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A new polymorph of cytosine, C4H5N3O, is reported half a century after the report of its first known crystal structure [Barker & Marsh (1964). Acta Cryst. 17, 1581-1587]. Cytosine thus provides the first polymorphic example in the category of parent nucleobases. The new form, denoted (Ib), was observed unexpectedly during an attempt to cocrystallize cytosine with catechol. Form (Ib) crystallizes in the ortho­rhom­bic centro­symmetric space group Pccn with two mol­ecules in the asymmetric unit. The previously known form, denoted (Ia), crystallizes in the ortho­rhom­bic non­centro­symmetric space group P212121. The cytosine mol­ecule is planar in both forms. Hydrogen-bonding inter­actions are also similar for both forms. Infinite one-dimensional ribbons composed of cytosine base-pair dimers in R22(8) arrangements are observed in both (Ia) and (Ib). However, the way that the ribbons are packed differs in (Ia) and (Ib). This appears to guide the centro­symmetric versus non­centro­symmetric space-group selection through the formation of an inversion-related motif in poly­morph (Ib) and a helical propagation in polymorph (Ia). A few selected polymorphic systems have been gathered from the Cambridge Structural Database to understand possible structural features responsible for achiral mol­ecules adopting centro- and non­centro­symmetric space groups.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229615000492/cu3072sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2053229615000492/cu3072Isup2.hkl
Contains datablock I

CCDC reference: 1042861

Introduction top

Polymorphism is the existence of two or more different crystal structures for the same compound. Gavezzotti (2007) has described the concept of polymorphism in more detail. According to his view, it is set of crystals having (a) identical chemical compositions, (b) the same molecular connectivity with different conformations and (c) different inter­molecular inter­actions. Apart from routine crystal structure analysis of polymorphic systems, studies have been carried out at different pressures and temperatures to understand their solid-state phase transformations and stability. Different polymorphic forms can lead to significant changes in physical properties, such as colour, solubility, bioavailability and thermodynamic stability (Timofeeva et al., 2003; Price et al., 2003; Vrcelj et al., 2003). One of the popular examples is glycine, which exhibits different physical and chemical properties. The β- and γ-forms exhibit piezoelectric properties (Iitaka, 1958, 1960), whereas the α-form shows pyroelectricity near room temperature (Chilcott et al., 1999). According to McCrone (1965), the number of polymorphic modifications of a particular compound is in direct proportion to the time and money spent on the search for them.

Recently, we published several research articles on multicomponent crystals of cytosine with carb­oxy­lic acid to study their supra­molecular hydrogen-bonded inter­actions and molecular recognition of nucleobases in the solid state (Sridhar & Ravikumar, 2008, 2010a,b; Sridhar et al., 2012). In continuation of this work, attempts were made to grow cocrystals of nucleobases and different hydroxyl-containing co-formers like catechol, resorcinol and hydro­quinone. Unexpectedly, a new form of cytosine was observed. Attempted cocrystallization leading to the discovery of new forms is not unprecedented (Rafilovich & Bernstein, 2006; Babu et al., 2008). Cytosine is one of the nucleobases in the building blocks of RNA and DNA, which store and transport genetic information within the cell. The first crystal structure of cytosine [referred to as polymorph (Ia)] was determined in 1964 by the photographic method (Barker & Marsh, 1964) and later redetermined using X-ray diffraction (McClure & Craven, 1973). Now, after half a century, a second polymorph of cytosine [referred to as polymorph (Ib)] has been identified in our laboratory.

No polymorphic forms have been reported for any of the parent nucleobases until now. Cytosine is the first polymorphic example. Notably, all the crystal structures of nucleobases crystallize in centrosymmetric space groups, with the exception of the cytosine system which crystallizes in both centro- and noncentrosymmetric space groups. Adenine, thymine and guanine are in the monoclinic space group P21/c (Ozeki et al., 1969; Guille & Clegg, 2006; Mahapatra et al., 2008) and uracil is in the P21/a space group (Stewart & Jensen, 1967), whereas polymorph (Ia) of cytosine is in the orthorhombic P212121 space group and polymorph (Ib) of cytosine is in the orthorhombic Pccn space group.

