A—C8A | −1.1 (3) | N7B—C8B—C9B—C10B | 0.0 (3) |
C4A—N7A—C8A—N14A | 178.79 (19) | N14B—C8B—C9B—C10B | −179.72 (17) |
C4A—N7A—C8A—C9A | −1.4 (3) | N12B—C9B—C10B—O11B | 0.9 (3) |
N7A—C8A—C9A—N12A | −179.3 (2) | C8B—C9B—C10B—O11B | −179.5 (2) |
N14A—C8A—C9A—N12A | 0.6 (2) | N12B—C9B—C10B—N5B | −179.33 (18) |
N7A—C8A—C9A—C10A | 1.7 (3) | C8B—C9B—C10B—N5B | 0.2 (3) |
N14A—C8A—C9A—C10A | −178.44 (18) | C4B—N5B—C10B—O11B | 179.60 (18) |
C4A—N5A—C10A—O11A | 176.87 (18) | C6B—N5B—C10B—O11B | −0.8 (3) |
C6A—N5A—C10A—O11A | −1.5 (3) | C4B—N5B—C10B—C9B | −0.2 (2) |
C4A—N5A—C10A—C9A | −2.7 (3) | C6B—N5B—C10B—C9B | 179.40 (18) |
C6A—N5A—C10A—C9A | 178.97 (18) | C8B—C9B—N12B—C13B | −0.2 (2) |
N12A—C9A—C10A—O11A | 2.1 (4) | C10B—C9B—N12B—C13B | 179.4 (2) |
C8A—C9A—C10A—O11A | −179.0 (2) | C9B—N12B—C13B—N14B | 0.4 (2) |
N12A—C9A—C10A—N5A | −178.36 (19) | N7B—C8B—N14B—C13B | −179.48 (19) |
C8A—C9A—C10A—N5A | 0.5 (3) | C9B—C8B—N14B—C13B | 0.3 (2) |
C8A—C9A—N12A—C13A | −0.5 (2) | N7B—C8B—N14B—C15B | 3.3 (3) |
C10A—C9A—N12A—C13A | 178.4 (2) | C9B—C8B—N14B—C15B | −176.89 (18) |
C9A—N12A—C13A—N14A | 0.2 (3) | N12B—C13B—N14B—C8B | −0.4 (2) |
N12A—C13A—N14A—C8A | 0.2 (3) | N12B—C13B—N14B—C15B | 176.87 (18) |
N12A—C13A—N14A—C15A | −178.6 (2) | C8B—N14B—C15B—O16B | 106.7 (2) |
N7A—C8A—N14A—C13A | 179.41 (19) | C13B—N14B—C15B—O16B | −70.0 (3) |
C9A—C8A—N14A—C13A | −0.5 (2) | O16C—C15B—O16B—C17B | 25.6 (4) |
N7A—C8A—N14A—C15A | −1.7 (3) | N14B—C15B—O16B—C17B | −68.5 (3) |
C9A—C8A—N14A—C15A | 178.4 (2) | C15B—O16B—C17B—C18B | 178.8 (2) |
C8A—N14A—C15A—O16A | −78.4 (3) | O16B—C17B—C18B—O19B | 74.6 (4) |
C13A—N14A—C15A—O16A | 100.2 (3) | O16B—C15B—O16C—C17C | −34.4 (5) |
N14A—C15A—O16A—C17A | −87.1 (3) | C8B—N14B—C15B—O16C | 65.0 (4) |
C15A—O16A—C17A—C18A | 171.4 (2) | C13B—N14B—C15B—O16C | −111.7 (3) |
O16A—C17A—C18A—O19A | 67.5 (3) | N14B—C15B—O16C—C17C | 67.1 (7) |
C6B—C2B—N3B—C4B | −0.3 (2) | C15B—O16C—C17C—C18B | 171.2 (5) |
C1B—C2B—N3B—C4B | 179.48 (18) | O16C—C17C—C18B—O19B | −59.5 (10) |
C2B—N3B—C4B—N7B | −179.90 (18) | O16C—C17C—C18B—C17B | 27.1 (5) |
C2B—N3B—C4B—N5B | 0.1 (2) | O16B—C17B—C18B—C17C | −37.7 (7) |
N7B—C4B—N5B—C6B | −179.83 (18) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N3A—H3A···N12Bi | 0.98 (2) | 1.85 (2) | 2.800 (2) | 163.4 (19) |
N3B—H3B···O11A | 0.86 (2) | 1.98 (2) | 2.747 (2) | 148 (2) |
O19B—H19B···O19Bii | 0.82 | 2.02 | 2.671 (4) | 135 |
O19A—H19A···O3Wiii | 1.02 (4) | 1.71 (4) | 2.731 (2) | 177 (3) |
O1W—H1WB···O19Biv | 0.89 | 1.84 | 2.706 (2) | 164 |
O2W—H2WA···N12Av | 0.84 | 1.96 | 2.797 (2) | 177 |
O2W—H2WB···N7Bv | 0.78 | 2.21 | 2.982 (2) | 173 |
O3W—H3WB···O11Bvi | 0.97 | 1.85 | 2.8219 (18) | 176 |
O4W—H4WB···O19Avii | 0.82 | 2.00 | 2.738 (2) | 149 |
O1W—H1WA···O2W | 1.00 | 1.69 | 2.679 | 170 |
O1W—H1WC···O1Wviii | 0.82 | 1.99 | 2.808 (2) | 175 |
O3W—H3WA···O4W | 0.84 | 1.94 | 2.751 | 163 |
O4W—H4WA···O1W | 0.77 | 2.11 | 2.852 | 163 |
Symmetry codes: (i) x−1, y−1, z; (ii) −x, −y+1, −z+2; (iii) −x−1, −y, −z+1; (iv) x, y, z−1; (v) −x, −y+1, −z+1; (vi) x, y−1, z; (vii) x+2, y, z−1; (viii) −x+1, −y+1, −z. |
Experimental details
Crystal data |
Chemical formula | C11H13N5O3.2H2O |
Mr | 299.30 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 293 |
a, b, c (Å) | 8.450 (1), 11.665 (2), 14.930 (3) |
α, β, γ (°) | 75.44 (2), 76.65 (2), 86.44 (2) |
V (Å3) | 1385.9 (4) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.12 |
Crystal size (mm) | 0.32 × 0.28 × 0.22 |
|
Data collection |
Diffractometer | Enraf-Nonius CAD4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 8414, 8047, 4182 |
