Crystal structure of a 1:1 salt of 4-amino­benzoic acid (vitamin B10) with pyrazinoic acid

Drozd, K.V.; Arkhipov, S.G.; Boldyreva, E.V.; Perlovich, G.L.

doi:10.1107/S2056989018016663

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ISSN: 2056-9890

Volume 74| Part 12| December 2018| Pages 1923-1927

https://doi.org/10.1107/S2056989018016663

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Crystal structure of a 1:1 salt of 4-aminobenzoic acid (vitamin B₁₀) with pyrazinoic acid

K. V. Drozd,^a ^* S. G. Arkhipov,^b,^c E. V. Boldyreva ^b,^d and G. L. Perlovich ^a

^aG. A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, 1, Academicheskaya, Ivanovo 153045, Russian Federation, ^bNovosibirsk State University, Pirogova str. 2, Novosibirsk, 630090, Russian Federation, ^cInstitute of Solid State Chemistry and Mechanochemistry SB RAS, Kutateladze str. 18, Novosibirsk 630128, Russian Federation, and ^dG. K. Boreskov Institute of Catalysis SB RAS, Laverentiev Ave. 5, Novosibirsk 630090, Russian Federation
^*Correspondence e-mail: ksdrozd@yandex.ru

Edited by C. Rizzoli, Universita degli Studi di Parma, Italy (Received 24 October 2018; accepted 23 November 2018; online 30 November 2018)

The title 1:1 salt, C₇H₈NO₂⁺·C₅H₃N₂O₂⁻ (systematic name: 4-carboxyanilinium pyrazine-2-carboxylate), was synthesized successfully by slow evaporation of a saturated solution from water–ethanol (1:1 v/v) mixture and characterized by X-ray diffraction (SCXRD, PXRD) and calorimetry (DSC). The crystal structure of the salt was solved and refined at 150 and 293 K. The salt crystallizes with one molecule of 4-aminobenzoic acid (PABA) and one molecule of pyrazinoic acid (POA) in the asymmetric unit. In the crystal, the PABA and POA molecules are associated via COOH⋯N_arom heterosynthons, which are connected by N—H⋯O hydrogen bonds, creating zigzag chains. The chains are further linked by N—H⋯O hydrogen bonds and π–π stacking interactions along the b axis [centroid-to-centroid distances = 3.7377 (13) and 3.8034 (13) Å at 150 and 293 K, respectively] to form a layered three-dimensional structure.

Keywords: crystal structure; 4-aminobenzoic acid; pyrazinoic acid; salt; hydrogen bonding; melting point.

CCDC references: 1880871; 1880870

1. Chemical context

4-Aminobenzoic acid (PABA) is known as vitamin B₁₀ and is involved in the production of folic acid in bacteria (Chang & Hu, 1996 ; Akberova, 2002 ). It is used as an antibacterial (Richards et al., 1995 ), anti-inflammatory (Flindt-Hansen & Ebbesen, 1991 ), antioxidant (Sirota et al., 2017 ; Galbinur et al., 2009 ), anticoagulant (Stroeva et al., 1999 ; Drozd et al., 2000 ), or dermatologic agent (Rothman & Henningsen, 1947 ; Xavier et al., 2006 ; Hanson et al., 2006 ). Moreover, it is a building block used in the design of drug candidates and is frequently found as a structural moiety in drugs (Kluczyk et al., 2002 ). PABA has been the subject of many scientific investigations, due not only to its pharmaceutical and biological properties, but also its ability to form various multi-component solid forms. PABA is a simple organic molecule with two functional groups: amine and carboxyl. This makes it unique in its ability to form various hydrogen-bonded network structures (Athimoolam & Natarajan, 2007 ). Among all the multi-component crystals of PABA known to date, co-crystals and salts of PABA are especially numerous.

Today, the formation of either salts or co-crystals of APIs is one of the promising strategies to modify the solid-state properties of pharmaceutical compounds, such as solubility, bioavailability, stability, etc. (Shevchenko et al., 2012 ; Perumalla & Sun, 2013 ; Manin et al., 2018 ). The main difference between a salt and a co-crystal is in the position of a proton. A salt is formed if a proton is transferred from an acid to a base (Aakeröy et al., 2007 ). Childs et al. (2007 ) and Cruz-Cabeza (2012 ) have noticed a linear correlation between ΔpK_a [pK_a(base) – pK_a(acid)] of the starting compounds and the probability of the formation of either a salt or a co-crystal. It is assumed that a salt is expected to be formed if ΔpK_a > 3 (Childs et al., 2007) or ΔpK_a > 4 (Cruz-Cabeza, 2012), whereas a co-crystal forms when ΔpK_a < 0 (Childs et al., 2007) or ΔpK_a < −1 (Cruz-Cabeza, 2012). In the intermediate ΔpK_a range, the nature of multi-component crystal is difficult to predict – a so called `salt–co-crystal continuum' (Childs et al., 2007; Hathwar et al., 2010 ). Several examples have been documented where both a salt and a co-crystal could be formed by the same components from the same solutions under different crystallization conditions (Fu et al., 2016 ; Losev & Boldyreva, 2018a ,b ). A co-crystal can also be converted into a salt in the solid state upon temperature variations (Grobelny et al., 2011 ).

