2-Amino-7-chloro-2′-deoxy­tubercidin

In 4-chloro-7-(2-de­oxy-β-D-erythro-pento­furanos­yl)-7H-pyr­rolo­[2,3-d]­pyrimidine-2,4-diamine, C₁₁H₁₄ClN₅O₃, the conformation of the N-glycosylic bond is between anti and high-anti [χ = −102.5 (6)°]. The 2′-deoxy­ribofuranosyl unit adopts the C3′-endo-C4′-exo (³T₄) sugar pucker (N-type) with P = 19.6° and τ_m = 32.9° [terminology: Saenger (1989). Landolt-Börnstein New Series, Vol. 1, Nucleic Acids, Subvol. a, edited by O. Madelung, pp. 1–21. Berlin: Springer-Verlag]. The orientation of the exocyclic C4′—C5′ bond is +ap (trans) with a torsion angle γ = 171.5 (4)°. The compound forms a three-dimensional network that is stabilized by four inter­molecular hydrogen bonds (N—H...O and O—H...N) and one intra­molecular hydrogen bond (N—H...Cl).

S1. Comment

Purin-2,6-diamine 2'-deoxyribonucleosides have attracted attention because of their capabilities to form tridentate base pairs with dT (Chollet & Kawashima, 1988; Lamm et al., 1991; Bailly & Waring, 1998) (purine numbering is used throughout the manuscript; IUPAC–IUB Joint Comission on Biochemical Nomenclature, 1983). 2-Amino-2'-deoxytubercidin was found to generate a stable base pair not only with 2'-deoxythymidine but also with 2'-deoxycytidine, which causes mutagenic events (Okamoto et al., 2002). This capability results from the strong basicity of 2-amino-2'-deoxytubercidin being protonated in neutral or weakly acid medium, which is underlined by the pK_a value (5.71). The introduction of 7-halogenated substituents as in the title compound, (I), decreases the basicity to a pK_a of 4.86 (Peng et al., 2006). Hybridization experiments show that nucleoside (I) shows better mismatch discrimination than 2-amino-2'-deoxytubercidin and also enhances the stability of duplex DNA (B-DNA) with antiparallel (aps) chain orientation as well as parallel (ps) chain orientation (Peng et al., 2006). The stabilizing effect of 7-substituted 7-deazapurines is different from that of 8-substituted purine nucleosides, the latter showing a syn conformation of the N-glycosylic bond, which destabilizes B-DNA (Tavale & Sobell, 1970; Kanaya et al., 1984; Sugiyama et al., 1996). It is therefore of interest to study the structure of (I) in the solid state. Up to now, there has been no reported crystal structure of a 7-deazapurin-2,6-diamine 2'-deoxyribonucleoside. The structure of 2-amino-7-chloro-7-deaza-2'-deoxytuberidin, (I), is described.

The structure of (I) is shown in Fig. 1 and selected geometric parameters are summarized in Table 1. The space group (P2₁2₁2₁) is identical to that of 2'-deoxytubercidin (IIa) (Zabel et al., 1987) but different from that of its 7-iodo derivative (IIb) (P2₁) (Seela et al., 1996).

The orientation of the base relative to the sugar (syn/anti) is defined by the torsion angle γ (O4'—C1'—N9—C4). For the `purine' 2'-deoxyribonucleosides, the preferred conformation around the N-glycosylic bond is in the anti range (Saenger, 1989; Sato, 1984). It was reported that the 7-substituents of 8-aza-7-deaza-2'-deoxyadenosines drive the conformation to high-anti (Seela et al., 1999; Seela et al., 2000). 7-Deazapurin-2,6-diamine nucleoside (I) adopts a high-anti conformation with γ = −102.5 (6)°, which is similar to that of 8-aza-7-bromo-7-deazapurin-2,6-diamine 2'-deoxyribonucleoside (III) [γ = −105.0 (6)°; Seela et al., 2005].

