The 1:2 co-crystal formed between N,N'-bis(pyridin-4-ylmeth-yl)ethanedi-amide and benzoic acid: crystal structure, Hirshfeld surface analysis and computational study.

The crystal and mol-ecular structures of the title 1:2 co-crystal, C14H14N4O2·2C7H6O2, are described. The oxalamide mol-ecule has a (+)-anti-periplanar conformation with the 4-pyridyl residues lying to either side of the central, almost planar C2N2O2 chromophore (r.m.s. deviation = 0.0555 Å). The benzoic acid mol-ecules have equivalent, close to planar conformations [C6/CO2 dihedral angle = 6.33 (14) and 3.43 (10)°]. The formation of hy-droxy-O-H⋯N(pyrid-yl) hydrogen bonds between the benzoic acid mol-ecules and the pyridyl residues of the di-amide leads to a three-mol-ecule aggregate. Centrosymmetrically related aggregates assemble into a six-mol-ecule aggregate via amide-N-H⋯O(amide) hydrogen bonds through a 10-membered {⋯HNC2O}2 synthon. These are linked into a supra-molecular tape via amide-N-H⋯O(carbon-yl) hydrogen bonds and 22-membered {⋯HOCO⋯NC4NH}2 synthons. The contacts between tapes to consolidate the three-dimensional architecture are of the type methyl-ene-C-H⋯O(amide) and pyridyl-C-H⋯O(carbon-yl). These inter-actions are largely electrostatic in nature. Additional non-covalent contacts are identified from an analysis of the calculated Hirshfeld surfaces. © Tan and Tiekink 2020.

Chemical context

Co-crystal technology continues to attract significant attention in a variety of endeavours with quite likely the most important of these relating to the development of more efficacious drugs by non-covalent derivatization of active pharmaceutical ingredients (Duggirala et al., 2016 ▸; Bolla & Nangia, 2016 ▸; Gunawardana & Aakeröy, 2018 ▸). In order to predictably form co-crystals, reliable and robust synthons are needed. One such synthon is that formed by a carb­oxy­lic acid and a pyridyl residue via an O—H⋯N hydrogen bond (Shattock et al., 2008 ▸). Very high propensities were noted, i.e. in the mid- to high-90%, in instances where there were no competing supra­molecular synthons involving hydrogen bonding (Shattock et al., 2008 ▸). This compares to 33% adoption of the more familiar eight-membered {⋯OCOH}2 homosynthon by carb­oxy­lic acids (Allen et al., 1999 ▸). This high propensity for O—H⋯N hydrogen-bond formation pertains to bis­(pyridin-n-ylmeth­yl)ethanedi­amide mol­ecules, i.e. species with the general formula n-NC5H4CH2N(H)C(=O)C(=O)CH2C5H4N-n, for n = 2, 3 and 4, hereafter abbreviated as H2. Indeed, in early studies on crystal engineering, the combination of bifunctional H2 with di­carb­oxy­lic acids such as bis­(carb­oxy­meth­yl)oxalamide (Nguyen et al., 1998 ▸) and bis­(carb­oxy­meth­yl)urea (Nguyen et al., 2001 ▸) enabled the systematic construction of two-dimensional arrays. As part of a long-term inter­est in the structural chemistry of H2 (Tiekink, 2017 ▸) and of systematic investigations of acid–pyridine co-crystals (Arman, Kaulgud et al., 2012 ▸; Arman & Tiekink, 2013 ▸; Arman et al., 2013 ▸, 2014 ▸), the title 1:2 co-crystal formed between 4 LH2 and benzoic acid was characterized by X-ray crystallography and the supra­molecular association further probed by Hirshfeld surface analysis and computational chemistry.