The present study reports the synthesis and crystallization of a novel salt of 4-aminobenzoic acid with pyrazinoic acid (pyrazine-2-carboxylic acid, POA), [PABA-POA], which was characterized using single crystal and powder X-ray diffraction (SCXRD, PXRD) and different scanning calorimetry (DSC).

2. Elucidation of the multi-component crystal nature

4-Aminobenzoic acid is an ampholyte molecule with basic (–NH₂) and acidic (–COOH) functional groups, and its pK_a values are 2.46 and 4.62 (Avdeef, 2017 ) respectively. Pyrazinoic acid is a weak acid with a pK_a of 2.9 (Zhang et al., 1999 ). According to the ΔpK_a of PABA and POA, the two-component crystal is within the range of the `salt–co-crystal continuum'. Both a salt and a co-crystal can be expected to crystallize.

The crystal structure of the title compound was solved and refined at 150 K (Ia) and 293 K (Ib). The nature of the crystal form (salt/co-crystal) was identified from the structural characteristics, namely the C—N bond length of PABA and the C—O bond lengths of the carboxylic/carboxylate groups of PABA and POA at both temperatures to eliminate the possibility of salt–co-crystal transition. In a neutral pure PABA molecule, the length of the C—N bond between the N atom of the amine group and the C atom of the benzene ring is ca 1.37–1.4 Å. In the title compound, the protonation of the PABA amine group results in a significantly longer C—N bond [1.455 (5) Å at 150 K and 1.467 (3) Å at 293 K]. To define the deprotonation site, the C—O bond lengths of both PABA and POA were compared. In a neutral carboxylic group, C—O is longer than C=O by 0.08 Å, or more. Deprotonation of a –COOH group leads to a decrease in this difference to 0.03 Å or less (Childs et al., 2007; Chen et al., 2012 ). In the title compound, the difference d(C—O) is 0.104 (6) or 0.102 (8) Å for PABA and 0.007 (6) or 0.012 (6) Å for POA at 150 K and 293 K, respectively, indicating deprotonation of the POA –COOH group and the formation of a salt.

3. Structural commentary

The title compound crystallizes in the monoclinic non-centrosymmetric space group Pc with one molecule of each component per asymmetric unit (Fig. 1). The carboxyl planes of PABA and POA are slightly twisted from the aromatic ring planes [2.76 (16) and 8.4 (2)° for Ia; 2.89 (19) and 9.2 (3)° for Ib], which is a characteristic feature found in almost all known multi-component complexes of both compounds. No phase transitions occur in the temperature range between 293 and 150 K.

Figure 1
The asymmetric unit of the title compound at 150 K, with displacement ellipsoids drawn at the 50% probability level for non-H atoms. H atoms are shown as spheres of arbitrary radii.

4. Supramolecular features

In the crystal, the O1—H1⋯N3 hydrogen bond involving the carboxyl group of PABA and the pyridine one of POA forms an acid⋯pyridine heterosynthon (COOH⋯N_arom, Tables 1 and 2). The neighboring two-component units are linked by N1—H1B⋯N2ⁱⁱ hydrogen bonds, forming a zigzag C₂²(13) chain motif. Adjacent chains are linked to each other via N1—H1C⋯O4ⁱⁱⁱ hydrogen bonds [C₂²(7)' chain motif] to form a 2D structure [Fig. 2(a)]. The crystal packing is stabilized by stacking of the parallel 2D structures along the b-axis direction through π–π interactions between neighboring benzene and pyrazine rings [Cg1⋯Cg2 = Cg3⋯Cg4 = 3.7377 (13) and 3.8034 (13) for Ia and Ib, respectively; Cg1 and Cg2 are centroids of the POA N2–C9 pyrazine ring, Cg3 and Cg4 are centroids of the PABA C2–C7 benzene ring], forming a 3D structure supported via N1—H1A⋯O3ⁱ hydrogen bonds [C₂²(7)'' chain motif] [Fig. 2(b)].

Table 1
Hydrogen-bond geometry (Å, °) for Ia

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O3ⁱ	0.89 (4)	1.83 (4)	2.707 (3)	167 (3)
N1—H1B⋯N2ⁱⁱ	0.79 (4)	2.21 (4)	2.907 (3)	148 (4)
N1—H1C⋯O4ⁱⁱⁱ	0.87 (4)	1.88 (4)	2.732 (3)	167 (4)
O1—H1⋯N3	0.80 (5)	1.87 (6)	2.670 (3)	175 (5)
Symmetry codes: (i) $[x+1, -y+2, z+{\script{1\over 2}}]$ ; (ii) $[x+1, -y+1, z+{\script{1\over 2}}]$ ; (iii) $[x, -y+2, z+{\script{1\over 2}}]$ .