For compound (I), the phase angle of pseudorotation (P) (Altona & Sundaralingam, 1972) is 19.6° and the maximum amplitude of puckering (τ_m) is 32.9°, which is unusual for a 2'-deoxyribonucleoside. This indicates that the sugar ring has C3'-endo conformation (³T₄) and its pucker can also be described as N (Saenger, 1989). This is similar to the 8-aza-7-deazapurin-2,6-diamine compound (III) (Seela et al., 2005) but different from that of the parent 2'-deoxytubercidin, which adopts an S-type sugar pucker with P = 186.6° (Zabel et al., 1987). In contrast to the behaviour in the solid state, nucleoside (I) shows two populations in solution with N (28%) and S (72%) pucker (Seela & Peng, 2004). The conformation around the C4'—C5' bond of (I) is in the +ap (trans) range (Saenger, 1989) with a torsion angle γ (C3'—C4'—C5'—O5') of 171.5 (4)°.

The base unit of (I) is essentially planar. The chloro substituent is located −0.078 (7) Å out of the 7-deazapurine plane. The exocyclic N atom of the 2-amino group lies 0.083 (6) below and that of the 6-amino group 0.060 (8) above the plane.

Compound (I) forms a compact three-dimensional network which is stabilized by four intermolecular hydrogen bonds and one intramolecular hydrogen bond formed between the H atom of the 6-amino group and the Cl atom (N6—H6B···Cl7; Table 2). The H6B···Cl7 contact distance is much shorter than the sum of the van der Waals radii (2.95 Å; Bondi, 1964). Fig. 2 shows a ball and stick model of nucleoside (I) with a chain-like arrangement in crystal. The sugar moieties of the neighbouring chain are positioned in an antiparallel orientation. The adjacent heterocyclic bases of nucleosides within a chain are directed to opposite sides. The distance between successive nucleobases on the same side of the chain is 7.636 (2) Å, which is much longer than the average base pair distance in B-DNA (3.5 Å). Thus, no base stacking is observed in the crystal stucture.

S2. Experimental

Compound (I) was synthesized as described by Seela & Peng (2004) and crystallized from MeOH (m.p. 483 K). Crystals suitable for single-crystal X-ray diffraction were selected directly from the sample as prepared.

S3. Refinement

Refinement of the Flack (1983) parameter led to inconclusive values. Therefore, 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 found in a difference Fourier synthesis. The H-atom coordinates of the OH groups were refined freely starting from difference map positions. The isotropic displacement parameter was constrained [U_iso(H) = 1.5U_eq(O)]. In order to maximize the data/parameter ratio, all other H atoms were placed in geometrically idealized positions (C—H = 0.93–0.98 Å and N—H = 0.86 Å) and constrained to ride on their parent atoms with U_iso(H) values of 1.2U_eq(C,N).

Computing details

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 and DIAMOND (Brandenburg, 1999); software used to prepare material for publication: SHELXTL and PLATON (Spek, 1999).

Figures

	Fig. 1. A perspective view of nucleoside (I) showing the atomic numbering. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as spheres of arbitrary size.
	Fig. 2. Ball and stick model of nucleoside (I) chains; The successive nucleobases on the same side of the chain are at a distance of 7.636 (2) Å.

4-chloro-7-(2-deoxy-β-D-erythro-pentofuranosyl)- 7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine

Crystal data

C11H14ClN5O3	F(000) = 624
Mr = 299.72	Dx = 1.563 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 54 reflections
a = 7.637 (2) Å	θ = 2.3–12.5°
b = 9.4576 (17) Å	µ = 0.32 mm^−1
c = 17.632 (4) Å	T = 293 K
V = 1273.4 (5) Å^3	Block, colourless
Z = 4	0.5 × 0.4 × 0.2 mm

Data collection

Bruker P4 diffractometer	Rint = 0.057
Radiation source: fine-focus sealed tube	θmax = 29.0°, θmin = 2.3°
Graphite monochromator	h = −1→10
2θ/ω scans	k = −12→1
2586 measured reflections	l = −1→24
1952 independent reflections	3 standard reflections every 97 reflections
1068 reflections with I > 2σ(I)	intensity decay: none

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.060	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.145	w = 1/[σ^2(Fo^2) + (0.0543P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.00	(Δ/σ)max < 0.001
1952 reflections	Δρmax = 0.28 e Å^−3
187 parameters	Δρmin = −0.30 e Å^−3
4 restraints	Absolute structure: established on the basis of the previously known absolute configuration of the molecule
Primary atom site location: structure-invariant direct methods