Structural commentary

The mol­ecular structures of the three constituents comprising the crystallographic asymmetric unit of (I) are shown in Fig. 1 ▸. The 4 LH2 mol­ecule lacks crystallographic symmetry but adopts a (+)-antiperiplanar conformation where the 4-pyridyl residues lie to either side of the central C2N2O2 chromophore. The six atoms comprising the central residue are close to co-planar with their r.m.s. deviation equal to 0.0555 Å, with the maximum deviations to either side of the plane being 0.0719 (5) and 0.0642 (5) Å for the N2 and O2 atoms, respectively; the C6 and C9 atoms lie 0.1908 (14) and 0.0621 (14) Å out of and to one side of the plane (towards the N2 atom), respectively. The N1- and N4-pyridyl rings form dihedral angles of 86.00 (3) and 83.34 (2)°, respectively, with the plane through the C2N2O2 atoms, so are close to perpendicular to the central plane. The dihedral angle between the pyridyl rings is 33.60 (5)°, indicating a splayed disposition as each pyridyl ring is folded away from the rest of the mol­ecule. The carbonyl groups are anti and the mol­ecule features intra­molecular amide-N—H⋯O(carbon­yl) hydrogen bonds that complete S(5) loops, Table 1 ▸.

Figure 1

The mol­ecular structures of the constituents of (I) showing the atom-labelling scheme and displacement ellipsoids at the 70% probability level.

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2N⋯O2	0.88 (1)	2.36 (1)	2.7192 (12)	105 (1)
N3—H3N⋯O1	0.88 (1)	2.36 (1)	2.7154 (12)	104 (1)
O4—H4O⋯N1i	0.86 (2)	1.78 (2)	2.6366 (12)	177 (2)
O6—H6O⋯N4ii	0.86 (2)	1.72 (2)	2.5731 (13)	169 (2)
N2—H2N⋯O2iii	0.88 (1)	2.05 (1)	2.8618 (12)	152 (1)
N3—H3N⋯O5iv	0.88 (1)	2.12 (1)	2.8516 (12)	140 (1)
C1—H1⋯O3v	0.95	2.58	3.2009 (14)	124
C2—H2⋯O5	0.95	2.47	3.3602 (14)	155
C6—H6B⋯O1iv	0.99	2.41	3.3826 (14)	166
C12—H12⋯O3vi	0.95	2.36	3.3025 (15)	171

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

There are two independent benzoic acid mol­ecules in (I). Each is approximately planar with the dihedral angle between the benzene ring and CO2 group being 6.33 (14) and 3.43 (10)° for the O3- and O5-benzoic acid mol­ecules, respectively. As expected, the C15—O3(carbon­yl) bond length of 1.2162 (13) Å is significantly shorter than the C15—O4(hy­droxy) bond of 1.3197 (13) Å; the bonds of the O5-benzoic acid follow the same trend with C22—O5 of 1.2237 (13) Å compared with C22—O6 of 1.3084 (13) Å.

Supra­molecular features

As anti­cipated from the chemical composition, significant conventional hydrogen bonding is noted in the crystal of (I) over and above the intra­molecular amide-N—H⋯O(carbon­yl) hydrogen bonds already noted. The geometric parameters characterizing the specified inter­molecular contacts are listed in Table 1 ▸. The most prominent feature in the crystal is the formation of the expected three-mol­ecule aggregate sustained by hy­droxy-O—H⋯N(pyrid­yl) hydrogen bonding. This is connected into a six-mol­ecule aggregate via amide-N—H⋯O(amide) hydrogen bonding, which leads to a centrosymmetric ten-membered {⋯HNC2O}2 synthon. The second amide forms an amide-N—H⋯O(carbon­yl) bond with the result of that adjacent six-mol­ecule aggregates are connected into a supra­molecular tape via 22-membered {⋯HOCO⋯NC4NH}2 synthons, Fig. 2 ▸(a). The other notable contact within the tape is a pyridyl-C—H⋯O(carbon­yl) inter­action, which cooperates with a hy­droxy-O—H⋯N(pyrid­yl) hydrogen bond to form a seven-membered {⋯OCOH⋯NCH} pseudo-heterosynthon; no analogous inter­action is noted for the O5-benzoic acid. The supra­molecular tapes are aligned along the c-axis direction and have a linear topology.

