In the title compound, 4-amino-1-(2-deoxy-β-
D-
erythro-pentofuranosyl)-6-methylsulfanyl-1
H-pyrazolo[3,4-
d]pyrimidine, C
11H
16N
5O
3S, the conformation of the glycosidic bond is between
anti and high
anti. The 2′-deoxyribofuranosyl moiety adopts the C3′-
exo–C4′-
endo conformation (
3T4, S-type sugar pucker), and the conformation at the exocyclic C—C bond is +
sc (+
gauche). The exocyclic 6-amine group and the 2-methylsulfanyl group lie on different sides of the heterocyclic ring system. The molecules form a three-dimensional hydrogen-bonded network that is stabilized by O—H
N, N—H
O and C—H
O hydrogen bonds.
Supporting information
CCDC reference: 285802
The synthesis of nucleoside (I) has recently been published (Seela et al., 2005). The melting point of (I) was determined to be 499 K. Suitable crystals were obtained from a solution in 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 absolute structure. Therefore, Friedel equivalents were merged before the final refinements. The known configuration of the parent molecule was used to define the enantiomer of the final model. All H atoms were initially found in a difference Fourier synthesis. In order to maximize the data/parameter ratio, the H atoms were placed in geometrically idealized positions (C—H = 0.93–0.98 Å, O—H = 0.82 Å and N—H = 0.86 Å) and constrained to ride on their parent atoms with Uiso(H) values of 1.2Ueq(C), 1.2Ueq(N) or 1.5Ueq(O).
Data collection: XSCANS (Siemens, 1996); cell refinement: XSCANS; data reduction: SHELXTL (Sheldrick, 1997b); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997a); molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 1999).
4-amino-1-(2-deoxy-
β-
D-
erythro-pentofuranosyl)-6-methylsulfanyl-1
H- pyrazolo[3,4-
d]pyrimidine
top
Crystal data top
C11H15N5O3S | F(000) = 312 |
Mr = 297.34 | Dx = 1.491 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 38 reflections |
a = 9.4470 (16) Å | θ = 5.4–12.8° |
b = 6.6805 (9) Å | µ = 0.26 mm−1 |
c = 10.6102 (17) Å | T = 293 K |
β = 98.563 (9)° | Needle, colourless, translucent |
V = 662.15 (18) Å3 | 0.4 × 0.3 × 0.2 mm |
Z = 2 | |
Data collection top
Bruker P4 diffractometer | Rint = 0.023 |
Radiation source: fine-focus sealed tube | θmax = 29.0°, θmin = 1.9° |
Graphite monochromator | h = −12→12 |
2θ/ω scans | k = −9→9 |
3965 measured reflections | l = −14→14 |
1900 independent reflections | 3 standard reflections every 97 reflections |
1785 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)] = 0.051 | H-atom parameters constrained |
wR(F2) = 0.163 | w = 1/[σ2(Fo2) + (0.1183P)2 + 0.1165P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max = 0.001 |
1900 reflections | Δρmax = 0.63 e Å−3 |
184 parameters | Δρmin = −0.42 e Å−3 |
1 restraint | Absolute structure: Flack, H. D. (1983). Acta Cryst. A39, 876–881. |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0 (10) |
Crystal data top
C11H15N5O3S | V = 662.15 (18) Å3 |
