α-d-2′-De­oxy­adenosine, an irradiation product of canonical DNA and a com­ponent of anomeric nucleic acids: crystal structure, packing and Hirshfeld surface analysis

Leonard, P.; Zhang, A.; Budow-Busse, S.; Daniliuc, C.; Seela, F.

doi:10.1107/S2053229624000457

research papers

STRUCTURAL
CHEMISTRY

ISSN: 2053-2296

Volume 80| Part 2| February 2024| Pages 21-29

https://doi.org/10.1107/S2053229624000457

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α-D-2′-Deoxyadenosine, an irradiation product of canonical DNA and a component of anomeric nucleic acids: crystal structure, packing and Hirshfeld surface analysis

Peter Leonard,^a Aigui Zhang,^a Simone Budow-Busse,^a Constantin Daniliuc ^b and Frank Seela ^a,^c ^*

^aLaboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Heisenbergstrasse 11, 48149 Münster, Germany, ^bOrganisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster, Germany, and ^cLaboratorium für Organische und Bioorganische Chemie, Institut für Chemie, Universität Osnabrück, Barbarastrasse 7, Osnabrück 49069, Germany
^*Correspondence e-mail: frank.seela@uni-osnabrueck.de

Edited by A. G. Oliver, University of Notre Dame, USA (Received 4 December 2023; accepted 11 January 2024; online 22 January 2024)

α-D-2′-Deoxyribonucleosides are products of the γ-irradiation of DNA under oxygen-free conditions and are constituents of anomeric DNA. They are not found as natural building blocks of canonical DNA. Reports on their conformational properties are limited. Herein, the single-crystal X-ray structure of α-D-2′-deoxyadenosine (α-dA), C₁₀H₁₃N₅O₃, and its conformational parameters were determined. In the crystalline state, α-dA forms two conformers in the asymmetric unit which are connected by hydrogen bonds. The sugar moiety of each conformer is arranged in a `clamp'-like fashion with respect to the other conformer, forming hydrogen bonds to its nucleobase and sugar residue. For both conformers, a syn conformation of the nucleobase with respect to the sugar moiety was found. This is contrary to the anti conformation usually preferred by α-nucleosides. The sugar conformation of both conformers is C2′-endo, and the 5′-hydroxyl groups are in a +sc orientation, probably due to the hydrogen bonds formed by the conformers. The formation of the supramolecular assembly of α-dA is controlled by hydrogen bonding and stacking interactions, which was verified by a Hirshfeld and curvedness surface analysis. Chains of hydrogen-bonded nucleobases extend parallel to the b direction and are linked to equivalent chains by hydrogen bonds involving the sugar moieties to form a sheet. A comparison of the solid-state structures of the anomeric 2′-deoxyadenosines revealed significant differences of their conformational parameters.

Keywords: α-2′-deoxyadenosine; anomer; crystal structure; crystal packing; nucleoside; Hirshfeld surface analysis.

CCDC reference: 2294190

1. Introduction

In canonical double-stranded DNA, all four canonical nucleosides display a β-D configuration; α-anomeric nucleosides are not found in native DNA. However, γ-irradiation of DNA under oxygen-free (anoxic) conditions can cause lesions that yield α-D nucleosides as single or multiple mutations (Amato & Wang, 2014 ). This is explained by the formation of C1′ radicals at the 2′-deoxyribose moiety formed during irradiation and the nonstereospecific recombination resulting in a mixture of anomers (β and α). Lesiak & Wheeler (1990 ) reported the formation of α-2′-deoxyadenosine (α-dA) (Fig. 1) as a major lesion product upon γ-irradiation of poly-dA–poly-dT duplexes and salmon testis DNA under a nitrogen atmosphere. These α-dA mutations can have a significant impact on DNA stability, which strongly depends on the nearest neighbours (Ide et al., 1995 ; Johnson et al., 2012 ). The NMR solution structure of a DNA duplex containing an α-dA modification revealed local helical changes at the modification site depending on the sequence context (Aramini et al., 2004 ). However, compared to other types of damage, this type of DNA damage perturbs the DNA helix only to a minor extent and, as a consequence, recognition by repair enzymes is very challenging (Johnson et al., 2012). The enzymatic repair machinery for α-anomeric lesions is conserved in mammalian cells which shows the biological significance (Johnson et al., 2012).

Figure 1
Structures of anomeric 2′-deoxyadenosines.

Our laboratory and others constructed oligonucleotides containing exclusively α-nucleosides (Morvan et al., 1987a ,b ; Paoletti et al., 1989 ; Chai et al., 2020 ; Zhang et al., 2022a ). They were hybridized with complementary strands with all the nucleoside residues in a β-D conformation. These duplexes are as stable as those of canonical DNA with both strands in a β-D configuration. However, strands are in a parallel and not an antiparallel orientation as in natural DNA. Moreover, α-oligonucleotides were used as invader strands in DNA displacement reactions (Zhang et al., 2022b ) or implemented in the construction of α/β-heterochiral DNA duplexes containing silver-mediated base pairs (Chai et al., 2020).

The chemical synthesis of nucleosides often produces α-D anomers as by-products during glycosylation. The outcome of the glycosylation reaction (α/β ratio) can be influenced by the structures of the starting materials and the experimental conditions. Various methods were established to synthesize α-D nucleosides by anomerization of β-D anomers or by stereoselective synthesis (Ni et al., 2019 ). Thus, a number of α-D nucleosides were prepared, including those with a modified nucleobase or sugar moiety. Due to the difference in the configuration at C1′, monomeric α-D nucleosides show altered properties compared to their β-anomers (Ciuffreda et al., 2007 ). According to the work of Sundaralingam (1971 ) and Latha & Yathindra (1992 ) on the solid-state conformations of α-nucleosides, the flexibility of the glycosylic bond, connecting the nucleobase and the sugar moiety, as well as the sugar conformation, seems to be more restricted compared to β-nucleosides. However, examples of α-nucleosides with properties outside the proposed favoured conformational range were reported recently (Seela et al., 2002 ; Budow-Busse et al., 2021 ).

A number of X-ray studies were performed to elucidate the solid-state structure of α-nucleosides, but to our surprise, from the four α-D-2′-deoxyribonucleosides with canonical nucleobases, only X-ray studies of the pyrimidine nucleosides α-2′-deoxythymidine (α-dT) (Görbitz et al., 2005 ) and α-2′-deoxycytidine (α-dC) (Budow-Busse, et al., 2021) have been reported. The crystal structure of the anomeric purine nucleoside α-2′-deoxyadenosine (α-dA, 1) (Fig. 1) is still unknown. Only a preliminary X-ray analysis of a complex of human endonucleoase 1 (APE1) with an oligonucleotide containing α-dA, 1, was published by Retailleau et al. (2010 ).

To obtain more knowledge of crystal structures of α-D-2′-deoxyribonucleosides with a canonical nucleobase, we performed a single-crystal X-ray analysis of α-D-2′-deoxyadenosine (1). α-D-2′-Deoxyadenosine (1) had been synthesized previously by Ness and Fletcher in 1960 (Ness & Fletcher, 1960 ), and improved synthetic methods were reported by Robins (Robins & Robins, 1965 ) and Shinozuka (Shinozuka et al., 1992 ).

