In the title compound, 4-amino-1-(2-deoxy-β-
D-
eythro-pentofuranosyl)-3-vinyl-1
H-pyrazolo[3,4-
d]pyrimidine monohydrate, C
12H
15N
5O
3·H
2O, the conformation of the glycosyl bond is
anti. The furanose moiety is in an
S conformation with an unsymmetrical twist, and the conformation at the exocyclic C—C(OH) bond is +
sc (
gauche,
gauche). The vinyl side chain is bent out of the heterocyclic ring plane by 147.5 (5)°. The three-dimensional packing is stabilized by O—H
O, O—H
N and N—H
O hydrogen bonds.
Supporting information
CCDC reference: 263069
Compound (I) was synthesized by a known procedure (Seela & Zulauf, 1998) and was crystallized as the monohydrate from aqueous methanol. For the diffraction experiment, a single-crystal was fixed at the top of a Lindemann capillary with epoxy resin.
In the absence of suitable anomalous scattering, Friedel equivalents could not be used to determine the absotute structure. Therefore, Friedel pairs were merged before the final refinements. The known configuration of the parent molecule was used to define the enantiomer of the final nucleoside. All H atoms were initially found in a difference Fourier synthesis. H atoms bonded to C and N atoms were placed in idealized positions (C—H = 0.93–0.98 Å and N—H = 0.86 Å) and constrained to ride on their parent atoms with Uiso(H) values of 1.2Ueq(C) and 1.5Ueq(N). Treatment of water H atoms?
Data collection: XSCANS (Siemens, 1996); cell refinement: XSCANS; data reduction: SHELXTL (Sheldrick, 1997); program(s) used to solve structure: SHELXTL; program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 1999).
Crystal data top
C12H15N5O3·H2O | F(000) = 624 |
Mr = 295.31 | Dx = 1.430 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 28 reflections |
a = 6.6513 (8) Å | θ = 4.9–12.5° |
b = 9.603 (5) Å | µ = 0.11 mm−1 |
c = 21.481 (3) Å | T = 293 K |
V = 1372.1 (7) Å3 | Block, colourless |
Z = 4 | 0.42 × 0.28 × 0.20 mm |
Data collection top
Bruker P4 diffractometer | Rint = 0.040 |
Radiation source: fine-focus sealed tube | θmax = 29.0°, θmin = 2.3° |
Graphite monochromator | h = −1→9 |
2θ/ω scans | k = −1→13 |
2800 measured reflections | l = −29→1 |
2100 independent reflections | 3 standard reflections every 97 reflections |
1180 reflections with I > 2σ(I) | intensity decay: none |
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)] = 0.058 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.113 | w = 1/[σ2(Fo2) + (0.0349P)2] where P = (Fo2 + 2Fc2)/3 |
S = 1.02 | (Δ/σ)max < 0.001 |
2100 reflections | Δρmax = 0.22 e Å−3 |
205 parameters | Δρmin = −0.21 e Å−3 |
5 restraints | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0074 (11) |
Crystal data top
C12H15N5O3·H2O | V = 1372.1 (7) Å3 |
Mr = 295.31 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 6.6513 (8) Å | µ = 0.11 mm−1 |
b = 9.603 (5) Å | T = 293 K |
