A study of the crystal structures, supra-molecular patterns and Hirshfeld surfaces of bromide salts of hypoxanthine and xanthine.

Two new crystalline salts, namely, hypoxanthinium bromide monohydrate, C5H5N4O+·Br-·H2O (I) and xanthinium bromide monohydrate, C5H5N4O2 +·Br-·H2O (II), were synthesized and characterized by single-crystal X-ray diffraction technique and Hirshfeld surface analysis. The hypoxanthinium and xanthinium cations in salts I and II are both in the oxo-N(9)-H tautomeric form. The crystal packing of the two salts is governed predominantly by N-H⋯O, N-H⋯Br, C-H⋯Br and O-H⋯Br inter-actions described by R 2 3(9) and R 2 2(8) synthons. The crystal packing is also consolidated by carbon-yl⋯π inter-actions between symmetry-related hypoxanthinium (HX+ ) cations in salt I and xanthinium cations (XA+ ) in salt II. The combination of all these inter-actions leads to the formation of wave- and staircase-like architectures in salts I and II, respectively. The largest contributions to the overall Hirshfeld surface are from Br⋯H/H⋯Br contacts (22.3% in I and 25.4% in II) . © Sathya et al. 2022.

Chemical context

Over the past several decades, non-covalent inter­actions have been found to play a prominent role in coordination chemistry, materials science and pharmaceutical science (Černý & Hobza, 2007 ▸; Desiraju, 2013 ▸; Perumalla & Sun, 2014 ▸). Understanding the role of non-covalent inter­actions is important in the context of crystal engineering (Aakeröy et al., 2010 ▸; Pogoda et al., 2018 ▸; Cavallo et al., 2016 ▸; Desiraju et al., 2013 ▸) in order to design solids with desired properties. When it comes to pharmaceutics, active pharmaceutical ingredients (APIs) are known to exist in different solid forms such as salts, co-crystals, solvates, polymorphs and amorphous solids (Aaltonen et al., 2009 ▸). The salt and co-crystal forms of APIs have improved their solubility and bioavailability when compared to pure APIs (Thackaberry, 2012 ▸; Xu, et al., 2014 ▸). Drugs with low solubility/bioavailability are usually converted to their salts or crystallized in their co-crystal/polymorphic/solvate forms to enhance their properties. Herein, we report two new salts of hypoxanthine (HX) and xanthine (XA).

Hypoxanthine (C5H4N4O) [systematic name: 1,9-di­hydro-purine-6-one] and xanthine (C5H4N4O2) [systematic name: 3,7-di­hydro-purine-2,6-dione] are well-known purine-based nucleotides (Emel’yanenko et al., 2017 ▸) present in t-RNA and DNA in the form of the nucleoside inosine (Plekan et al., 2012 ▸). Purine derivatives are widely known for their therapeutic applications such as antagonization of the adenosine receptor, anti-inflammatory, anti­microbial, anti­oxidant, anti-tumour, anti-asthmatic and psycho-stimulant drug activity (Meskini et al., 1994 ▸; Burbiel et al., 2006 ▸). HX and XA are also found as inter­mediates in the biological degradation of nucleic acid to uric acid. Furthermore, HX is used as an indicator of hypoxia and it is known to inhibit the effect of several drugs (Dubler et al., 1987a ▸,b ▸). It is also used to destroy harmful agents such as cancer cells (Susithra et al., 2018 ▸). Purine-based derivatives of HX and XA bind with the DNA base pairs through weak hydrogen bonds (Latosińska et al., 2014 ▸; Rutledge et al., 2007 ▸). Additionally, hypoxanthine-guanine phospho­ribosyl transferase plays an important role in activating anti­viral drugs in the human body and xanthine has been used as a mild stimulant drug (Faheem et al., 2020 ▸).

The structure of hypoxanthine and xanthine consists of fused six-membered pyrimidine and five-membered imidazole rings. HX and XA can exist in two tautomeric forms, oxo-N(7)–H and oxo-N(9)–H (Plekan et al., 2012 ▸; Gulevskaya & Pozharskii, 1991 ▸), as shown below. So far, two polymorphic forms of HX (Schmalle et al., 1988 ▸; Yang & Xie, 2007 ▸) and a limited number of hypoxanthinium and xanthinium salts have been reported in the literature; hypoxanthinium nitrate monohydrate, hypoxanthinium chloride monohydrate (Cabaj et al., 2019 ▸; Schmalle et al., 1990 ▸; Sletten & Jensen, 1969 ▸), xanthinium nitrate monohydrate and xanthinium hydrogensulfate monohydrate (Sridhar, 2011 ▸).

In the hypoxanthinium salts, the hypoxanthine mol­ecule is usually also protonated at the N7 position, resulting in the oxo-N(9)–H tautomer. Similarly, xanthinium nitrate monohydrate, xanthinium hydrogensulfate monohydrate (Sridhar, 2011 ▸) and xanthinium perchlorate dihydrate (Biradha et al., 2010 ▸) are also in the oxo-N(9)–H tautomeric form and are therefore protonated on the N7 position. Studies of non-covalent inter­actions involving hypoxanthine and xanthine bases with inorganic acids have increased because their hydrogen-bonding patterns are similar to those of purine bases (Maixner & Zachova, 1991 ▸; Sridhar, 2011 ▸; Kistenmancher & Shigematsu, 1974 ▸). In the current work, the crystal structures, supra­molecular packing patterns and Hirshfeld surface analyses of hypoxanthinium bromide monohydrate (I) and xanthinium bromide monohydrate (II) are reported.