Experimental top

Synthesis and crystallization top

Cytosine (Sigma–Aldrich India) and catechol (Himedia Laboratories, Hyderabad) were used as received for the attempted preparation of cocrystals in a methanol–water mixture. Cytosine (0.025 g, 0.23 mmol) and catechol (0.025 g, 0.23 mmol) were dissolved in a mixture of methanol and water (20 ml, 80:20 v/v). The resulting solution was warmed and allowed to stand for slow evaporation at room temperature. On completion of the evaporation of the solvent, we found that most of the material (black in colour) had deposited on the walls of the container, leaving a few transparent crystals at the bottom, which were later found to be the new form of cytosine by single-crystal X-ray diffraction. Despite several attempts, it was not possible to obtain crystals of (Ib) again. A powder X-ray diffraction (PXRD) spectrum for the cytosine single crystals could not be measured due to an insufficient qu­antity of crystals, but it was possible to record NMR and ESI–MS spectra using the few available crystals of (Ib).

Mass spectrometry analysis top

Electrospray ionization (ESI) mass spectrometry analyses were carried out in both positive and negative ion modes using an Exactive Orbitrap mass spectrometer (Thermo Scientific, Waltham, Massachusetts, USA). The samples were dissolved in methanol and infused directly into the source of the mass spectrometer at a flow rate of 5 µl min-1. The ESI mass spectra were recorded for pure cytosine, pure catechol, cytosine crystals and the black material (residue). Pure cytosine was detected as a protonated molecule ion, [M+H]+ (m/z 112.05053) under positive ion mode, and pure catechol was detected as a deprotonated molecule ion, [M - H]- (m/z 109.02808) under negative ion mode. The accurate mass values of these pseudo-molecular ions match well with their exact mass values (112.05054 and 109.02841) to within ±3 p.p.m. The spectrum recorded for the cytosine crystals showed a peak at m/z 112.05036, matching with the spectrum of pure cytosine. The black material showed the presence of cytosine (m/z 112.05075) and catechol (109.02823) under positive and negative ion modes of analysis, respectively.

NMR analysis top

The NMR studies were carried out in DMSO-d6 solvent at 298 K using a Bruker AVANCE 500 MHz spectrometer. 1H NMR spectrum of cytosine: 10.50 (bs, 1H), 7.30 (d, 1H, J = 6.89 Hz), 7.06 (bs, 2H), 5.57 (d, 1H, J = 6.89 Hz); 1H NMR spectrum of catechol: 8.80 (bs, 2H), 6.72 (m, 2H), 6.60 (m, 2H); 1H NMR spectrum of cytosine crystals: 10.33 (bs, 1H), 7.30 (d, 1H, J = 6.9 Hz), 6.9–7.1 (bd, 2H), 5.56 (d, 1H, J = 6.9 Hz); 1H NMR spectrum of black material (residue): 10.47 (bs, 1H), 8.80 (bs, 2H), 7.32 (d, 1H, J = 6.9 Hz), 7.09 (bs, 2H), 6.72 (m, 2H), 6.59(m, 2H), 5.60 (d, 1H, J = 6.9 Hz). From these NMR analyses, the transparent crystals match pure cytosine and the black material corresponds to a mixture of cytosine and catechol.

Powder X-ray diffraction (PXRD) top

The PXRD patterns were recorded for pure cytosine, pure catechol and the black material at room temperature using a Bruker D8 Advance diffractometer with Cu Kα radiation (λ = 1.5406 Å), running at 40 kV and 30 mA. The 2θ range covered from 2 to 50° with a step size of 0.0005° and a step time of 13.6 s. The PXRD spectrum clearly confirms the presence of both cytosine and catechol in the black material.

Refinement top

Crystal data, data collection and structure refinement details are summarized in Table 1. Crystal data, data collection and structure refinement details are summarized in Table 1. All N-bound H atoms were located in a difference density map and refined isotropically. C-bound H atoms were also located in difference density maps but were positioned geometrically and included as riding atoms, with C—H = 0.93 Å and Uiso(H) = 1.2Ueq(C).

Results and discussion top

The asymmetric unit of polymorph (Ib) contains two crystallographically independent molecules (labelled with the suffixes A and B), whereas polymorph (Ia) has only one molecule in the asymmetric unit. The molecular structure of polymorph (Ib), together with the atom-numbering scheme, is shown in Fig. 1. The molecules have very similar geometries in the two polymorphs. Bond lengths and angles are all within normal ranges and the molecules are flat [the r.m.s. deviation from planarity is 0.0042 (14) Å for molecule A and 0.0117 (15) Å for molecule B for the non-H atoms in polymorph (Ib)]. The two molecules are perpendicular to each other, with a dihedral angle between the mean planes of 81.67 (6)°. It is known from the literature that neutral cytosine can exist in six tautomeric forms. However, the 2H-enol and the 1H-keto-amino forms are the predominant species in the gas phase (Szczesniak et al., 1988), whereas in the solid state only the 1H-keto-amino tautomer is observed in both polymorphs.