The work described herein is the first study of the crystal structure of an α-anomeric canonical purine 2′-deoxyribonucleoside. The crystal structure of α-dA (1) revealed an unexpected syn conformation of the nucleobase. The solid-state conformational properties of 1 were studied in detail and compared to those of the corresponding β-D nucleoside (β-dA, 2) (Fig. 1) (Sato, 1984 ). The interactions of the molecules within the crystalline network were analysed. Hirshfeld surface analyses were performed for both anomers (α-dA, 1, and β-dA, 2) to support the X-ray data.

2. Experimental

2.1. Synthesis and crystallization of α-2′-deoxyadenosine (1)

α-2′-Deoxyadenosine (1) was synthesized following the glycosylation protocol reported by Ness (1968 ). N-Benzoyladenine and Hoffer's chlorosugar (Hoffer, 1960 ) were used as starting materials and, in our hands, a 1:1 anomeric mixture of the protected α-dA and β-dA was obtained. Deprotection in 0.2 M NaOMe (room temperature, overnight) afforded α-dA (1).

For crystallization, compound 1 was dissolved in methanol and was obtained as colourless plates by slow evaporation of the solvent (room temperature, 8 d). A plate-like specimen of 1 was used for the X-ray crystallographic analysis.

2.2. X-ray diffraction and refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. All carbon-bound H atoms were placed in idealized positions and refined using a riding model, with C—H = 0.95 Å for aromatic CH groups, 0.99 Å for secondary CH₂ groups and 1.00 Å for tertiary CH groups, using U_iso(H) = 1.2U_eq(C). The positions of the H atoms at N6A, N6B, O3′A, O3′B, O5′A and O5′B were located in a difference map and were refined freely.

Table 1
Experimental details

Crystal data
Chemical formula	C₁₀H₁₃N₅O₃
M_r	251.25
Crystal system, space group	Triclinic, P1
Temperature (K)	100
a, b, c (Å)	5.2027 (2), 8.9738 (3), 12.3715 (4)
α, β, γ (°)	78.249 (1), 83.171 (1), 76.338 (1)
V (Å³)	547.97 (3)
Z	2
Radiation type	Cu Kα
μ (mm⁻¹)	0.98
Crystal size (mm)	0.19 × 0.08 × 0.05

Data collection
Diffractometer	Bruker D8 Venture Photon III
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.84, 0.95
No. of measured, independent and observed [I > 2σ(I)] reflections	17188, 3858, 3752
R_int	0.041
(sin θ/λ)_max (Å⁻¹)	0.603

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.027, 0.065, 1.08
No. of reflections	3858
No. of parameters	357
No. of restraints	3
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.17
Absolute structure	Flack x determined using 1744 quotients [(I⁺) − (I⁻)]/[(I⁺) + (I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	−0.01 (8)
Computer programs: APEX4 (Bruker, 2021 ), SAINT (Bruker, 2019 ), SHELXT2018 (Sheldrick, 2015a ), SHELXL2018 (Sheldrick, 2015b ) and DIAMOND (Putz & Brandenburg, 2022 ).

3. Results and discussion

3.1. Molecular geometry and conformation of α-2′-deoxyadenosine (1)

The crystals of α-2′-deoxyadenosine (1) are triclinic with the space group P1 (Table 1). There are two molecules in the asymmetric unit, denoted as conformer α-1a and conformer α-1b, which are connected via hydrogen bonds. The three-dimensional (3D) structures of α-1a and α-1b are shown in Fig. 2 and indicate an α-orientation of the nucleobases. The anomeric centre at C1′ shows an S-configuration, confirming the α-D anomeric structure of 1 which, in addition, is supported by the Flack parameter. Throughout the article, purine numbering is used instead of systematic numbering for the molecules. Selected geometric parameters are summarized in Table 2.

Table 2
Selected geometric parameters of the anomeric 2′-deoxyadenosines α-1a, α-1b and β-dA (2)

	Conformer α-1a	Conformer α-1b	β-dA (2) (Sato, 1984)
Glycosylic bond length (N9—C1′) (Å)	1.473 (3)	1.474 (3)	1.474 (2)
Torsion angle χ (O4′—C1′—N9—C4) (°)	78.0 (3)	72.7 (3)	−165.0 (7)
Relative sugar/base orientation	syn	syn	anti
Pseudorotational phase angle P (°)	135.67	143.35	13.28
Maximum amplitude τ_m (°)	30.51	31.68	36.34
Sugar pucker	S-type, C2′-endo, ₁T²	S-type, C2′-endo, ₁T²	N-type, C3′-endo, ³T₂
Torsion angle γ (O5′—C5′—C4′—C3′) (°)	50.2 (3)	46.8 (3)	175.5 (1)
Relative orientation of exocyclic 5′-OH	+synclinal (gauche)	+synclinal (gauche)	+antiperiplanar (trans)

Figure 2
Perspective view and atomic numbering scheme of the two conformers of α-dA (α-1a and α-1b), being connected to each other by two hydrogen bonds (dashed lines). Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary size.

The crystal structure of β-2′-deoxyadenosine monohydrate was reported in 1965 by Watson and co-workers (Watson et al., 1965 ), while the crystal structure of anhydrous β-dA (2) was published 20 years later (Sato, 1984). The geometric parameters of β-dA (2) (Table 2) (Sato, 1984) were used as a comparison for the two conformers of α-dA (1) (α-1a and α-1b). For the remodelled 3D structure of β-dA (2), see Fig. S1 in the supporting information. Remodelling was carried out using the original structure data (CIF file) of 2 (Sato, 1984) downloaded from the Cambridge Structural Database (CCDC deposition code 1124124; Groom et al., 2016 ).

The shape of nucleosides is characterized by four conformational parameters (Saenger, 1984 ): (i) the glycosylic torsion angle, (ii) the puckering of the furanose ring, (iii) the degree of deviation from planarity of the furanose ring and (iv) the orientation of the 5′-hydroxyl group. The geometric parameters (i)–(iv) of conformers α-1a and α-1b are discussed in the following.

(i) The positioning of the nucleobase with respect to the sugar moiety (syn/anti) is defined by the torsion angle χ (O4′—C1′—N9—C4) (IUPAC–IUB Joint Commission on Biochemical Nomenclature, 1983 ). In the anti conformation (180 to ±90°) of purine nucleosides, the six-membered pyrimidine ring is pointing away from the sugar moiety, and there is no particular hindrance of the nucleobase and the sugar residue. On the contrary, in the syn conformation (0 to ±90°), the pyrimidine ring is located above the sugar ring, giving rise to close interatomic contacts. A C2′-endo conformation of the sugar ring reduces the intramolecular strain, wherein the nucleobase and the C5′ atom are in an equatorial orientation and at a maximum distance (Saenger, 1984). Purine β-nucleosides are rather flexible and adopt anti, high-anti and even syn conformations, whereas α-nucleosides seem to prefer a rather narrow range of anti conformations (Sundaralingam, 1971; Latha & Yathindra, 1992). Therefore, we were very surprised to find χ torsion angles of 78.0 (3) and 72.7 (3)° for α-1a and α-1b, respectively, which are in the range of the syn conformation. To the best of our knowledge, this is the first report on α-nucleosides with the nucleobase in a syn conformation.

