In the title compound, 2′-deoxy-7-propynyl-7-deazaadenosine, C
14H
16N
4O
3, the torsion angle of the N-glycosylic bond is
anti [χ = −130.7 (2)°]. The sugar pucker of the 2′-deoxyribofuranosyl moiety is C2′-
endo–C3′-
exo,
2T3 (
S-type), with
P = 185.9 (2)° and τ
m = 39.1 (1)°, and the orientation of the exocyclic C4′—C5′ bond is −
ap (
trans). The 7-substituted propynyl group is nearly coplanar with the heterocyclic base moiety. Molecules of the nucleoside form a layered network in which the heterocyclic bases are stacked head-to-tail with a closest distance of 3.197 (1) Å. The crystal structure of the nucleoside is stabilized by three intermolecular hydrogen bonds of types N—H
O, O—H
N and O—H
O.
Supporting information
CCDC reference: 609411
Compound (I) was synthesized from (IIIb) as described previously by Buhr et al. (1996) and was crystallized slowly from double-distilled water as colourless crystals (m.p. 479–480 K). 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, the Flack (1983) parameter could not be used to determine the absolute structure. Therefore, 508 Friedel equivalents were merged before the final refinement. The known configuration of the parent molecule was used to define the enantiomer employed in the refined 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, with C—H = 0.93–0.98 Å and N—H = 0.86 Å, and constrained to ride on their parent atoms, with Uiso(H) = 1.2Ueq(C,N). The OH groups were refined as a rotating group, with O—H = 0.82 Å [Please clarify - CIF data show their positions were refined] and Uiso(H) = 1.5Ueq(O).
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, 2003).
2'-Deoxy-7-propynyl-7-deazaadenosine
top
Crystal data top
C14H16N4O3 | F(000) = 608 |
Mr = 288.31 | Dx = 1.441 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 63 reflections |
a = 6.5812 (11) Å | θ = 4.9–14.0° |
b = 10.5084 (13) Å | µ = 0.10 mm−1 |
c = 19.216 (2) Å | T = 293 K |
V = 1328.9 (3) Å3 | Block, colourless |
Z = 4 | 0.5 × 0.3 × 0.3 mm |
Data collection top
Bruker P4 diffractometer | Rint = 0.037 |
Radiation source: fine-focus sealed tube | θmax = 30.0°, θmin = 2.1° |
Graphite monochromator | h = −9→1 |
2θ/ω scans | k = −14→1 |
2918 measured reflections | l = −27→1 |
2214 independent reflections | 3 standard reflections every 97 reflections |
1852 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)] = 0.052 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.146 | w = 1/[σ2(Fo2) + (0.0951P)2 + 0.1584P] where P = (Fo2 + 2Fc2)/3 |
S = 1.03 | (Δ/σ)max = 0.001 |
2214 reflections | Δρmax = 0.40 e Å−3 |
197 parameters | Δρmin = −0.30 e Å−3 |