Cytosine has been extensively studied for its self-assembling ability arising from its multiple complementary hydrogen bonds. Polymorphs (Ia) and (Ib) are both stabilized by N—H···N and N—H···O hydrogen bonds [Table 2 gives data for (Ib)]. In polymorph (Ib), each cytosine molecule is held together with its glide-related molecule (i.e. AA and BB) through N—H···O and N—H···N hydrogen bonds, forming an R22(8) dimer (Etter, 1990; Etter et al., 1990; Bernstein et al., 1995). Similarly, polymorph (Ia) forms an R22(8) dimer with its screw-related cytosine molecule. In polymorph (Ib), the R22(8) dimers are propagated as two independent infinite one-dimensional hydrogen-bonded ribbons (AAA and BBB) along the c axis (Fig. 2), whereas in polymorph (Ia) it forms an infinite one-dimensional hydrogen-bonded ribbon along the b axis. In polymorph (Ib), ribbon A connects to ribbon B through an N7A—H3N···O8B hydrogen bond, thereby forming a hexameric hydrogen-bonded cavity which can be described by graph-set notation as an R66(30) motif. In turn, ribbon B connects a symmetry-related [at (x - 1/2, y + 1/2, -z + 1)] ribbon A through an N7B—H6N···O8A hydrogen bond and forms another set of hexameric hydrogen-bonded cavities with the R66(30) motif. Thus, the two infinite ribbons formed by molecules A and B are inter­linked with each other through N—H···O hydrogen bonds, thereby forming a three-dimensional hydrogen-bonded network (Fig. 2). Also in polymorph (Ia), the screw-related ribbons are inter­linked by N3—H3···O1(x + 1/2, -y + 1/2, -z - 1) hydrogen bonds to form a similar hexameric hydrogen-bonded cavity, i.e. R66(30) (Fig. 3).

In both polymorphs (Ia) and (Ib), the combination of N—H···N and N—H···O hydrogen bonds is responsible for the formation of supra­molecular three-dimensional hydrogen-bonded networks. However, the arrangement of molecules in the crystal packing of polymorphs (Ia) and (Ib) is different. In polymorph (Ib), two ribbons formed by molecules A and B are perpendicular to each other [dihedral angle = 89.58 (8)°], whereas in polymorph (Ia) the corresponding angle between the symmetry-related ribbons is 56.88(s.u.?)°. The arrangement of molecules can be described as a square-grid network in polymorph (Ib) (Fig. 4a), whereas it is in a helical fashion in the crystal packing of polymorph (Ia) (Fig. 4b).

The stability of polymorphs can be correlated with their densities Dx and their packing coefficients. According to the `density rule' (Bernstein et al., 1999; Gavezzotti & Filippini, 1995), the higher the density of a polymorph, the higher is its stability. The crystal density of polymorph (Ib) is significantly less than that of polymorph (Ia) [1.391 versus 1.562 Mg m-3]. Similarly, the packing coefficient of polymorph (Ib) is less than that of polymorph (Ia) (65.7 versus 74.5%). From these values one can assume that form (Ia) is more stable than form (Ib). Within systems exhibiting polymorphism with different Z' values, many researchers (Anderson & Steed, 2007; Sarma et al., 2006) have shown that higher Z' forms are frequently (but not always) less stable, exhibiting low densities. Cytosine falls in this category.

In the crystallization process, the formation of the `nuclei' starting with the first inter­acting pair seems to be critical in deciding the outcome of the polymorph, as exemplified by the two polymorphic forms of hexa-o-benzyl-myo-inosital (Gonnade et al., 2004). This compound crystallizes in both centrosymmetric (space group P1) and noncentrosymmetric (space group P61) systems. The first inter­acting molecular pair in the former is related by centrosymmetry, while the same is predisposed for helical propagation in the latter. A similar feature is also seen in the present study. The cytosine base pair (dimer) can be considered as the first inter­acting pair, which is the same in both of forms (Ia) and (Ib), but the way the dimers are arranged in the crystal structures appears to guide the centrosymmetric versus noncentrosymmetric space-group selection through the formation of an inversion-related motif in polymorph (Ib) and helical propagation in polymorph (Ia).