Figure 2

Mol­ecular packing in the crystal of (I): (a) supra­molecular tape sustained by hy­droxy-O—H⋯N(pyrid­yl) (orange dashed lines) and amide-N—H⋯O(amide, carbon­yl) hydrogen bonds and (b) a view of the unit-cell contents in projection down the c axis with C—H⋯O inter­actions shown as pink dashed lines.

The connections between chains leading to a three-dimensional architecture are of the type C—H⋯O, i.e. methyl­ene-C—H⋯O(amide) and pyridyl-C—H⋯O(carbon­yl), the latter involving both pyridyl rings and each carbonyl-O atom, Table 1 ▸ and Fig. 2 ▸(b).

Hirshfeld surface analysis

The program Crystal Explorer 17 (Turner et al., 2017 ▸) was used for the calculation of the Hirshfeld surfaces and two-dimensional fingerprint plots based on the procedures described previously (Tan, Jotani et al., 2019 ▸). The three-mol­ecule aggregate whereby the two benzoic acid (BA) mol­ecules are connected to 4 LH2 via the hy­droxy-O—H⋯N(pyrid­yl) hydrogen bonds was used as the input for calculations. A list of the short inter­atomic contacts discussed below is given in Table 2 ▸. Through this analysis, several red spots were identified on the d norm surfaces, Fig. 3 ▸, of the individual 4 LH2 and BA mol­ecules, hereafter BA-I for the O3-containing mol­ecule and BA-II for the O5-mol­ecule, which indicate the presence of close contacts with distances shorter than the sum of the respective van der Waals radii (Spackman & Jayatilaka, 2009 ▸). Among all contacts, the terminal benzoic acid-O4—H4O⋯N1(pyrid­yl), benzoic acid-O6—H6O⋯N4(pyrid­yl), amide-N2—H2N⋯O2(amide) and amide-N3—H3N⋯O5(carbon­yl) hydrogen-bonding inter­actions exhibit the most intense red spots on the d norm surfaces, suggestive of strong inter­actions.

Table 2

A summary of short inter­atomic contacts (Å) in (I)

Contact	Distance	Symmetry operation
O2⋯H2Nb	1.94	1 − x, 1 − y, 1 − z
C1⋯H13	2.79	−1 + x, y, −1 + z
N1⋯H4Ob	1.65	−1 + x, −1 + y, −1 + z
O3⋯H1	2.50	1 + x, 1 + y, 1 + z
N4⋯H6Ob	1.60	1 + x, y, 1 + z
O5⋯H3Nb	2.02	−x, 1 − y, 1 − z
O1⋯H28	2.57	−x, 1 − y, 1 − z
O1⋯H6B	2.32	−x, 1 − y, 1 − z
C8⋯H20	2.61	x, y, z
C12⋯C21	3.39	x, y, z
C8⋯C26	3.35	x, −1 + y, z
O5⋯H2	2.35	x, y, z
O3⋯H9B	2.56	x, 1 + y, z
C17⋯H9B	2.69	x, 1 + y, z
O3⋯H12	2.23	1 − x, 2 − y, 2 − z
C21⋯H25	2.62	1 − x, 2 − y, 1 − z
C18⋯H27	2.67	x, y, z
O4⋯H24	2.58	1 − x, 2 − y, 1 − z

Notes: (a) The inter­atomic distances are calculated in Crystal Explorer 17 (Turner et al., 2017 ▸) whereby the X—H bond lengths are adjusted to their neutron values; (b) these inter­actions correspond to conventional hydrogen bonds.

Figure 3

The d norm map showing N—H⋯O (yellow dashed line), C—H⋯O (green), C—H⋯C (red) and C⋯C (blue) close contacts as indicated by the corresponding red spots with varying intensities within the range of −0.1004 to 1.1803 arbitrary units for (a) 4 LH2, (b) 4 LH2 viewed from a different perspective, (c) BA-II and (d) BA-II (left) and BA-I (right).