2 restraints | Absolute structure: established by known chemical absolute configuration |
Primary atom site location: structure-invariant direct methods | |
Crystal data top
C14H16N4O3 | V = 1328.9 (3) Å3 |
Mr = 288.31 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 6.5812 (11) Å | µ = 0.10 mm−1 |
b = 10.5084 (13) Å | T = 293 K |
c = 19.216 (2) Å | 0.5 × 0.3 × 0.3 mm |
Data collection top
Bruker P4 diffractometer | Rint = 0.037 |
2918 measured reflections | 3 standard reflections every 97 reflections |
2214 independent reflections | intensity decay: none |
1852 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.052 | 2 restraints |
wR(F2) = 0.146 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.03 | Δρmax = 0.40 e Å−3 |
2214 reflections | Δρmin = −0.30 e Å−3 |
197 parameters | Absolute structure: established by known chemical absolute configuration |
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 | 0.7891 (3) | 0.19520 (19) | 0.41491 (9) | 0.0251 (4) | |
C2 | 0.7834 (4) | 0.0893 (2) | 0.45434 (12) | 0.0275 (5) | |
H2A | 0.7854 | 0.0129 | 0.4300 | 0.033* | |
N3 | 0.7753 (4) | 0.07896 (17) | 0.52299 (10) | 0.0244 (4) | |
C4 | 0.7771 (4) | 0.1931 (2) | 0.55401 (10) | 0.0198 (4) | |
C5 | 0.7872 (4) | 0.31155 (19) | 0.52130 (10) | 0.0198 (4) | |
C6 | 0.7916 (4) | 0.3085 (2) | 0.44775 (11) | 0.0209 (4) | |
N6 | 0.7970 (4) | 0.4155 (2) | 0.40838 (11) | 0.0307 (5) | |
H6A | 0.7988 | 0.4098 | 0.3637 | 0.037* | |
H6B | 0.7987 | 0.4890 | 0.4280 | 0.037* | |
C7 | 0.7874 (4) | 0.4065 (2) | 0.57526 (12) | 0.0223 (4) | |
C7A | 0.7989 (5) | 0.5414 (2) | 0.56718 (13) | 0.0273 (5) | |
C7B | 0.8110 (6) | 0.6529 (3) | 0.55909 (15) | 0.0381 (7) | |
C7C | 0.8216 (7) | 0.7918 (3) | 0.5508 (2) | 0.0571 (10) | |
H7C1 | 0.8267 | 0.8312 | 0.5959 | 0.086* | |
H7C2 | 0.7036 | 0.8211 | 0.5262 | 0.086* | |
H7C3 | 0.9415 | 0.8137 | 0.5250 | 0.086* | |
C8 | 0.7755 (4) | 0.34148 (19) | 0.63713 (11) | 0.0239 (5) | |
H8A | 0.7724 | 0.3789 | 0.6810 | 0.029* | |
N9 | 0.7689 (3) | 0.21201 (16) | 0.62443 (9) | 0.0215 (4) | |
C1' | 0.7348 (4) | 0.1104 (2) | 0.67468 (11) | 0.0224 (4) | |
H1' | 0.6884 | 0.0346 | 0.6496 | 0.027* | |
C2' | 0.9155 (4) | 0.0739 (3) | 0.71961 (13) | 0.0313 (5) | |
H2'A | 1.0029 | 0.1465 | 0.7283 | 0.038* | |
H2'B | 0.9946 | 0.0066 | 0.6982 | 0.038* | |
C3' | 0.8131 (4) | 0.0283 (2) | 0.78641 (12) | 0.0285 (5) | |
H3'A | 0.9050 | 0.0349 | 0.8264 | 0.034* | |
O3' | 0.7446 (4) | −0.09864 (17) | 0.77677 (10) | 0.0380 (5) | |
H3'B | 0.744 (6) | −0.140 (4) | 0.815 (2) | 0.057* | |
O4' | 0.5776 (3) | 0.14999 (17) | 0.72107 (9) | 0.0274 (4) | |