(ii) The five-membered 2′-deoxyribofuranosyl moiety is nonplanar, with one or two atoms twisted out of plane, referred to as sugar puckering and defined by the phase angle of pseudorotation P (Altona & Sundaralingam, 1972 ). In general, nucleosides prefer either of the two principal sugar puckering modes, named C3′-endo (N) or C2′-endo (S) (Fig. 3). They correspond to the major displacement of C3′ or C2′ from the median C1′/O4′/C4′ plane and place the more electronegative substituents of C2′ and C3′ in a preferred axial orientation (Saenger, 1984). β-2′-Deoxyribonucleosides favour C2′-endo conformations, while α-nucleosides show a preference for C2′-exo, C3′-exo and C4′-endo conformations (Sundaralingam, 1971; Latha & Yathindra, 1992). However, in the cases of α-1a and α-1b, phase angles of pseudorotation of P = 135.7° for α-1a and P = 143.4° for α-1b were found. They correspond to C2′-endo conformations (Table 2) and lie clearly outside the preferred conformational range. This is in line with studies on α-2′-deoxycytosine (Budow-Busse et al., 2021), α-5-acetyl-2′-deoxyuridine (Hamor et al., 1977 ) and α-5-aza-7-deaza-2′-deoxyguanosine (Seela et al., 2002), also reporting C2′-endo conformations.

Figure 3
N and S conformations of α-D and β-D-2′-deoxyribonucleosides in solution. `A' corresponds to adenine, `ax 'is axial and `eq' is equatorial.

(iii) The second parameter used to characterize the geometry of the furanose ring is the maximum out-of-plane puckering amplitude τ_m. The puckering amplitude τ_m indicates the degree of deviation from planarity of the furanose ring and generally shows an average value of 39° for β-nucleosides, ranging from about 35 to 45° (Altona & Sundaralingam, 1972). The particular environment of the sugar moiety, e.g. hydrogen-bonding and stacking interactions, has an effect on the degree of sugar puckering (small or large τ_m) and, as a result, the puckering amplitude τ_m and the phase angle of pseudorotation P are independent parameters. For α-nucleosides, the range of τ_m is significantly broadened (28–50°), though the average τ_m value remains around 39°. The two conformers α-1a and α-1b support this finding and adopt τ_m values of 30.5 and 31.7°, respectively. These values correspond to a flattening of the 2′-deoxyribose moiety, probably a consequence of hydrogen-bonding and stacking interactions (see next section).

(iv) The conformation around the exocyclic C4′—C5′ bond relative to the sugar ring is determined by the torsion angle γ (O5′—C5′—C4′—C3′) (Saenger, 1984). The distribution of conformers around the C4′—C5′ bond depends on the nature of the nucleobase and the sugar pucker. However, the difference between the conformational preference about the C4′—C5′ bond of β- and α-nucleosides (Sundaralingam, 1971) seems to be neglectable. For conformers α-1a and α-1b, γ torsion angles of 50.2 (3) and 46.8 (3)° are found (Table 2), corresponding to a +synclinal (+sc) conformation. In β-nucleosides, a +synclinal conformation around the exocyclic C4′—C5′ bond, in combination with a syn orientation of the nucleobase, positions the nucleobase and atom O5′ above the ribosyl moiety (Saenger, 1984). For these β-nucleosides, interactions between atom O5′ and the nucleobase might pull the torsion angles γ in the +sc range. On the contrary, due to the α-anomeric orientation of the nucleobase, this combination (+sc and syn) leads to an arrangement in α-nucleoside 1 in which atom O5′ is located `above' the sugar residue, while the nucleobase is positioned on the other (`below') side of the sugar moiety. As can be clearly seen from Fig. 2, possible interactions between the 5′-hydroxyl group and the nucleobase as in β-nucleosides can be ruled out. Instead, the hydrogen bonds formed between conformers α-1a and α-1b might account for the +sc orientation of the 5′-hydroxyl groups.

Taken together, both conformers (α-1a and α-1b) show a high correlation in their overall structural shape (see geometric parameters given in Table 2). Moreover, it is surprising that although the α-anomeric conformers α-1a and α-1b, and the canonical β-dA (2) differ only in their configuration (α versus β), significant differences of the solid-state structures are apparent from their conformational parameters (Table 2) (for a perspective view of 2, see Fig. S1 in the supporting information). This is particularly true for the torsion angle χ, the pseudorotational phase angle P, the maximum amplitude τ_m and the torsion angle γ.

3.2. Crystal packing and hydrogen bonding

The asymmetric unit of α-2′-deoxyadenosine (1) contains two molecules (α-1a and α-1b) which show different conformational properties. Both molecules are connected via hydrogen bonds in an unsymmetrical fashion. From the representation of the extended crystalline network shown in Fig. 4(a), it is evident that the sugar moiety of each conformer is arranged in such a way that this moiety functions as a `clamp' with respect to the other conformer, forming hydrogen bonds to its nucleobase and sugar residue. In detail, the exocyclic 5′-hydroxyl group forms a hydrogen bond to atom N3 of the nucleobase (O5′B—H5′B⋯N3A and O5′A—H5′A⋯N3B^v; for symmetry codes, see Table 3). The sugar-to-sugar contact is observed between the O3′-hydroxyl group as hydrogen donor and O5′ as hydrogen acceptor (O3′A—H3′A⋯O5′B^v and O3′B—H3′B⋯O5′A). In addition, bifurcated hydrogen bonds are formed by the amino groups, connecting two neighbouring molecules via N1 (N6A—H01A⋯N1Bⁱⁱⁱ and N6B—H01B⋯N1Aⁱ) and N7 (N6A—H02B⋯N7B^iv and N6B—H02B⋯N7Aⁱⁱ) of the nucleobase. Despite the fact that conformational differences exist for conformers α-1a and α-1b, both molecules form hydrogen bonds with an identical donor–acceptor pattern.

Table 3
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N6B—H01B⋯N1Aⁱ	0.89 (4)	2.36 (4)	3.239 (3)	170 (1)
N6B—H02B⋯N7Aⁱⁱ	0.86 (4)	2.14 (4)	2.998 (3)	173 (1)
O5′B—H5′B⋯N3A	0.90 (4)	1.91 (4)	2.787 (3)	163 (1)
O3′B—H3′B⋯O5′A	0.90 (4)	1.78 (4)	2.680 (3)	171 (1)
N6A—H01A⋯N1Bⁱⁱⁱ	0.92 (3)	2.33 (3)	3.243 (3)	172 (1)
N6A—H02A⋯N7B^iv	0.94 (4)	2.12 (4)	3.056 (3)	178 (1)
O5′A—H5′A⋯N3B^v	0.95 (5)	1.85 (5)	2.758 (3)	159 (1)
O3′A—H3′A⋯O5′B^v	0.92 (4)	1.80 (4)	2.691 (2)	163 (1)
Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) .

Figure 4
Detailed view of the hydrogen-bonding schemes (dashed lines) of (a) α-dA (1) (viewed in the bc plane) and (b) β-dA (2) (viewed in the ab plane).

As it was of interest to figure out the differences between the anomers of 2′-deoxyadenosine in the solid state, images of the crystalline network of β-2′-deoxyadenosine (2) were generated, using the original CIF file of Sato (1984). As indicated by Fig. 4(b), the arrangement of the individual molecules of β-dA (2) is completely different compared to that of the α-anomer (1), resulting in another hydrogen-bonding scheme. In β-dA (2), the amino group is in a `clamp'-like position with respect to the neighbouring molecule, forming a bifurcated hydrogen bond to N7 of the nucleobase and O5′ of the sugar moiety as acceptors. Nucleobase-to-sugar contacts use N1 and N3 as hydrogen acceptors and the exocyclic O3′- and O5′-hydroxyl groups as hydrogen donors. Contrary to the crystal structure of α-dA (1), sugar-to-sugar contacts do not exist in β-dA (2).