Structural commentary

Hypoxanthinium bromide monohydrate (I) crystallizes in the monoclinic space group P21/c with one hypoxanthinium cation (HX), one bromide anion (Br) and one water mol­ecule in the asymmetric unit, as shown in Fig. 1 ▸. Here, the HX cation exists in the oxo-N(9)–H tautomeric form with the N7 atom of the purine ring protonated, as can be seen from the N—C bond distance [N7—C8 = 1.3219 (17) Å vs N9—C8 = 1.3419 (18) Å] and C—N—C bond angles [C5—N7—C8 = 107.98 (11)° and C4—N9—C8 = 108.32 (10)°]. Those values are similar to those in the crystal structure of hypoxanthinium chloride monohydrate [N7—C8 = 1.325 (2) Å and N9—C8 = 1.336 (2) Å, C5—N7—C8 = 107.35 (16)° and C4—N9—(C8 = 108.28 (15)°; Kalyanaraman et al., 2007 ▸; Sletten & Jensen, 1969 ▸]. The N3—C4—C5—N7 and N9—C4—C5—C6 torsion angles are 179.07 (12) and −179.58 (12)°, respectively. These values are similar to those observed in the crystal structure of the neutral hypoxanthine mol­ecule (Schmalle et al., 1988 ▸; Yang & Xie, 2007 ▸). The HX cation, Br anion and the water mol­ecule inter­act through N—H⋯Br, N—H⋯O and C—H⋯Br hydrogen bonds with donor–acceptor distances N⋯Br = 3.2419 (13) Å, N9⋯O6 = 2.7579 (14) Å and C8⋯Br1 = 3.4875 (15) Å (Table 1 ▸), forming an (9) motif. The water mol­ecule present in the lattice prevents the formation of base pairs (Varani & McClain, 2000 ▸) between the HX cations.

Figure 1

ORTEP view of the mol­ecular components of salts I and II, showing the atom-labelling scheme. Displacement ellipsoids are drawn at 50% probability level. Hydrogen bonds are shown as dashed lines.

Table 1

Hydrogen-bond geometry (Å, °) for I

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N9—H9⋯Br1i	0.85 (1)	3.08 (2)	3.5397 (12)	117 (2)
N9—H9⋯O6i	0.85 (1)	1.98 (2)	2.7579 (14)	153 (2)
N1—H1⋯Br1	0.84 (1)	2.41 (1)	3.2419 (12)	170 (2)
N7—H7⋯O1W ii	0.85 (1)	1.81 (2)	2.6401 (16)	165 (2)
O1W—H1W⋯N3iii	0.86 (1)	2.08 (1)	2.9200 (16)	165 (2)
O1W—H2W⋯Br1	0.85 (1)	2.48 (1)	3.2894 (12)	161 (2)
C8—H8⋯Br1i	0.93	2.89	3.4875 (15)	123

Symmetry codes: (i) ; (ii) ; (iii) .

Xanthinium bromide monohydrate (II) also crystallizes in the monoclinic space group P21/c with one xanthinium cation (XA), one bromide anion (Br) and one water mol­ecule in the asymmetric unit (Fig. 1 ▸). The XA cation has the N7—C8 bond [1.312 (5) Å] shorter than N9–C8 one [1.344 (5) Å]. The C—N—C bond angles are C5—N7—C8 = 108.2 (3)° and C4—N9—C8 = 107.7 (3)° and, therefore, the cation can also be described as the oxo-N(9)–H tautomer. These values are similar to those in xanthinium perchlorate dihydrate [N7—C8 = 1.314 (3) Å, N9—C8 = 1.341 (3) Å, C5—N7—C8 = 108.3 (16)° and C4—N9—C8 = 107.58 (15)°; Biradha et al., 2010 ▸). The N3—C4—C5—N7 and N9—C4—C5—C6 torsion angles in II are 179.07 (12)° and −179.58 (12)°, respectively. Finally, the two symmetry-related XA cations in II form a base pair similar to that observed between guanine and uracil (Varani & McClain, 2000 ▸).

Supra­molecular features

In I, the protonated HX cation inter­acts with another inversion-related HX and Br pair via N1—H1⋯Br1, C8—H8⋯Br1ii and N9—H9⋯O6ii hydrogen bonds (Table 1 ▸). These inter­actions lead to the formation of a nine-membered ring with (9) (type ) primary graph-set motif (Sletten & Jensen, 1969 ▸). Along with this, the HX cation inter­acts with another inversion-related HX cation and a water mol­ecule through O1W—H1W⋯N3iii and N7—H7⋯O1W ii hydrogen bonds. The combination of these inter­actions leads to the formation of an eleven-membered (11) (type ) ring motif. The inter­action is very similar to the water-mediated base pairs observed in the crystal structure of hypoxanthinium chloride and the nucleobase pairs in DNA and RNA (Sletten & Jensen, 1969 ▸; Reddy et al., 2001 ▸; Brandl et al., 2000 ▸). Here the O1W atom of the water mol­ecule acts as both a hydrogen-bond donor and a hydrogen-bond acceptor. The (9) and (11) ring motifs combine to form a supra­molecular ribbon. Adjacent ribbons are connected through pairs of O1W—H2W⋯Br1 hydrogen bonds with (16) and (14) (types and motifs) ring motifs, respectively, through pairs of C8—H8⋯Br1i and N7—H7⋯O1W ii hydrogen bonds (Fig. 2 ▸). The combination of all these inter­actions leads to the formation of a wave-like supra­molecular architecture that extends along the b-axis direction (Fig. 3 ▸). The crystal structure is further consolidated by carbon­yl⋯π inter­actions (C6=O6 and π cloud of the imidazole (centroid Cg1) and pyridine (centroid Cg2) rings of the HX cation) between symmetry-related cations with C=O⋯Cg1iv, C=O⋯Cg1v, C=O⋯Cg2iv and C=O⋯Cg2v distances of 3.5796 (12), 3.2478 (12) Å, 3.3862 (12) and 3.4747 (12) Å, respectively, and angles of 101.58 (8), 91.45 (8), 105.03 (8) and 103.46 (8)°, respectively [symmetry codes: (iv) −1 + x, y, z; (v) x,  − y,  + z] (Fig. 4 ▸). Salt I is isomorphous with hypoxanthinium chloride monohydrate (Sletten & Jensen, 1969 ▸).