C4' | 0.6376 (4) | 0.1225 (2) | 0.79213 (12) | 0.0277 (5) | |
H4'A | 0.5241 | 0.0834 | 0.8173 | 0.033* | |
C5' | 0.7019 (6) | 0.2450 (3) | 0.82831 (15) | 0.0449 (8) | |
H5'A | 0.7360 | 0.2255 | 0.8763 | 0.054* | |
H5'B | 0.8239 | 0.2768 | 0.8060 | 0.054* | |
O5' | 0.5549 (6) | 0.3412 (3) | 0.82777 (15) | 0.0737 (11) | |
H5'C | 0.469 (8) | 0.336 (6) | 0.792 (3) | 0.088* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
N1 | 0.0289 (10) | 0.0262 (9) | 0.0201 (8) | −0.0012 (9) | 0.0000 (8) | −0.0013 (7) |
C2 | 0.0361 (13) | 0.0229 (10) | 0.0233 (9) | −0.0031 (11) | −0.0002 (10) | −0.0039 (9) |
N3 | 0.0341 (11) | 0.0162 (7) | 0.0228 (8) | 0.0000 (8) | 0.0004 (9) | −0.0011 (7) |
C4 | 0.0247 (10) | 0.0158 (8) | 0.0187 (9) | −0.0010 (9) | −0.0003 (8) | 0.0005 (7) |
C5 | 0.0233 (10) | 0.0166 (8) | 0.0193 (8) | −0.0006 (8) | −0.0007 (9) | 0.0025 (8) |
C6 | 0.0193 (9) | 0.0226 (9) | 0.0207 (9) | −0.0025 (9) | −0.0009 (8) | 0.0055 (8) |
N6 | 0.0397 (12) | 0.0267 (9) | 0.0256 (9) | 0.0002 (10) | −0.0005 (9) | 0.0103 (8) |
C7 | 0.0284 (11) | 0.0144 (8) | 0.0240 (9) | −0.0018 (9) | 0.0000 (9) | 0.0005 (8) |
C7A | 0.0351 (13) | 0.0181 (9) | 0.0286 (10) | 0.0006 (10) | −0.0004 (11) | 0.0010 (9) |
C7B | 0.0511 (18) | 0.0203 (11) | 0.0429 (14) | 0.0002 (12) | 0.0007 (14) | 0.0028 (11) |
C7C | 0.076 (3) | 0.0179 (12) | 0.078 (2) | −0.0001 (15) | 0.004 (2) | 0.0126 (14) |
C8 | 0.0334 (12) | 0.0155 (8) | 0.0229 (9) | −0.0007 (9) | −0.0006 (10) | −0.0013 (8) |
N9 | 0.0339 (10) | 0.0144 (7) | 0.0164 (7) | −0.0007 (8) | 0.0004 (7) | 0.0019 (6) |
C1' | 0.0309 (11) | 0.0174 (8) | 0.0190 (8) | −0.0012 (9) | 0.0023 (8) | 0.0047 (8) |
C2' | 0.0318 (12) | 0.0329 (12) | 0.0291 (11) | 0.0029 (10) | 0.0011 (11) | 0.0095 (11) |
C3' | 0.0389 (14) | 0.0248 (10) | 0.0218 (9) | 0.0024 (10) | −0.0030 (10) | 0.0070 (9) |
O3' | 0.0651 (14) | 0.0217 (8) | 0.0272 (8) | −0.0007 (10) | −0.0008 (9) | 0.0061 (7) |
O4' | 0.0299 (9) | 0.0310 (8) | 0.0212 (7) | 0.0035 (7) | 0.0021 (7) | 0.0050 (7) |
C4' | 0.0388 (13) | 0.0263 (11) | 0.0179 (9) | 0.0012 (10) | 0.0031 (9) | 0.0036 (9) |
C5' | 0.068 (2) | 0.0321 (12) | 0.0345 (13) | 0.0079 (15) | −0.0109 (16) | −0.0094 (12) |
O5' | 0.112 (3) | 0.0491 (13) | 0.0596 (16) | 0.0358 (17) | −0.0289 (18) | −0.0261 (14) |
Geometric parameters (Å, º) top
N1—C2 | 1.346 (3) | C8—H8A | 0.9300 |
N1—C6 | 1.347 (3) | N9—C1' | 1.457 (3) |
C2—N3 | 1.325 (3) | C1'—O4' | 1.427 (3) |
C2—H2A | 0.9300 | C1'—C2' | 1.519 (3) |
N3—C4 | 1.339 (3) | C1'—H1' | 0.9800 |
C4—N9 | 1.369 (3) | C2'—C3' | 1.527 (3) |
C4—C5 | 1.396 (3) | C2'—H2'A | 0.9700 |
C5—C6 | 1.414 (3) | C2'—H2'B | 0.9700 |
C5—C7 | 1.439 (3) | C3'—O3' | 1.420 (3) |