Another typical feature of the crystal structures of nucleosides are stacking interactions. Due to the aromatic nature of the heterocyclic nucleobase, this moiety is prone to form stacking interactions. Fig. 5 shows that also in the case of α-2′-deoxyadenosine (1) the nucleobases of the two conformers (α-1a and α-1b) are stacked. Always one type of conformer forms piles of stacked molecules (see inset of Fig. 5). Moreover, the nucleobases of α-1a and α-1b are facing each other, forming a rather flat entity. Accordingly, the sugar moieties of α-1a and α-1b are also sited opposite each other. The pattern of alternating conformers is continued and the above and below pairs of neighbouring nucleobases are identically positioned (non-alternating), but shifted in such a way that the nucleobases of identical conformers form a staircase-like arrangement. As a result, the two conformers (α-1a and α-1b) form a highly-ordered packing arrangement.

Figure 5
Staircase-like arrangement of conformers α-1a and α-1b within the extended crystalline network (viewed in the ca plane). Inset: stacking interactions of the conformers.

In the earlier crystal study on β-dA (2) of Sato (1984), no relevant stacking interactions were reported. We inspected thoroughly the crystal data of 2 and performed a Hirshfeld surface analysis (for details, see the next section) and found large flat areas in the curvedness plots of 2 which indicate stacking interactions. Indeed, remodelling of the extended crystalline network of β-dA (2) proves the occurrence of stacking interactions of the aromatic nucleobases (see Figs. S3 and S4 in the supporting information).

3.3. Hirshfeld surface analyses of α-2′-deoxyadenosine (1) and β-2′-deoxyadenosine (2)

To obtain additional information on the role of crystal packing forces and to visualize the relative strengths of the intermolecular interactions, a Hirshfeld surface analysis of α-2′-deoxyadenosine (1) was carried out. For this purpose, the program CrystalExplorer (Version 17; Spackman & Jayatilaka, 2009 ; Turner et al., 2017 ) was used. The Hirshfeld surfaces of the two conformers of α-dA (1) mapped over a d_norm range of −0.5 to 1.5 Å are represented, together with close-contact molecules of the central molecules inside the Hirshfeld surface [Fig. 6(a) and Fig. S5 in the supporting information]. Therein, the red surface areas denote strong interactions with distances shorter than the sum of the van der Waals radii and negative d_norm, white surface areas represent contacts with distances equal to the sum of the van der Waals radii and blue surfaces refer to weak contacts. Surfaces of the two conformers of 1 plotted over curvedness are shown in Figs. 6(b) and S7 (see supporting information). For shape-index plots, see Fig. S6 in the supporting information.

Figure 6
The Hirshfeld surfaces of α-dA (1) (upper part) and β-dA (2) (lower part) with close-contact molecules, (a)/(c) mapped over d_norm (−0.5 to 1.5 Å) and (b)/(d) mapped over the curvedness (−4.0 to 4.0 Å). Green areas represent flat regions and blue lines indicate edges.

Inspection of the Hirshfeld surface of conformers α-1a and α-1b reveals a large unperturbed area [Fig. 6(a)], with the major red spots located on the top view area. These spots correspond to the short-range hydrogen bonds connecting the sugar moiety of one conformer to the nucleobase and sugar residue of the other conformer, as described in the previous section. Additional and less intense spots indicate the presence of weaker contacts formed by the amino groups. As a result, the Hirshfeld analyses are consistent with the hydrogen-bonding data (Table 3). Moreover, the curvedness plot of 1 [Fig. 6(b)] shows large flat areas due to the presence of the aromatic nucleobase and confirms the contribution of stacking interactions to the overall crystal packing.

Two-dimensional (2D) fingerprint plots (Fig. 7 and Fig. S11 in the supporting information) provide a visual summary of the contribution of each contact type and their relative proportion to the Hirshfeld surface. The plots are resolved into N⋯H/H⋯N, O⋯H/H⋯O, C⋯H/H⋯C and H⋯H contacts [Figs. 7(b)–(e)]. The N⋯H/H⋯N (25.2%) and O⋯H/H⋯O (13.3%) contacts provide a significant contribution to the surface and form the two characteristic spikes. They represent the strong hydrogen bonds interconnecting conformers α-1a and α-1b. The wings of the plot are occupied by C⋯H/H⋯C interactions (13.6%), which include numerous weak hydrogen bonds. The nonspecific van der Waals H⋯H contacts (41.8%) occupy the major portion of the surface.

Figure 7
2D fingerprint plots showing the percentage contributions of the various interactions to the total Hirshfeld surface area of α-dA (1), showing (a) all interactions and resolved contacts of (b) N⋯H/H⋯N, (c) O⋯H/H⋯O, (d) C⋯H/H⋯C and (e) H⋯H.

Due to the early publication date of the crystal structure of β-2′-deoxyadenosine (2) (Sato, 1984), to the best of our knowledge, a Hirshfeld surface analysis has not yet been performed for β-dA (2). Therefore, we also carried out a Hirshfeld surface analysis of 2 [Fig. 6(c) and Fig. S8 in the supporting information] using the crystal structure data (CCDC deposition number 1124124; Sato, 1984). For shape index and curvedness plots of 2, see Fig. 6(d) and Figs. S9 and S10 in the supporting information. The Hirshfeld surface analysis of β-dA mapped over d_norm and curvedness supports the hydrogen-bonding (Sato, 1984) and stacking interactions of 2. The calculated 2D fingerprint plots for 2 are shown in Fig. S11 in the supporting information and confirm the significant contribution of the N⋯H/H⋯N (22.2%) and O⋯H/H⋯O (18.7%) contacts to the overall crystal packing forces.

4. Conclusion

The present work is the first report on a single-crystal X-ray analysis of an α-D-2′-deoxyribonucleoside carrying a canonical purine nucleobase. In the crystalline state, α-dA forms two conformers (α-1a and α-1b) in the asymmetric unit which are connected via hydrogen bonds. In contrast to the anti conformation commonly preferred by α-nucleosides, the nucleobase moiety of α-1a and α-1b adopts a syn conformation. For both conformers, the sugar conformation is C2′-endo and the 5′-hydroxyl group is in a +sc orientation.

Comparison of the solid-state structure of α-dA to canonical β-2′-deoxyadenosine (2) (Sato, 1984) revealed significant differences in the conformational parameters and in the packing of their supramolecular networks (see space-filling models in Fig. 8). In the supramolecular network of α-dA (1), the sugar moieties of each conformer act as clamps by forming hydrogen bonds to the nucleobases and sugar residues of the other conformer. The nucleobases form hydrogen-bonded chains which are linked to equivalent chains by hydrogen bonds involving the sugar moieties to form sheets. The nucleobases and the sugar moieties of alternating α-1a and α-1b conformers are organized face-to-face with respect to each other. A staircase-like arrangement is formed by the nucleobases of each conformer. In addition, piles of stacked molecules are formed by always one type of conformer. The hydrogen-bonding pattern is supported by a Hirshfeld surface analysis, and curvedness surfaces confirm the contribution of stacking interactions to the overall crystal packing.