Mr = 297.34 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 9.4470 (16) Å | µ = 0.26 mm−1 |
b = 6.6805 (9) Å | T = 293 K |
c = 10.6102 (17) Å | 0.4 × 0.3 × 0.2 mm |
β = 98.563 (9)° | |
Data collection top
Bruker P4 diffractometer | Rint = 0.023 |
3965 measured reflections | 3 standard reflections every 97 reflections |
1900 independent reflections | intensity decay: none |
1785 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.051 | H-atom parameters constrained |
wR(F2) = 0.163 | Δρmax = 0.63 e Å−3 |
S = 1.04 | Δρmin = −0.42 e Å−3 |
1900 reflections | Absolute structure: Flack, H. D. (1983). Acta Cryst. A39, 876–881. |
184 parameters | Absolute structure parameter: 0 (10) |
1 restraint | |
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 | 0.5865 (2) | 0.8244 (5) | 1.1776 (2) | 0.0414 (5) | |
C2 | 0.4523 (3) | 0.8231 (5) | 1.2013 (3) | 0.0417 (5) | |
S2 | 0.42382 (10) | 0.8229 (2) | 1.36132 (7) | 0.0614 (3) | |
C2A | 0.6031 (6) | 0.8044 (13) | 1.4469 (4) | 0.0836 (15) | |
H2A1 | 0.6519 | 0.6949 | 1.4135 | 0.125* | |
H2A2 | 0.5991 | 0.7817 | 1.5357 | 0.125* | |
H2A3 | 0.6538 | 0.9266 | 1.4371 | 0.125* | |
N3 | 0.3287 (2) | 0.8206 (6) | 1.1208 (2) | 0.0436 (5) | |
C4 | 0.3532 (2) | 0.8184 (5) | 0.9991 (2) | 0.0361 (5) | |
C5 | 0.4875 (2) | 0.8136 (5) | 0.9585 (2) | 0.0348 (5) | |
C6 | 0.6075 (2) | 0.8204 (5) | 1.0549 (3) | 0.0381 (5) | |
N6 | 0.7427 (2) | 0.8273 (6) | 1.0308 (3) | 0.0504 (6) | |
H6A | 0.8125 | 0.8339 | 1.0927 | 0.061* | |
H6B | 0.7596 | 0.8250 | 0.9534 | 0.061* | |
C7 | 0.4578 (3) | 0.8091 (5) | 0.8231 (3) | 0.0389 (5) | |
H7 | 0.5269 | 0.8037 | 0.7693 | 0.047* | |
N8 | 0.3183 (2) | 0.8137 (5) | 0.7847 (2) | 0.0414 (5) | |
N9 | 0.2543 (2) | 0.8215 (5) | 0.8930 (2) | 0.0390 (5) | |
C1' | 0.0997 (2) | 0.8342 (6) | 0.8846 (2) | 0.0405 (6) | |
H1' | 0.0759 | 0.8725 | 0.9681 | 0.049* | |
C2' | 0.0329 (3) | 0.9858 (5) | 0.7854 (4) | 0.0468 (7) | |
H2'1 | 0.0049 | 1.1064 | 0.8262 | 0.056* | |
H2'2 | 0.0997 | 1.0214 | 0.7279 | 0.056* | |
C3' | −0.0970 (3) | 0.8800 (5) | 0.7143 (3) | 0.0416 (6) | |
H3'1 | −0.1126 | 0.9170 | 0.6239 | 0.050* | |
O3' | −0.2222 (2) | 0.9147 (5) | 0.7715 (3) | 0.0604 (7) | |
H3' | −0.2266 | 1.0336 | 0.7898 | 0.091* | |
C4' | −0.0602 (3) | 0.6587 (5) | 0.7317 (3) | 0.0419 (6) | |
H4' | −0.1477 | 0.5843 | 0.7402 | 0.050* | |
O4' | 0.0367 (2) | 0.6451 (4) | 0.8498 (2) | 0.0455 (5) | |
C5' | 0.0067 (5) | 0.5695 (8) | 0.6239 (4) | 0.0658 (10) | |
H5'1 | 0.0503 | 0.4432 | 0.6533 | 0.079* | |
H5'2 | −0.0698 | 0.5393 | 0.5549 | 0.079* | |
O5' | 0.1090 (4) | 0.6816 (8) | 0.5738 (4) | 0.0846 (11) | |
H5' | 0.1713 | 0.7173 | 0.6316 | 0.127* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
N1 | 0.0377 (10) | 0.0361 (10) | 0.0462 (11) | −0.0015 (11) | −0.0073 (8) | 0.0025 (12) |
C2 | 0.0433 (12) | 0.0366 (12) | 0.0426 (11) | −0.0039 (14) | −0.0021 (9) | 0.0009 (14) |