Figure 2

Hypoxanthinium and bromide ions in salt I forming ribbons together with water mol­ecules through O—H⋯Br, N—H⋯Br and C—H⋯Br inter­action. [Symmetry codes: (i) −1 − x, −  + y,  − z; (ii) 1 + x,  − y, −  + z; (iii) −x, 1 − y, 1 − z].

Figure 3

A view of three-dimensional wave-like supra­molecular architecture along the b-axis direction.

Figure 4

A view of the C=O(carbon­yl)⋯π inter­actions (dashed lines) between the HX cations in salt I. [Symmetry codes: (i) −1 + x, y, z; (ii) x,  − y,  + z].

In the crystal structure of salt II, the XA cation inter­acts with its inversion-related equivalent to form a dimer through a pair of N1—H1⋯O2i hydrogen bonds (Table 2 ▸) with an (8) graph-set motif (type in the scheme above). The dimer is flanked on both sides by a water mol­ecule (O1W), forming a pair of O1W—H2W⋯O2iv and O1W—H1W⋯O6ii hydrogen bonds with an (8) graph-set motif (type ), leading to the formation of a tetra­meric unit. The tetra­meric unit is formed by an alternate arrangement of (8) and (8) ring motifs, which extend as DADA array (dimeric units held together by four hydrogen bonds between the self-complementary DADA arrays; D = donor and A = acceptor) along the ac plane. Neighbouring tetra­meric units are then connected through two sets of (7) motifs (Jeffrey & Saenger, 1991 ▸) formed by N7—H7⋯O1W and O1W—H1W⋯O6ii hydrogen bonds and an (4) (type ) motif formed by a pair of O1W—H1W⋯O6ii inter­actions. The tetra­meric units combine into a supra­molecular ribbon extended along the ac plane (Fig. 5 ▸). Neighbouring perpendicular supra­molecular ribbons are then inter­connected through pairs of N3—H3⋯Br1iii and N9—H9⋯Br1 hydrogen bonds with an (28) ring motif, which assembles them into a staircase-like supra­molecular architecture as shown in Figs. 6 ▸ and 7 ▸. The crystal structure is further consolidated by carbon­yl⋯π inter­actions between symmetry-related XA cations [C6=O6 and π cloud of the pyridine ring (centroid Cg2) of the XA unit) with C=O⋯Cg2vi and C=O⋯Cg2vii distances of 3.366 (3) and 3.477 (3) Å, respectively, and angles of 108.2 (2) and 118.7 (2)° [symmetry codes: (vi) 1 + x, y, z; (vii) 1 − x, 1 − y, 1 − z; Fig. 8 ▸).

Table 2

Hydrogen-bond geometry (Å, °) for II

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O2i	0.82 (2)	2.09 (2)	2.903 (4)	175 (4)
N3—H3⋯Br1ii	0.82 (2)	2.48 (2)	3.301 (3)	176 (4)
N7—H7⋯O1W	0.82 (2)	1.81 (2)	2.609 (4)	163 (4)
N9—H9⋯Br1	0.82 (2)	2.43 (2)	3.237 (3)	172 (4)
O1W—H1WA⋯O6iii	0.86 (1)	1.95 (1)	2.802 (4)	171 (5)
O1W—H1WB⋯Br1iv	0.86 (1)	3.03 (4)	3.490 (3)	115 (3)
O1W—H1WB⋯O2v	0.86 (1)	2.05 (3)	2.816 (4)	149 (4)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) .

Figure 5

Formation of a supra­molecular ribbon with a DADA array in salt II via N—H⋯O and O—H⋯O hydrogen bonds between cations and water mol­ecules.

Figure 6

Supra­molecular ribbons connecting adjacent ribbons through N—H⋯Br inter­actions. [Symmetry codes: (i) 1 − x, 1 − y, 2 − z; (ii) 2 − x, 1 − y, 1 − z; (iii) x,  − y,  + z; (iv) 1 + x, y, −1 + z].

Figure 7

The formation of a three-dimensional supra­molecular staircase structure along the ac plane.

Figure 8

A view of the C=O(carbon­yl)⋯π inter­actions between XA cations in salt II. [Symmetry codes: (i) 1 + x, y, z; (ii) 1 − x, 1 − y, 1 − z].

Hirshfeld surface analysis

Hirshfeld surface analyses and their associated two-dimensional fingerprint plots (McKinnon et al., 2007 ▸; Spackman & Jayatilaka, 2009 ▸) were generated using Crystal Explorer 17.5 (Turner et al., 2017 ▸). The Hirshfeld surfaces of the title compounds mapped over d norm feature several red spots in the regions of D–A (D = donor, A = acceptor) inter­actions (Cárdenas-Valenzuela et al., 2018 ▸; Atioğlu et al., 2018 ▸). In this regard, the contribution of the inter­atomic contacts to the d norm surface map can help differentiate whether the contact is longer (blue) or shorter (red) than the sum of the van der Waals radii of the two inter­acting atoms. The Hirshfeld surfaces of salts I and II are shown in Fig. 9 ▸ a and 10a ▸, respectively and the hydrogen-bonding inter­actions between the hydrated ion pairs I and II and the respective neighbouring moieties are shown in Fig. 9 ▸ b and 10b ▸, respectively. The intense red spots on the Hirshfeld surface indicate the shortest inter­atomic distances corresponding to the hydrogen bonds. They are also clearly identified by the two long spikes in the fingerprint plots and can be qu­anti­fied using the percentage distribution of the inter­acting types. Such analyses of the salts I and II are shown in Figs. 11 ▸ and 12 ▸ giving the following contributions: All (100%), O⋯H/H⋯O (I 19.7%, II 23.4%), N⋯H/H⋯N (I 13.5%, II 7.5%) C⋯H/H⋯C (I 6.4%, II 9.6%), H⋯H/H⋯H (I 23.4%, II 15.9%) and C⋯C/C⋯C (I 0.9%, II 0.1%) (Table 5), indicating that the most abundant contact is Br⋯H/H⋯Br with 22.3% in I and 25.4% in II, respectively.