Other, relatively less intense red spots in Fig. 3 ▸(a) and (b) [in the order of moderate intensity (m) to weak intensity (w)] were identified for C6—H6B⋯O1 (m), C12—H12⋯O3 (m), C2—H2⋯O5 (m) and C1—H1⋯O3 (w), Table 1 ▸, and C20—H20⋯C8 (m), C28—H28⋯O1 (w), C9—H9B⋯C17 (w), C9—H9B⋯O3 (w), C13—H13⋯C1 (w), C12⋯C21 (w) and C8⋯C26 (w), Table 2 ▸. With the exception of the moderately intense red spot observed for C20—H20⋯C8 as well as those with relatively weak intensity, the other contacts are consistent with the inter­actions detected through an analysis with PLATON (Spek, 2020 ▸). As for the two benzoic acid mol­ecules in the asymmetric unit, the contacts between them are established through C25—H25⋯C21, C27—H27⋯C18 as well as C24—H24⋯O4 inter­actions with diminutive intensity on the d norm maps shown in Fig. 3 ▸(c) and (d).

The electrostatic potential mapping was performed on the individual 4 LH2, BA-I and BA-II mol­ecules through DFT-B3LYP/6-31G(d,p) to further study the nature of the close contacts, Fig. 4 ▸. The results are consistent with the above in that the O-–H⋯N and N—H⋯O hydrogen-bonding contacts that exhibited the most intense red spots on the d norm map are highly electrostatic in nature, as evidenced from the intense electronegative (red) and electropositive (blue) regions on the Hirshfeld surfaces of the individual mol­ecules. Other regions are relatively pale, indicating the complementary role of the remaining contacts in sustaining the mol­ecular network in the crystal.

Figure 4

The electrostatic potential mapped onto the Hirshfeld surface within the isosurface range of −0.0562 to 0.0861 atomic units for (a) 4 LH2, (b) 4 LH2, (c) BA-II and (d) BA-II (left) and BA-I (right).

The two-dimensional fingerprint plots were generated in order to qu­antify the close contacts for compound (I) overall, i.e. the three-mol­ecule aggregate specified above, as well as its individual 4 LH2, BA-I and BA-II components, Fig. 5 ▸. The overall fingerprint plot of (I) exhibits a shield-like profile with a pair of symmetric spikes and contrasts those for the indiv­idual components with asymmetric spikes, indicating the inter­dependency between 4 LH2 and benzoic acid in constructing the mol­ecular packing of the system, in contrast to the previously reported benzene monosolvate of 4 LH2 (Tan, Halcovitch et al., 2019 ▸).

Figure 5

(a) The overall two-dimensional fingerprint plots for 4 LH2, BA-I, BA-II and the three-mol­ecule aggregate in (I), and those delineated into (b) H⋯H, (c) H⋯O/O⋯H, (d) H⋯C/C⋯H and (e) H⋯N/N⋯H contacts, with the percentage contributions specified in each plot.

The major surface contacts for (I) can be split four ways: into H⋯H (38.0%), C⋯H/H⋯C (27.5%), O⋯H/H⋯O (25.2%) and N⋯H/H⋯N (3.5%) contacts. The distributions for H⋯H and N⋯H/H⋯N are evenly distributed between the inter­nal (i.e. the donor or acceptor atoms inter­nal to the surface) and external (i.e. the donor or acceptor atoms external to the surface) contacts. In contrast, for H⋯C/C⋯H and H⋯O/O⋯H, the distributions are slightly inclined towards (inter­nal)-C⋯H-(external) (15.8%) and (inter­nal)-O⋯H-(external) (13.4%) as compared to the corresponding counterparts at 11.7 and 11.8%, respectively. A detailed analysis of the d i + d e distances shows that the closest H⋯O/O⋯H and H⋯C/C⋯H contacts of ∼1.95 Å and ∼2.62 Å, respectively, occur at distances shorter than the sum of the respective van der Waals radii of 2.61 and 2.79 Å, while the H⋯H (∼2.20 Å) and N⋯H/ H⋯N (2.80 Å) contacts are longer than the sum of van der Waals radii of 2.18 and 2.64 Å, respectively.