Table 2
Hydrogen-bond geometry (Å, °) for Ib

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯N3	0.82	1.87	2.677 (3)	167
N1—H1A⋯O3ⁱ	0.89	1.85	2.716 (3)	164
N1—H1B⋯N2ⁱⁱ	0.89	2.13	2.920 (3)	148
N1—H1C⋯O4ⁱⁱⁱ	0.89	1.87	2.732 (3)	163
Symmetry codes: (i) $[x+1, -y+2, z+{\script{1\over 2}}]$ ; (ii) $[x+1, -y+1, z+{\script{1\over 2}}]$ ; (iii) $[x, -y+2, z+{\script{1\over 2}}]$ .

Figure 2
(a) The formation of zigzag C₂²(13) chains through O1—H1⋯N3 and N1—H1B⋯N2ⁱⁱ interactions joined by an N1—H1C⋯O4ⁱⁱⁱ hydrogen bond [C₂²(7)' chain motif] to generate the two-dimensional structure. (b) Layered arrangements of the salt via N1—H1A⋯O3ⁱ interactions [C₂²(7)'' chain motif] and aromatic π–π stacking interactions (dotted black lines) to generate the three-dimensional structure. Symmetry codes are in Table 1

5. Thermal analysis

The thermal behavior of the title compound was investigated by DSC techniques. The DSC curve [PABA+POA] is shown in Fig. 3. For a comparison, the DSC curves of the starting compounds are also plotted. PABA and POA show single endothermic peaks at 188.5 and 224.8°C, respectively. [PABA+POA] exhibits a sharp endothermic peak at 166.1°C. The melting temperature of the salt is ca 20 and 60°C lower than that of the starting compounds, suggesting the formation of a new crystalline phase. A single endothermic peak for the salt indicates that the solid state is homogeneous, and also suggests that there is no solvent in the crystal.

Figure 3
DSC curves of PABA (black), POA (red) and [PABA+POA] (blue).

6. Database survey

A search of the Cambridge Structural Database (CSD version 5.39, May 2018 update; Groom et al., 2016 ) for organic multi-component crystals (salts/co-crystals, their polymorphs and solvates) gave 88 structures for PABA and only five structures for POA. Analysis of the PABA crystal structures showed that the two most typical hydrogen-bonded motifs for them are: the acid⋯pyridine (COOH⋯N_arom) heterosynthon as in the title compound and the acid⋯acid (COOH⋯COOH) homosynthon between PABA molecules or PABA and conformer molecules with carboxylic functional group.

7. Synthesis and crystallization

A commercial sample of PABA (Merck, 99%) was co-crystallized with POA (Acros organics, 99%) by either liquid-assisted grinding, or by slow evaporation from solution under ambient conditions. Single crystals of [PABA+POA] were grown at room temperature by slow evaporation of a water–ethanol (1:1 v/v) solution in a 1:1 stoichiometric ratio. The powder sample of the title compound for DSC analysis was obtained by liquid-assisted grinding of the physical mixture in the presence of ethanol using a planetary micro mill. The ground material was characterized using PXRD to verify the formation of a new phase by comparing the diffraction pattern with the powder pattern calculated based on the single crystal X-ray diffraction data obtained in this work (Fig. 4).

Figure 4
Comparison of the experimental PXRD patterns of [PABA+POA] prepared by liquid-assisted grinding (blue) of PABA (black) and POA (red) and calculated (green) using single-crystal X-ray diffraction data.

8. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3. The positions of all H atoms at 293 K were optimized geometrically and refined using a riding model, with the following assumptions and restraints: N—H = 0.89 Å, C—H = 0.93 Å and O—H = 0.82 Å with U_iso(H) = 1.5U_eq(O) for the hydroxyl groups, and 1.2U_eq(C, N) otherwise. The positions of the H atoms at 150 K were refined freely in an isotropic approximation.

Table 3
Experimental details

	150 K	293 K
Crystal data
Chemical formula	C₇H₈NO₂⁺·C₅H₃N₂O₂⁻	C₇H₈NO₂⁺·C₅H₃N₂O₂⁻
M_r	261.24	261.24
Crystal system, space group	Monoclinic, Pc	Monoclinic, Pc
a, b, c (Å)	5.95842 (16), 3.73769 (10), 25.5943 (6)	5.95233 (16), 3.80345 (11), 25.6879 (7)
β (°)	95.362 (2)	95.037 (2)
V (Å³)	567.51 (3)	579.31 (3)
Z	2	2
Radiation type	Mo Kα	Mo Kα
μ (mm⁻¹)	0.12	0.12
Crystal size (mm)	0.24 × 0.19 × 0.18	0.24 × 0.19 × 0.18

Data collection
Diffractometer	Rigaku Oxford Diffraxction Xcalibur Ruby Gemini ultra	Rigaku Oxford Diffraction Xcalibur Ruby Gemini ultra
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ )	Multi-scan (CrysAlis PRO; Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ )
T_min, T_max	0.933, 1.000	0.822, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	9340, 3426, 3244	8036, 2981, 2746
R_int	0.024	0.033
(sin θ/λ)_max (Å⁻¹)	0.727	0.694