Figure 9

(a) Hirshfeld surface mapped over d norm for salt I. (b) Inter­molecular inter­actions and the three-dimensional Hirshfeld surface for salt I.

Figure 10

(a) Hirshfeld surface mapped over d norm for salt II. (b) Inter­molecular inter­actions and the three-dimensional Hirshfeld surface for salt II.

Figure 11

Hirshfeld surface analysis and two-dimensional fingerprint plots for salt I plotted over d norm, with inter­actions to neighbouring fragments shown as dashed lines.

Figure 12

Hirshfeld surface analysis and two-dimensional fingerprint plots for salt II plotted over d norm, with inter­actions to neighbouring fragments shown as dashed lines.

Comparative analysis

The data obtained by comparative analysis of the crystal structures, supra­molecular inter­actions, hydrogen-bonding motifs and packing patterns of structurally similar halide salts such as adeninium bromide, adeninium chloride, guaninium bromide, guaninium chloride and hypoxanthinium chloride (Maixner & Zachova, 1991 ▸; Sridhar, 2011 ▸; Kistenmancher & Shigematsu, 1974 ▸; Langer & Huml, 1978 ▸) are listed and compared in Table 3 ▸.

Table 3

Comparison of purine derivatives with hydro­bromic acid and hydro­chloric acid

	Adeninium bromide hemihydrate	Adeninium chloride monohydrate	Guaninium chloride monohydrate	Guaninium bromide monohydrate	Hypoxanthinium chloride monohydrate	Hypoxanthinium bromide monohydrate (I)	Xanthinium bromide monohydrate (II)
Cell parameters (a, b, c, β; Å, °)	9.018 (2), 4.845 (2), 19.693 (5), 112.8	8.771 (2), 4.834 (2), 19.46 (1), 114.25	4.591 (1), 9.886 (2), 18.985 (1), 99.62	4.8708 (7), 13.237 (3), 14.638 (2), 93.906 (10)	4.8295 (9), 17.7285 (22), 9.0077 (21), 94.59 (3)	4.8487 (4), 18.4455 (15), 9.0782 (7), 94.808 (1)	4.9225 (2), 22.7572 (17), 7.5601 (5) 103.003 (3)
Crystal system	Monoclinic	Monoclinic	Monoclinic	Monoclinic	Monoclinic	Monoclinic	Monoclinic
Space group	P2/c	P2/c	P21/c	P21/c	P21/c	P21/c	P21/c
Protonation site	N1	N1	N7	N7	N7	N7	N9
Type of hydrogen bonding	N—H⋯O, N—H⋯Br, N—H⋯N, O—H⋯O, C—H⋯Br	N—H⋯O, N—H⋯Cl, N—H⋯N, O—H⋯Cl, C—H⋯Cl	N—H⋯O, N—H⋯Br, N—H⋯N, O—H⋯Br, C—H⋯Br	N—H⋯O, N—H⋯Cl, N—H⋯N, O—H⋯Cl, C—H⋯Cl	N—H⋯Cl, N—H⋯O, O—H⋯N, O—H⋯Cl, C—H⋯Cl	N—H⋯Br, N—H⋯O, O—H⋯N, O—H⋯Br, C—H⋯Br	N—H⋯O, N—H⋯Br, O—H⋯O
Type of stacking	–	–	C=O⋯π	C=O⋯π	C=O⋯π	C=O⋯π	C=O⋯π
Primary motif	(10)	(10)	(8)	(8)	(9)	(9)	(8)
Secondary motif	(7), (14)	(7), (14)	(7), (10), (11)	(7), (10), (11)	(11), (16), (14)	(11), (16), (14)	(7), (4)
Type of packing architecture	Ribbon	Ribbon	Ribbon	Ribbon	Wave	Wave	Staircase

Salt I has similar unit-cell parameters and packing patterns to the hypoxanthinium chloride salt. The mol­ecular recog­nition between the hypoxanthine base and acid happens via N—H⋯O, C—H⋯Br/Cl and N—H⋯Br/Cl hydrogen-bond motifs with (9) (type ), (11) (type ), (16) (type ) and (14) (type ) graph-set motifs. Salt II forms base pairs via N—H⋯O hydrogen bonds described by (8) (type ), (8) (type ) (Wei, 1977 ▸; Maixner & Zachova, 1991 ▸), (7) (type ) and (4) (type ) graph-set motifs. Salt II cannot be compared with its chloride analogue since its crystal structure has not yet been reported.

A comparison between some related purine-based chloride and bromide salts revealed that type , and hydrogen-bond motifs are predominant. The commonly observed motifs in purine based salts are shown in the scheme. A comparison of salts I and II with the reported crystal structures revealed that the bromide and chloride salts of I are isomorphous and therefore, one might predict, the unreported xanthinium chloride monohydrate could be isomorphous with its bromide salt II.

