Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270103011430/ln1167sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270103011430/ln1167Isup2.hkl |
CCDC reference: 217157
Compound (I) was prepared as described by He et al. (2003). Light-yellow crystals (m.p. 535 K) were grown from acetone. For the diffraction experiment, a single-crystal was fixed at the top of a Lindemann capillary with epoxy resin.
Methyl H atoms were constrained to an ideal geometry [C—H = 0.96 Å and Uiso(H) = 1.5Ueq(C)] but were allowed to rotate freely about the C—C bonds. The positions of the amine and hydroxy H atoms were refined freely, with Uiso(H) values of 1.2Ueq(N) and 1.5Ueq(O), respectively. Water H atoms were placed in positions determined from a difference Fourier map and were constrained to ride on their parent atoms, with Uiso(H) values of 1.5Ueq(O). All remaining H atoms were placed in idealized positions (C—H = 0.97–0.98 Å) and were constrained to ride on their parent atoms, with Uiso(H) values of 1.2Ueq(C). The absolute configuration was determined conclusively by this experiment and was found to agree with that expected for a D-nucleoside.
Data collection: Bruker XSCANS (Siemens, 1996); cell refinement: Bruker XSCANS; data reduction: Bruker SHELXTL (Sheldrick, 1997); program(s) used to solve structure: Bruker SHELXTL; program(s) used to refine structure: Bruker SHELXTL; molecular graphics: Bruker SHELXTL; software used to prepare material for publication: Bruker SHELXTL and PLATON (Spek, 1999).
C10H11BrFN5O4·C3H6O·H2O | F(000) = 448 |
Mr = 440.24 | Dx = 1.641 Mg m−3 |
Monoclinic, P21 | Melting point: 535 K |
Hall symbol: P 2yb | Mo Kα radiation, λ = 0.71073 Å |
a = 10.8449 (10) Å | Cell parameters from 39 reflections |
b = 7.3649 (9) Å | θ = 5.0–14.0° |
c = 11.1537 (17) Å | µ = 2.36 mm−1 |
β = 90.182 (8)° | T = 293 K |
V = 890.86 (19) Å3 | Transparent plate, light yellow |
Z = 2 | 0.54 × 0.34 × 0.26 mm |
Bruker P4 diffractometer | 2466 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.017 |
Graphite monochromator | θmax = 28.0°, θmin = 1.8° |
2θ/ω scans | h = −14→1 |
Absorption correction: ψ scan (SHELXTL; Sheldrick, 1997) | k = −9→1 |
Tmin = 0.193, Tmax = 0.456 | l = −14→14 |
3029 measured reflections | 3 standard reflections every 97 reflections |
2639 independent reflections | intensity decay: none |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H atoms treated by a mixture of independent and constrained refinement |