Achiral molecules crystallizing in noncentrosymmetric space groups are not uncommon. Recently, Pidcock revealed that about 15.2% of achiral molecules crystallize in noncentrosymmetric space groups (Pidcock, 2005). But how often an achiral compound shows polymorphism through centro- versus noncentrosymmetric space-group selection has not been established so far. To accomplish this task, a systematic search was performed of the Cambridge Structural Database (CSD, Version 5.35 with May 2014 updates; Groom & Allen, 2014). Our search criteria included the keywords `polymorph and/or form', structures with three-dimensional coordinates well defined, no errors, no polymeric, no powder, no ions, number of chemical unit = 1 and only organic restrictions, and resulted in 7290 hits. Using the chiral algorithm of Eppel & Bernstein (2008), the 7290 hits were segregated into four categories, viz. achiral (6021), chiral (549), meso (127) and racemic (411). The remaining 182 structures were excluded due to errors. Among the 6021 achiral structures, 4796 crystallize in centrosymmetric space groups, while the remaining 1225 structures crystallize in noncentrosymmetric space groups. The statistics clearly show that the percentage of achiral compounds crystallizing in noncentrosymmetric space groups (approximately 20%) is slightly higher in polymorphic systems than in the general class of molecules (15.2%), as shown earlier by Pidcock.

We then examined achiral polymorphic systems which crystallize in both centrosymmetric and noncentrosymmetric systems and concluded that there are 516 such systems. Our next idea was to understand possible structural features responsible for achiral molecules crystallizing in centro- and noncentrosymmetric space groups. We analysed these examples and classified them under four different categories. A few representative examples are discussed in each case.

(i) Polymorphs with the same hydrogen-bonding inter­actions but different crystal packing.

5-Fluoro­cytosine (MEBQEQ; Hulme & Tocher, 2006) has two polymorphic forms. Infinite hydrogen-bonded ribbons formed by the fluoro­cytosine base-pair dimer with the R22(8) motif are observed in both forms. The way the ribbons are arranged in the crystal packing creates the difference between the forms. In the noncentrosymmetric form, adjacent ribbons are arranged in a helical fashion (Fig. 5a), while in the centrosymmetric form, the corresponding ribbons are packed in an inversion-related fashion (Fig. 5b). Methyl paraben (CEBGOF; Nath et al., 2011; Gelbrich et al., 2013) is reported with four polymorphic forms. The catemer motif is preserved in all the forms. In the centrosymmetric form, inversion-related molecules are inter­linked by catemers (Fig. 5c), while in the noncentrosymmetric form, the corresponding catemer inter­links the glide-related molecules (Fig. 5d). Inter­estingly, cytosine falls in this category.

(ii) Polymorphs with different hydrogen-bonding inter­actions and different crystal packing.

5-Nitro­uracil (NIMFOE; Kennedy et al., 1998; Srinivasa Gopalan et al., 2000) has three polymorphic forms. The centrosymmetric form has centrosymmetric R22(8) dimers (Fig. 6a), while the noncentrosymmetric form has D(2)-type helical chains (Fig. 6b). 5-Fluoro­uracil-1-acetic acid (WEFVIN; Qu et al., 2006; Zhang et al., 2007) has two polymorphic forms. In the centrosymmetric form, adjacent inversion-related chains are inter­linked by R22(8) dimers (Fig. 6c), whereas only one R22(8) dimer is observed in the noncentrosymmetric form and these are arranged in a helical fashion (Fig. 6d).

(iii) Polymorphs with different conformations and the same hydrogen-bonding inter­actions

The anti­diabetic drug tolbutamide (ZZZPUS; Donaldson et al., 1981; Nath & Nangia, 2011) is reported with five polymorphic forms. The orientations of the phenyl and alkyl chains are different for the five forms. Although the five forms have a similar urea tape motif and similar hydrogen bonding to a sulfonyl group, the molecular orientations in the hydrogen bonding are different due to conformational differences. In the centrosymmetric form, the butyl chain is in an extended conformation and inversion-related molecules are inter­linked by the urea tape motifs (Fig. 7a), whereas in the noncentrosymmetric form the butyl chain is in a folded conformation and screw-related molecules are linked by the urea tape motif (Fig. 7b).

(iv) Polymorphs with different conformations and different hydrogen-bonding inter­actions

The anti­psychotic drug aripiprazole (MELFIT; Braun et al., 2009; Nanubolu et al., 2012) is the most structurally characterized, with seven polymorphs reported in the CSD in this category. Very recently, a low-temperature phase with an eighth polymorphic form was reported (Delaney et al., 2014). The existence of eight polymorphic forms of aripiprazole can be attributed to a very high degree of conformational freedom, significant differences in the hydrogen bonding and the influence of crystal-packing effects (Nanubolu et al., 2012). Centrosymmetric forms have the amide dimer (Fig. 7c), while the noncentrosymmetric forms exist as amide catemers (Fig. 7d).