Database survey

A survey of the Cambridge Structural Database (CSD, version 5.43, update of March 2022; Groom et al., 2016 ▸) for reported structures of hypoxanthine and xanthine derivatives identified the hypoxanthine mol­ecule (CSD refcodes GEBTUC and GETBUC01; Schmalle et al., 1988 ▸; Yang & Xie, 2007 ▸) and the following salts: hypoxanthinium nitrate monohydrate (BONKOE and BONKOE54; Cabaj et al., 2019 ▸; Schmalle et al., 1990 ▸), hypoxanthinium chloride monohydrate (HYPXCL and HYPXCL01; Sletten & Jensen, 1969 ▸; Kalyanaraman et al., 2007 ▸) as well as three xanthine salts, viz. xanthinium perchlorate monohydrate (VURMUR; Biradha et al., 2010 ▸), xanthinium nitrate monohydrate (YADJAQ; Sridhar, 2011 ▸) and xanthinium hydrogensulfate monohydrate (YADJEU; Sridhar, 2011 ▸). In all of the hypoxanthinium salts, the hypoxanthine mol­ecule is protonated at the N7 position and inter­acts with the anion through N—H⋯Cl/O and C=O⋯π inter­actions. In the xanthinium salts, the xanthine mol­ecules are protonated at the N7 position in xanthinium nitrate monohydrate and xanthinium hydrogensulfate monohydrate and at the N9 position in xanthinium perchlorate monohydrate. In all of the crystal structures, the xanthinium cation inter­acts with the anion through N—H⋯O, O—H⋯O and C=O⋯π inter­actions.

Synthesis and crystallization

A general method was used for the preparation and crystallization of the hypoxanthinium bromide monohydrate (I) and xanthinium bromide monohydrate (II) using the following qu­anti­ties: 0.0340 mg (0.25mmol) of hypoxanthine for I and 0.0380 mg (0.25 mmol) of xanthine for II.

The indicated amount of the base was dissolved in 20 mL of distilled water and 2 mL of hydro­bromic acid (5% in water) were added. The reaction mixture was heated to 358 K for 30 min using a water bath. The resulting solution was allowed to slowly evaporate at room temperature. After a few days, colourless plate-like crystals were obtained.

Refinement

Crystal data, data collection and structure refinement details for salts I and II are summarized in Table 4 ▸. All C-bound hydrogen atoms were placed in idealized positions and refined using a riding model, with C—H = 0.93 Å and U iso(H) = 1.2U eq (C). The H atoms of the water mol­ecule were located in a difference-Fourier map and refined with the O—H distance restrained to 0.85–0.86 Å and with U iso(H) = 1.5 U eq(O). The hydrogen atoms bound to the nitro­gen atoms in salts I and II were located in difference-Fourier maps and either refined freely (in I) or with the distance restraint N—H = 0.82 Å and with U iso(H) = 1.2U eq(N) (in II).

Table 4

Experimental details

	I	II
Crystal data
Chemical formula	C5H5N4O+·Br−·H2O	C5H5N4O2 +·Br−·H2O
M r	235.06	251.06
Crystal system, space group	Monoclinic, P21/c	Monoclinic, P21/c
Temperature (K)	296	303
a, b, c (Å)	4.8487 (4), 18.4455 (15), 9.0782 (7)	4.9225 (2), 22.7572 (17), 7.5601 (5)
β (°)	94.808 (1)	103.003 (3)
V (Å3)	809.07 (11)	825.18 (9)
Z	4	4
Radiation type	Mo Kα	Mo Kα
μ (mm−1)	5.05	4.96
Crystal size (mm)	0.46 × 0.26 × 0.21	0.55 × 0.37 × 0.31
Data collection
Diffractometer	Bruker APEXII CCD	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2016 ▸)	Multi-scan (SADABS; Bruker, 2016 ▸)
T min, T max	0.403, 0.641	0.316, 0.561
No. of measured, independent and observed [I > 2σ(I)] reflections	17895, 2383, 2037	5810, 1855, 1418
R int	0.028	0.045
(sin θ/λ)max (Å−1)	0.707	0.696
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.021, 0.056, 1.05	0.036, 0.080, 1.10
No. of reflections	2383	1855
No. of parameters	128	139
No. of restraints	6	9
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement	Only H-atom coordinates refined
Δρmax, Δρmin (e Å−3)	0.34, −0.29	0.42, −0.62

Computer programs: APEX2 and SAINT (Bruker, 2016 ▸), SHELXS97 (Sheldrick 2008 ▸), SHELXT2014/5 (Sheldrick, 2015a ▸), SHELXL2018/3 (Sheldrick, 2015b ▸), PLATON (Spek, 2020 ▸), Mercury (Macrae et al., 2020 ▸), POVRay (Cason, 2004 ▸) and publCIF (Westrip,2010 ▸).

Crystal structure: contains datablock(s) I, II. DOI: 10.1107/S2056989022005278/jq2017sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989022005278/jq2017Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989022005278/jq2017Isup4.cml

Structure factors: contains datablock(s) II. DOI: 10.1107/S2056989022005278/jq2017IIsup3.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989022005278/jq2017IIsup5.cml

CCDC references: 2170923, 2170922

Additional supporting information: crystallographic information; 3D view; checkCIF report

C5H5N4O+·Br−·H2O	F(000) = 464
Mr = 235.06	Dx = 1.930 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 4.8487 (4) Å	Cell parameters from 2383 reflections
b = 18.4455 (15) Å	θ = 2.2–30.2°
c = 9.0782 (7) Å	µ = 5.05 mm−1
β = 94.808 (1)°	T = 296 K
V = 809.07 (11) Å3	Plate, colourless
Z = 4	0.46 × 0.26 × 0.21 mm