R[F2 > 2σ(F2)] = 0.042 | w = 1/[σ2(Fo2) + (0.0927P)2] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.124 | (Δ/σ)max < 0.001 |
S = 1.16 | Δρmax = 0.83 e Å−3 |
2639 reflections | Δρmin = −0.88 e Å−3 |
251 parameters | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
71 restraints | Extinction coefficient: 0.152 (9) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack & Bernardinelli, (2000); 328 Friedel pairs |
Secondary atom site location: difference Fourier map | Absolute structure parameter: 0.009 (11) |
C10H11BrFN5O4·C3H6O·H2O | V = 890.86 (19) Å3 |
Mr = 440.24 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 10.8449 (10) Å | µ = 2.36 mm−1 |
b = 7.3649 (9) Å | T = 293 K |
c = 11.1537 (17) Å | 0.54 × 0.34 × 0.26 mm |
β = 90.182 (8)° |
Bruker P4 diffractometer | 2466 reflections with I > 2σ(I) |
Absorption correction: ψ scan (SHELXTL; Sheldrick, 1997) | Rint = 0.017 |
Tmin = 0.193, Tmax = 0.456 | 3 standard reflections every 97 reflections |
3029 measured reflections | intensity decay: none |
2639 independent reflections |
R[F2 > 2σ(F2)] = 0.042 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.124 | Δρmax = 0.83 e Å−3 |
S = 1.16 | Δρmin = −0.88 e Å−3 |
2639 reflections | Absolute structure: Flack & Bernardinelli, (2000); 328 Friedel pairs |
251 parameters | Absolute structure parameter: 0.009 (11) |
71 restraints |
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. |
x | y | z | Uiso*/Ueq | ||
Br1 | 0.54227 (3) | 0.02296 (9) | 0.10751 (3) | 0.0522 (2) | |
F1 | 0.1774 (2) | 0.4452 (4) | −0.0749 (2) | 0.0390 (5) | |
O1 | 0.4215 (3) | 0.0166 (8) | 0.4052 (2) | 0.0573 (10) | |
N1 | 0.1909 (3) | 0.1393 (5) | 0.0665 (2) | 0.0283 (6) | |
N2 | 0.3087 (3) | 0.1054 (5) | 0.0244 (3) | 0.0323 (7) | |
C3 | 0.3746 (3) | 0.0762 (6) | 0.1213 (3) | 0.0299 (7) | |
C3A | 0.3060 (3) | 0.0879 (6) | 0.2285 (3) | 0.0300 (7) | |
C4 | 0.3263 (3) | 0.0601 (6) | 0.3531 (3) | 0.0336 (9) | |
N5 | 0.2179 (3) | 0.0881 (6) | 0.4189 (3) | 0.0376 (8) | |
H5A | 0.222 (4) | 0.034 (8) | 0.488 (3) | 0.045* | |
C6 | 0.1051 (3) | 0.1370 (6) | 0.3721 (3) | 0.0318 (8) | |
N6 | 0.0142 (3) | 0.1628 (7) | 0.4511 (3) | 0.0440 (9) | |
H6A | −0.050 (4) | 0.217 (8) | 0.422 (5) | 0.053* | |
H6B | 0.042 (4) | 0.185 (8) | 0.520 (3) | 0.053* | |
N7 | 0.0841 (3) | 0.1553 (5) | 0.2552 (2) | 0.0296 (6) | |
C7A | 0.1861 (3) | 0.1288 (5) | 0.1890 (3) | 0.0258 (7) | |