Figure 8
Space-filling models of (a) α-dA (1) and (b) β-dA (2).

α-D-2′-Deoxyadenosine (1) is not found in native DNA, but it is formed as a major lesion product upon γ-irradiation of DNA under anoxic conditions. Furthermore, it is a component of anomeric DNA formed by one strand in an α-D and the other in a β-D configuration. The latter is as stable as canonical DNA and shows similar base recognition. One of the recent developments in the realm of anomeric DNA is the construction of entirely new nucleic acid structures and the design of new recognition systems to expand the genetic code.

Supporting information

CCDC reference: 2294190

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2053229624000457/ov3171sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2053229624000457/ov3171Isup2.hkl

Additional packing schemes, Hirshfeld surfaces of the anomers and fingerprint plots. DOI: https://doi.org/10.1107/S2053229624000457/ov3171sup3.pdf

Computing details top

α-D-2'-Deoxyadenosine top

Crystal data top

C₁₀H₁₃N₅O₃	Z = 2
M_r = 251.25	F(000) = 264
Triclinic, P1	D_x = 1.523 Mg m⁻³
a = 5.2027 (2) Å	Cu Kα radiation, λ = 1.54178 Å
b = 8.9738 (3) Å	Cell parameters from 9907 reflections
c = 12.3715 (4) Å	θ = 3.7–68.5°
α = 78.249 (1)°	µ = 0.98 mm⁻¹
β = 83.171 (1)°	T = 100 K
γ = 76.338 (1)°	Plate, colourless
V = 547.97 (3) Å³	0.19 × 0.08 × 0.05 mm

Data collection top

Single crystal diffractometer	3858 independent reflections
Radiation source: CuKα, micro focus tube	3752 reflections with I > 2σ(I)
MX mirror monochromator	R_int = 0.041
Detector resolution: 7.3910 pixels mm^-1	θ_max = 68.3°, θ_min = 3.7°
phi/ω scans	h = −6→6
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	k = −10→10
T_min = 0.84, T_max = 0.95	l = −14→14
17188 measured reflections

Refinement top

Refinement on F²	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.027	w = 1/[σ²(F_o²) + (0.0256P)² + 0.1416P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.065	(Δ/σ)_max < 0.001
S = 1.08	Δρ_max = 0.18 e Å⁻³
3858 reflections	Δρ_min = −0.17 e Å⁻³
357 parameters	Absolute structure: Flack x determined using 1744 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
3 restraints	Absolute structure parameter: −0.01 (8)
Primary atom site location: structure-invariant direct methods

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Reflections were merged by SHELXL according to the crystal class for the calculation of statistics and refinement.