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.131, 1.13	0.049, 0.145, 1.11
No. of reflections	3426	2981
No. of parameters	216	174
No. of restraints	2	2
H-atom treatment	All H-atom parameters refined	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.39, −0.28	0.29, −0.28
Computer programs: CrysAlis PRO (Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ ), SHELXT2014 (Sheldrick, 2015a ), SHELXL2017 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Supporting information

CCDC references: 1880871; 1880870

Crystal structure: contains datablocks Ia, Ib. DOI: https://doi.org/10.1107/S2056989018016663/rz5246sup1.cif

Structure factors: contains datablock Ia. DOI: https://doi.org/10.1107/S2056989018016663/rz5246Iasup4.hkl

Structure factors: contains datablock Ib. DOI: https://doi.org/10.1107/S2056989018016663/rz5246Ibsup5.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989018016663/rz5246Iasup4.cml

checkCIF report

Computing details top

For both structures, data collection: CrysAlis PRO (Rigaku OD, 2018); cell refinement: CrysAlis PRO (Rigaku OD, 2018); data reduction: CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2017 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

4-Carboxyanilinium pyrazine-2-carboxylate (Ia) top

Crystal data top

C₇H₈NO₂⁺·C₅H₃N₂O₂⁻	F(000) = 272
M_r = 261.24	D_x = 1.529 Mg m⁻³
Monoclinic, Pc	Mo Kα radiation, λ = 0.71073 Å
a = 5.95842 (16) Å	Cell parameters from 5674 reflections
b = 3.73769 (10) Å	θ = 3.2–30.9°
c = 25.5943 (6) Å	µ = 0.12 mm⁻¹
β = 95.362 (2)°	T = 150 K
V = 567.51 (3) Å³	Block, light colourless
Z = 2	0.24 × 0.19 × 0.18 mm

Data collection top

Rigaku Oxford Diffraction Xcalibur Ruby Gemini ultra diffractometer	3426 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance (Mo) X-ray Source	3244 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.024
Detector resolution: 10.3457 pixels mm^-1	θ_max = 31.1°, θ_min = 3.2°
ω scans	h = −8→8
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2018)	k = −5→5
T_min = 0.933, T_max = 1.000	l = −36→36
9340 measured reflections

Refinement top

Refinement on F²	2 restraints
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F² > 2σ(F²)] = 0.044	All H-atom parameters refined
wR(F²) = 0.131	w = 1/[σ²(F_o²) + (0.0925P)²] where P = (F_o² + 2F_c²)/3
S = 1.13	(Δ/σ)_max = 0.001
3426 reflections	Δρ_max = 0.39 e Å⁻³
216 parameters	Δρ_min = −0.28 e Å⁻³

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.