C1' | 0.0885 (3) | 0.1560 (5) | −0.0160 (3) | 0.0265 (7) | |
H1'A | 0.0137 | 0.1866 | 0.0289 | 0.032* | |
C2' | 0.1085 (4) | 0.2970 (5) | −0.1139 (3) | 0.0293 (7) | |
H2'A | 0.0280 | 0.3402 | −0.1420 | 0.035* | |
C3' | 0.1709 (4) | 0.1942 (5) | −0.2150 (3) | 0.0274 (7) | |
H3'A | 0.2600 | 0.1872 | −0.2007 | 0.033* | |
O3' | 0.1468 (3) | 0.2669 (5) | −0.3300 (2) | 0.0413 (7) | |
H3'B | 0.203 (5) | 0.337 (8) | −0.344 (6) | 0.062* | |
O4' | 0.0689 (2) | −0.0073 (4) | −0.0800 (2) | 0.0329 (6) | |
C4' | 0.1124 (3) | 0.0063 (6) | −0.2023 (2) | 0.0265 (6) | |
H4'A | 0.0416 | −0.0018 | −0.2569 | 0.032* | |
O5' | 0.2224 (3) | −0.1481 (6) | −0.3524 (3) | 0.0471 (8) | |
H5'A | 0.263 (6) | −0.239 (6) | −0.365 (6) | 0.071* | |
C5' | 0.1982 (4) | −0.1495 (6) | −0.2272 (4) | 0.0346 (9) | |
H5'B | 0.2743 | −0.1352 | −0.1822 | 0.042* | |
H5'C | 0.1602 | −0.2634 | −0.2041 | 0.042* | |
O11 | 0.2518 (4) | 0.5508 (11) | 0.3712 (3) | 0.0844 (19) | |
C11 | 0.3157 (5) | 0.5721 (9) | 0.2840 (4) | 0.0555 (14) | |
C12 | 0.4513 (6) | 0.5515 (15) | 0.2909 (6) | 0.080 (2) | |
H12A | 0.4752 | 0.5265 | 0.3722 | 0.120* | |
H12B | 0.4901 | 0.6617 | 0.2646 | 0.120* | |
H12D | 0.4767 | 0.4529 | 0.2403 | 0.120* | |
C13 | 0.2556 (7) | 0.6156 (12) | 0.1665 (4) | 0.0693 (17) | |
H13A | 0.1682 | 0.6277 | 0.1777 | 0.104* | |
H13D | 0.2716 | 0.5195 | 0.1105 | 0.104* | |
H13B | 0.2884 | 0.7274 | 0.1360 | 0.104* | |
O21 | 0.6759 (2) | 0.0126 (6) | 0.3981 (2) | 0.0435 (7) | |
H211 | 0.5911 | 0.0538 | 0.3898 | 0.065* | |
H212 | 0.6901 | −0.0012 | 0.4831 | 0.065* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Br1 | 0.0308 (2) | 0.0937 (4) | 0.0320 (2) | 0.0098 (2) | 0.00591 (13) | 0.0071 (3) |
F1 | 0.0562 (14) | 0.0361 (12) | 0.0247 (10) | −0.0083 (11) | −0.0004 (9) | −0.0049 (10) |
O1 | 0.0382 (12) | 0.108 (3) | 0.0257 (12) | 0.012 (3) | −0.0023 (10) | 0.014 (2) |
N1 | 0.0293 (13) | 0.0447 (17) | 0.0108 (11) | 0.0023 (13) | 0.0031 (9) | 0.0026 (12) |
N2 | 0.0305 (13) | 0.0495 (19) | 0.0170 (12) | 0.0020 (13) | 0.0043 (10) | 0.0020 (13) |
C3 | 0.0273 (14) | 0.045 (2) | 0.0174 (13) | 0.0024 (14) | 0.0029 (11) | 0.0040 (14) |
C3A | 0.0282 (14) | 0.0441 (19) | 0.0176 (13) | 0.0014 (14) | 0.0014 (11) | 0.0006 (14) |
C4 | 0.0325 (15) | 0.050 (3) | 0.0186 (13) | 0.0018 (15) | −0.0005 (12) | 0.0039 (15) |
N5 | 0.0377 (15) | 0.062 (2) | 0.0128 (12) | 0.0030 (15) | 0.0027 (11) | 0.0044 (14) |