From the above discussion, polymorphism and centrosymmetric versus noncentrosymmetric space-group selections may be attributed to differences in hydrogen bonding, molecular arrangements and conformational flexibility.

Conclusions top

A second polymorphic form of cytosine is reported for the first time, half a century after the first report of its known form (Ia). The new form (Ib) crystallizes in the centrosymmetric orthorhombic space group Pccn, while form (Ia) crystallizes in the noncentrosymmetric orthorhombic space group P212121. Both forms show similar hydrogen-bonding inter­actions but differ in their molecular arrangements in the crystal structure. Inversion-related motifs are seen in (Ib), while helical propagation is observed in (Ia), and this might contribute to the different space-group selections. 516 polymorphic systems from the CSD crystallize in both centrosymmetric and noncentrosymmetric space groups, and these were analysed for strutural insights. Four possible categories are seen, based on the features responsible for deciding the space-group selections within the polymorphic systems, viz. (i) the same hydrogen-bonding inter­actions but different molecular arrangements, (ii) different hydrogen-bonding inter­actions and different crystal packing, (iii) different conformations and the same hydrogen-bonding inter­actions and (iv) different conformations and different hydrogen-bonding inter­actions. The present structure falls into the first category.

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2015); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: DIAMOND (Brandenburg & Putz, 2005); software used to prepare material for publication: SHELXL97 (Sheldrick, 2015).