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
N1	0.6098 (6)	1.2394 (4)	−0.1563 (2)	0.0353 (11)
C2	0.5909 (7)	1.0958 (6)	−0.1620 (3)	0.0331 (13)
N2	0.5700 (6)	1.0457 (5)	−0.2338 (2)	0.0435 (14)
H2A	0.5608	0.9562	−0.2415	0.052*
H2B	0.5660	1.1035	−0.2714	0.052*
N3	0.5963 (5)	1.0012 (4)	−0.1062 (2)	0.0294 (10)
C4	0.6111 (8)	1.0609 (5)	−0.0365 (3)	0.0300 (12)
C5	0.6220 (8)	1.2061 (5)	−0.0218 (3)	0.0352 (13)
C6	0.6233 (8)	1.2948 (5)	−0.0866 (3)	0.0390 (14)
N6	0.6391 (8)	1.4357 (4)	−0.0791 (3)	0.0533 (15)
H6A	0.6404	1.4888	−0.1187	0.064*
H6B	0.6478	1.4727	−0.0347	0.064*
C7	0.6330 (9)	1.2191 (5)	0.0586 (3)	0.0397 (15)
Cl7	0.6452 (3)	1.37639 (14)	0.10839 (8)	0.0584 (5)
C8	0.6340 (9)	1.0887 (5)	0.0889 (3)	0.0445 (16)
H8A	0.6417	1.0681	0.1404	0.053*
N9	0.6218 (7)	0.9891 (4)	0.0305 (2)	0.0357 (11)
C1'	0.6034 (7)	0.8363 (5)	0.0415 (3)	0.0319 (12)
H1'A	0.6169	0.7884	−0.0074	0.038*
C2'	0.7335 (7)	0.7744 (6)	0.0982 (3)	0.0365 (13)
H2'A	0.7768	0.6836	0.0809	0.044*
H2'B	0.8321	0.8376	0.1055	0.044*
C3'	0.6298 (7)	0.7582 (6)	0.1711 (3)	0.0334 (12)
H3'A	0.6326	0.8467	0.2000	0.040*
O3'	0.6858 (6)	0.6440 (4)	0.21770 (19)	0.0460 (11)
H3'B	0.743 (7)	0.6762 (17)	0.2532 (19)	0.069*
C4'	0.4453 (7)	0.7312 (5)	0.1413 (3)	0.0288 (12)
H4'A	0.4309	0.6299	0.1313	0.035*
C5'	0.3034 (7)	0.7797 (6)	0.1937 (3)	0.0389 (14)
H5'A	0.3065	0.7217	0.2391	0.047*
H5'B	0.3278	0.8763	0.2088	0.047*
O5'	0.1317 (5)	0.7738 (4)	0.1626 (2)	0.0385 (9)
H5'C	0.118 (3)	0.697 (2)	0.142 (3)	0.058*
O4'	0.4327 (5)	0.8074 (4)	0.07129 (18)	0.0397 (10)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.046 (3)	0.026 (2)	0.034 (2)	0.000 (2)	−0.001 (3)	0.0088 (18)
C2	0.026 (3)	0.040 (3)	0.034 (3)	0.002 (3)	−0.003 (3)	0.002 (2)
N2	0.063 (4)	0.037 (3)	0.031 (2)	−0.001 (3)	0.001 (2)	0.001 (2)
N3	0.033 (3)	0.026 (2)	0.0293 (19)	0.003 (2)	0.000 (2)	0.0024 (19)
C4	0.032 (3)	0.027 (2)	0.031 (2)	0.000 (3)	0.002 (3)	−0.002 (2)
C5	0.042 (3)	0.027 (3)	0.036 (3)	0.000 (3)	0.002 (3)	0.002 (2)
C6	0.040 (3)	0.031 (3)	0.046 (3)	−0.003 (3)	−0.004 (3)	0.005 (2)
N6	0.085 (4)	0.025 (2)	0.050 (3)	−0.011 (3)	−0.002 (3)	0.002 (2)
C7	0.065 (4)	0.024 (2)	0.031 (3)	0.001 (3)	−0.009 (3)	−0.006 (2)
Cl7	0.1011 (14)	0.0294 (6)	0.0446 (7)	−0.0003 (10)	−0.0078 (10)	−0.0079 (7)
C8	0.076 (5)	0.035 (3)	0.023 (2)	−0.004 (4)	−0.007 (3)	−0.003 (2)
N9	0.053 (3)	0.025 (2)	0.029 (2)	−0.007 (3)	−0.007 (3)	0.0051 (19)
C1'	0.038 (3)	0.031 (3)	0.027 (2)	0.003 (3)	0.002 (3)	0.003 (2)
C2'	0.037 (3)	0.032 (3)	0.041 (3)	−0.003 (3)	−0.003 (3)	0.004 (3)
C3'	0.040 (3)	0.031 (3)	0.029 (2)	−0.003 (3)	−0.001 (3)	0.002 (2)
O3'	0.061 (3)	0.035 (2)	0.042 (2)	0.001 (2)	−0.016 (2)	0.0091 (18)
C4'	0.036 (3)	0.025 (2)	0.025 (2)	−0.004 (3)	−0.005 (2)	0.004 (2)
C5'	0.046 (4)	0.042 (3)	0.030 (3)	0.002 (3)	0.002 (3)	−0.001 (3)
O5'	0.034 (2)	0.038 (2)	0.043 (2)	0.001 (2)	0.002 (2)	−0.0060 (18)
O4'	0.033 (2)	0.053 (2)	0.0332 (18)	−0.0057 (19)	−0.0052 (18)	0.0121 (19)