C6 | 0.0344 (15) | 0.047 (2) | 0.0135 (13) | −0.0011 (15) | 0.0012 (11) | −0.0022 (15) |
N6 | 0.0367 (15) | 0.079 (3) | 0.0157 (12) | 0.0040 (19) | 0.0031 (12) | −0.0026 (17) |
N7 | 0.0318 (13) | 0.0447 (17) | 0.0123 (11) | 0.0027 (13) | 0.0016 (10) | −0.0016 (12) |
C7A | 0.0314 (15) | 0.0327 (18) | 0.0134 (13) | −0.0029 (13) | 0.0012 (11) | −0.0005 (13) |
C1' | 0.0287 (14) | 0.0372 (17) | 0.0138 (13) | −0.0003 (14) | 0.0010 (11) | −0.0012 (13) |
C2' | 0.0365 (17) | 0.0364 (18) | 0.0149 (14) | −0.0024 (14) | 0.0003 (12) | 0.0004 (13) |
C3' | 0.0356 (17) | 0.0357 (18) | 0.0108 (13) | −0.0040 (15) | 0.0003 (12) | −0.0008 (13) |
O3' | 0.0608 (18) | 0.0511 (18) | 0.0119 (11) | −0.0122 (15) | −0.0011 (11) | 0.0068 (12) |
O4' | 0.0441 (12) | 0.0396 (16) | 0.0149 (9) | −0.0068 (12) | 0.0093 (8) | 0.0001 (11) |
C4' | 0.0322 (13) | 0.0370 (17) | 0.0103 (11) | −0.0057 (17) | 0.0024 (9) | 0.0009 (15) |
O5' | 0.0600 (19) | 0.060 (2) | 0.0215 (13) | 0.0162 (16) | 0.0128 (13) | −0.0038 (14) |
C5' | 0.044 (2) | 0.039 (2) | 0.0204 (17) | 0.0039 (17) | 0.0037 (15) | 0.0000 (16) |
O11 | 0.079 (2) | 0.144 (6) | 0.0299 (15) | −0.013 (3) | 0.0048 (15) | 0.008 (3) |
C11 | 0.064 (3) | 0.072 (4) | 0.0303 (19) | −0.016 (3) | 0.0042 (18) | −0.006 (2) |
C12 | 0.069 (3) | 0.109 (6) | 0.063 (3) | −0.006 (4) | 0.004 (3) | −0.008 (4) |
C13 | 0.093 (4) | 0.085 (5) | 0.030 (2) | −0.018 (4) | −0.002 (2) | 0.002 (3) |
O21 | 0.0404 (12) | 0.0613 (18) | 0.0288 (11) | 0.0037 (18) | 0.0035 (9) | 0.0029 (18) |
Br1—C3 | 1.867 (3) | C3'—O3' | 1.414 (4) |
F1—C2' | 1.391 (5) | C3'—C4' | 1.529 (6) |
O1—C4 | 1.226 (5) | C3'—H3'A | 0.9800 |
N1—C7A | 1.370 (4) | O3'—H3'B | 0.81 (6) |
N1—N2 | 1.386 (4) | O4'—C4' | 1.448 (3) |
N1—C1' | 1.445 (4) | C4'—C5' | 1.504 (6) |
N2—C3 | 1.311 (4) | C4'—H4'A | 0.9800 |
C3—C3A | 1.413 (5) | O5'—C5' | 1.422 (5) |
C3A—C7A | 1.405 (5) | O5'—H5'A | 0.81 (6) |
C3A—C4 | 1.421 (5) | C5'—H5'B | 0.9700 |
C4—N5 | 1.403 (5) | C5'—H5'C | 0.9700 |
N5—C6 | 1.377 (5) | O11—C11 | 1.205 (6) |
N5—H5A | 0.86 (2) | C11—C12 | 1.481 (9) |
C6—N7 | 1.330 (4) | C11—C13 | 1.496 (8) |
C6—N6 | 1.337 (5) | C12—H12A | 0.9600 |
N6—H6A | 0.86 (4) | C12—H12B | 0.9600 |
N6—H6B | 0.84 (4) | C12—H12D | 0.9600 |
N7—C7A | 1.346 (4) | C13—H13A | 0.9600 |
C1'—O4' | 1.415 (5) | C13—H13D | 0.9600 |
C1'—C2' | 1.523 (5) | C13—H13B | 0.9600 |
C1'—H1'A | 0.9800 | O21—H211 | 0.9729 |
C2'—C3' | 1.519 (5) | O21—H212 | 0.9648 |
C2'—H2'A | 0.9800 | ||