_reflns_Friedel_fraction is defined as the number of unique Friedel pairs measured divided by the number that would be possible theoretically, ignoring centric projections and systematic absences.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
N1B	−0.2612 (4)	−0.0771 (2)	0.91430 (16)	0.0156 (4)
N3B	0.1000 (4)	−0.0209 (2)	0.78214 (16)	0.0153 (4)
N9B	0.1791 (4)	0.2381 (2)	0.77689 (17)	0.0148 (4)
N7B	−0.1333 (4)	0.3158 (2)	0.90854 (16)	0.0159 (4)
N6B	−0.5149 (4)	0.1031 (3)	1.01668 (18)	0.0173 (5)
H01B	−0.565 (7)	0.201 (5)	1.028 (3)	0.033 (9)*
H02B	−0.614 (8)	0.036 (5)	1.038 (3)	0.040 (10)*
O4'B	0.2679 (4)	0.2614 (2)	0.58235 (14)	0.0180 (4)
O5'B	0.6105 (3)	0.3959 (2)	0.39970 (15)	0.0194 (4)
H5'B	0.666 (8)	0.455 (5)	0.337 (4)	0.049 (11)*
O3'B	0.1877 (3)	0.6054 (2)	0.65699 (15)	0.0206 (4)
H3'B	0.229 (6)	0.700 (4)	0.640 (3)	0.026 (8)*
C2B	−0.0621 (5)	−0.1102 (3)	0.8379 (2)	0.0168 (5)
H2B	−0.031478	−0.211828	0.820936	0.020000*
C4B	0.0495 (5)	0.1181 (3)	0.81508 (19)	0.0134 (5)
C5B	−0.1428 (5)	0.1674 (3)	0.89507 (19)	0.0142 (5)
C6B	−0.3109 (5)	0.0658 (3)	0.94379 (19)	0.0145 (5)
C8B	0.0599 (5)	0.3528 (3)	0.8369 (2)	0.0154 (5)
H8B	0.112205	0.449471	0.827461	0.018000*
C2'B	0.5353 (5)	0.3676 (3)	0.6706 (2)	0.0164 (5)
H200	0.716982	0.335757	0.636456	0.020000*
H201	0.546691	0.395337	0.743077	0.020000*
C3'B	0.3725 (5)	0.5039 (3)	0.5950 (2)	0.0166 (5)
H300	0.492005	0.563193	0.543473	0.020000*
C4'B	0.2276 (5)	0.4250 (3)	0.5301 (2)	0.0170 (5)
H400	0.033723	0.473554	0.535398	0.020000*
C1'B	0.3843 (5)	0.2381 (3)	0.6838 (2)	0.0158 (5)
H100	0.513258	0.135125	0.693995	0.019000*
C5'B	0.3270 (5)	0.4360 (3)	0.4093 (2)	0.0187 (5)
H501	0.256106	0.364234	0.375837	0.022000*
H502	0.263989	0.543512	0.369022	0.022000*
N1A	1.2440 (4)	0.4435 (2)	0.08135 (17)	0.0173 (5)
N3A	0.8746 (4)	0.5300 (2)	0.20877 (17)	0.0162 (4)
N9A	0.8311 (4)	0.8015 (2)	0.22604 (16)	0.0139 (4)
N7A	1.1731 (4)	0.8578 (2)	0.10746 (17)	0.0160 (4)
N6A	1.5141 (4)	0.6061 (3)	−0.01629 (18)	0.0189 (5)
H01A	1.564 (6)	0.700 (4)	−0.031 (3)	0.023 (8)*
H02A	1.621 (7)	0.517 (5)	−0.041 (3)	0.035 (9)*
O4'A	0.6986 (4)	0.74763 (19)	0.41755 (14)	0.0190 (4)
O5'A	0.3529 (3)	0.8734 (2)	0.59441 (15)	0.0179 (4)
H5'A	0.301 (9)	0.921 (6)	0.658 (4)	0.064 (13)*
O3'A	0.8166 (3)	1.1095 (2)	0.35321 (15)	0.0207 (4)
H3'A	0.777 (7)	1.204 (5)	0.375 (3)	0.039 (10)*
C2A	1.0339 (5)	0.4264 (3)	0.1534 (2)	0.0179 (5)
H2A	0.992823	0.326258	0.166822	0.021000*
C4A	0.9469 (5)	0.6684 (3)	0.1840 (2)	0.0146 (5)
C5A	1.1565 (5)	0.7041 (3)	0.11119 (19)	0.0145 (5)
C6A	1.3098 (5)	0.5850 (3)	0.05724 (19)	0.0150 (5)
C8A	0.9771 (5)	0.9092 (3)	0.1765 (2)	0.0159 (5)
H8A	0.939186	1.012478	0.190988	0.019000*
C2'A	0.4711 (5)	0.9828 (3)	0.3188 (2)	0.0170 (5)
H203	0.281089	0.990702	0.343694	0.020000*
H204	0.485722	1.052096	0.246080	0.020000*
C3'A	0.6181 (5)	1.0253 (3)	0.4036 (2)	0.0169 (5)
H301	0.489052	1.087611	0.452963	0.020000*
C4'A	0.7470 (5)	0.8669 (3)	0.4707 (2)	0.0170 (5)
H401	0.942486	0.858648	0.468554	0.020000*
C1'A	0.6087 (5)	0.8148 (3)	0.3116 (2)	0.0164 (5)
H101	0.475785	0.759094	0.296019	0.020000*
C5'A	0.6359 (5)	0.8410 (3)	0.5899 (2)	0.0187 (5)
H503	0.704050	0.731678	0.625585	0.022000*
H504	0.693462	0.910244	0.630574	0.022000*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1B	0.0186 (10)	0.0141 (11)	0.0144 (10)	−0.0046 (8)	0.0007 (8)	−0.0029 (8)
N3B	0.0164 (10)	0.0145 (10)	0.0151 (10)	−0.0045 (8)	0.0017 (8)	−0.0035 (8)
N9B	0.0160 (10)	0.0138 (10)	0.0140 (10)	−0.0049 (8)	0.0023 (8)	−0.0013 (8)
N7B	0.0178 (10)	0.0158 (11)	0.0136 (10)	−0.0043 (9)	0.0019 (8)	−0.0027 (8)
N6B	0.0180 (11)	0.0157 (12)	0.0179 (11)	−0.0058 (10)	0.0050 (8)	−0.0036 (9)
O4'B	0.0261 (9)	0.0161 (9)	0.0125 (8)	−0.0084 (7)	0.0025 (7)	−0.0019 (6)
O5'B	0.0200 (9)	0.0176 (9)	0.0187 (9)	−0.0054 (7)	0.0063 (7)	−0.0018 (7)
O3'B	0.0241 (10)	0.0131 (9)	0.0223 (10)	−0.0025 (7)	0.0072 (7)	−0.0049 (7)
C2B	0.0208 (13)	0.0165 (13)	0.0142 (12)	−0.0056 (10)	−0.0003 (10)	−0.0039 (9)
C4B	0.0143 (12)	0.0152 (12)	0.0111 (11)	−0.0051 (10)	−0.0005 (9)	−0.0011 (9)
C5B	0.0143 (11)	0.0150 (12)	0.0129 (12)	−0.0024 (10)	−0.0019 (9)	−0.0019 (9)
C6B	0.0161 (12)	0.0156 (12)	0.0111 (11)	−0.0026 (10)	−0.0026 (9)	−0.0007 (9)
C8B	0.0179 (12)	0.0136 (12)	0.0149 (12)	−0.0039 (10)	0.0007 (9)	−0.0041 (9)
C2'B	0.0146 (12)	0.0151 (12)	0.0190 (13)	−0.0034 (10)	0.0019 (10)	−0.0035 (9)
C3'B	0.0171 (12)	0.0139 (12)	0.0176 (12)	−0.0036 (9)	0.0039 (9)	−0.0028 (9)
C4'B	0.0166 (12)	0.0143 (12)	0.0186 (13)	−0.0036 (10)	0.0008 (10)	−0.0007 (9)
C1'B	0.0149 (12)	0.0162 (12)	0.0148 (12)	−0.0029 (10)	0.0040 (9)	−0.0026 (9)
C5'B	0.0198 (12)	0.0189 (13)	0.0166 (12)	−0.0050 (10)	−0.0012 (10)	−0.0003 (10)
N1A	0.0182 (11)	0.0169 (11)	0.0168 (11)	−0.0056 (9)	0.0024 (8)	−0.0033 (8)
N3A	0.0174 (10)	0.0152 (11)	0.0161 (10)	−0.0050 (8)	0.0014 (8)	−0.0029 (8)
N9A	0.0132 (10)	0.0142 (10)	0.0141 (10)	−0.0030 (8)	0.0029 (8)	−0.0046 (8)
N7A	0.0173 (10)	0.0156 (10)	0.0156 (10)	−0.0054 (8)	0.0013 (8)	−0.0032 (8)
N6A	0.0192 (11)	0.0176 (12)	0.0196 (12)	−0.0052 (9)	0.0065 (9)	−0.0057 (9)
O4'A	0.0285 (10)	0.0137 (9)	0.0138 (9)	−0.0057 (7)	0.0045 (7)	−0.0028 (6)
O5'A	0.0179 (9)	0.0190 (9)	0.0173 (9)	−0.0057 (7)	0.0043 (7)	−0.0057 (7)
O3'A	0.0209 (10)	0.0169 (10)	0.0261 (10)	−0.0092 (8)	0.0088 (7)	−0.0080 (8)
C2A	0.0213 (13)	0.0151 (13)	0.0173 (13)	−0.0055 (10)	0.0010 (10)	−0.0024 (10)
C4A	0.0153 (12)	0.0160 (12)	0.0128 (12)	−0.0032 (10)	−0.0022 (9)	−0.0027 (9)
C5A	0.0149 (12)	0.0163 (12)	0.0127 (12)	−0.0043 (10)	−0.0002 (9)	−0.0028 (10)
C6A	0.0147 (12)	0.0168 (12)	0.0130 (12)	−0.0029 (10)	−0.0018 (10)	−0.0018 (9)
C8A	0.0160 (12)	0.0147 (13)	0.0166 (12)	−0.0044 (10)	0.0008 (10)	−0.0018 (9)
C2'A	0.0146 (12)	0.0165 (12)	0.0187 (12)	−0.0034 (10)	0.0039 (9)	−0.0034 (9)
C3'A	0.0160 (12)	0.0155 (13)	0.0197 (13)	−0.0060 (10)	0.0048 (9)	−0.0051 (10)
C4'A	0.0159 (12)	0.0163 (12)	0.0197 (13)	−0.0041 (10)	0.0012 (10)	−0.0063 (10)
C1'A	0.0166 (12)	0.0193 (13)	0.0139 (12)	−0.0066 (10)	0.0029 (9)	−0.0037 (10)
C5'A	0.0173 (12)	0.0189 (13)	0.0195 (13)	−0.0025 (10)	−0.0003 (10)	−0.0049 (10)