Figures top
[Figure 1] Fig. 1. The molecular structure of cytosine (Ib), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. The dashed line indicates a hydrogen bond.
[Figure 2] Fig. 2. Part of the crystal structure of (Ib), showing the hydrogen-bonding interactions. Adjacent inversion-related ribbons formed by cytosine molecules A and B are interlinked by N—H···O hydrogen bonds, forming a hexameric hydrogen-bonded cavity with an R66(30) motif. Hydrogen bonds are shown as dashed lines and H atoms not involved in hydrogen bonding have been omitted for clarity. Only atoms involved in hydrogen bonding are labelled. [Symmetry codes: (i) x, -y + 1/2, z - 1/2; (ii) x, -y + 1/2, z + 1/2; (iii) -x + 1/2, y, z - 1/2; (iv) -x + 1/2, y, z + 1/2; (v) x - 1/2, y + 1/2, -z + 1.]
[Figure 3] Fig. 3. Part of the crystal structure of (Ia), showing the one-dimensional ribbons formed by the R22(8) dimer. Further adjacent screw-related ribbons are interconnected through N—H···O hydrogen bonds, thereby forming a hexameric hydrogen-bonded cavity of R66(30) motif. Hydrogen bonds are shown as dashed lines and H atoms not involved in hydrogen bonding have been omitted for clarity.
[Figure 4] Fig. 4. (a) Part of the crystal structure of (Ib), showing the perpendicular orientation of the R22(8) dimers formed by molecules A and B. The inversion relationship is also seen between the pairs of dimers, which form a square-grid network. (b) Part of the crystal structure of (Ia), showing the helical arrangement of the molecules in the crystal packing. Hydrogen bonds are shown as dashed lines and H atoms not involved in hydrogen bonding have been omitted for clarity.
[Figure 5] Fig. 5. Partial packing diagrams showing the same hydrogen-bonding interactions among polymorphic forms having different molecular arrangements in the crystal packing. (a) Ribbons formed by R22(8) dimers are arranged in a helical fashion in the noncentrosymmetric form of 5-fluorocytosine (CSD refcode MEBQEQ01; Reference?). (b) Centrosymmetrically related ribbons are observed in the centrosymmetric form of MEBQEQ (Hulme & Tocher, 2006). (c) Inversion-related molecules are linked by O—H···O catemers in the centrosymmetric form of methyl paraben (CSD refcode CEBGOF03; Nath et al., 2011 [OK?]; Gelbrich et al., 2013). (d) Glide-related molecules are connected by O—H···O catemers in the noncentrosymmetric form of CEBGOF05 (Gelbrich et al., 2013 [OK?]).
[Figure 6] Fig. 6. Partial packing diagrams showing the different hydrogen-bonding interactions and different molecular arrangements in the crystal packing of some polymorphic forms. (a) Helical chain of the D(2) type in the noncentrosymmetric form of 5-nitrouracil (CSD refcode NIMFOE02; Kennedy et al., 1998 [OK?]). (b) Centrosymmetric R22(8) dimers in the centrosymmetric form of NIMFOE01 (Srinivasa Gopalan et al., 2000 [OK?]). (c) Inversion-related chains interconnected by R22(8) dimers in the centrosymmetric form of 5-fluorouracil-1-acetic acid (CSD refcode WEFVIN; Qu et al., 2006 [OK?]). (d) Helical arrangement of R22(8) dimers in the noncentrosymmetric form of WEFVIN02 (Zhang et al., 2007 [OK?]).
[Figure 7] Fig. 7. Partial packing diagrams showing the different conformations and different molecular arrangements in the crystal packing of some polymorphic forms. (a) The butyl chain is in an extended conformation and inversion-related molecules are interlinked by a urea tape motif in the centrosymmetric form of tolbutamide (CSD refcode ZZZPUS10; Donaldson et al., 1981 [OK?]). (b) The folded conformation of the butyl chain and the screw-related molecules are held together by the urea tape motif in the noncentrosymmetric form of ZZZPUS02 (Nath & Nangia, 2011 [OK?]). (c) The formation of an amide dimer in the centrosymmetric form of aripiprazole (CSD refcode MELFIT06; Braun et al., 2009 [OK?]). (d) Amide catemer formation in the noncentrosymmetric form of MELFIT02 (Nanubolu et al., 2012 [OK?]).
4-Aminopyrimidin-2(1H)-one top
Crystal data top
C4H5N3ODx = 1.391 Mg m3
Mr = 111.11Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, PccnCell parameters from 6012 reflections
a = 15.104 (1) Åθ = 2.7–26.7°
b = 15.1212 (10) ŵ = 0.11 mm1
c = 9.2948 (6) ÅT = 294 K
V = 2122.8 (2) Å3Needle, colourless
Z = 160.21 × 0.12 × 0.08 mm
F(000) = 928
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
1933 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.029
Absorption correction: multi-scan
(SADABS; Bruker, 2001)
θmax = 26.2°, θmin = 1.9°
Tmin = 0.97, Tmax = 0.99h = 1818
20913 measured reflectionsk = 1818
2137 independent reflectionsl = 1111
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.052H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.136 w = 1/[σ2(Fo2) + (0.0623P)2 + 0.5633P]
where P = (Fo2 + 2Fc2)/3
S = 1.20(Δ/σ)max < 0.001
2137 reflectionsΔρmax = 0.25 e Å3
169 parametersΔρmin = 0.18 e Å3
Crystal data top
C4H5N3OV = 2122.8 (2) Å3
Mr = 111.11Z = 16
Orthorhombic, PccnMo Kα radiation
a = 15.104 (1) ŵ = 0.11 mm1