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

	x	y	z	U_iso*/U_eq
O3	0.3138 (3)	0.3939 (5)	0.25476 (7)	0.0243 (4)
O4	0.6224 (3)	0.5432 (6)	0.30735 (7)	0.0277 (4)
O1	0.4407 (3)	0.5831 (6)	0.53444 (8)	0.0294 (4)
O2	0.7570 (4)	0.7455 (6)	0.50022 (7)	0.0315 (5)
N2	0.1012 (3)	0.1876 (5)	0.33842 (7)	0.0188 (4)
N1	0.9340 (3)	1.2049 (5)	0.74469 (7)	0.0168 (3)
N3	0.2855 (3)	0.3515 (6)	0.43916 (8)	0.0216 (4)
C8	0.4243 (4)	0.4341 (6)	0.29860 (8)	0.0182 (4)
C5	0.8626 (3)	1.0835 (6)	0.69173 (8)	0.0158 (4)
C9	0.3040 (4)	0.3411 (6)	0.34657 (8)	0.0166 (4)
C6	0.6482 (4)	0.9450 (6)	0.68152 (8)	0.0183 (4)
C1	0.6445 (4)	0.7247 (6)	0.53737 (9)	0.0215 (4)
C7	0.5784 (3)	0.8259 (6)	0.63124 (8)	0.0186 (4)
C2	0.7220 (4)	0.8505 (6)	0.59139 (8)	0.0176 (4)
C3	0.9376 (4)	0.9931 (7)	0.60225 (9)	0.0200 (4)
C12	0.3970 (4)	0.4200 (6)	0.39723 (8)	0.0188 (4)
C4	1.0095 (4)	1.1100 (6)	0.65252 (9)	0.0187 (4)
C10	−0.0077 (4)	0.1148 (6)	0.38037 (9)	0.0208 (4)
C11	0.0822 (4)	0.1982 (6)	0.43081 (9)	0.0210 (4)
H7	0.437 (6)	0.717 (10)	0.6221 (13)	0.021 (8)*
H10	−0.150 (8)	−0.003 (11)	0.3727 (18)	0.037 (10)*
H4	1.156 (6)	1.214 (9)	0.6619 (14)	0.020 (8)*
H3	1.033 (6)	1.003 (9)	0.5770 (15)	0.021 (8)*
H12	0.550 (6)	0.517 (9)	0.4054 (14)	0.020 (8)*
H1A	1.046 (7)	1.362 (10)	0.7450 (15)	0.028 (9)*
H11	0.005 (6)	0.147 (10)	0.4628 (15)	0.027 (9)*
H1B	0.978 (7)	1.037 (11)	0.7611 (17)	0.034 (10)*
H6	0.553 (6)	0.919 (9)	0.7079 (14)	0.020 (7)*
H1C	0.823 (7)	1.291 (9)	0.7600 (15)	0.026 (8)*
H1	0.399 (8)	0.505 (14)	0.506 (2)	0.046 (12)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O3	0.0226 (8)	0.0359 (9)	0.0146 (7)	0.0076 (7)	0.0026 (6)	−0.0009 (7)
O4	0.0201 (8)	0.0422 (10)	0.0210 (8)	−0.0057 (7)	0.0034 (6)	0.0067 (7)
O1	0.0264 (9)	0.0470 (11)	0.0151 (8)	−0.0116 (8)	0.0028 (6)	−0.0063 (8)
O2	0.0337 (10)	0.0464 (11)	0.0157 (8)	−0.0122 (9)	0.0085 (7)	−0.0059 (7)
N2	0.0165 (8)	0.0229 (9)	0.0171 (8)	0.0001 (7)	0.0014 (6)	−0.0016 (7)
N1	0.0163 (8)	0.0204 (8)	0.0138 (8)	0.0004 (7)	0.0013 (6)	−0.0006 (6)
N3	0.0238 (10)	0.0272 (9)	0.0138 (8)	−0.0024 (7)	0.0021 (7)	−0.0009 (7)
C8	0.0174 (9)	0.0237 (10)	0.0140 (9)	0.0042 (8)	0.0042 (7)	0.0021 (7)
C5	0.0174 (9)	0.0183 (9)	0.0118 (8)	0.0014 (7)	0.0017 (7)	−0.0003 (7)
C9	0.0166 (9)	0.0196 (9)	0.0138 (9)	0.0021 (7)	0.0018 (7)	−0.0008 (7)
C6	0.0166 (9)	0.0243 (10)	0.0144 (9)	−0.0017 (7)	0.0036 (7)	0.0005 (7)
C1	0.0253 (11)	0.0242 (10)	0.0147 (9)	−0.0018 (8)	0.0005 (8)	−0.0011 (8)
C7	0.0172 (9)	0.0243 (10)	0.0142 (8)	−0.0033 (8)	0.0017 (7)	−0.0005 (7)
C2	0.0191 (9)	0.0216 (10)	0.0122 (8)	0.0001 (7)	0.0018 (7)	−0.0002 (7)
C3	0.0208 (10)	0.0271 (10)	0.0128 (9)	−0.0017 (8)	0.0057 (7)	−0.0019 (8)
C12	0.0161 (9)	0.0242 (10)	0.0161 (9)	−0.0029 (8)	0.0015 (7)	−0.0004 (8)
C4	0.0160 (9)	0.0243 (10)	0.0161 (9)	−0.0033 (7)	0.0034 (7)	−0.0015 (7)
C10	0.0183 (9)	0.0248 (10)	0.0193 (10)	−0.0035 (8)	0.0027 (7)	−0.0017 (8)
C11	0.0214 (10)	0.0255 (10)	0.0168 (10)	−0.0019 (8)	0.0050 (8)	0.0015 (8)

Geometric parameters (Å, º) top

O3—C8	1.256 (3)	C5—C4	1.395 (3)
O4—C8	1.249 (3)	C9—C12	1.393 (3)
O1—C1	1.320 (3)	C6—C7	1.388 (3)
O1—H1	0.80 (5)	C6—H6	0.93 (4)
O2—C1	1.216 (3)	C1—C2	1.492 (3)
N2—C9	1.336 (3)	C7—C2	1.394 (3)
N2—C10	1.334 (3)	C7—H7	0.95 (4)
N1—C5	1.455 (3)	C2—C3	1.394 (3)
N1—H1A	0.89 (4)	C3—C4	1.388 (3)
N1—H1B	0.79 (4)	C3—H3	0.90 (4)
N1—H1C	0.87 (4)	C12—H12	0.99 (4)
N3—C12	1.338 (3)	C4—H4	0.97 (4)
N3—C11	1.340 (3)	C10—C11	1.386 (3)
C8—C9	1.519 (3)	C10—H10	0.96 (5)
C5—C6	1.380 (3)	C11—H11	0.99 (4)