Geometric parameters (Å, º) top

N1B—C2B	1.338 (3)	N1A—C2A	1.343 (3)
N1B—C6B	1.362 (3)	N1A—C6A	1.358 (3)
N3B—C2B	1.336 (3)	N3A—C2A	1.334 (3)
N3B—C4B	1.349 (3)	N3A—C4A	1.348 (3)
N9B—C8B	1.377 (3)	N9A—C8A	1.372 (3)
N9B—C4B	1.377 (3)	N9A—C4A	1.377 (3)
N9B—C1'B	1.474 (3)	N9A—C1'A	1.473 (3)
N7B—C8B	1.316 (3)	N7A—C8A	1.309 (3)
N7B—C5B	1.389 (3)	N7A—C5A	1.393 (3)
N6B—C6B	1.334 (3)	N6A—C6A	1.337 (3)
N6B—H01B	0.89 (4)	N6A—H01A	0.92 (3)
N6B—H02B	0.86 (4)	N6A—H02A	0.94 (4)
O4'B—C1'B	1.414 (3)	O4'A—C1'A	1.411 (3)
O4'B—C4'B	1.455 (3)	O4'A—C4'A	1.447 (3)
O5'B—C5'B	1.430 (3)	O5'A—C5'A	1.428 (3)
O5'B—H5'B	0.90 (4)	O5'A—H5'A	0.95 (5)
O3'B—C3'B	1.428 (3)	O3'A—C3'A	1.431 (3)
O3'B—H3'B	0.90 (4)	O3'A—H3'A	0.92 (4)
C2B—H2B	0.9500	C2A—H2A	0.9500
C4B—C5B	1.382 (3)	C4A—C5A	1.385 (3)
C5B—C6B	1.410 (3)	C5A—C6A	1.409 (3)
C8B—H8B	0.9500	C8A—H8A	0.9500
C2'B—C1'B	1.523 (3)	C2'A—C1'A	1.524 (4)
C2'B—C3'B	1.524 (3)	C2'A—C3'A	1.525 (4)
C2'B—H200	0.9900	C2'A—H203	0.9900
C2'B—H201	0.9900	C2'A—H204	0.9900
C3'B—C4'B	1.530 (4)	C3'A—C4'A	1.537 (3)
C3'B—H300	1.0000	C3'A—H301	1.0000
C4'B—C5'B	1.513 (4)	C4'A—C5'A	1.511 (4)
C4'B—H400	1.0000	C4'A—H401	1.0000
C1'B—H100	1.0000	C1'A—H101	1.0000
C5'B—H501	0.9900	C5'A—H503	0.9900
C5'B—H502	0.9900	C5'A—H504	0.9900

C2B—N1B—C6B	118.0 (2)	C2A—N1A—C6A	118.1 (2)
C2B—N3B—C4B	111.1 (2)	C2A—N3A—C4A	111.2 (2)
C8B—N9B—C4B	105.42 (19)	C8A—N9A—C4A	105.31 (19)
C8B—N9B—C1'B	130.5 (2)	C8A—N9A—C1'A	129.4 (2)
C4B—N9B—C1'B	123.8 (2)	C4A—N9A—C1'A	125.2 (2)
C8B—N7B—C5B	104.2 (2)	C8A—N7A—C5A	103.84 (19)
C6B—N6B—H01B	119 (2)	C6A—N6A—H01A	120 (2)
C6B—N6B—H02B	117 (3)	C6A—N6A—H02A	117 (2)
H01B—N6B—H02B	122 (3)	H01A—N6A—H02A	122 (3)
C1'B—O4'B—C4'B	109.90 (19)	C1'A—O4'A—C4'A	109.97 (18)
C5'B—O5'B—H5'B	108 (3)	C5'A—O5'A—H5'A	103 (3)
C3'B—O3'B—H3'B	108 (2)	C3'A—O3'A—H3'A	108 (2)
N3B—C2B—N1B	129.3 (2)	N3A—C2A—N1A	129.3 (2)
N3B—C2B—H2B	115.3000	N3A—C2A—H2A	115.4000
N1B—C2B—H2B	115.3000	N1A—C2A—H2A	115.4000
N3B—C4B—N9B	127.2 (2)	N3A—C4A—N9A	127.5 (2)
N3B—C4B—C5B	126.3 (2)	N3A—C4A—C5A	126.3 (2)
N9B—C4B—C5B	106.5 (2)	N9A—C4A—C5A	106.3 (2)
C4B—C5B—N7B	110.2 (2)	C4A—C5A—N7A	110.3 (2)
C4B—C5B—C6B	117.1 (2)	C4A—C5A—C6A	117.3 (2)
N7B—C5B—C6B	132.6 (2)	N7A—C5A—C6A	132.4 (2)
N6B—C6B—N1B	118.9 (2)	N6A—C6A—N1A	119.3 (2)
N6B—C6B—C5B	123.2 (2)	N6A—C6A—C5A	122.8 (2)
N1B—C6B—C5B	117.9 (2)	N1A—C6A—C5A	117.9 (2)
N7B—C8B—N9B	113.6 (2)	N7A—C8A—N9A	114.3 (2)
N7B—C8B—H8B	123.2000	N7A—C8A—H8A	122.8000
N9B—C8B—H8B	123.2000	N9A—C8A—H8A	122.8000
C1'B—C2'B—C3'B	104.2 (2)	C1'A—C2'A—C3'A	104.4 (2)
C1'B—C2'B—H200	110.9000	C1'A—C2'A—H203	110.9000
C3'B—C2'B—H200	110.9000	C3'A—C2'A—H203	110.9000
C1'B—C2'B—H201	110.9000	C1'A—C2'A—H204	110.9000
C3'B—C2'B—H201	110.9000	C3'A—C2'A—H204	110.9000
H200—C2'B—H201	108.9000	H203—C2'A—H204	108.9000
O3'B—C3'B—C2'B	111.5 (2)	O3'A—C3'A—C2'A	112.6 (2)
O3'B—C3'B—C4'B	110.7 (2)	O3'A—C3'A—C4'A	110.4 (2)
C2'B—C3'B—C4'B	103.6 (2)	C2'A—C3'A—C4'A	103.9 (2)
O3'B—C3'B—H300	110.3000	O3'A—C3'A—H301	109.9000
C2'B—C3'B—H300	110.3000	C2'A—C3'A—H301	109.9000
C4'B—C3'B—H300	110.3000	C4'A—C3'A—H301	109.9000
O4'B—C4'B—C5'B	108.9 (2)	O4'A—C4'A—C5'A	108.83 (19)
O4'B—C4'B—C3'B	107.2 (2)	O4'A—C4'A—C3'A	107.12 (19)
C5'B—C4'B—C3'B	113.4 (2)	C5'A—C4'A—C3'A	113.3 (2)
O4'B—C4'B—H400	109.1000	O4'A—C4'A—H401	109.2000
C5'B—C4'B—H400	109.1000	C5'A—C4'A—H401	109.2000
C3'B—C4'B—H400	109.1000	C3'A—C4'A—H401	109.2000
O4'B—C1'B—N9B	110.40 (19)	O4'A—C1'A—N9A	110.6 (2)
O4'B—C1'B—C2'B	105.17 (19)	O4'A—C1'A—C2'A	105.50 (19)
N9B—C1'B—C2'B	114.2 (2)	N9A—C1'A—C2'A	113.5 (2)
O4'B—C1'B—H100	109.0000	O4'A—C1'A—H101	109.0000
N9B—C1'B—H100	109.0000	N9A—C1'A—H101	109.0000
C2'B—C1'B—H100	109.0000	C2'A—C1'A—H101	109.0000
O5'B—C5'B—C4'B	109.8 (2)	O5'A—C5'A—C4'A	109.8 (2)
O5'B—C5'B—H501	109.7000	O5'A—C5'A—H503	109.7000
C4'B—C5'B—H501	109.7000	C4'A—C5'A—H503	109.7000
O5'B—C5'B—H502	109.7000	O5'A—C5'A—H504	109.7000
C4'B—C5'B—H502	109.7000	C4'A—C5'A—H504	109.7000
H501—C5'B—H502	108.2000	H503—C5'A—H504	108.2000