c = 21.481 (3) Å | 0.42 × 0.28 × 0.20 mm |
Data collection top
Bruker P4 diffractometer | Rint = 0.040 |
2800 measured reflections | 3 standard reflections every 97 reflections |
2100 independent reflections | intensity decay: none |
1180 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.058 | 5 restraints |
wR(F2) = 0.113 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.02 | Δρmax = 0.22 e Å−3 |
2100 reflections | Δρmin = −0.21 e Å−3 |
205 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 | |
N1 | 0.7445 (6) | 0.5975 (3) | 0.54376 (12) | 0.0360 (7) | |
C2 | 0.7462 (7) | 0.5638 (4) | 0.48368 (14) | 0.0372 (9) | |
H2 | 0.7467 | 0.4687 | 0.4755 | 0.045* | |
N3 | 0.7474 (6) | 0.6450 (3) | 0.43335 (11) | 0.0329 (7) | |
C4 | 0.7511 (7) | 0.7810 (3) | 0.44955 (14) | 0.0309 (8) | |
C5 | 0.7518 (7) | 0.8351 (3) | 0.50977 (13) | 0.0283 (8) | |
N6 | 0.7363 (5) | 0.7665 (3) | 0.61930 (10) | 0.0383 (8) | |
H6A | 0.7328 | 0.7013 | 0.6467 | 0.057* | |
H6B | 0.7352 | 0.8523 | 0.6308 | 0.057* | |
C6 | 0.7433 (7) | 0.7341 (4) | 0.55823 (14) | 0.0309 (8) | |
C7 | 0.7561 (7) | 0.9829 (3) | 0.50242 (12) | 0.0306 (8) | |
C71 | 0.7639 (7) | 1.0921 (4) | 0.54974 (14) | 0.0367 (9) | |
H71 | 0.7004 | 1.0757 | 0.5876 | 0.044* | |
C72 | 0.8549 (7) | 1.2113 (4) | 0.54196 (19) | 0.0523 (13) | |
H72A | 0.9197 | 1.2306 | 0.5046 | 0.063* | |
H72B | 0.8549 | 1.2769 | 0.5738 | 0.063* | |
N8 | 0.7576 (5) | 1.0140 (3) | 0.44211 (10) | 0.0321 (7) | |
N9 | 0.7518 (6) | 0.8909 (3) | 0.40996 (10) | 0.0327 (7) | |
C1' | 0.7540 (7) | 0.8897 (4) | 0.34202 (13) | 0.0343 (9) | |
H1' | 0.7249 | 0.7951 | 0.3274 | 0.041* | |
C2' | 0.6036 (6) | 0.9899 (4) | 0.31293 (16) | 0.0415 (10) | |
H2'1 | 0.4883 | 0.9398 | 0.2967 | 0.050* | |
H2'2 | 0.5575 | 1.0573 | 0.3434 | 0.050* | |
C3' | 0.7170 (6) | 1.0614 (4) | 0.26076 (13) | 0.0341 (10) | |
H3'1 | 0.6723 | 1.1579 | 0.2555 | 0.041* | |
O3' | 0.7050 (5) | 0.9861 (3) | 0.20340 (11) | 0.0461 (8) | |
H3' | 0.586 (2) | 0.977 (5) | 0.194 (2) | 0.069* | |
O4' | 0.9466 (4) | 0.9300 (3) | 0.32001 (11) | 0.0378 (7) | |
C4' | 0.9360 (7) | 1.0549 (4) | 0.28232 (17) | 0.0367 (10) | |
H4' | 1.0219 | 1.0421 | 0.2457 | 0.044* | |
O5' | 0.8724 (6) | 1.2346 (3) | 0.36217 (12) | 0.0588 (10) | |
H5' | 0.844 (8) | 1.181 (4) | 0.3912 (15) | 0.088* | |
C5' | 1.0097 (7) | 1.1807 (4) | 0.31795 (19) | 0.0545 (13) | |
H5'1 | 1.1331 | 1.1559 | 0.3393 | 0.065* | |
H5'2 | 1.0420 | 1.2537 | 0.2884 | 0.065* | |
O10 | 0.3108 (5) | 0.9789 (3) | 0.17403 (11) | 0.0519 (9) | |
H10A | 0.305 (7) | 1.040 (3) | 0.1415 (11) | 0.078* | |
H10B | 0.262 (8) | 0.898 (2) | 0.1583 (14) | 0.078* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
N1 | 0.038 (2) | 0.0340 (17) | 0.0360 (14) | −0.002 (2) | 0.0022 (19) | 0.0077 (13) |
C2 | 0.043 (2) | 0.0257 (17) | 0.0423 (18) | 0.001 (3) | 0.002 (3) | −0.0004 (16) |