C7A—N1—N2 | 111.5 (3) | O3'—C3'—C2' | 113.8 (3) |
C7A—N1—C1' | 127.4 (3) | O3'—C3'—C4' | 110.5 (3) |
N2—N1—C1' | 120.5 (3) | C2'—C3'—C4' | 101.3 (3) |
C3—N2—N1 | 104.5 (3) | O3'—C3'—H3'A | 110.3 |
N2—C3—C3A | 113.6 (3) | C2'—C3'—H3'A | 110.3 |
N2—C3—Br1 | 119.7 (3) | C4'—C3'—H3'A | 110.3 |
C3A—C3—Br1 | 126.7 (2) | C3'—O3'—H3'B | 106 (5) |
C7A—C3A—C3 | 103.7 (3) | C1'—O4'—C4' | 111.6 (3) |
C7A—C3A—C4 | 118.5 (3) | O4'—C4'—C5' | 108.9 (3) |
C3—C3A—C4 | 137.6 (3) | O4'—C4'—C3' | 106.6 (3) |
O1—C4—N5 | 119.7 (3) | C5'—C4'—C3' | 114.6 (3) |
O1—C4—C3A | 128.9 (3) | O4'—C4'—H4'A | 108.8 |
N5—C4—C3A | 111.3 (3) | C5'—C4'—H4'A | 108.8 |
C6—N5—C4 | 125.8 (3) | C3'—C4'—H4'A | 108.8 |
C6—N5—H5A | 120 (3) | C5'—O5'—H5'A | 105 (5) |
C4—N5—H5A | 111 (3) | O5'—C5'—C4' | 107.0 (3) |
N7—C6—N6 | 120.4 (3) | O5'—C5'—H5'B | 110.3 |
N7—C6—N5 | 123.2 (3) | C4'—C5'—H5'B | 110.3 |
N6—C6—N5 | 116.4 (3) | O5'—C5'—H5'C | 110.3 |
C6—N6—H6A | 115 (4) | C4'—C5'—H5'C | 110.3 |
C6—N6—H6B | 111 (4) | H5'B—C5'—H5'C | 108.6 |
H6A—N6—H6B | 123 (4) | O11—C11—C12 | 121.2 (5) |
C6—N7—C7A | 112.6 (3) | O11—C11—C13 | 119.0 (5) |
N7—C7A—N1 | 125.0 (3) | C12—C11—C13 | 119.8 (5) |
N7—C7A—C3A | 128.4 (3) | C11—C12—H12A | 109.5 |
N1—C7A—C3A | 106.7 (3) | C11—C12—H12B | 109.5 |
O4'—C1'—N1 | 111.3 (3) | H12A—C12—H12B | 109.5 |
O4'—C1'—C2' | 103.8 (3) | C11—C12—H12D | 109.5 |
N1—C1'—C2' | 113.8 (3) | H12A—C12—H12D | 109.5 |
O4'—C1'—H1'A | 109.3 | H12B—C12—H12D | 109.5 |
N1—C1'—H1'A | 109.3 | C11—C13—H13A | 109.5 |
C2'—C1'—H1'A | 109.3 | C11—C13—H13D | 109.5 |
F1—C2'—C3' | 112.5 (3) | H13A—C13—H13D | 109.5 |
F1—C2'—C1' | 112.9 (3) | C11—C13—H13B | 109.5 |
C3'—C2'—C1' | 104.9 (3) | H13A—C13—H13B | 109.5 |
F1—C2'—H2'A | 108.8 | H13D—C13—H13B | 109.5 |
C3'—C2'—H2'A | 108.8 | H211—O21—H212 | 106.0 |
C1'—C2'—H2'A | 108.8 | ||
C7A—N1—N2—C3 | −0.5 (5) | C4—C3A—C7A—N7 | 3.7 (7) |
C1'—N1—N2—C3 | −172.4 (4) | C3—C3A—C7A—N1 | −0.3 (4) |
N1—N2—C3—C3A | 0.3 (5) | C4—C3A—C7A—N1 | −176.9 (4) |
N1—N2—C3—Br1 | 179.7 (3) | C7A—N1—C1'—O4' | −108.0 (4) |
N2—C3—C3A—C7A | 0.0 (5) | N2—N1—C1'—O4' | 62.4 (4) |
Br1—C3—C3A—C7A | −179.4 (3) | C7A—N1—C1'—C2' | 135.1 (4) |
N2—C3—C3A—C4 | 175.5 (5) | N2—N1—C1'—C2' | −54.4 (5) |
Br1—C3—C3A—C4 | −3.8 (8) | O4'—C1'—C2'—F1 | −155.0 (3) |
C7A—C3A—C4—O1 | 176.8 (5) | N1—C1'—C2'—F1 | −33.9 (4) |
C3—C3A—C4—O1 | 1.7 (9) | O4'—C1'—C2'—C3' | −32.2 (3) |
C7A—C3A—C4—N5 | −2.9 (6) | N1—C1'—C2'—C3' | 88.9 (4) |