Bruker APEXII CCD diffractometer	2037 reflections with I > 2σ(I)
φ and ω scans	Rint = 0.028
Absorption correction: multi-scan (SADABS; Bruker, 2016)	θmax = 30.2°, θmin = 2.2°
Tmin = 0.403, Tmax = 0.641	h = −6→6
17895 measured reflections	k = −25→26
2383 independent reflections	l = −12→12

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.021	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.056	w = 1/[σ2(Fo2) + (0.0273P)2 + 0.2516P] where P = (Fo2 + 2Fc2)/3
S = 1.05	(Δ/σ)max = 0.002
2383 reflections	Δρmax = 0.34 e Å−3
128 parameters	Δρmin = −0.29 e Å−3
6 restraints	Extinction correction: SHELXL2018/3 (Sheldrick 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0080 (9)

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.

	x	y	z	Uiso*/Ueq
Br1	−0.30053 (4)	0.47161 (2)	0.77208 (2)	0.04456 (8)
O6	−0.2120 (2)	0.27474 (6)	0.73221 (11)	0.0337 (2)
N9	0.4049 (2)	0.18412 (7)	0.42420 (13)	0.0278 (2)
H9	0.529 (3)	0.1816 (10)	0.3639 (18)	0.041 (5)*
N3	0.3696 (2)	0.31647 (6)	0.43388 (13)	0.0288 (2)
N1	0.0413 (3)	0.35239 (6)	0.59830 (14)	0.0293 (2)
H1	−0.035 (4)	0.3873 (9)	0.638 (2)	0.045 (5)*
N7	0.1015 (3)	0.15533 (6)	0.57823 (13)	0.0283 (2)
H7	0.000 (4)	0.1316 (10)	0.6329 (19)	0.044 (5)*
C5	0.1107 (3)	0.22987 (7)	0.57102 (14)	0.0232 (2)
C8	0.2792 (3)	0.12926 (8)	0.48894 (16)	0.0309 (3)
H8	0.312119	0.080303	0.473349	0.037*
C2	0.2315 (3)	0.36593 (8)	0.50019 (16)	0.0309 (3)
H2	0.266402	0.414166	0.478442	0.037*
O1W	−0.7539 (3)	0.60447 (7)	0.73814 (15)	0.0447 (3)
H1W	−0.653 (4)	0.6346 (10)	0.695 (2)	0.067*
H2W	−0.671 (4)	0.5639 (7)	0.741 (2)	0.067*
C4	0.3015 (3)	0.24822 (7)	0.47360 (13)	0.0235 (2)
C6	−0.0384 (3)	0.28405 (7)	0.64259 (14)	0.0245 (2)

	U11	U22	U33	U12	U13	U23
Br1	0.05176 (12)	0.02567 (9)	0.06016 (13)	0.00535 (6)	0.02789 (9)	−0.00045 (7)
O6	0.0347 (5)	0.0341 (5)	0.0352 (5)	0.0018 (4)	0.0205 (5)	−0.0004 (4)
N9	0.0272 (5)	0.0312 (6)	0.0267 (5)	0.0032 (4)	0.0122 (5)	−0.0009 (4)
N3	0.0292 (6)	0.0287 (6)	0.0299 (6)	−0.0017 (5)	0.0116 (5)	0.0026 (5)
N1	0.0325 (6)	0.0257 (5)	0.0316 (6)	0.0025 (5)	0.0133 (5)	−0.0016 (5)
N7	0.0311 (6)	0.0251 (5)	0.0301 (6)	−0.0029 (4)	0.0123 (5)	−0.0005 (4)
C5	0.0223 (6)	0.0259 (6)	0.0224 (6)	−0.0010 (5)	0.0072 (5)	−0.0009 (5)
C8	0.0344 (7)	0.0267 (6)	0.0328 (7)	0.0024 (5)	0.0105 (6)	−0.0019 (5)
C2	0.0333 (7)	0.0273 (6)	0.0334 (7)	−0.0011 (5)	0.0103 (6)	0.0033 (5)
O1W	0.0458 (7)	0.0321 (6)	0.0608 (8)	0.0075 (5)	0.0319 (6)	0.0077 (5)
C4	0.0216 (6)	0.0282 (6)	0.0215 (6)	0.0006 (5)	0.0066 (5)	−0.0008 (5)
C6	0.0234 (6)	0.0285 (6)	0.0223 (6)	0.0012 (5)	0.0060 (5)	−0.0014 (5)