S2 | 0.0662 (5) | 0.0752 (6) | 0.0407 (4) | −0.0104 (6) | 0.0005 (3) | −0.0023 (5) |
C2A | 0.084 (3) | 0.105 (4) | 0.0529 (18) | −0.012 (3) | −0.0183 (19) | 0.013 (3) |
N3 | 0.0370 (10) | 0.0485 (12) | 0.0434 (11) | −0.0046 (12) | 0.0000 (8) | −0.0036 (12) |
C4 | 0.0298 (9) | 0.0348 (10) | 0.0414 (11) | −0.0020 (12) | −0.0026 (8) | −0.0051 (12) |
C5 | 0.0297 (10) | 0.0294 (10) | 0.0434 (11) | −0.0026 (11) | −0.0007 (8) | −0.0026 (12) |
C6 | 0.0300 (10) | 0.0279 (9) | 0.0536 (13) | −0.0007 (11) | −0.0029 (9) | −0.0019 (13) |
N6 | 0.0275 (9) | 0.0551 (14) | 0.0652 (14) | −0.0015 (13) | −0.0046 (9) | −0.0040 (16) |
C7 | 0.0296 (10) | 0.0405 (12) | 0.0462 (12) | −0.0020 (12) | 0.0043 (9) | −0.0023 (13) |
N8 | 0.0317 (9) | 0.0501 (12) | 0.0414 (10) | −0.0005 (12) | 0.0027 (7) | −0.0029 (13) |
N9 | 0.0272 (8) | 0.0485 (12) | 0.0397 (10) | −0.0018 (11) | −0.0002 (7) | −0.0052 (12) |
C1' | 0.0272 (9) | 0.0503 (15) | 0.0421 (11) | −0.0012 (12) | −0.0010 (8) | −0.0050 (13) |
C2' | 0.0328 (12) | 0.0410 (14) | 0.0641 (19) | 0.0006 (11) | −0.0011 (12) | 0.0010 (14) |
C3' | 0.0280 (10) | 0.0496 (15) | 0.0450 (13) | 0.0014 (10) | −0.0019 (9) | 0.0079 (12) |
O3' | 0.0312 (9) | 0.0620 (15) | 0.0899 (19) | 0.0093 (11) | 0.0155 (11) | 0.0133 (15) |
C4' | 0.0337 (11) | 0.0484 (16) | 0.0407 (13) | −0.0033 (12) | −0.0043 (10) | 0.0014 (12) |
O4' | 0.0346 (9) | 0.0455 (12) | 0.0516 (12) | −0.0055 (9) | −0.0088 (8) | 0.0093 (10) |
C5' | 0.072 (2) | 0.066 (2) | 0.059 (2) | 0.005 (2) | 0.0108 (18) | −0.008 (2) |
O5' | 0.083 (2) | 0.099 (3) | 0.0720 (19) | 0.010 (2) | 0.0142 (16) | −0.005 (2) |
Geometric parameters (Å, º) top
N1—C2 | 1.329 (4) | N9—C1' | 1.453 (3) |
N1—C6 | 1.346 (4) | C1'—O4' | 1.422 (4) |
C2—N3 | 1.340 (3) | C1'—C2' | 1.528 (5) |
C2—S2 | 1.758 (3) | C1'—H1' | 0.9800 |
S2—C2A | 1.803 (5) | C2'—C3' | 1.516 (4) |
C2A—H2A1 | 0.9600 | C2'—H2'1 | 0.9700 |
C2A—H2A2 | 0.9600 | C2'—H2'2 | 0.9700 |
C2A—H2A3 | 0.9600 | C3'—O3' | 1.427 (4) |
N3—C4 | 1.346 (3) | C3'—C4' | 1.523 (5) |
C4—N9 | 1.352 (3) | C3'—H3'1 | 0.9800 |
C4—C5 | 1.399 (3) | O3'—H3' | 0.8200 |
C5—C6 | 1.410 (3) | C4'—O4' | 1.440 (3) |
C5—C7 | 1.422 (4) | C4'—C5' | 1.510 (5) |
C6—N6 | 1.340 (3) | C4'—H4' | 0.9800 |
N6—H6A | 0.8600 | C5'—O5' | 1.389 (6) |
N6—H6B | 0.8600 | C5'—H5'1 | 0.9700 |
C7—N8 | 1.321 (3) | C5'—H5'2 | 0.9700 |
C7—H7 | 0.9300 | O5'—H5' | 0.8200 |
N8—N9 | 1.377 (3) | | |
| | | |
C2—N1—C6 | 117.7 (2) | O4'—C1'—C2' | 107.2 (2) |
N1—C2—N3 | 130.1 (3) | N9—C1'—C2' | 112.9 (2) |
N1—C2—S2 | 118.1 (2) | O4'—C1'—H1' | 108.9 |
N3—C2—S2 | 111.8 (2) | N9—C1'—H1' | 108.9 |
C2—S2—C2A | 102.7 (2) | C2'—C1'—H1' | 108.9 |
S2—C2A—H2A1 | 109.5 | C3'—C2'—C1' | 104.7 (3) |
S2—C2A—H2A2 | 109.5 | C3'—C2'—H2'1 | 110.8 |
H2A1—C2A—H2A2 | 109.5 | C1'—C2'—H2'1 | 110.8 |
S2—C2A—H2A3 | 109.5 | C3'—C2'—H2'2 | 110.8 |
H2A1—C2A—H2A3 | 109.5 | C1'—C2'—H2'2 | 110.8 |
H2A2—C2A—H2A3 | 109.5 | H2'1—C2'—H2'2 | 108.9 |
C2—N3—C4 | 110.7 (2) | O3'—C3'—C2' | 111.9 (3) |