C3—C3A—C4—N5 | −178.0 (5) | F1—C2'—C3'—O3' | −85.2 (4) |
O1—C4—N5—C6 | −180.0 (5) | C1'—C2'—C3'—O3' | 151.7 (3) |
C3A—C4—N5—C6 | −0.3 (6) | F1—C2'—C3'—C4' | 156.1 (3) |
C4—N5—C6—N7 | 3.4 (7) | C1'—C2'—C3'—C4' | 33.1 (3) |
C4—N5—C6—N6 | −177.8 (4) | N1—C1'—O4'—C4' | −104.7 (3) |
N6—C6—N7—C7A | 178.5 (4) | C2'—C1'—O4'—C4' | 18.1 (3) |
N5—C6—N7—C7A | −2.8 (6) | C1'—O4'—C4'—C5' | 127.1 (3) |
C6—N7—C7A—N1 | −180.0 (4) | C1'—O4'—C4'—C3' | 2.9 (4) |
C6—N7—C7A—C3A | −0.7 (6) | O3'—C3'—C4'—O4' | −143.4 (3) |
N2—N1—C7A—N7 | 180.0 (4) | C2'—C3'—C4'—O4' | −22.5 (3) |
C1'—N1—C7A—N7 | −8.8 (7) | O3'—C3'—C4'—C5' | 96.0 (4) |
N2—N1—C7A—C3A | 0.5 (5) | C2'—C3'—C4'—C5' | −143.1 (3) |
C1'—N1—C7A—C3A | 171.7 (4) | O4'—C4'—C5'—O5' | 170.6 (3) |
C3—C3A—C7A—N7 | −179.7 (4) | C3'—C4'—C5'—O5' | −70.0 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N5—H5A···O5′i | 0.86 (2) | 2.23 (2) | 3.087 (5) | 170 (6) |
N6—H6A···O5′ii | 0.86 (5) | 2.25 (5) | 3.117 (6) | 178 (6) |
N6—H6B···O3′i | 0.84 (4) | 2.11 (2) | 2.932 (4) | 167 (6) |
O3′—H3′B···O21iii | 0.81 (6) | 1.94 (6) | 2.749 (5) | 172 (7) |
O5′—H5′A···O21iv | 0.81 (6) | 1.98 (3) | 2.779 (6) | 167 (7) |
O21—H211···O1 | 0.97 | 1.87 | 2.760 (4) | 151 |
O21—H212···O11v | 0.96 | 1.78 | 2.702 (5) | 158 |
Symmetry codes: (i) x, y, z+1; (ii) −x, y+1/2, −z; (iii) −x+1, y+1/2, −z; (iv) −x+1, y−1/2, −z; (v) −x+1, y−1/2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C10H11BrFN5O4·C3H6O·H2O |
Mr | 440.24 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 293 |
a, b, c (Å) | 10.8449 (10), 7.3649 (9), 11.1537 (17) |
β (°) | 90.182 (8) |
V (Å3) | 890.86 (19) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 2.36 |
Crystal size (mm) | 0.54 × 0.34 × 0.26 |
Data collection | |
Diffractometer | Bruker P4 diffractometer |
Absorption correction | ψ scan (SHELXTL; Sheldrick, 1997) |
Tmin, Tmax | 0.193, 0.456 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3029, 2639, 2466 |
Rint | 0.017 |
(sin θ/λ)max (Å−1) | 0.660 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.042, 0.124, 1.16 |
No. of reflections | 2639 |
No. of parameters | 251 |
No. of restraints | 71 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.83, −0.88 |
Absolute structure | Flack & Bernardinelli, (2000); 328 Friedel pairs |
Absolute structure parameter | 0.009 (11) |
Computer programs: Bruker XSCANS (Siemens, 1996), Bruker XSCANS, Bruker SHELXTL (Sheldrick, 1997), Bruker SHELXTL and PLATON (Spek, 1999).