b = 15.1212 (10) ÅT = 294 K
c = 9.2948 (6) Å0.21 × 0.12 × 0.08 mm
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
2137 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2001)
1933 reflections with I > 2σ(I)
Tmin = 0.97, Tmax = 0.99Rint = 0.029
20913 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0520 restraints
wR(F2) = 0.136H atoms treated by a mixture of independent and constrained refinement
S = 1.20Δρmax = 0.25 e Å3
2137 reflectionsΔρmin = 0.18 e Å3
169 parameters
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C2A0.36076 (9)0.25736 (11)0.33348 (16)0.0354 (4)
C4A0.35442 (10)0.39365 (11)0.44934 (18)0.0396 (4)
C5A0.34746 (12)0.43885 (12)0.31544 (19)0.0464 (5)
H5A0.34330.50020.31120.056*
C6A0.34720 (12)0.38950 (12)0.19591 (19)0.0444 (4)
H6A0.34230.41670.10650.053*
N1A0.35402 (9)0.30049 (10)0.20392 (15)0.0395 (4)
H1N0.3531 (13)0.2657 (14)0.123 (2)0.058 (6)*
N3A0.36037 (9)0.30577 (9)0.45595 (15)0.0388 (3)
N7A0.35521 (12)0.43858 (12)0.57286 (18)0.0516 (4)
H2N0.3593 (14)0.4080 (17)0.652 (3)0.069 (7)*
H3N0.3487 (13)0.4947 (15)0.567 (2)0.054 (6)*
O8A0.36800 (8)0.17532 (8)0.33514 (12)0.0444 (3)
C2B0.24228 (12)0.63787 (10)0.50619 (16)0.0363 (4)
C4B0.10553 (12)0.64706 (10)0.62079 (18)0.0398 (4)
C5B0.06004 (13)0.64921 (13)0.4864 (2)0.0511 (5)
H5B0.00140.65190.48160.061*
C6B0.11022 (13)0.64711 (13)0.3671 (2)0.0506 (5)
H6B0.08320.64900.27720.061*
N1B0.19912 (10)0.64229 (10)0.37604 (16)0.0438 (4)
H4N0.2326 (15)0.6443 (13)0.298 (2)0.060 (6)*
N3B0.19336 (9)0.64050 (9)0.62792 (14)0.0383 (3)
N7B0.06063 (12)0.65109 (11)0.74390 (18)0.0508 (4)
H5N0.0916 (16)0.6474 (14)0.829 (3)0.066 (7)*
H6N0.0043 (17)0.6539 (13)0.736 (2)0.059 (6)*
O8B0.32430 (8)0.63072 (8)0.50888 (12)0.0446 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C2A0.0337 (8)0.0425 (9)0.0299 (8)0.0019 (7)0.0012 (6)0.0005 (7)
C4A0.0399 (9)0.0433 (9)0.0357 (9)0.0033 (7)0.0016 (7)0.0004 (7)
C5A0.0624 (11)0.0368 (9)0.0400 (10)0.0033 (8)0.0035 (8)0.0046 (7)
C6A0.0529 (10)0.0469 (10)0.0334 (9)0.0031 (8)0.0016 (7)0.0084 (7)
N1A0.0475 (8)0.0446 (8)0.0265 (7)0.0012 (6)0.0012 (6)0.0000 (6)
N3A0.0458 (8)0.0422 (8)0.0283 (7)0.0028 (6)0.0010 (6)0.0016 (6)
N7A0.0750 (12)0.0428 (9)0.0372 (9)0.0060 (8)0.0010 (8)0.0044 (7)
O8A0.0573 (8)0.0391 (7)0.0368 (7)0.0034 (5)0.0040 (5)0.0002 (5)
C2B0.0457 (9)0.0338 (8)0.0294 (8)0.0014 (7)0.0008 (7)0.0021 (6)
C4B0.0454 (9)0.0386 (9)0.0353 (9)0.0037 (7)0.0006 (7)0.0014 (7)
C5B0.0413 (10)0.0707 (13)0.0412 (10)0.0065 (9)0.0059 (8)0.0019 (9)
C6B0.0517 (11)0.0666 (12)0.0335 (9)0.0067 (9)0.0078 (8)0.0007 (8)
N1B0.0487 (9)0.0552 (9)0.0275 (7)0.0031 (7)0.0018 (6)0.0012 (6)
N3B0.0444 (8)0.0430 (8)0.0274 (7)0.0034 (6)0.0003 (5)0.0026 (6)
N7B0.0449 (9)0.0699 (11)0.0376 (9)0.0100 (8)0.0043 (7)0.0025 (7)
O8B0.0416 (7)0.0553 (8)0.0370 (7)0.0027 (5)0.0012 (5)0.0001 (6)
Geometric parameters (Å, º) top
C2A—O8A1.245 (2)C2B—O8B1.244 (2)
C2A—N3A1.353 (2)C2B—N3B1.352 (2)
C2A—N1A1.373 (2)C2B—N1B1.376 (2)
C4A—N3A1.333 (2)C4B—N7B1.332 (2)
C4A—N7A1.334 (2)C4B—N3B1.332 (2)
C4A—C5A1.424 (2)C4B—C5B1.426 (2)
C5A—C6A1.338 (3)C5B—C6B1.343 (3)
C5A—H5A0.9300C5B—H5B0.9300
C6A—N1A1.352 (2)C6B—N1B1.347 (3)
C6A—H6A0.9300C6B—H6B0.9300
N1A—H1N0.91 (2)N1B—H4N0.88 (2)
N7A—H2N0.87 (3)N7B—H5N0.92 (2)
N7A—H3N0.86 (2)N7B—H6N0.86 (2)
O8A—C2A—N3A121.92 (14)O8B—C2B—N3B122.02 (15)
O8A—C2A—N1A119.36 (14)O8B—C2B—N1B119.59 (15)
N3A—C2A—N1A118.71 (15)N3B—C2B—N1B118.38 (16)
N3A—C4A—N7A117.86 (16)N7B—C4B—N3B117.90 (16)
N3A—C4A—C5A121.58 (15)N7B—C4B—C5B120.42 (17)
N7A—C4A—C5A120.56 (17)N3B—C4B—C5B121.68 (16)
C6A—C5A—C4A117.27 (17)C6B—C5B—C4B116.78 (17)
C6A—C5A—H5A121.4C6B—C5B—H5B121.6
C4A—C5A—H5A121.4C4B—C5B—H5B121.6
C5A—C6A—N1A120.60 (16)C5B—C6B—N1B120.85 (17)
C5A—C6A—H6A119.7C5B—C6B—H6B119.6
N1A—C6A—H6A119.7N1B—C6B—H6B119.6
C6A—N1A—C2A121.79 (15)C6B—N1B—C2B121.94 (16)
C6A—N1A—H1N121.8 (13)C6B—N1B—H4N121.1 (14)
C2A—N1A—H1N116.4 (13)C2B—N1B—H4N116.9 (14)
C4A—N3A—C2A120.04 (14)C4B—N3B—C2B120.33 (14)
C4A—N7A—H2N117.2 (16)C4B—N7B—H5N118.5 (15)
C4A—N7A—H3N116.9 (14)C4B—N7B—H6N115.6 (16)
H2N—N7A—H3N126 (2)H5N—N7B—H6N126 (2)
N3A—C4A—C5A—C6A0.1 (3)N7B—C4B—C5B—C6B178.36 (18)
N7A—C4A—C5A—C6A179.90 (17)N3B—C4B—C5B—C6B2.0 (3)
C4A—C5A—C6A—N1A0.5 (3)C4B—C5B—C6B—N1B0.7 (3)
C5A—C6A—N1A—C2A0.5 (3)C5B—C6B—N1B—C2B1.1 (3)
O8A—C2A—N1A—C6A179.12 (15)O8B—C2B—N1B—C6B177.75 (16)
N3A—C2A—N1A—C6A0.1 (2)N3B—C2B—N1B—C6B1.5 (2)
N7A—C4A—N3A—C2A179.32 (15)N7B—C4B—N3B—C2B178.74 (15)
C5A—C4A—N3A—C2A0.6 (2)C5B—C4B—N3B—C2B1.6 (2)
O8A—C2A—N3A—C4A178.55 (15)O8B—C2B—N3B—C4B179.12 (15)
N1A—C2A—N3A—C4A0.7 (2)N1B—C2B—N3B—C4B0.1 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1A—H1N···N3Ai0.91 (2)1.90 (2)2.811 (2)175.9 (18)
N7A—H2N···O8Aii0.87 (3)2.12 (3)2.991 (2)176 (2)
N7A—H3N···O8B0.86 (2)2.16 (2)3.002 (2)168 (2)
N1B—H4N···N3Biii0.88 (2)1.94 (2)2.821 (2)176.3 (18)
N7B—H5N···O8Biv0.92 (2)2.12 (3)3.030 (2)173 (2)
N7B—H6N···O8Av0.86 (2)2.19 (3)3.023 (2)166 (2)
Symmetry codes: (i) x, y+1/2, z1/2; (ii) x, y+1/2, z+1/2; (iii) x+1/2, y, z1/2; (iv) x+1/2, y, z+1/2; (v) x1/2, y+1/2, z+1.