N3 | 0.0355 (18) | 0.0308 (15) | 0.0323 (13) | −0.003 (2) | 0.0000 (19) | −0.0002 (12) |
C4 | 0.031 (2) | 0.0325 (18) | 0.0295 (15) | −0.003 (3) | −0.005 (2) | 0.0037 (14) |
C5 | 0.027 (2) | 0.0308 (16) | 0.0269 (15) | 0.001 (2) | 0.003 (2) | −0.0004 (14) |
N6 | 0.055 (2) | 0.0372 (15) | 0.0222 (12) | −0.001 (2) | 0.0005 (17) | 0.0064 (12) |
C6 | 0.024 (2) | 0.0363 (19) | 0.0323 (17) | 0.002 (2) | −0.002 (2) | 0.0059 (15) |
C7 | 0.030 (2) | 0.0340 (18) | 0.0280 (15) | −0.001 (3) | −0.005 (2) | 0.0009 (14) |
C71 | 0.048 (3) | 0.035 (2) | 0.0276 (15) | −0.001 (3) | 0.002 (2) | 0.0009 (15) |
C72 | 0.071 (4) | 0.041 (2) | 0.045 (2) | −0.003 (3) | 0.008 (2) | −0.008 (2) |
N8 | 0.0401 (18) | 0.0293 (15) | 0.0268 (13) | −0.001 (2) | 0.0001 (19) | 0.0009 (12) |
N9 | 0.048 (2) | 0.0266 (15) | 0.0236 (12) | −0.002 (2) | −0.0020 (19) | 0.0032 (11) |
C1' | 0.042 (2) | 0.0365 (18) | 0.0245 (14) | −0.001 (3) | −0.001 (2) | −0.0023 (14) |
C2' | 0.037 (2) | 0.056 (2) | 0.032 (2) | 0.004 (2) | −0.0028 (19) | 0.006 (2) |
C3' | 0.046 (3) | 0.0311 (18) | 0.0253 (15) | 0.003 (2) | −0.0019 (18) | 0.0030 (15) |
O3' | 0.056 (2) | 0.0555 (16) | 0.0270 (12) | 0.002 (2) | −0.0017 (14) | −0.0029 (12) |
O4' | 0.0384 (17) | 0.0426 (15) | 0.0324 (13) | 0.0081 (14) | 0.0032 (13) | 0.0077 (13) |
C4' | 0.043 (3) | 0.037 (2) | 0.0297 (18) | 0.000 (2) | 0.0044 (19) | 0.0057 (18) |
O5' | 0.100 (3) | 0.0368 (16) | 0.0397 (15) | −0.001 (2) | 0.0022 (19) | 0.0011 (13) |
C5' | 0.063 (3) | 0.047 (2) | 0.053 (2) | −0.009 (3) | 0.002 (3) | −0.001 (2) |
O10 | 0.065 (2) | 0.0538 (17) | 0.0372 (13) | −0.0075 (18) | −0.0046 (16) | 0.0010 (13) |
Geometric parameters (Å, º) top
N1—C2 | 1.331 (4) | C1'—O4' | 1.419 (5) |
N1—C6 | 1.348 (4) | C1'—C2' | 1.523 (5) |
C2—N3 | 1.333 (4) | C1'—H1' | 0.9800 |
C2—H2 | 0.9300 | C2'—C3' | 1.515 (5) |
N3—C4 | 1.352 (4) | C2'—H2'1 | 0.9700 |
C4—N9 | 1.355 (4) | C2'—H2'2 | 0.9700 |
C4—C5 | 1.394 (4) | C3'—O3' | 1.431 (4) |
C5—C6 | 1.424 (4) | C3'—C4' | 1.530 (6) |
C5—C7 | 1.429 (5) | C3'—H3'1 | 0.9800 |
N6—C6 | 1.349 (4) | O3'—H3' | 0.823 (10) |
N6—H6A | 0.8600 | O4'—C4' | 1.449 (4) |
N6—H6B | 0.8600 | C4'—C5' | 1.512 (5) |
C7—N8 | 1.330 (3) | C4'—H4' | 0.9800 |
C7—C71 | 1.461 (4) | O5'—C5' | 1.416 (5) |
C71—C72 | 1.306 (5) | O5'—H5' | 0.83 (4) |
C71—H71 | 0.9300 | C5'—H5'1 | 0.9700 |
C72—H72A | 0.9300 | C5'—H5'2 | 0.9700 |
C72—H72B | 0.9300 | O10—H10A | 0.910 (15) |
N8—N9 | 1.370 (3) | O10—H10B | 0.910 (15) |
N9—C1' | 1.460 (4) | | |
| | | |
C2—N1—C6 | 117.4 (3) | N9—C1'—C2' | 113.5 (3) |
N1—C2—N3 | 130.1 (3) | O4'—C1'—H1' | 109.0 |
N1—C2—H2 | 114.9 | N9—C1'—H1' | 109.0 |
N3—C2—H2 | 114.9 | C2'—C1'—H1' | 109.0 |
C2—N3—C4 | 110.9 (3) | C3'—C2'—C1' | 105.2 (3) |
N3—C4—N9 | 126.2 (3) | C3'—C2'—H2'1 | 110.7 |
N3—C4—C5 | 126.8 (3) | C1'—C2'—H2'1 | 110.7 |
N9—C4—C5 | 107.0 (3) | C3'—C2'—H2'2 | 110.7 |