Rint | 0.023 |
(sin θ/λ)max (Å−1) | 0.703 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.062, 0.155, 1.02 |
No. of reflections | 8047 |
No. of parameters | 389 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.26, −0.20 |
Selected geometric parameters (Å, º) topC4A—N5A | 1.389 (2) | C4B—N5B | 1.381 (2) |
N5A—C6A | 1.405 (3) | N5B—C6B | 1.393 (3) |
N7A—C8A | 1.336 (3) | N7B—C8B | 1.357 (2) |
C8A—C9A | 1.395 (3) | C8B—C9B | 1.390 (3) |
| | | |
N7A—C4A—N3A | 127.11 (17) | N7B—C4B—N3B | 127.55 (17) |
N3A—C4A—N5A | 106.59 (17) | N3B—C4B—N5B | 105.70 (17) |
| | | |
C8A—N14A—C15A—O16A | −78.4 (3) | C15B—O16B—C17B—C18B | 178.8 (2) |
C13A—N14A—C15A—O16A | 100.2 (3) | O16B—C17B—C18B—O19B | 74.6 (4) |
N14A—C15A—O16A—C17A | −87.1 (3) | C8B—N14B—C15B—O16C | 65.0 (4) |
C15A—O16A—C17A—C18A | 171.4 (2) | C13B—N14B—C15B—O16C | −111.7 (3) |
O16A—C17A—C18A—O19A | 67.5 (3) | N14B—C15B—O16C—C17C | 67.1 (7) |
C8B—N14B—C15B—O16B | 106.7 (2) | C15B—O16C—C17C—C18B | 171.2 (5) |
C13B—N14B—C15B—O16B | −70.0 (3) | O16C—C17C—C18B—O19B | −59.5 (10) |
N14B—C15B—O16B—C17B | −68.5 (3) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N3A—H3A···N12Bi | 0.98 (2) | 1.85 (2) | 2.800 (2) | 163.4 (19) |
N3B—H3B···O11A | 0.86 (2) | 1.98 (2) | 2.747 (2) | 148 (2) |
O19B—H19B···O19Bii | 0.82 | 2.02 | 2.671 (4) | 135 |
O19A—H19A···O3Wiii | 1.02 (4) | 1.71 (4) | 2.731 (2) | 177 (3) |
O1W—H1WB···O19Biv | 0.89 | 1.84 | 2.706 (2) | 164 |
O2W—H2WA···N12Av | 0.84 | 1.96 | 2.797 (2) | 177 |
O2W—H2WB···N7Bv | 0.78 | 2.21 | 2.982 (2) | 173 |
O3W—H3WB···O11Bvi | 0.97 | 1.85 | 2.8219 (18) | 176 |
O4W—H4WB···O19Avii | 0.82 | 2.00 | 2.738 (2) | 149 |
O1W—H1WA···O2W | 1.00 | 1.69 | 2.679 | 170 |
O1W—H1WC···O1Wviii | 0.82 | 1.99 | 2.808 (2) | 175 |
O3W—H3WA···O4W | 0.84 | 1.94 | 2.751 | 163 |
O4W—H4WA···O1W | 0.77 | 2.11 | 2.852 | 163 |
Symmetry codes: (i) x−1, y−1, z; (ii) −x, −y+1, −z+2; (iii) −x−1, −y, −z+1; (iv) x, y, z−1; (v) −x, −y+1, −z+1; (vi) x, y−1, z; (vii) x+2, y, z−1; (viii) −x+1, −y+1, −z. |
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Acyclovir, (I), has been demonstrated to be of great clinical importance as an antiherpetic agent (Elion et al., 1997). Tricyclic acyclovir, (II), in which the exocyclic amine group of (I) is incorporated into a new fused ring, was expected to be inactive, but instead exhibited potent and selective antiherpes activity. The spectrum of its activity was narrower than that of acyclovir and resulted in a higher selectivity index compared with acyclovir itself (Boryski et al., 1988; Golankiewicz, 1996). Recently, complex physicocemical studies of the title compound, (II), were undertaken and included determination of aqueous solubilities, infinite dilution activity coefficients and octanol-water partition coefficients, as well as other thermodynamic properties of the compound in aqueous solution (Zielenkiewicz et al., 1998, 1999). Thermogravimetric studies (Perlovich & Zielenkiewicz, 1998) have demonstrated that, in crystalline (II), there are always solvent molecules present, independent of the solvent used (water or water/organic solvent mixture). The present study was undertaken to determine the nature of the solvation of (II) in the solid state and we hope it will contribute to an understanding of the relationships between the structure and thermodynamic parameters of the compounds examined. \sch