O6—C6	1.2308 (15)	N7—C8	1.3219 (17)
N9—C8	1.3419 (18)	N7—C5	1.3774 (17)
N9—C4	1.3741 (16)	N7—H7	0.849 (14)
N9—H9	0.847 (14)	C5—C4	1.3748 (17)
N3—C2	1.3078 (18)	C5—C6	1.4221 (17)
N3—C4	1.3579 (16)	C8—H8	0.9300
N1—C2	1.3581 (17)	C2—H2	0.9300
N1—C6	1.3879 (17)	O1W—H1W	0.857 (9)
N1—H1	0.840 (14)	O1W—H2W	0.848 (9)
C8—N9—C4	108.32 (10)	N7—C8—N9	109.73 (12)
C8—N9—H9	127.8 (13)	N7—C8—H8	125.1
C4—N9—H9	123.8 (13)	N9—C8—H8	125.1
C2—N3—C4	112.29 (11)	N3—C2—N1	125.15 (13)
C2—N1—C6	125.30 (12)	N3—C2—H2	117.4
C2—N1—H1	119.4 (14)	N1—C2—H2	117.4
C6—N1—H1	115.3 (14)	H1W—O1W—H2W	107.4 (17)
C8—N7—C5	107.98 (11)	N3—C4—N9	127.42 (11)
C8—N7—H7	127.6 (13)	N3—C4—C5	126.22 (12)
C5—N7—H7	124.4 (13)	N9—C4—C5	106.36 (11)
C4—C5—N7	107.61 (11)	O6—C6—N1	122.73 (12)
C4—C5—C6	121.08 (12)	O6—C6—C5	127.31 (13)
N7—C5—C6	131.31 (11)	N1—C6—C5	109.96 (11)
C8—N7—C5—C4	−0.02 (16)	N7—C5—C4—N3	179.07 (12)
C8—N7—C5—C6	179.24 (14)	C6—C5—C4—N3	−0.3 (2)
C5—N7—C8—N9	0.27 (17)	N7—C5—C4—N9	−0.23 (15)
C4—N9—C8—N7	−0.42 (17)	C6—C5—C4—N9	−179.58 (12)
C4—N3—C2—N1	0.2 (2)	C2—N1—C6—O6	179.92 (14)
C6—N1—C2—N3	−0.6 (2)	C2—N1—C6—C5	0.5 (2)
C2—N3—C4—N9	179.41 (14)	C4—C5—C6—O6	−179.46 (14)
C2—N3—C4—C5	0.3 (2)	N7—C5—C6—O6	1.4 (3)
C8—N9—C4—N3	−178.90 (14)	C4—C5—C6—N1	−0.12 (18)
C8—N9—C4—C5	0.39 (16)	N7—C5—C6—N1	−179.30 (14)

D—H···A	D—H	H···A	D···A	D—H···A
N9—H9···Br1i	0.85 (1)	3.08 (2)	3.5397 (12)	117 (2)
N9—H9···O6i	0.85 (1)	1.98 (2)	2.7579 (14)	153 (2)
N1—H1···Br1	0.84 (1)	2.41 (1)	3.2419 (12)	170 (2)
N7—H7···O1Wii	0.85 (1)	1.81 (2)	2.6401 (16)	165 (2)
O1W—H1W···N3iii	0.86 (1)	2.08 (1)	2.9200 (16)	165 (2)
O1W—H2W···Br1	0.85 (1)	2.48 (1)	3.2894 (12)	161 (2)
C8—H8···Br1i	0.93	2.89	3.4875 (15)	123

C5H5N4O2+·Br−·H2O	F(000) = 496
Mr = 251.06	Dx = 2.021 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 4.9225 (2) Å	Cell parameters from 1418 reflections
b = 22.7572 (17) Å	θ = 2.9–29.6°
c = 7.5601 (5) Å	µ = 4.96 mm−1
β = 103.003 (3)°	T = 303 K
V = 825.18 (9) Å3	Plate, colourless
Z = 4	0.55 × 0.37 × 0.31 mm

Bruker APEXII CCD diffractometer	1418 reflections with I > 2σ(I)
φ and ω scans	Rint = 0.045
Absorption correction: multi-scan (SADABS; Bruker, 2016)	θmax = 29.7°, θmin = 2.9°
Tmin = 0.316, Tmax = 0.561	h = −6→6
5810 measured reflections	k = −30→30
1855 independent reflections	l = −9→9

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.036	Hydrogen site location: difference Fourier map
wR(F2) = 0.080	Only H-atom coordinates refined
S = 1.10	w = 1/[σ2(Fo2) + (0.0151P)2 + 1.7175P] where P = (Fo2 + 2Fc2)/3
1855 reflections	(Δ/σ)max < 0.001
139 parameters	Δρmax = 0.42 e Å−3
9 restraints	Δρmin = −0.62 e Å−3

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.

	x	y	z	Uiso*/Ueq
Br1	−0.16454 (8)	0.20412 (2)	0.47569 (6)	0.03200 (14)
O6	0.8033 (5)	0.47823 (12)	0.6033 (4)	0.0318 (6)
C6	0.6301 (7)	0.44615 (16)	0.6465 (5)	0.0241 (8)
N1	0.5267 (7)	0.45642 (14)	0.7988 (4)	0.0273 (7)
H1	0.578 (8)	0.4867 (13)	0.855 (5)	0.033*
C2	0.3313 (8)	0.42399 (16)	0.8628 (5)	0.0254 (8)
O2	0.2541 (6)	0.43894 (13)	0.9992 (4)	0.0380 (7)
N3	0.2278 (6)	0.37489 (13)	0.7647 (4)	0.0251 (7)
H3	0.126 (7)	0.3545 (16)	0.812 (5)	0.030*
C4	0.3212 (7)	0.36166 (15)	0.6147 (5)	0.0238 (8)
C5	0.5108 (7)	0.39456 (16)	0.5538 (5)	0.0237 (8)
N7	0.5509 (7)	0.36852 (14)	0.3972 (4)	0.0273 (7)
H7	0.651 (8)	0.3804 (18)	0.332 (5)	0.033*
C8	0.3919 (8)	0.32168 (18)	0.3652 (6)	0.0304 (9)
H8	0.384 (9)	0.2947 (18)	0.265 (6)	0.036*
N9	0.2477 (7)	0.31597 (14)	0.4956 (5)	0.0279 (7)
H9	0.148 (7)	0.2876 (14)	0.503 (6)	0.033*
O1W	0.8947 (7)	0.42353 (14)	0.2374 (4)	0.0434 (8)
H1WA	0.983 (9)	0.4523 (16)	0.298 (6)	0.065*
H1WB	0.980 (9)	0.415 (2)	0.154 (5)	0.065*