C6—N6 | 1.356 (3) | C3'—C4' | 1.525 (4) |
N6—H6A | 0.8600 | C3'—H3'A | 0.9800 |
N6—H6B | 0.8600 | O3'—H3'B | 0.86 (4) |
C7—C8 | 1.374 (3) | O4'—C4' | 1.450 (3) |
C7—C7A | 1.427 (3) | C4'—C5' | 1.523 (4) |
C7A—C7B | 1.185 (3) | C4'—H4'A | 0.9800 |
C7B—C7C | 1.470 (4) | C5'—O5' | 1.400 (4) |
C7C—H7C1 | 0.9600 | C5'—H5'A | 0.9700 |
C7C—H7C2 | 0.9600 | C5'—H5'B | 0.9700 |
C7C—H7C3 | 0.9600 | O5'—H5'C | 0.90 (5) |
C8—N9 | 1.383 (3) | | |
| | | |
C2—N1—C6 | 117.82 (18) | O4'—C1'—N9 | 108.19 (18) |
N3—C2—N1 | 129.0 (2) | O4'—C1'—C2' | 106.61 (18) |
N3—C2—H2A | 115.5 | N9—C1'—C2' | 116.1 (2) |
N1—C2—H2A | 115.5 | O4'—C1'—H1' | 108.6 |
C2—N3—C4 | 111.66 (19) | N9—C1'—H1' | 108.6 |
N3—C4—N9 | 124.75 (19) | C2'—C1'—H1' | 108.6 |
N3—C4—C5 | 126.77 (18) | C1'—C2'—C3' | 102.2 (2) |
N9—C4—C5 | 108.49 (18) | C1'—C2'—H2'A | 111.3 |
C4—C5—C6 | 115.50 (19) | C3'—C2'—H2'A | 111.3 |
C4—C5—C7 | 107.10 (18) | C1'—C2'—H2'B | 111.3 |
C6—C5—C7 | 137.4 (2) | C3'—C2'—H2'B | 111.3 |
N1—C6—N6 | 118.14 (19) | H2'A—C2'—H2'B | 109.2 |
N1—C6—C5 | 119.21 (19) | O3'—C3'—C4' | 112.2 (2) |
N6—C6—C5 | 122.6 (2) | O3'—C3'—C2' | 109.0 (2) |
C6—N6—H6A | 120.0 | C4'—C3'—C2' | 101.00 (19) |
C6—N6—H6B | 120.0 | O3'—C3'—H3'A | 111.4 |
H6A—N6—H6B | 120.0 | C4'—C3'—H3'A | 111.4 |
C8—C7—C7A | 126.2 (2) | C2'—C3'—H3'A | 111.4 |
C8—C7—C5 | 106.17 (18) | C3'—O3'—H3'B | 112 (3) |
C7A—C7—C5 | 127.6 (2) | C1'—O4'—C4' | 109.42 (19) |
C7B—C7A—C7 | 178.5 (3) | O4'—C4'—C5' | 109.7 (2) |
C7A—C7B—C7C | 178.2 (4) | O4'—C4'—C3' | 105.53 (18) |
C7B—C7C—H7C1 | 109.5 | C5'—C4'—C3' | 111.8 (2) |
C7B—C7C—H7C2 | 109.5 | O4'—C4'—H4'A | 109.9 |
H7C1—C7C—H7C2 | 109.5 | C5'—C4'—H4'A | 109.9 |
C7B—C7C—H7C3 | 109.5 | C3'—C4'—H4'A | 109.9 |
H7C1—C7C—H7C3 | 109.5 | O5'—C5'—C4' | 114.5 (3) |
H7C2—C7C—H7C3 | 109.5 | O5'—C5'—H5'A | 108.6 |
C7—C8—N9 | 109.79 (19) | C4'—C5'—H5'A | 108.6 |
C7—C8—H8A | 125.1 | O5'—C5'—H5'B | 108.6 |
N9—C8—H8A | 125.1 | C4'—C5'—H5'B | 108.6 |
C4—N9—C8 | 108.44 (17) | H5'A—C5'—H5'B | 107.6 |
C4—N9—C1' | 123.67 (18) | C5'—O5'—H5'C | 113 (4) |
C8—N9—C1' | 127.51 (18) | | |
| | | |
C6—N1—C2—N3 | 1.6 (4) | N3—C4—N9—C1' | −7.0 (4) |
N1—C2—N3—C4 | −1.2 (4) | C5—C4—N9—C1' | 173.0 (2) |
C2—N3—C4—N9 | 179.6 (3) | C7—C8—N9—C4 | 0.2 (3) |
C2—N3—C4—C5 | −0.4 (4) | C7—C8—N9—C1' | −173.0 (2) |
N3—C4—C5—C6 | 1.4 (4) | C4—N9—C1'—O4' | −130.7 (2) |
N9—C4—C5—C6 | −178.5 (2) | C8—N9—C1'—O4' | 41.5 (3) |
N3—C4—C5—C7 | −179.4 (3) | C4—N9—C1'—C2' | 109.6 (3) |
N9—C4—C5—C7 | 0.7 (3) | C8—N9—C1'—C2' | −78.3 (3) |
C2—N1—C6—N6 | −179.9 (3) | O4'—C1'—C2'—C3' | 29.7 (2) |
C2—N1—C6—C5 | −0.3 (3) | N9—C1'—C2'—C3' | 150.3 (2) |