Experimental details

Crystal data
Chemical formulaC4H5N3O
Mr111.11
Crystal system, space groupOrthorhombic, Pccn
Temperature (K)294
a, b, c (Å)15.104 (1), 15.1212 (10), 9.2948 (6)
V3)2122.8 (2)
Z16
Radiation typeMo Kα
µ (mm1)0.11
Crystal size (mm)0.21 × 0.12 × 0.08
Data collection
DiffractometerBruker SMART APEX CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2001)
Tmin, Tmax0.97, 0.99
No. of measured, independent and
observed [I > 2σ(I)] reflections
20913, 2137, 1933
Rint0.029
(sin θ/λ)max1)0.622
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.052, 0.136, 1.20
No. of reflections2137
No. of parameters169
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.25, 0.18

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2001), SHELXS97 (Sheldrick, 2015), SHELXL2014 (Sheldrick, 2015), DIAMOND (Brandenburg & Putz, 2005), SHELXL97 (Sheldrick, 2015).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1A—H1N···N3Ai0.91 (2)1.90 (2)2.811 (2)175.9 (18)
N7A—H2N···O8Aii0.87 (3)2.12 (3)2.991 (2)176 (2)
N7A—H3N···O8B0.86 (2)2.16 (2)3.002 (2)168 (2)
N1B—H4N···N3Biii0.88 (2)1.94 (2)2.821 (2)176.3 (18)
N7B—H5N···O8Biv0.92 (2)2.12 (3)3.030 (2)173 (2)
N7B—H6N···O8Av0.86 (2)2.19 (3)3.023 (2)166 (2)
Symmetry codes: (i) x, y+1/2, z1/2; (ii) x, y+1/2, z+1/2; (iii) x+1/2, y, z1/2; (iv) x+1/2, y, z+1/2; (v) x1/2, y+1/2, z+1.
 

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