C4B—N3B—C2B—N1B	2.7 (4)	C4A—N3A—C2A—N1A	0.4 (4)
C6B—N1B—C2B—N3B	−1.4 (4)	C6A—N1A—C2A—N3A	−1.1 (4)
C2B—N3B—C4B—N9B	179.1 (2)	C2A—N3A—C4A—N9A	−179.2 (2)
C2B—N3B—C4B—C5B	−0.3 (3)	C2A—N3A—C4A—C5A	0.2 (3)
C8B—N9B—C4B—N3B	−178.9 (2)	C8A—N9A—C4A—N3A	179.4 (2)
C1'B—N9B—C4B—N3B	5.9 (4)	C1'A—N9A—C4A—N3A	3.0 (4)
C8B—N9B—C4B—C5B	0.7 (2)	C8A—N9A—C4A—C5A	−0.1 (3)
C1'B—N9B—C4B—C5B	−174.6 (2)	C1'A—N9A—C4A—C5A	−176.5 (2)
N3B—C4B—C5B—N7B	178.8 (2)	N3A—C4A—C5A—N7A	−179.3 (2)
N9B—C4B—C5B—N7B	−0.8 (3)	N9A—C4A—C5A—N7A	0.1 (3)
N3B—C4B—C5B—C6B	−3.0 (4)	N3A—C4A—C5A—C6A	0.1 (3)
N9B—C4B—C5B—C6B	177.4 (2)	N9A—C4A—C5A—C6A	179.6 (2)
C8B—N7B—C5B—C4B	0.5 (3)	C8A—N7A—C5A—C4A	−0.1 (3)
C8B—N7B—C5B—C6B	−177.3 (3)	C8A—N7A—C5A—C6A	−179.4 (3)
C2B—N1B—C6B—N6B	177.5 (2)	C2A—N1A—C6A—N6A	−178.4 (2)
C2B—N1B—C6B—C5B	−2.4 (3)	C2A—N1A—C6A—C5A	1.3 (3)
C4B—C5B—C6B—N6B	−175.6 (2)	C4A—C5A—C6A—N6A	178.8 (2)
N7B—C5B—C6B—N6B	2.1 (4)	N7A—C5A—C6A—N6A	−1.9 (4)
C4B—C5B—C6B—N1B	4.3 (3)	C4A—C5A—C6A—N1A	−0.8 (3)
N7B—C5B—C6B—N1B	−178.0 (2)	N7A—C5A—C6A—N1A	178.4 (2)
C5B—N7B—C8B—N9B	0.0 (3)	C5A—N7A—C8A—N9A	0.1 (3)
C4B—N9B—C8B—N7B	−0.4 (3)	C4A—N9A—C8A—N7A	0.0 (3)
C1'B—N9B—C8B—N7B	174.4 (2)	C1'A—N9A—C8A—N7A	176.2 (2)
C1'B—C2'B—C3'B—O3'B	93.7 (2)	C1'A—C2'A—C3'A—O3'A	97.7 (2)
C1'B—C2'B—C3'B—C4'B	−25.4 (2)	C1'A—C2'A—C3'A—C4'A	−21.8 (2)
C1'B—O4'B—C4'B—C5'B	133.1 (2)	C1'A—O4'A—C4'A—C5'A	136.4 (2)
C1'B—O4'B—C4'B—C3'B	10.0 (3)	C1'A—O4'A—C4'A—C3'A	13.5 (2)
O3'B—C3'B—C4'B—O4'B	−109.2 (2)	O3'A—C3'A—C4'A—O4'A	−114.8 (2)
C2'B—C3'B—C4'B—O4'B	10.4 (2)	C2'A—C3'A—C4'A—O4'A	6.2 (2)
O3'B—C3'B—C4'B—C5'B	130.5 (2)	O3'A—C3'A—C4'A—C5'A	125.2 (2)
C2'B—C3'B—C4'B—C5'B	−109.8 (2)	C2'A—C3'A—C4'A—C5'A	−113.9 (2)
C4'B—O4'B—C1'B—N9B	97.2 (2)	C4'A—O4'A—C1'A—N9A	95.5 (2)
C4'B—O4'B—C1'B—C2'B	−26.4 (2)	C4'A—O4'A—C1'A—C2'A	−27.7 (2)
C8B—N9B—C1'B—O4'B	−101.2 (3)	C8A—N9A—C1'A—O4'A	−97.5 (3)
C4B—N9B—C1'B—O4'B	72.7 (3)	C4A—N9A—C1'A—O4'A	78.0 (3)
C8B—N9B—C1'B—C2'B	17.0 (4)	C8A—N9A—C1'A—C2'A	20.9 (3)
C4B—N9B—C1'B—C2'B	−169.0 (2)	C4A—N9A—C1'A—C2'A	−163.6 (2)
C3'B—C2'B—C1'B—O4'B	32.2 (2)	C3'A—C2'A—C1'A—O4'A	30.6 (2)
C3'B—C2'B—C1'B—N9B	−89.0 (2)	C3'A—C2'A—C1'A—N9A	−90.8 (2)
O4'B—C4'B—C5'B—O5'B	−72.4 (2)	O4'A—C4'A—C5'A—O5'A	−68.8 (3)
C3'B—C4'B—C5'B—O5'B	46.8 (3)	C3'A—C4'A—C5'A—O5'A	50.2 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N6B—H01B···N1Aⁱ	0.89 (4)	2.36 (4)	3.239 (3)	170 (1)
N6B—H02B···N7Aⁱⁱ	0.86 (4)	2.14 (4)	2.998 (3)	173 (1)
O5′B—H5′B···N3A	0.90 (4)	1.91 (4)	2.787 (3)	163 (1)
O3′B—H3′B···O5′A	0.90 (4)	1.78 (4)	2.680 (3)	171 (1)
N6A—H01A···N1Bⁱⁱⁱ	0.92 (3)	2.33 (3)	3.243 (3)	172 (1)
N6A—H02A···N7B^iv	0.94 (4)	2.12 (4)	3.056 (3)	178 (1)
O5′A—H5′A···N3B^v	0.95 (5)	1.85 (5)	2.758 (3)	159 (1)
O3′A—H3′A···O5′B^v	0.92 (4)	1.80 (4)	2.691 (2)	163 (1)

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

Selected geometric parameters of the anomeric 2'-deoxyadenosines α-1a, α-1b and β-dA (2) top

	Conformer α-1a	Conformer α-1b	β-dA (2) (Sato, 1984)
Glycosylic bond length (N9—C1') (Å)	1.473 (3)	1.474 (3)	1.474 (2)
Torsion angle χ (O4'—C1'—N9—C4) (°)	78.0 (3)	72.7 (3)	-165.0 (7)
Relative sugar/base orientation	syn	syn	anti
Pseudorotational phase angle P (°)	135.67	143.35	13.28
Maximum amplitude τ_m (°)	30.51	31.68	36.34
Sugar pucker	S-type, C2'-endo, ₁T²	S-type, C2'-endo, ₁T²	N-type, C3'-endo, ³T₂
Torsion angle γ (O5'—C5'—C4'—C3') (°)	50.2 (3)	46.8 (3)	175.5 (1)
Relative orientation of exocyclic 5'-OH	+synclinal (gauche)	+synclinal (gauche)	+antiperiplanar (trans)

Acknowledgements

Funding by ChemBiotech, Münster, Germany, is gratefully acknowledged. Open access funding enabled and organized by Projekt DEAL.

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