C1—O1—H1	114 (4)	O2—C1—C2	124.0 (2)
C10—N2—C9	117.57 (18)	C6—C7—C2	120.38 (19)
C5—N1—H1A	112 (2)	C6—C7—H7	123 (2)
C5—N1—H1B	108 (3)	C2—C7—H7	116 (2)
C5—N1—H1C	112 (2)	C7—C2—C1	119.9 (2)
H1A—N1—H1B	108 (4)	C7—C2—C3	119.75 (19)
H1A—N1—H1C	111 (3)	C3—C2—C1	120.30 (19)
H1B—N1—H1C	107 (4)	C2—C3—H3	120 (2)
C12—N3—C11	117.6 (2)	C4—C3—C2	120.2 (2)
O3—C8—C9	116.57 (19)	C4—C3—H3	120 (2)
O4—C8—O3	127.4 (2)	N3—C12—C9	121.5 (2)
O4—C8—C9	116.05 (19)	N3—C12—H12	115 (2)
C6—C5—N1	118.57 (18)	C9—C12—H12	124 (2)
C6—C5—C4	121.47 (19)	C5—C4—H4	118 (2)
C4—C5—N1	119.95 (19)	C3—C4—C5	119.0 (2)
N2—C9—C8	117.39 (18)	C3—C4—H4	123 (2)
N2—C9—C12	120.8 (2)	N2—C10—C11	122.0 (2)
C12—C9—C8	121.83 (19)	N2—C10—H10	115 (3)
C5—C6—C7	119.17 (19)	C11—C10—H10	123 (3)
C5—C6—H6	121 (2)	N3—C11—C10	120.7 (2)
C7—C6—H6	119 (2)	N3—C11—H11	116 (2)
O1—C1—C2	112.5 (2)	C10—C11—H11	124 (2)
O2—C1—O1	123.6 (2)

O3—C8—C9—N2	7.2 (3)	C5—C6—C7—C2	−0.9 (3)
O3—C8—C9—C12	−171.1 (2)	C9—N2—C10—C11	0.9 (3)
O4—C8—C9—N2	−172.9 (2)	C6—C5—C4—C3	−0.2 (3)
O4—C8—C9—C12	8.7 (3)	C6—C7—C2—C1	−179.4 (2)
O1—C1—C2—C7	−2.9 (3)	C6—C7—C2—C3	0.5 (4)
O1—C1—C2—C3	177.2 (2)	C1—C2—C3—C4	−180.0 (2)
O2—C1—C2—C7	178.0 (2)	C7—C2—C3—C4	0.1 (3)
O2—C1—C2—C3	−1.9 (4)	C2—C3—C4—C5	−0.2 (3)
N2—C9—C12—N3	−1.3 (3)	C12—N3—C11—C10	0.0 (3)
N2—C10—C11—N3	−1.1 (4)	C4—C5—C6—C7	0.7 (3)
N1—C5—C6—C7	−179.6 (2)	C10—N2—C9—C8	−178.14 (19)
N1—C5—C4—C3	−179.9 (2)	C10—N2—C9—C12	0.2 (3)
C8—C9—C12—N3	177.0 (2)	C11—N3—C12—C9	1.1 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O3ⁱ	0.89 (4)	1.83 (4)	2.707 (3)	167 (3)
N1—H1B···N2ⁱⁱ	0.79 (4)	2.21 (4)	2.907 (3)	148 (4)
N1—H1C···O4ⁱⁱⁱ	0.87 (4)	1.88 (4)	2.732 (3)	167 (4)
O1—H1···N3	0.80 (5)	1.87 (6)	2.670 (3)	175 (5)

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

4-Carboxyanilinium pyrazine-2-carboxylate (Ib) top

Crystal data top

C₇H₈NO₂⁺·C₅H₃N₂O₂⁻	F(000) = 272
M_r = 261.24	D_x = 1.498 Mg m⁻³
Monoclinic, Pc	Mo Kα radiation, λ = 0.71073 Å
a = 5.95233 (16) Å	Cell parameters from 4235 reflections
b = 3.80345 (11) Å	θ = 3.2–29.2°
c = 25.6879 (7) Å	µ = 0.12 mm⁻¹
β = 95.037 (2)°	T = 293 K
V = 579.31 (3) Å³	Block, light colourless
Z = 2	0.24 × 0.19 × 0.18 mm

Data collection top

Rigaku Oxford Diffraction Xcalibur Ruby Gemini ultra diffractometer	2981 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance (Mo) X-ray Source	2746 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.033
Detector resolution: 10.3457 pixels mm^-1	θ_max = 29.6°, θ_min = 1.6°
ω scans	h = −7→8
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2018)	k = −5→5
T_min = 0.822, T_max = 1.000	l = −35→33
8036 measured reflections

Refinement top

Refinement on F²	2 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.049	H-atom parameters constrained
wR(F²) = 0.145	w = 1/[σ²(F_o²) + (0.0973P)²] where P = (F_o² + 2F_c²)/3
S = 1.11	(Δ/σ)_max = 0.001
2981 reflections	Δρ_max = 0.29 e Å⁻³
174 parameters	Δρ_min = −0.28 e Å⁻³