C4—C5—C6 | 115.1 (3) | C1'—C2'—H2'2 | 110.7 |
C4—C5—C7 | 105.5 (3) | H2'1—C2'—H2'2 | 108.8 |
C6—C5—C7 | 139.3 (3) | O3'—C3'—C2' | 112.4 (3) |
C6—N6—H6A | 120.0 | O3'—C3'—C4' | 107.1 (3) |
C6—N6—H6B | 120.0 | C2'—C3'—C4' | 103.4 (3) |
H6A—N6—H6B | 120.0 | O3'—C3'—H3'1 | 111.2 |
N1—C6—N6 | 116.7 (3) | C2'—C3'—H3'1 | 111.2 |
N1—C6—C5 | 119.6 (3) | C4'—C3'—H3'1 | 111.2 |
N6—C6—C5 | 123.7 (3) | C3'—O3'—H3' | 108 (3) |
N8—C7—C5 | 109.3 (3) | C1'—O4'—C4' | 111.6 (3) |
N8—C7—C71 | 121.1 (3) | O4'—C4'—C5' | 111.3 (3) |
C5—C7—C71 | 129.6 (3) | O4'—C4'—C3' | 104.4 (3) |
C72—C71—C7 | 123.8 (4) | C5'—C4'—C3' | 115.5 (4) |
C72—C71—H71 | 118.1 | O4'—C4'—H4' | 108.5 |
C7—C71—H71 | 118.1 | C5'—C4'—H4' | 108.5 |
C71—C72—H72A | 120.0 | C3'—C4'—H4' | 108.5 |
C71—C72—H72B | 120.0 | C5'—O5'—H5' | 115 (4) |
H72A—C72—H72B | 120.0 | O5'—C5'—C4' | 115.0 (4) |
C7—N8—N9 | 107.3 (3) | O5'—C5'—H5'1 | 108.5 |
C4—N9—N8 | 110.8 (2) | C4'—C5'—H5'1 | 108.5 |
C4—N9—C1' | 128.4 (3) | O5'—C5'—H5'2 | 108.5 |
N8—N9—C1' | 120.7 (3) | C4'—C5'—H5'2 | 108.5 |
O4'—C1'—N9 | 109.9 (3) | H5'1—C5'—H5'2 | 107.5 |
O4'—C1'—C2' | 106.5 (3) | H10A—O10—H10B | 105 (3) |
| | | |
C6—N1—C2—N3 | 0.1 (8) | C5—C4—N9—N8 | 1.4 (5) |
N1—C2—N3—C4 | 1.3 (7) | N3—C4—N9—C1' | −1.7 (8) |
C2—N3—C4—N9 | −179.5 (5) | C5—C4—N9—C1' | 179.2 (4) |
C2—N3—C4—C5 | −0.5 (7) | C7—N8—N9—C4 | −1.3 (5) |
N3—C4—C5—C6 | −1.5 (7) | C7—N8—N9—C1' | −179.3 (4) |
N9—C4—C5—C6 | 177.7 (4) | C4—N9—C1'—O4' | −106.9 (5) |
N3—C4—C5—C7 | 180.0 (5) | N8—N9—C1'—O4' | 70.7 (5) |
N9—C4—C5—C7 | −0.9 (5) | C4—N9—C1'—C2' | 134.0 (5) |
C2—N1—C6—N6 | 178.3 (4) | N8—N9—C1'—C2' | −48.3 (6) |
C2—N1—C6—C5 | −2.4 (7) | O4'—C1'—C2'—C3' | 15.0 (4) |
C4—C5—C6—N1 | 3.0 (6) | N9—C1'—C2'—C3' | 136.0 (4) |
C7—C5—C6—N1 | −179.2 (6) | C1'—C2'—C3'—O3' | 88.1 (4) |
C4—C5—C6—N6 | −177.8 (5) | C1'—C2'—C3'—C4' | −27.0 (4) |
C7—C5—C6—N6 | 0.0 (9) | N9—C1'—O4'—C4' | −119.2 (3) |
C4—C5—C7—N8 | 0.1 (6) | C2'—C1'—O4'—C4' | 4.1 (4) |
C6—C5—C7—N8 | −177.9 (5) | C1'—O4'—C4'—C5' | 104.0 (4) |
C4—C5—C7—C71 | −178.2 (5) | C1'—O4'—C4'—C3' | −21.2 (4) |
C6—C5—C7—C71 | 3.9 (11) | O3'—C3'—C4'—O4' | −89.6 (3) |
N8—C7—C71—C72 | −30.6 (7) | C2'—C3'—C4'—O4' | 29.3 (4) |
C5—C7—C71—C72 | 147.5 (5) | O3'—C3'—C4'—C5' | 147.9 (3) |
C5—C7—N8—N9 | 0.8 (5) | C2'—C3'—C4'—C5' | −93.2 (4) |
C71—C7—N8—N9 | 179.2 (4) | O4'—C4'—C5'—O5' | −76.7 (4) |
N3—C4—N9—N8 | −179.5 (5) | C3'—C4'—C5'—O5' | 42.1 (4) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N6—H6A···O4′i | 0.86 | 2.39 | 2.995 (4) | 128 |
N6—H6B···O3′ii | 0.86 | 2.24 | 3.010 (4) | 150 |
O3′—H3′···O10 | 0.82 (2) | 1.88 (2) | 2.698 (5) | 173 (5) |
O5′—H5′···N8 | 0.83 (4) | 2.02 (4) | 2.832 (4) | 164 (4) |
O10—H10A···N3iii | 0.91 (3) | 1.93 (3) | 2.831 (4) | 169 (4) |
O10—H10B···O5′iv | 0.91 (3) | 1.86 (3) | 2.755 (4) | 169 (4) |
Symmetry codes: (i) x−1/2, −y+3/2, −z+1; (ii) −x+3/2, −y+2, z+1/2; (iii) −x+1, y+1/2, −z+1/2; (iv) −x+1, y−1/2, −z+1/2. |