Geometric parameters (Å, º)

N1—C6	1.339 (7)	N9—C1'	1.464 (6)
N1—C2	1.370 (6)	C1'—O4'	1.432 (6)
C2—N3	1.331 (6)	C1'—C2'	1.526 (7)
C2—N2	1.360 (7)	C1'—H1'A	0.9800
N2—H2A	0.8600	C2'—C3'	1.518 (7)
N2—H2B	0.8600	C2'—H2'A	0.9700
N3—C4	1.356 (6)	C2'—H2'B	0.9700
C4—N9	1.366 (6)	C3'—O3'	1.423 (6)
C4—C5	1.400 (6)	C3'—C4'	1.525 (7)
C5—C6	1.417 (7)	C3'—H3'A	0.9800
C5—C7	1.426 (7)	O3'—H3'B	0.82 (4)
C6—N6	1.345 (6)	C4'—O4'	1.432 (5)
N6—H6A	0.8600	C4'—C5'	1.497 (7)
N6—H6B	0.8600	C4'—H4'A	0.9800
C7—C8	1.344 (7)	C5'—O5'	1.423 (6)
C7—Cl7	1.729 (5)	C5'—H5'A	0.9700
C8—N9	1.399 (6)	C5'—H5'B	0.9700
C8—H8A	0.9300	O5'—H5'C	0.82 (3)
C6—N1—C2	117.6 (5)	N9—C1'—C2'	113.8 (4)
N3—C2—N2	117.2 (5)	O4'—C1'—H1'A	109.3
N3—C2—N1	127.5 (5)	N9—C1'—H1'A	109.3
N2—C2—N1	115.3 (5)	C2'—C1'—H1'A	109.3
C2—N2—H2A	120.0	C3'—C2'—C1'	104.7 (4)
C2—N2—H2B	120.0	C3'—C2'—H2'A	110.8
H2A—N2—H2B	120.0	C1'—C2'—H2'A	110.8
C2—N3—C4	113.1 (4)	C3'—C2'—H2'B	110.8
N3—C4—N9	125.6 (4)	C1'—C2'—H2'B	110.8
N3—C4—C5	125.5 (5)	H2'A—C2'—H2'B	108.9
N9—C4—C5	108.9 (4)	O3'—C3'—C2'	114.1 (4)
C4—C5—C6	115.6 (5)	O3'—C3'—C4'	110.5 (4)
C4—C5—C7	105.8 (5)	C2'—C3'—C4'	101.9 (4)
C6—C5—C7	138.6 (5)	O3'—C3'—H3'A	110.0
N1—C6—N6	119.0 (5)	C2'—C3'—H3'A	110.0
N1—C6—C5	120.5 (4)	C4'—C3'—H3'A	110.0
N6—C6—C5	120.5 (5)	C3'—O3'—H3'B	108.5 (11)
C6—N6—H6A	120.0	O4'—C4'—C5'	109.2 (4)
C6—N6—H6B	120.0	O4'—C4'—C3'	106.0 (4)
H6A—N6—H6B	120.0	C5'—C4'—C3'	113.8 (4)
C8—C7—C5	108.4 (4)	O4'—C4'—H4'A	109.2
C8—C7—Cl7	126.0 (4)	C5'—C4'—H4'A	109.2
C5—C7—Cl7	125.6 (4)	C3'—C4'—H4'A	109.2
C7—C8—N9	109.0 (4)	O5'—C5'—C4'	114.6 (4)
C7—C8—H8A	125.5	O5'—C5'—H5'A	108.6
N9—C8—H8A	125.5	C4'—C5'—H5'A	108.6
C4—N9—C8	107.8 (4)	O5'—C5'—H5'B	108.6