The two symmetry-independent molecules of (II) have different conformations and, additionally, the (2-hydroxyethoxy)methyl side chain in molecule B is conformationally disordered, with two different conformations, B and C, observed in the crystal structure (Fig. 1). The distribution of the different conformers A:B:C in the crystal is 4:3:1. Conformations A and C are fairly similar, but not identical, while conformation B is different. For conformations A and C, the corresponding torsion angles C13—N14—C15—O16 and C8—N14—C15—O16 are, respectively, anticlinal and synclinal, according to the notation of Klyne & Prelog (1960), while for conformation B the analogous torsion angles are reversed. In both cases, this leads to a partially folded conformation of the (2-hydroxyethoxy)methyl side chain. Details of the two types of conformations are given in Table 1 (it should be noted that in centrosymmetric space groups the signs of the torsion angles in Table 1 may be reversed). When compared with (I), where three symmetry-independent molecules are also found, the side-chain conformations of two of the molecules of (I) are similar to those of molecules A and C, but the third molecule adopts a different conformation, with the side chain more fully extended (Birnbaum et al., 1984).
The bond lengths and angles of the guanine moiety (Table 1) are in good agreement with values derived from other crystal-structure analyses and those found for (I). The differences are N7—C8 in molecule A, which is 0.019 Å shorter, and C8—C9 in both molecules, which is 0.019 (molecule A) and 0.014 Å (molecule B) longer, than in (I). The bonds C4—N5 and N5—C6 are elongated by approximately 0.02 Å because of the additional ring fusion in (II). For the bond angles, the differences are at C4 for both molecules, where the N3—C4—N5 angles are more acute and the N3—C4—N7 angles are more obtuse than in (I). This is again related to the presence of the additional fused ring.
The 12 atoms involved in the formation of the three condensed rings are planar. The r.m.s. deviations of the fitted atoms are 0.021 Å and 0.007 Å for molecules A and B, respectively. In addition, the ring systems of molecules A and B are coplanar. The molecules are almost parallel, with the angle between the planes of the two molecules being 4.41 (7)°, and the largest deviations from planarity are for atoms C6A [0.039 (2) Å] and C13B [0.013 (2) Å]. The atoms substituted directly to the condensed ring systems are displaced from the r.m.s. planes by -0.012 (3), -0.054 (2) and 0.095 (3) Å for C1A, O11A and C15A, respectively, and by 0.003 (3), -0.017 (2) and -0.055 (3) Å for C1B, O11B and C15B, respectively.
The hydrogen-bonding pattern in (II) (Table 2) is remarkable. It joins all the bases into infinite –A—B—A—B-type chains (Fig. 2). Each base of molecule A is connected to adjacent molecules B by donating a proton in a hydrogen bond (N3A—H···N12B) and by accepting a proton in a hydrogen bond (N3B—H···O11A). Atoms N7 of both molecules and atom O11B are not involved in hydrogen bonding between the bases, although they are involved in hydrogen bonding with the water molecules. Each water molecule is involved in hydrogen bonds to molecules of (II) as well as to adjacent water molecules. In the structure, the water molecules form (H2O)8 clusters - four symmetry-independent molecules interact with four others across a centre of symmetry. One of the H atoms of water molecule O1W is disordered, with a site occupancy factor of 0.50. Fig. 1c shows the (H2O)8 cluster. The hydrogen bonds between (II) and water in the solid state may mimic those found in solution for the solvated molecule of (II).