C4—C5—C6—N1 | −1.0 (3) | C1'—C2'—C3'—O3' | 80.4 (2) |
C7—C5—C6—N1 | −179.9 (3) | C1'—C2'—C3'—C4' | −38.0 (2) |
C4—C5—C6—N6 | 178.6 (2) | N9—C1'—O4'—C4' | −134.14 (19) |
C7—C5—C6—N6 | −0.3 (5) | C2'—C1'—O4'—C4' | −8.5 (2) |
C4—C5—C7—C8 | −0.6 (3) | C1'—O4'—C4'—C5' | 104.2 (2) |
C6—C5—C7—C8 | 178.4 (3) | C1'—O4'—C4'—C3' | −16.4 (3) |
C4—C5—C7—C7A | 179.0 (3) | O3'—C3'—C4'—O4' | −82.0 (2) |
C6—C5—C7—C7A | −2.0 (5) | C2'—C3'—C4'—O4' | 33.9 (2) |
C7A—C7—C8—N9 | −179.3 (3) | O3'—C3'—C4'—C5' | 158.8 (2) |
C5—C7—C8—N9 | 0.3 (3) | C2'—C3'—C4'—C5' | −85.3 (2) |
N3—C4—N9—C8 | 179.5 (2) | O4'—C4'—C5'—O5' | 56.0 (3) |
C5—C4—N9—C8 | −0.5 (3) | C3'—C4'—C5'—O5' | 172.7 (3) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N6—H6A···O4′i | 0.86 | 2.53 | 3.173 (3) | 132 |
O3′—H3′B···N1ii | 0.86 (4) | 2.02 (4) | 2.851 (3) | 165 (4) |
O5′—H5′C···O3′iii | 0.90 (5) | 2.05 (5) | 2.884 (4) | 155 (5) |
Symmetry codes: (i) x+1/2, −y+1/2, −z+1; (ii) −x+3/2, −y, z+1/2; (iii) −x+1, y+1/2, −z+3/2. |
Experimental details
Crystal data |
Chemical formula | C14H16N4O3 |
Mr | 288.31 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 293 |
a, b, c (Å) | 6.5812 (11), 10.5084 (13), 19.216 (2) |
V (Å3) | 1328.9 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.10 |
Crystal size (mm) | 0.5 × 0.3 × 0.3 |
|
Data collection |
Diffractometer | Bruker P4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2918, 2214, 1852 |
Rint | 0.037 |
(sin θ/λ)max (Å−1) | 0.703 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.052, 0.146, 1.03 |
No. of reflections | 2214 |
No. of parameters | 197 |
No. of restraints | 2 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.40, −0.30 |
Absolute structure | Established by known chemical absolute configuration |
Selected geometric parameters (Å, º) topC7—C7A | 1.427 (3) | C7B—C7C | 1.470 (4) |
C7A—C7B | 1.185 (3) | N9—C1' | 1.457 (3) |
| | | |
N1—C6—N6 | 118.14 (19) | C4—N9—C1' | 123.67 (18) |
N6—C6—C5 | 122.6 (2) | C8—N9—C1' | 127.51 (18) |
C8—C7—C7A | 126.2 (2) | O4'—C1'—N9 | 108.19 (18) |
C7A—C7—C5 | 127.6 (2) | N9—C1'—C2' | 116.1 (2) |
C7B—C7A—C7 | 178.5 (3) | O5'—C5'—C4' | 114.5 (3) |
C7A—C7B—C7C | 178.2 (4) | | |
| | | |
C2—N1—C6—N6 | −179.9 (3) | C4—N9—C1'—C2' | 109.6 (3) |
C4—C5—C6—N6 | 178.6 (2) | C8—N9—C1'—C2' | −78.3 (3) |
C7—C5—C6—N6 | −0.3 (5) | O4'—C4'—C5'—O5' | 56.0 (3) |
C4—N9—C1'—O4' | −130.7 (2) | C3'—C4'—C5'—O5' | 172.7 (3) |
C8—N9—C1'—O4' | 41.5 (3) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N6—H6A···O4'i | 0.86 | 2.53 | 3.173 (3) | 132 |
O3'—H3'B···N1ii | 0.86 (4) | 2.02 (4) | 2.851 (3) | 165 (4) |
O5'—H5'C···O3'iii | 0.90 (5) | 2.05 (5) | 2.884 (4) | 155 (5) |