N3—C4—N9 | 127.1 (2) | O3'—C3'—C4' | 107.1 (3) |
N3—C4—C5 | 126.1 (2) | C2'—C3'—C4' | 103.8 (2) |
N9—C4—C5 | 106.8 (2) | O3'—C3'—H3'1 | 111.2 |
C4—C5—C6 | 116.3 (2) | C2'—C3'—H3'1 | 111.2 |
C4—C5—C7 | 105.1 (2) | C4'—C3'—H3'1 | 111.2 |
C6—C5—C7 | 138.6 (2) | C3'—O3'—H3' | 109.5 |
N6—C6—N1 | 117.8 (2) | O4'—C4'—C5' | 110.5 (3) |
N6—C6—C5 | 123.3 (3) | O4'—C4'—C3' | 105.7 (2) |
N1—C6—C5 | 119.0 (2) | C5'—C4'—C3' | 113.9 (3) |
C6—N6—H6A | 120.0 | O4'—C4'—H4' | 108.9 |
C6—N6—H6B | 120.0 | C5'—C4'—H4' | 108.9 |
H6A—N6—H6B | 120.0 | C3'—C4'—H4' | 108.9 |
N8—C7—C5 | 110.4 (2) | C1'—O4'—C4' | 110.9 (2) |
N8—C7—H7 | 124.8 | O5'—C5'—C4' | 118.1 (4) |
C5—C7—H7 | 124.8 | O5'—C5'—H5'1 | 107.8 |
C7—N8—N9 | 106.5 (2) | C4'—C5'—H5'1 | 107.8 |
C4—N9—N8 | 111.07 (19) | O5'—C5'—H5'2 | 107.8 |
C4—N9—C1' | 128.0 (2) | C4'—C5'—H5'2 | 107.8 |
N8—N9—C1' | 120.9 (2) | H5'1—C5'—H5'2 | 107.1 |
O4'—C1'—N9 | 110.0 (3) | C5'—O5'—H5' | 109.5 |
| | | |
C6—N1—C2—N3 | −0.8 (6) | N3—C4—N9—C1' | 2.1 (6) |
C6—N1—C2—S2 | 178.7 (3) | C5—C4—N9—C1' | −177.5 (3) |
N1—C2—S2—C2A | −4.4 (4) | C7—N8—N9—C4 | −1.0 (4) |
N3—C2—S2—C2A | 175.2 (4) | C7—N8—N9—C1' | 178.1 (3) |
N1—C2—N3—C4 | 0.2 (6) | C4—N9—C1'—O4' | −105.9 (4) |
S2—C2—N3—C4 | −179.3 (3) | N8—N9—C1'—O4' | 75.1 (4) |
C2—N3—C4—N9 | −177.9 (4) | C4—N9—C1'—C2' | 134.4 (4) |
C2—N3—C4—C5 | 1.7 (5) | N8—N9—C1'—C2' | −44.7 (4) |
N3—C4—C5—C6 | −2.9 (5) | O4'—C1'—C2'—C3' | 14.3 (3) |
N9—C4—C5—C6 | 176.8 (3) | N9—C1'—C2'—C3' | 135.6 (3) |
N3—C4—C5—C7 | 178.9 (4) | C1'—C2'—C3'—O3' | 90.2 (3) |
N9—C4—C5—C7 | −1.4 (4) | C1'—C2'—C3'—C4' | −25.0 (3) |
C2—N1—C6—N6 | 178.2 (3) | O3'—C3'—C4'—O4' | −91.3 (3) |
C2—N1—C6—C5 | −0.5 (5) | C2'—C3'—C4'—O4' | 27.3 (3) |
C4—C5—C6—N6 | −176.5 (3) | O3'—C3'—C4'—C5' | 147.2 (3) |
C7—C5—C6—N6 | 0.9 (6) | C2'—C3'—C4'—C5' | −94.2 (3) |
C4—C5—C6—N1 | 2.1 (4) | N9—C1'—O4'—C4' | −120.0 (2) |
C7—C5—C6—N1 | 179.5 (4) | C2'—C1'—O4'—C4' | 3.2 (3) |
C4—C5—C7—N8 | 0.8 (4) | C5'—C4'—O4'—C1' | 104.3 (3) |
C6—C5—C7—N8 | −176.7 (4) | C3'—C4'—O4'—C1' | −19.3 (3) |
C5—C7—N8—N9 | 0.1 (4) | O4'—C4'—C5'—O5' | −76.9 (5) |
N3—C4—N9—N8 | −178.8 (4) | C3'—C4'—C5'—O5' | 41.9 (5) |
C5—C4—N9—N8 | 1.6 (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 | 2.54 | 3.110 (4) | 124 |
N6—H6B···O3′ii | 0.86 | 2.05 | 2.879 (5) | 161 |
O3′—H3′···N3iii | 0.82 | 2.40 | 3.164 (5) | 155 |
O5′—H5′···N8 | 0.82 | 2.08 | 2.895 (5) | 176 |
C7—H7···O3′ii | 0.93 | 2.48 | 3.229 (3) | 138 |
Symmetry codes: (i) −x+1, y+1/2, −z+2; (ii) x+1, y, z; (iii) −x, y+1/2, −z+2. |
Experimental details
Crystal data |
Chemical formula | C11H15N5O3S |
Mr | 297.34 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 293 |
a, b, c (Å) | 9.4470 (16), 6.6805 (9), 10.6102 (17) |
β (°) | 98.563 (9) |
V (Å3) | 662.15 (18) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.26 |
Crystal size (mm) | 0.4 × 0.3 × 0.2 |
|
Data collection |
Diffractometer | Bruker P4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3965, 1900, 1785 |