Br1—C3 | 1.867 (3) | C1'—O4' | 1.415 (5) |
F1—C2' | 1.391 (5) | O4'—C4' | 1.448 (3) |
N1—C1' | 1.445 (4) | ||
N2—C3—Br1 | 119.7 (3) | F1—C2'—C3' | 112.5 (3) |
C7A—C3A—C3 | 103.7 (3) | F1—C2'—C1' | 112.9 (3) |
O4'—C1'—C2' | 103.8 (3) | C3'—C2'—C1' | 104.9 (3) |
C7A—N1—N2—C3 | −0.5 (5) | F1—C2'—C3'—O3' | −85.2 (4) |
N1—N2—C3—Br1 | 179.7 (3) | N1—C1'—O4'—C4' | −104.7 (3) |
Br1—C3—C3A—C7A | −179.4 (3) | C2'—C1'—O4'—C4' | 18.1 (3) |
C7A—N1—C1'—O4' | −108.0 (4) | C1'—O4'—C4'—C5' | 127.1 (3) |
N2—N1—C1'—O4' | 62.4 (4) | C1'—O4'—C4'—C3' | 2.9 (4) |
O4'—C1'—C2'—F1 | −155.0 (3) | C2'—C3'—C4'—O4' | −22.5 (3) |
N1—C1'—C2'—F1 | −33.9 (4) | C2'—C3'—C4'—C5' | −143.1 (3) |
O4'—C1'—C2'—C3' | −32.2 (3) | O4'—C4'—C5'—O5' | 170.6 (3) |
N1—C1'—C2'—C3' | 88.9 (4) | C3'—C4'—C5'—O5' | −70.0 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N5—H5A···O5'i | 0.86 (2) | 2.23 (2) | 3.087 (5) | 170 (6) |
N6—H6A···O5'ii | 0.86 (5) | 2.25 (5) | 3.117 (6) | 178 (6) |
N6—H6B···O3'i | 0.84 (4) | 2.11 (2) | 2.932 (4) | 167 (6) |
O3'—H3'B···O21iii | 0.81 (6) | 1.94 (6) | 2.749 (5) | 172 (7) |
O5'—H5'A···O21iv | 0.81 (6) | 1.98 (3) | 2.779 (6) | 167 (7) |
O21—H211···O1 | 0.97 | 1.87 | 2.760 (4) | 151 |
O21—H212···O11v | 0.96 | 1.78 | 2.702 (5) | 158 |
Symmetry codes: (i) x, y, z+1; (ii) −x, y+1/2, −z; (iii) −x+1, y+1/2, −z; (iv) −x+1, y−1/2, −z; (v) −x+1, y−1/2, −z+1. |
The introduction of an F atom into nucleoside molecules leads to compounds with antiviral or anticancer activity (Pankiewicz, 2000). More than 75% of the fluorinated nucleosides synthesized to date contain F atoms at the C-2'-position of the sugar moiety. This modification, although causing only minor changes to the size of the molecule, strongly influences its physical and biological properties. Thus, the 2'-fluoroarabinonucleoside FMAU (2'-fluoro-5-methyl-β-D-arabinofuranosyluracil) is an antivirally active compound (Watanabe et al., 1979), while the 2',2'-difluorocytidine, gemcitabine (Hertel et al., 1988), shows anticancer activity. The 2'-fluoro substituent is also able to stabilize the glycosylic bond, thereby increasing the life span of the nucleoside in vivo (Marquez et al., 1990; Singhal et al., 1997). Moreover, the fluorine substituent shifts the conformational equilibrium of the sugar moiety of a nucleoside depending on its configuration (Guschlbauer & Jankowski, 1980; Berger et al., 1998; Ikeda et al., 1998; Thibaudeau et al., 1998) Oligonucleotide duplexes incorporating 2'-fluoroarabino sugars become susceptible to RNase H cleavage, which makes them useful for antisense therapeutics (Damha et al., 1998; Ikeda et al., 1998; Yazbeck et al., 2002).
The title compound, (I), has been synthesized recently (He & Seela, 2003), and its sugar conformation in aqueous solution has been determined as 98% N (Van Wijk et al., 1999; He et al., 2003). This behaviour differs from that of most other nucleosides with a fluoro substituent at the 2'-up position; for example, the 2'-deoxy-2'-fluoroarabinoguanosine (II) shows only a 55% N-conformer population in solution (Tennilä et al., 2000). The conformation of (I) also differs from that of the non-fluorinated compounds (III) and (IV), which show a preferred S-conformation [61% S for (III) and 64% S for (IV) (Seela et al., 1999)] that is typical for 2'-deoxyribonucleosides (Rosemeyer et al., 1997). The unusual conformational properties of (I) in solution prompted us to study its solid-state structure.