	U11	U22	U33	U12	U13	U23
Br1	0.0307 (2)	0.0253 (2)	0.0413 (2)	−0.00152 (17)	0.01087 (16)	−0.00286 (18)
O6	0.0317 (15)	0.0309 (15)	0.0360 (16)	−0.0110 (12)	0.0147 (13)	−0.0028 (12)
C6	0.0231 (18)	0.0217 (18)	0.028 (2)	−0.0001 (14)	0.0057 (16)	0.0046 (15)
N1	0.0294 (17)	0.0253 (17)	0.0292 (19)	−0.0097 (14)	0.0111 (15)	−0.0046 (14)
C2	0.0255 (19)	0.0224 (19)	0.029 (2)	−0.0030 (15)	0.0079 (17)	0.0042 (16)
O2	0.0431 (17)	0.0432 (18)	0.0338 (17)	−0.0118 (14)	0.0216 (14)	−0.0079 (14)
N3	0.0246 (16)	0.0232 (16)	0.0305 (18)	−0.0041 (12)	0.0128 (14)	0.0050 (13)
C4	0.0236 (18)	0.0193 (17)	0.027 (2)	0.0011 (14)	0.0028 (15)	0.0039 (15)
C5	0.0231 (18)	0.0246 (18)	0.0232 (19)	−0.0018 (14)	0.0050 (15)	−0.0008 (15)
N7	0.0291 (17)	0.0286 (17)	0.0265 (18)	−0.0023 (14)	0.0109 (14)	0.0005 (14)
C8	0.035 (2)	0.028 (2)	0.028 (2)	−0.0013 (17)	0.0051 (18)	−0.0048 (17)
N9	0.0299 (17)	0.0186 (15)	0.0346 (19)	−0.0040 (13)	0.0061 (15)	0.0000 (14)
O1W	0.0484 (19)	0.0449 (19)	0.046 (2)	−0.0199 (15)	0.0290 (16)	−0.0172 (15)

O6—C6	1.221 (4)	C4—N9	1.370 (5)
C6—N1	1.380 (5)	C5—N7	1.378 (5)
C6—C5	1.425 (5)	N7—C8	1.312 (5)
N1—C2	1.383 (5)	N7—H7	0.82 (2)
N1—H1	0.82 (2)	C8—N9	1.344 (5)
C2—O2	1.224 (5)	C8—H8	0.97 (4)
C2—N3	1.374 (5)	N9—H9	0.82 (2)
N3—C4	1.350 (5)	O1W—H1WA	0.857 (10)
N3—H3	0.82 (2)	O1W—H1WB	0.860 (10)
C4—C5	1.355 (5)
O6—C6—N1	122.2 (3)	C5—C4—N9	107.2 (3)
O6—C6—C5	126.6 (4)	C4—C5—N7	107.3 (3)
N1—C6—C5	111.2 (3)	C4—C5—C6	121.8 (3)
C6—N1—C2	128.1 (3)	N7—C5—C6	130.9 (3)
C6—N1—H1	116 (3)	C8—N7—C5	108.2 (3)
C2—N1—H1	115 (3)	C8—N7—H7	125 (3)
O2—C2—N3	122.2 (3)	C5—N7—H7	127 (3)
O2—C2—N1	121.2 (3)	N7—C8—N9	109.6 (4)
N3—C2—N1	116.6 (3)	N7—C8—H8	125 (3)
C4—N3—C2	118.7 (3)	N9—C8—H8	125 (3)
C4—N3—H3	126 (3)	C8—N9—C4	107.7 (3)
C2—N3—H3	115 (3)	C8—N9—H9	123 (3)
N3—C4—C5	123.6 (3)	C4—N9—H9	129 (3)
N3—C4—N9	129.2 (3)	H1WA—O1W—H1WB	107 (2)
O6—C6—N1—C2	179.8 (4)	N9—C4—C5—C6	179.6 (3)
C5—C6—N1—C2	−0.7 (5)	O6—C6—C5—C4	179.3 (4)
C6—N1—C2—O2	−178.6 (4)	N1—C6—C5—C4	−0.1 (5)
C6—N1—C2—N3	0.8 (6)	O6—C6—C5—N7	−1.2 (7)
O2—C2—N3—C4	179.3 (4)	N1—C6—C5—N7	179.3 (4)
N1—C2—N3—C4	−0.1 (5)	C4—C5—N7—C8	−0.1 (4)
C2—N3—C4—C5	−0.6 (5)	C6—C5—N7—C8	−179.6 (4)
C2—N3—C4—N9	−179.3 (4)	C5—N7—C8—N9	0.1 (5)
N3—C4—C5—N7	−178.8 (3)	N7—C8—N9—C4	0.0 (4)
N9—C4—C5—N7	0.1 (4)	N3—C4—N9—C8	178.7 (4)
N3—C4—C5—C6	0.8 (6)	C5—C4—N9—C8	−0.1 (4)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2i	0.82 (2)	2.09 (2)	2.903 (4)	175 (4)
N3—H3···Br1ii	0.82 (2)	2.48 (2)	3.301 (3)	176 (4)
N7—H7···O1W	0.82 (2)	1.81 (2)	2.609 (4)	163 (4)
N9—H9···Br1	0.82 (2)	2.43 (2)	3.237 (3)	172 (4)
O1W—H1WA···O6iii	0.86 (1)	1.95 (1)	2.802 (4)	171 (5)
O1W—H1WB···Br1iv	0.86 (1)	3.03 (4)	3.490 (3)	115 (3)
O1W—H1WB···O2v	0.86 (1)	2.05 (3)	2.816 (4)	149 (4)

CONTACT	SALT (I)	SALT (II)
H···Br /Br···H	22.3%	25.4%
O···H/H···O	19.7%	23.4%
H···N/N···H	13.5%	7.5%
C···H/H···C	6.4%	9.6%
H···H	23.4%	15.9%