Rint | 0.023 |
(sin θ/λ)max (Å−1) | 0.682 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.051, 0.163, 1.04 |
No. of reflections | 1900 |
No. of parameters | 184 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.63, −0.42 |
Absolute structure | Flack, H. D. (1983). Acta Cryst. A39, 876–881. |
Absolute structure parameter | 0 (10) |
Selected geometric parameters (Å, º) topC2—S2 | 1.758 (3) | N8—N9 | 1.377 (3) |
S2—C2A | 1.803 (5) | N9—C1' | 1.453 (3) |
| | | |
N1—C2—N3 | 130.1 (3) | N3—C2—S2 | 111.8 (2) |
N1—C2—S2 | 118.1 (2) | C2—S2—C2A | 102.7 (2) |
| | | |
N1—C2—S2—C2A | −4.4 (4) | C4—N9—C1'—C2' | 134.4 (4) |
N3—C2—S2—C2A | 175.2 (4) | N8—N9—C1'—C2' | −44.7 (4) |
C4—N9—C1'—O4' | −105.9 (4) | O4'—C4'—C5'—O5' | −76.9 (5) |
N8—N9—C1'—O4' | 75.1 (4) | C3'—C4'—C5'—O5' | 41.9 (5) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N6—H6A···O4'i | 0.86 | 2.54 | 3.110 (4) | 124 |
N6—H6B···O3'ii | 0.86 | 2.05 | 2.879 (5) | 161 |
O3'—H3'···N3iii | 0.82 | 2.40 | 3.164 (5) | 155 |
O5'—H5'···N8 | 0.82 | 2.08 | 2.895 (5) | 176 |
C7—H7···O3'ii | 0.93 | 2.48 | 3.229 (3) | 138 |
Symmetry codes: (i) −x+1, y+1/2, −z+2; (ii) x+1, y, z; (iii) −x, y+1/2, −z+2. |
Extensive studies have been performed on modified nucleosides as analogues of natural DNA constituents. In this context, 8-aza-7-deaza-2'-deoxyadenosine [4-amino-1-(2-deoxy-β-D-erythro- pentofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine], (II), is an ideal substitute for 2'-deoxyadenosine (Seela & Steker, 1985; Seela & Kaiser, 1988; Seela et al., 1999). Purine numbering is used throughout the manuscript. The thermal stability of DNA does not change even with multiple incorporations of (II)–dT base pairs in place of dA–dT pairs (Seela & Kaiser, 1988; Seela et al., 2000). Moreover, the introduction of chloro, bromo, iodo, propynyl and hexynyl substituents at the 7-position of (II) results in a significant stabilization of the duplex DNA. Because of the size and nature of these 7-substituents, they were found to be well accommodated into the major groove of B-DNA (Seela et al., 2000; Seela & Zulauf, 1999; He & Seela, 2002; Seela et al., 2004). In contrast, the 2-substituents of purine residues are located in the minor groove of B-DNA and are limited by their narrow size. Recently, we studied DNA duplexes containing 2-chloro-8-aza-7-deaza-2'-deoxyadenosine, and found that they showed a destabilization compared with duplexes lacking the 2-chloro group (He & Seela, 2003). The consideration of the even bulkier methylthio group for the modification at the 2-position was prompted by the fact that this group is of particular biological importance in nature. The 2-methylthio adenosine analogues are constituents of tRNA and stabilize anticodon–anticodon interactions in the single-stranded state by increased stacking interactions (Esberg & Björk, 1995; Kierzek & Kierzek, 2003).