Symmetry codes: (i) x+1/2, −y+1/2, −z+1; (ii) −x+3/2, −y, z+1/2; (iii) −x+1, y+1/2, −z+3/2. |
7-Deazapurine (pyrrolo[2,3-d]pyrimidine) nucleosides occur naturally and have been isolated as monomers and as constituents of nucleic acids (Suhadolnik, 1970, 1979). Among them are ribonucleosides such as tubercidin, (IIa), isolated from Streptomyces tubercidicus (Nakamura, 1961), as well as its 7-substituted derivatives toyocamycin, (IIb), and sangivamycin, (IIc), which are produced by Streptomyces toyocaensis or other Streptomyces strains (Nishimura et al., 1956; Ohkuma, 1961) (see scheme; unless otherwise stated, purine numbering is used throughout this discussion). The natural occurrence and extraordinary biological and pharmacological properties of 7-deazapurine nucleosides have been the reasons for active study of their synthesis, their biochemical and physical properties, and their incorporation into nucleic acids. 7-Deazapurine 2'-deoxyribonucleosides are used as biochemical probes (Mizusawa et al., 1986; Prober et al., 1987; Seela et al., 1993; Murchie & Lilley, 1994), in nucleic acid diagnostics (Bailly & Waring, 1998) and in antisense technology (Lamm et al., 1991; Uhlmann et al., 2000).
Among the various modifications carried out on purine and pyrimidine nucleosides to stabilize duplex and triplex DNA, the propynyl group has attracted particular attention. This group has been introduced into the 5-position of pyrimidine nucleosides (Froehler et al., 1992; Sági et al., 1993; Barnes & Turner, 2001a,b; Gutierrez et al., 1997; Ahmadian et al., 1998; Graham et al., 1998) and the 7-position of 7-deazapurine or 8-aza-7-deazapurine nucleosides (Buhr et al., 1996; He & Seela, 2002a,b; Seela & Shaikh, 2005). Our laboratory has shown that a propynyl group introduced into the 7-position of 8-aza-7-deazapurine exerts a stronger stabilizing effect on DNA duplexes (He & Seela, 2002a,b) than do the pyrimidine bases.
The introduction of the propynyl group at the 7-position of 7-deazaadenosine, (IIIa) (Seela & Thomas, 1995), lowers the pKa value. The title compound, (I), shows a pKa of 4.5, while the non-fuctionalized nucleoside (IIIa) has a pKa value of 4.9. The incorporation of (I) into oligonucleotides significantly increases the stability of the Watson–Crick base pair dA–dT and the tandem base pair dA–dG in DNA (Seela, Budow et al., 2005). The 7-propynyl residue of (I) also stabilizes DNA–RNA duplexes (Buhr et al., 1996). Against this background, we became interested in undertaking a single-crystal X-ray analysis of compound (I) and present the results here.