C4—N9—C1'	126.8 (4)	C4'—C5'—H5'B	108.6
C8—N9—C1'	125.0 (4)	H5'A—C5'—H5'B	107.6
O4'—C1'—N9	108.9 (4)	C5'—O5'—H5'C	108.7 (12)
O4'—C1'—C2'	106.2 (4)	C1'—O4'—C4'	110.5 (4)
C6—N1—C2—N3	−5.1 (9)	C5—C4—N9—C8	1.8 (8)
C6—N1—C2—N2	177.2 (5)	N3—C4—N9—C1'	−6.0 (10)
N2—C2—N3—C4	−177.8 (5)	C5—C4—N9—C1'	175.3 (5)
N1—C2—N3—C4	4.5 (8)	C7—C8—N9—C4	−0.7 (8)
C2—N3—C4—N9	−179.1 (6)	C7—C8—N9—C1'	−174.3 (6)
C2—N3—C4—C5	−0.6 (8)	C4—N9—C1'—O4'	−102.5 (6)
N3—C4—C5—C6	−2.3 (10)	C8—N9—C1'—O4'	69.9 (7)
N9—C4—C5—C6	176.4 (5)	C4—N9—C1'—C2'	139.2 (6)
N3—C4—C5—C7	179.1 (6)	C8—N9—C1'—C2'	−48.4 (8)
N9—C4—C5—C7	−2.2 (8)	O4'—C1'—C2'—C3'	−19.4 (5)
C2—N1—C6—N6	−178.9 (6)	N9—C1'—C2'—C3'	100.4 (5)
C2—N1—C6—C5	1.5 (9)	C1'—C2'—C3'—O3'	149.6 (4)
C4—C5—C6—N1	1.8 (9)	C1'—C2'—C3'—C4'	30.5 (5)
C7—C5—C6—N1	179.7 (8)	O3'—C3'—C4'—O4'	−153.1 (4)
C4—C5—C6—N6	−177.8 (6)	C2'—C3'—C4'—O4'	−31.5 (5)
C7—C5—C6—N6	0.2 (13)	O3'—C3'—C4'—C5'	86.8 (5)
C4—C5—C7—C8	1.8 (8)	C2'—C3'—C4'—C5'	−151.5 (4)
C6—C5—C7—C8	−176.3 (8)	O4'—C4'—C5'—O5'	53.3 (6)
C4—C5—C7—Cl7	−178.8 (5)	C3'—C4'—C5'—O5'	171.5 (4)
C6—C5—C7—Cl7	3.1 (13)	N9—C1'—O4'—C4'	−123.6 (4)
C5—C7—C8—N9	−0.7 (8)	C2'—C1'—O4'—C4'	−0.7 (5)
Cl7—C7—C8—N9	179.9 (5)	C5'—C4'—O4'—C1'	143.6 (4)
N3—C4—N9—C8	−179.5 (6)	C3'—C4'—O4'—C1'	20.6 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2B···O5′^i	0.86	2.23	2.937 (5)	139
N6—H6A···O5′^ii	0.86	2.38	3.117 (6)	145
N6—H6B···Cl7	0.86	2.68	3.353 (5)	136
O3′—H3′B···N1^iii	0.82 (4)	2.11 (4)	2.930 (6)	179 (5)
O5′—H5′C···N3^iv	0.82 (3)	1.99 (3)	2.798 (5)	172 (5)

Symmetry codes: (i) −x+1/2, −y+2, z−1/2; (ii) x+1/2, −y+5/2, −z; (iii) −x+3/2, −y+2, z+1/2; (iv) x−1/2, −y+3/2, −z.