The orientation of the nucleobase relative to the sugar moiety (syn/anti) of purine nucleosides is defined by the torsion angle χ (O4'—C1'—N1—C7a) (IUPAC - IUB Joint Commission of Biochemical Nomenclature, 1983). In the crystalline state of nucleoside (I), the glycosylic bond torsion angle is in the anti range, with χ equal to −108.0 (4)° (Fig. 1 and Table 1). Compound (III), in which the 2'-fluoro substituent is missing, is closer to the high-anti conformation [χ = 93.2 (6)°; Seela et al., 1999]. The more pronounced anti conformation of (I) compared with (III) reflects an intramolecular repulsion between the 2'-fluoro `up'-substituent and the ring N atom next to the glycosylation position (N2).
The sugar moiety of nucleoside (I) shows a pseudorotation phase angle, P, of 346.5 (4)° and an amplitude, τm, of 34.5 (2)° (Rao et al., 1981), which indicates the N-conformation. The sugar puckering is 2E, with atom C2' located in the exo position, while atom C3' is close to the C1'—O4'—C4' plane, which is also indicated by the C1'—O4'—C4'—C3' and C2'—C3'—C4'—O4' torsion angles (Table 1). Although both (I) and (III) show an N-type sugar pucker, the conformation of the fluoro nucleoside (I) is closer to envelope, while (III) shows a twist conformation (3T2). The torsion angle around the C4'—C5' bond, defined as γ (O5'—C5'—C4'—C3'), is also different for these two nucleosides. For (I), angle γ [−70.0 (4)°] represents a -sc (gauche) conformation, while an ap conformation is observed for (III) [γ = −169.2 (6)°].
The bond lengths in the sugar moiety are only slightly affected by the 2'-fluoro substituent. The C1'—O4' distance in (I) is about 0.03 Å shorter than the C4'—O4' distance. This difference is more pronounced than that in (III) (0.01 Å). The bond angles around the sugar ring vary unevenly relative to those in (III) (Table 1). The length of the N1—C1' glycosylic bond is 1.445 (4) Å, which is close to that in (III) [1.443 (7) Å]. The F2'—C2' distance agrees with C—F bonds found in other 2'-fluoroarabinonucleosides (Birnbaum et al., 1982) and 2'-fluororibonucleosides (Suck et al., 1974; Hakoshima et al., 1981). The atoms of the pyrazolo[3,4-d]pyrimidine ring system of (I) are coplanar; the least-squares deviations of the ring atoms range from −0.021 (3) to 0.027 (4) Å, with an r.m.s. deviation of 0.017 Å. The bromo substituent and 6-NH2 group deviate from this plane by 0.026 (5) and 0.054 (6) Å, respectively.
Compound (I) was crystallized from aqueous acetone, and one acetone molecule and one water molecule are found in the asymmetric unit. An intermolecular three-dimensional hydrogen-bonded framework is observed, which involves the nucleoside molecules and the solvent molecules (Fig. 2). One water molecule donates two hydrogen bonds, viz. one to the 4-oxo group of (I) and one to the oxo group of an acetone molecule, and accepts another two hydrogen bonds, viz. one each from the 3'-OH and 5'-OH groups of sugar moieties of two neighbouring nucleoside molecules. The nucleoside molecules are linked by three intermolecular hydrogen bonds; the 6-NH2 and 5-NH groups interact with the 3'-OH and 5'-OH groups, respectively, of the same neighbouring nucleoside molecule, and the 6-NH2 group has a second intermolecular interaction involving 5'-OH of a different neighbouring molecule. The F atom of the sugar moiety of one nucleoside molecule is within the van der Waals contact distance of the bromo substituent of a second molecule [3.115 (4) Å].
Although (I) can be considered as a derivative of 2'-deoxyguanosine, (I) shows the sugar conformation of a ribonucleoside. This conformation is not just observed the solid state; a nearly 100% population of the N-conformer is also found in solution, which is uncommon for nucleosides with 2'-up fluoro substituent (He et al., 2003). This unusual N-conformation is probably due to the counteractive influence of the gauche effect of the 2'-fluoro atom and the anomeric effect of the nucleobase with the N atom next to the glycosylation side (Plavec et al., 1996). We have therefore looked for other compounds showing the same properties, and found that the 2'-fluoroarabino derivative of 6-aza-2'-deoxyuridine exhibits such behaviour (He & Seela, 2003).