Compound (I) was synthesized from (IIIb) (Buhr et al., 1996). The three-dimensional structure of (I) (7-(2-deoxy-β-D-erythro-pentofuranosyl)-5-(prop-1-ynyl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine) is shown in Fig. 1 and selected geometric parameters are listed in Table 1. The orientation of the nucleobase relative to the sugar moiety (syn/anti) is defined, in analogy with the purine nucleosides, by the torsion angle χ (O4'—C1'—N9—C4) (purine numbering; IUPAC–IUB Joint Commission on Biochemical Nomenclature, 1983); the preferred conformation around the N-glycosylic bond for natural purine 2'-deoxyribonucleosides is usually in the anti range. In the crystalline state of (I), the glycosylic bond torsion angle is anti [χ = −130.7 (2)°], which is similar to that of 2'-deoxy-7-iodotubercidin, (IIIb) [χ = −147.1 (8)°; Seela et al., 1996] as well as that of 7-deaza-2'-deoxy-7-propynylguanosine (χ = −117.1 (5)°; Seela et al., 2004), while for 2'-deoxytubercidin, (IIIa), and 2'-deoxy-7-fluorotubercidin the glycosylic bond torsion angles are χ = −104.4 (2) and −101.1 (3)°, respectively, which are in the range of the high-anti conformation (Zabel et al., 1987; Seela, Xu & Eickmeier, 2005).
The sugar moiety of (I) exhibits a pseudorotational phase angle P = 185.9 (2)° with an amplitude τm = 39.1 (1)°, indicating an S-type sugar pucker (2'-endo-3'-exo, 2T3) (Rao et al., 1981). This type of sugar conformation is also found for 2'-deoxytubercidin (Zabel et al., 1987), while 2'-deoxy-7-iodotubercidin shows an envelope sugar ring conformation (3E) (Seela et al., 1996). The torsion angle γ [O5'—C5'—C4'—C3' = −172.7 (3)°] describing the orientation of the 5'-hydroxyl group relative to the sugar ring shows that the C4'—C5' bond is in an -ap (trans) orientation (Saenger, 1984). The S-type sugar puckering of compound (I) in the solid state is similar to the preferred conformation found in solution (71% S). The conformational analysis was carried out on the basis of 1H NMR vicinal [1H, 1H] coupling constants using the program PSEUROT6.3 (Van Wijk et al., 1999).
The base moiety of (I) is almost planar, the r.m.s. deviation of ring atoms from their calculated least-squares planes being 0.0095 Å. The propynyl group of (I) is slightly inclined by 1.6° with respect to the aromatic ring of the molecule. This is smaller than the angles observed for 7-deaza-7-propynyl-2'-deoxyguanosine (4.6°; Seela et al., 2004) and 8-aza-7-deaza-7-propynyladenosine (4.0°; Lin et al., 2005). The group is almost linear, with dihedral bond angles C7—C7A—C7B = 178.5 (3)° and C7A—C7B—C7C = 178.2 (4)°. The triple-bond length of (I) is 1.185 (3) Å, which is within the range of non-conjugated triple bonds (Reference?).
The structure of nucleoside (I) is stabilized by three intermolecular hydrogen bonds (N6—H6··· O4', O3'—H3'···N1 and O5'-H5'···O3'), leading to the formation of a layered network (Fig. 2 and Table 2) with head-to-tail stacking of the nucleobases, which is different from the head-to-head stacking of 7-deaza-2'-deoxy-7-propynylguanosine (Seela et al., 2004). The shortest distance between the stacked bases for nucleoside (I) is 3.197 (1) Å, which is less than the average base-pair stacking distance in B-DNA (3.5 Å). It is also smaller than that observed for the related 7-deaza-2'-deoxy-7-propynylguanosine [3.728 (1) Å; Seela et al., 2004].