The present manuscript reports the single-crystal X-ray structure of the title compound, (I).
The canonical 2'-deoxyadenosine unit shows 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) (purine numbering; IUPAC–IUB Joint Commission on Biochemical Nomenclature, 1983). In the crystal structure of (I) (Fig. 1 and Table 1), the conformation of the glycosyl bond is between anti and high anti [χ = −105.9 (4)°] and is stabilized by an intramolecular hydrogen bond between the nucleobase and the sugar moiety (O5'—H5'···N8). The torsion angle of (I) is nearly identical to that of the related compound (II) [χ = −106.3 (2)°; Seela et al., 1999]. The glycosylic bond length in (I) [N9—C1' = 1.453 (3) Å] is only slightly longer than that in (II) [1.442 (2) Å].
The other major conformational parameter of interest is the puckering of the 2'-deoxyribofuranosyl moiety. The 2'-deoxyribonucleosides usually prefer the S-type (C2'-endo) sugar pucker (Saenger, 1984). This is also observed for compound (I), but it adopts an unusual unsymmetrical C3'-exo–C4'-endo (3T4) conformation with a pseudorotation phase angle, P, of 204.7 (4)° and a puckering amplitude, τm, of 28.0 (2)° (Rao & Sundaralingam, 1981). In contrast to this observation, an unsymmetrical C2'-endo–C3'-exo (2T3) sugar-ring conformation [P = 182.2 (2)° and τm = 41.2 (1)°] was found for (II).
The conformation around the C4'—C5' bond of (I) is +sc (+gauche), with a dihedral angle, γ, of 41.9 (5)°, whereas in (II), the C4'—C5' bond adopts a -ap (trans) conformation [γ = −178.7 (16)°].
The base moiety of nucleoside (I) is nearly planar, but the exocyclic substituents deviate from the plane. The r.m.s. deviation of the ring atoms N1/C2/N3/C4–C7/N8/N9 from their least-squares plane is 0.0173 Å, with a maximum deviation of 0.0303 (s.u.?) Å for atom N9. Atoms N6 and S2 of the exocyclic substituents show only minor deviations from this plane [0.0790 (s.u.?) Å for N6 and −0.0455 (s.u?) Å for S2] and are therefore situated on opposite sides of the heterocyclic ring system. Atom C1' of the sugar moiety is localized 0.1043 Å above the plane, on the same side of the nucleobase as atom N6 of the exocyclic NH2 group.
The N3═C2—S2—C2A torsion angle is 175.2 (4)°, corresponding to a `trans' conformation around the C2—S2 bond. As a consequence, in base pairing the bulky 2-methylthio group of (I) leads to a steric clash with the 2-oxo group of dT, resulting in duplex destabilization.
In the three-dimensional hydrogen-bonded network of compound (I), the molecules are stacked head to tail. The intermolecular distance between the planes of neighbouring heterocycles is about 3.41 (4) Å and therefore in the range of B-DNA. The crystal structure is stabilized by several intermolecular hydrogen bonds with the H atoms of the exocyclic amine group as donors and atoms O4' and O3' of adjacent sugar moieties (N6—H6B···O3' and N6—H6A···O4') as acceptors. The heterocyclic ring atom N3 is a hydrogen-bond acceptor for the neighbouring sugar moiety (N3···H3'—O3'). A hydrogen bond between atom O3' of the sugar moiety and atom H7 (C7—H7···O3') connects the nucleobase of one molecule with the sugar unit of another. These interactions link the molecules to form thick layers parallel to the xy plane (Fig. 2). Hydrogen bonds are summarized in Table 2.