Special details top

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

	x	y	z	U_iso*/U_eq
O3	0.3114 (4)	0.4159 (6)	0.25493 (8)	0.0428 (6)
O4	0.6195 (4)	0.5580 (8)	0.30677 (9)	0.0505 (6)
O1	0.4431 (4)	0.5870 (8)	0.53404 (9)	0.0547 (7)
H1	0.415003	0.501947	0.504859	0.082*
O2	0.7585 (5)	0.7517 (8)	0.50073 (10)	0.0588 (7)
N2	0.1020 (4)	0.2017 (6)	0.33869 (9)	0.0328 (5)
N1	0.9323 (4)	1.1834 (6)	0.74503 (8)	0.0282 (5)
H1A	1.042185	1.341470	0.744245	0.034*
H1B	0.982136	0.999337	0.764065	0.034*
H1C	0.815616	1.279554	0.759180	0.034*
N3	0.2877 (4)	0.3635 (7)	0.43878 (10)	0.0383 (6)
C8	0.4229 (4)	0.4514 (8)	0.29826 (10)	0.0314 (6)
C5	0.8611 (4)	1.0681 (7)	0.69163 (9)	0.0262 (5)
C9	0.3039 (4)	0.3555 (7)	0.34649 (10)	0.0273 (5)
C6	0.6491 (4)	0.9282 (8)	0.68141 (10)	0.0312 (6)
H6	0.552972	0.909327	0.707932	0.037*
C1	0.6453 (5)	0.7272 (9)	0.53745 (10)	0.0365 (6)
C7	0.5796 (4)	0.8159 (8)	0.63147 (11)	0.0319 (6)
H7	0.436812	0.718844	0.624423	0.038*
C2	0.7226 (4)	0.8473 (8)	0.59157 (10)	0.0301 (5)
C3	0.9362 (5)	0.9920 (8)	0.60255 (11)	0.0356 (6)
H3	1.032069	1.014408	0.576030	0.043*
C12	0.3970 (5)	0.4333 (8)	0.39670 (11)	0.0335 (6)
H12	0.538987	0.536543	0.401120	0.040*
C4	1.0070 (4)	1.1027 (8)	0.65257 (11)	0.0330 (6)
H4	1.149948	1.198795	0.659963	0.040*
C10	−0.0051 (5)	0.1270 (8)	0.38076 (13)	0.0376 (6)
H10	−0.144761	0.016045	0.376452	0.045*
C11	0.0861 (5)	0.2102 (9)	0.43080 (12)	0.0390 (7)
H11	0.005353	0.158345	0.459237	0.047*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O3	0.0390 (12)	0.0655 (15)	0.0241 (10)	0.0140 (10)	0.0039 (8)	−0.0003 (9)
O4	0.0356 (12)	0.0830 (18)	0.0336 (12)	−0.0103 (11)	0.0068 (9)	0.0122 (11)
O1	0.0491 (13)	0.0908 (18)	0.0241 (10)	−0.0236 (13)	0.0034 (9)	−0.0131 (11)
O2	0.0618 (16)	0.0920 (19)	0.0244 (10)	−0.0238 (15)	0.0149 (10)	−0.0122 (12)
N2	0.0273 (10)	0.0424 (12)	0.0285 (11)	−0.0009 (9)	0.0011 (8)	−0.0052 (9)
N1	0.0288 (10)	0.0343 (11)	0.0211 (10)	0.0011 (8)	0.0007 (7)	−0.0007 (8)
N3	0.0429 (14)	0.0498 (14)	0.0221 (11)	−0.0049 (10)	0.0027 (9)	−0.0028 (10)
C8	0.0295 (12)	0.0427 (14)	0.0226 (12)	0.0078 (10)	0.0059 (9)	0.0036 (10)
C5	0.0292 (12)	0.0305 (13)	0.0190 (11)	0.0026 (9)	0.0022 (9)	0.0009 (9)
C9	0.0269 (12)	0.0331 (12)	0.0218 (11)	0.0028 (9)	0.0022 (9)	−0.0011 (9)
C6	0.0288 (12)	0.0441 (15)	0.0215 (12)	−0.0042 (10)	0.0067 (9)	0.0011 (10)
C1	0.0420 (15)	0.0458 (15)	0.0217 (12)	−0.0049 (12)	0.0033 (11)	−0.0035 (11)
C7	0.0278 (12)	0.0429 (14)	0.0253 (12)	−0.0056 (11)	0.0045 (10)	−0.0015 (10)
C2	0.0339 (13)	0.0363 (14)	0.0202 (11)	0.0010 (10)	0.0028 (9)	−0.0004 (9)
C3	0.0349 (14)	0.0514 (16)	0.0218 (12)	−0.0053 (11)	0.0092 (10)	−0.0024 (11)
C12	0.0287 (12)	0.0443 (16)	0.0274 (13)	−0.0059 (11)	0.0017 (10)	−0.0027 (11)
C4	0.0265 (12)	0.0441 (15)	0.0286 (13)	−0.0065 (10)	0.0042 (9)	−0.0035 (11)
C10	0.0303 (13)	0.0466 (16)	0.0364 (15)	−0.0082 (12)	0.0061 (10)	−0.0033 (12)
C11	0.0413 (16)	0.0484 (16)	0.0285 (14)	−0.0042 (12)	0.0109 (11)	−0.0001 (11)