The 4 LH2 mol­ecule also displays a shield-like profile with asymmetric spikes which upon further decomposition could be delineated into H⋯H (38.0%), H⋯O/O⋯H (25.6%), H⋯C/C⋯H (21.4%) and H⋯N/N⋯H (9.9%) contacts. The H⋯O/O⋯H contact exhibits a forceps-like profile with the distribution inclined towards inter­nal-H⋯O-external (15.2%) as compared to inter­nal-O⋯H-external (10.4%), and both with tips at d i + d e ∼1.94 Å which is indicative of significant hydrogen bonding. Similarly, the asymmetric, needle-like profile for the H⋯N/N⋯H contact is inclined towards the inter­nal-N⋯H-external (9.0%) with the tip at d i + d e = ∼1.6 Å, while the remaining 0.9% is attributed to the inter­nal-H⋯N-external contact with d i + d e of ∼2.94 Å (> sum of van der Waals radii). The H⋯C/C⋯H contacts are evenly distributed on both sides of the contacts with the d i + d e of ∼2.64 Å which is slightly shorter than the sum of van der Waals radii. On the other hand, the H⋯H contacts have little direct influence in sustaining the mol­ecular packing as shown from the shortest d i + d e value of ∼2.2 Å, which is longer than the sum of the van der Waals radii despite the prominent contributions these make to the overall surface

As for the pair of BA mol­ecules, both BA-I and BA-II possess similar, claw-like profiles which differ in the diffuse region, with the former being the characteristic of H⋯H contacts while the latter is due to H⋯C/C⋯H inter­actions. Qu­anti­tatively, differences mainly relate to the percentage contribution by H⋯H contacts, i.e. 31.9% for BA-I cf. 38.7% for BA-II. The discrepancy in the distribution for BA-I is compensated by the increase in O⋯C/C⋯O and C⋯C contacts with the distribution being 4.8 and 2.9%, respectively. The distribution for H⋯C/C⋯H (29.0 vs 29.1%), H⋯O/O⋯H (23.8 vs 24.2%) and H⋯N (6.7 vs 5.7%) contacts is approximately the same in both BA-I and BA-II, except that the H⋯C/C⋯H distribution for BA-II is significantly more inclined towards inter­nal-C⋯H-external (20.5%) than the inter­nal-H⋯C-external (8.6%) in contrast to the relatively balanced distribution for BA-I 15.5% for inter­nal-C⋯H-external vs 13.5% for inter­nal-H⋯C-external. In BA-I, the d i + d e values for H⋯O/O⋯H, H⋯C/C⋯H and H⋯N/N⋯H at the tips are ∼2.26–2.70, 2.62 and 1.64 Å, respectively, while the equivalent values for the analogous contacts for BA-II have tips at 2.02–2.56, 2.62–2.86 and 1.58 Å, respectively. Among these contact distances, the O⋯H, H⋯C/C⋯H and H⋯N for BA-I as well as H⋯O/O⋯H, H⋯C and H⋯N for BA-II are shorter than the sum of van der Waals radii. As expected, the minimum d i + d e value for the H⋯H contacts is longer than the sum of van der Waals radii, even if it is the most dominant contact for each mol­ecule. The aforementioned data for BA-I and BA-II clearly distinguishes the independent mol­ecules.

Computational chemistry

To assess the strength of the specified inter­actions in the Hirshfeld surface analysis, the mol­ecules in (I) were subjected to energy calculations through CrystalExplorer17 (Turner et al., 2017 ▸); the results are collated in Table 3 ▸. Among all close contacts present in (I), the pairwise inter­actions of the amide-N2—H2N⋯O2(amide) hydrogen bonds complemented by a pair of pyridyl-C13—H13⋯C1(pyrid­yl) inter­actions between two oxamide mol­ecules led to the greatest inter­action energy (E tot) of −75.2 kJ mol−1. This value is comparable to E tot of −71.7 kJ mol−1 calculated for the classical eight-membered {⋯HOCO}2 inter­action (Tan & Tiekink, 2019a ▸). The second strongest inter­action arises from the hy­droxy-O4—H4O⋯N1(pyrid­yl) and pyridyl-C1—H1⋯O3(carbon­yl) contacts, which combine to generate a seven-membered heterosynthon with E tot of −50.1 kJ mol−1. A diminution in E tot is observed for the other pyridyl terminus, which only comprises a carb­oxy­lic-O6—H6O⋯N4(pyrid­yl) hydrogen bond without a supporting pyridyl-C—H⋯O(carbon­yl) inter­action, showing an energy of −43.9 kJ mol−1 and ranked third strongest among all inter­actions in (I).