Experimental details
Crystal data |
Chemical formula | C12H15N5O3·H2O |
Mr | 295.31 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 293 |
a, b, c (Å) | 6.6513 (8), 9.603 (5), 21.481 (3) |
V (Å3) | 1372.1 (7) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.11 |
Crystal size (mm) | 0.42 × 0.28 × 0.20 |
|
Data collection |
Diffractometer | Bruker P4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2800, 2100, 1180 |
Rint | 0.040 |
(sin θ/λ)max (Å−1) | 0.681 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.058, 0.113, 1.02 |
No. of reflections | 2100 |
No. of parameters | 205 |
No. of restraints | 5 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.22, −0.21 |
Selected geometric parameters (Å, º) topC7—C71 | 1.461 (4) | N8—N9 | 1.370 (3) |
C71—C72 | 1.306 (5) | N9—C1' | 1.460 (4) |
| | | |
N8—C7—C5 | 109.3 (3) | C5—C7—C71 | 129.6 (3) |
N8—C7—C71 | 121.1 (3) | C72—C71—C7 | 123.8 (4) |
| | | |
N8—C7—C71—C72 | −30.6 (7) | C4—N9—C1'—C2' | 134.0 (5) |
C5—C7—C71—C72 | 147.5 (5) | N8—N9—C1'—C2' | −48.3 (6) |
C4—N9—C1'—O4' | −106.9 (5) | O4'—C4'—C5'—O5' | −76.7 (4) |
N8—N9—C1'—O4' | 70.7 (5) | C3'—C4'—C5'—O5' | 42.1 (4) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N6—H6A···O4'i | 0.86 | 2.39 | 2.995 (4) | 128 |
N6—H6B···O3'ii | 0.86 | 2.24 | 3.010 (4) | 150 |
O3'—H3'···O10 | 0.82 (2) | 1.88 (2) | 2.698 (5) | 173 (5) |
O5'—H5'···N8 | 0.83 (4) | 2.02 (4) | 2.832 (4) | 164 (4) |
O10—H10A···N3iii | 0.91 (3) | 1.93 (3) | 2.831 (4) | 169 (4) |
O10—H10B···O5'iv | 0.91 (3) | 1.86 (3) | 2.755 (4) | 169 (4) |
Symmetry codes: (i) x−1/2, −y+3/2, −z+1; (ii) −x+3/2, −y+2, z+1/2; (iii) −x+1, y+1/2, −z+1/2; (iv) −x+1, y−1/2, −z+1/2. |
The 7-substituted 8-aza-7-deazapurine 2'-deoxyribonucleosides (3-substituted pyrazolo[3,4-d]pyrimidine 2'-deoxyribonucleosides) are studied as analogues of natural DNA constituents. Compound (II) (Seela & Steker, 1985; Seela et al., 1999a; Seela & Kaiser, 1988) has attracted attention as it is in ideal shape mimic of 2'-deoxyadenosine. Purine numbering is used throughout the manuscript. The 7-substited derivatives of compound (II) have a stabilizing effect on oligonucleotide duplexes (Seela et al., 1999b; Seela & Zulauf, 1999). Thus, the 7-position of an 8-aza-7-deazapurine 2'-deoxyribonucleoside is an attractive site for modification as it is the 5-position of a pyrimidine nucleoside (Gourlain et al., 2001). Cheng et al. (1976) reported that 5-vinyl-2'-deoxyuridine, (III), has the capacity for viral and tumour inhibition. A single-crystal X-ray analysis of (III) was reported in 1978 (Hamor et al., 1978). This manuscript reports on the single-crystal X-ray structure of 4-amino-1-(2-deoxy-β-D-eythro- pentofuranosyl)-3-vinyl-1H-pyrazolo[3,4-d]pyrimidine monohydrate, (I), containing a vinyl side chain in the 7-position.