Geometric parameters (Å, º) top

O3—C8	1.252 (3)	C5—C4	1.390 (4)
O4—C8	1.240 (4)	C9—C12	1.390 (4)
O1—H1	0.8200	C6—H6	0.9300
O1—C1	1.313 (4)	C6—C7	1.380 (4)
O2—C1	1.210 (4)	C1—C2	1.497 (4)
N2—C9	1.336 (4)	C7—H7	0.9300
N2—C10	1.332 (4)	C7—C2	1.394 (4)
N1—H1A	0.8900	C2—C3	1.391 (4)
N1—H1B	0.8900	C3—H3	0.9300
N1—H1C	0.8900	C3—C4	1.382 (4)
N1—C5	1.467 (3)	C12—H12	0.9300
N3—C12	1.336 (4)	C4—H4	0.9300
N3—C11	1.334 (4)	C10—H10	0.9300
C8—C9	1.524 (4)	C10—C11	1.388 (4)
C5—C6	1.374 (3)	C11—H11	0.9300

C1—O1—H1	109.5	O2—C1—C2	123.6 (3)
C10—N2—C9	117.4 (2)	C6—C7—H7	119.8
H1A—N1—H1B	109.5	C6—C7—C2	120.3 (2)
H1A—N1—H1C	109.5	C2—C7—H7	119.8
H1B—N1—H1C	109.5	C7—C2—C1	119.9 (2)
C5—N1—H1A	109.5	C3—C2—C1	120.6 (2)
C5—N1—H1B	109.5	C3—C2—C7	119.4 (2)
C5—N1—H1C	109.5	C2—C3—H3	119.8
C11—N3—C12	117.3 (3)	C4—C3—C2	120.5 (2)
O3—C8—C9	116.7 (2)	C4—C3—H3	119.8
O4—C8—O3	127.6 (3)	N3—C12—C9	121.7 (3)
O4—C8—C9	115.7 (2)	N3—C12—H12	119.1
C6—C5—N1	118.7 (2)	C9—C12—H12	119.1
C6—C5—C4	121.4 (2)	C5—C4—H4	120.5
C4—C5—N1	120.0 (2)	C3—C4—C5	118.9 (2)
N2—C9—C8	117.3 (2)	C3—C4—H4	120.5
N2—C9—C12	120.8 (2)	N2—C10—H10	119.1
C12—C9—C8	121.8 (2)	N2—C10—C11	121.8 (3)
C5—C6—H6	120.2	C11—C10—H10	119.1
C5—C6—C7	119.5 (2)	N3—C11—C10	121.0 (3)
C7—C6—H6	120.2	N3—C11—H11	119.5
O1—C1—C2	113.0 (2)	C10—C11—H11	119.5
O2—C1—O1	123.3 (3)

O3—C8—C9—N2	8.0 (4)	C5—C6—C7—C2	−0.7 (4)
O3—C8—C9—C12	−170.1 (3)	C9—N2—C10—C11	1.1 (5)
O4—C8—C9—N2	−172.4 (3)	C6—C5—C4—C3	−0.3 (4)
O4—C8—C9—C12	9.5 (4)	C6—C7—C2—C1	−179.6 (3)
O1—C1—C2—C7	−2.3 (4)	C6—C7—C2—C3	0.2 (4)
O1—C1—C2—C3	177.9 (3)	C1—C2—C3—C4	180.0 (3)
O2—C1—C2—C7	178.7 (3)	C7—C2—C3—C4	0.2 (4)
O2—C1—C2—C3	−1.0 (5)	C2—C3—C4—C5	−0.2 (4)
N2—C9—C12—N3	−1.1 (5)	C12—N3—C11—C10	0.1 (5)
N2—C10—C11—N3	−1.2 (5)	C4—C5—C6—C7	0.7 (4)
N1—C5—C6—C7	−179.6 (3)	C10—N2—C9—C8	−178.1 (2)
N1—C5—C4—C3	180.0 (3)	C10—N2—C9—C12	0.0 (4)
C8—C9—C12—N3	176.9 (3)	C11—N3—C12—C9	1.1 (5)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N3	0.82	1.87	2.677 (3)	167
N1—H1A···O3ⁱ	0.89	1.85	2.716 (3)	164
N1—H1B···N2ⁱⁱ	0.89	2.13	2.920 (3)	148
N1—H1C···O4ⁱⁱⁱ	0.89	1.87	2.732 (3)	163

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

Acknowledgements

KD thanks Dr Alex Manin and Dr Denis Rychkov for their interest in this work and helpful discussions.

Funding information

Funding for this research was provided by: RFBR (grant No. 17-33-50073 mol_nr).

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