Canonical purine 2'-deoxyribonucleosides tend to adopt an anti conformation. The orientation of the base relative to the sugar moiety (syn/anti) of purine nucleosides is defined by the torsion angle χ (O4'—C1'—N9—C4) (IUPAC–IUB Joint Commission on Biochemical Nomenclature, 1983). In the crystal structure of (I) (Fig. 1), the conformation of the glycosylic bond is between anti and high-anti [χ = −106.9 (5)°]. A similar conformation was observed for the parent 8-aza-7-deazapurine 2'-deoxyribonucleoside (II), with χ = −106.3 (2)° (Seela et al., 1999a). Halogen substituents at the 7-position drive the conformation to high-anti, with χ = −74.1 (4) (7-bromo) and −73.2 (4)° (7-iodo) (Seela et al., 2000). This phenomenon might be caused by stereoelectronic effects of the base. As the vinyl group has an electron withdrawing influence on the heterocyclic base, the pKa value of protonation is decreased from 4.0 in (II) to 3.54 in (I). The glycosylic bond length in (I) (N9—C1' = 1.460 (4) Å] is slightly longer than that in (II) [1.442 (2) Å].
The pseudorotation phase, P, and the puckering amplitude, τ, angles (Rao et al., 1981) show that the sugar ring of (I) adopts an S conformation, with an unsymmetrical twist of the C4'-endo—C3'-exo bond (between 3E and 3T4), having a P value of 205.6 (4)° and τ of 30.2 (2)°. In (II), the sugar ring conformation is 3T2, [P = 182.2 (2)° and τ = 41.2 (2)°]. The conformation about the C4'—C5' bond of (I) is +sc (gauche, gauche), with dihedral angle γ 42.1 (4)°, whereas in (II), the C4'—C5' bond adopts an -ap (trans) conformation with γ equal to −178.73 (16)°.
The base moiety of (I) is nearly planar, but the vinyl side chain deviates from the plane. The r.m.s. deviation of ring atoms N9, N8, C7, C5, C6, N1, C2, N3 and C4 from the least-squares plane through these atoms is 0.012 Å, with a maximum deviation of −0.024 (4) Å (atom C6). Atom C1' is displaced from this plane by −0.014 (6) Å. The torsion angle of the vinyl group to the C5/C7/C71/C72 heterocycle is 147.5 (5)°. In (III), the vinyl group is inclined by 12° to the pyrimidine ring (Hamor et al., 1978). Such a deviation was also observed in the propynyl group in 8-aza-7-deaza-7-propynyladenosine (Lin et al., 2004). The conformation of the conjugated diene system (N8—C7—C71=C72) is s-Z. This conformation occurs because of the steric repulsion between the vinyl chain and the 6-amine group.
In the three-dimensional network, the bases are stacked (3.3 Å apart; Fig. 2). Each nucleoside is connected to one water molecule, which is coordinated by hydrogen bonds. The water molecule acts as an acceptor, [O10], of a hydrogen bond from atom O3' and as a donor of two H atoms in bonds to atoms N3 and O5' (Table 2). Hence three nucleosides are connected by one water molecule. There is an intramolecular hydrogen bond between the O5'/H5' group and atom N8, which we have not observed in related nucleosides. Other intermolecular and intramolecular hydrogen bonds are summarized in Table 2.