Table 3

A summary of inter­action energies (kJ mol−1) calculated for (I)

Contact	E ele	E pol	E dis	E rep	E tot	Symmetry operation
N2—H2N⋯O2/
C13—H13⋯C1	−60.9	−14.6	−58.5	82.5	−75.2	1 − x, 1 − y, 1 − z
O4—H4O⋯N1/
C1—H1⋯O3	−90.7	−21.3	−13.0	118.0	−50.1	−1 + x, −1 + y, −1 + z
O6—H6O⋯N4	−95.2	−22.2	−11.3	134.4	−43.9	1 + x, y, 1 + z
N3—H3N⋯O5/
C28—H28⋯O1	−32.8	−8.6	−16.1	30.3	−36.3	−x, 1 − y, 1 − z
C6—H6B⋯O1	−11.4	−5.1	−29.5	26.4	−25.1	−x, 1 − y, 1 − z
C20—H20⋯C8/
C12⋯C21	−5.8	−1.5	−32.7	23.8	−21.0	x, y, z
C8⋯C26	−3.7	−1.0	−31.9	21.1	−19.4	x, −1 + y, z
C2—H2⋯O5	−9.4	−1.9	−14.0	12.9	−15.6	x, y, z
C9—H9B⋯O3/
C9—H9B⋯C17	−6.0	−2.2	−17.3	13.5	−14.7	x, 1 + y, z
C12—H12⋯O3	−9.5	−2.4	−4.9	12.6	−8.3	1 − x, 2 − y, 2 − z

The next highest inter­action energy with E tot of −36.3 kJ mol−1 involves contributions from the amide-N3—H3N⋯O5(carb­oxy­lic acid) and phenyl-C28—H28⋯O1(amide) contacts. Other inter­actions include the methyl­ene-C6—H6B⋯O1(amide) contacts (–25.1 kJ mol−1), the combination of benzoic acid-C20—H20⋯C8(amide) and benzoic acid-C12⋯C21(pyrid­yl) (–21.0 kJ mol−1), amide-C8⋯C26(benzoic acid) (–19.4 kJ mol−1), pyridyl-C2—H2⋯O5(carb­oxy­lic acid) (–15.6 kJ mol−1), a combination of (pyridine meth­yl)-C9—H9B⋯O3(carb­oxy­lic acid) and methyl­ene-C9—H9B⋯C17(benzoic acid) (−14.7 kJ mol−1), as well as pyridyl-C12—H12⋯O3(carb­oxy­lic acid) (–8.3 kJ mol−1). Some inconsistencies are observed between the calculated E tot and Hirshfeld surface analysis, particularly for C2—H2⋯O5 and C12—H12⋯O3. These inter­actions can be considered weak even though they possess a relatively short contact distance compared to the sum of van der Waals radii, as indicated from the moderately intense red spots on the Hirshfeld surface. The contradiction could arise as a result of the relatively high repulsion terms, which weaken the inter­action energy.

Overall, the crystal of (I) is mainly sustained by electrostatic forces owing to the strong ten-membered {⋯HNC2O}2 synthon as well as the terminal inter­actions between 4 LN2 and BA mol­ecules, through hy­droxy-O—H4⋯N(pyrid­yl) hydrogen bonds, lead to a zigzag electrostatic energy framework, Fig. 6 ▸(a). The packing system is further stabilized by the dispersion forces contributed by the ten-membered {⋯HNC2O}2 synthon complemented by other peripheral inter­actions such the pairwise C20—H20⋯C8/C12⋯C21, C8⋯C26 and C6—H6B⋯O1 inter­actions, which result in a dispersion energy framework resembling a spider web, Fig. 6 ▸(b). The combination of the electrostatic and dispersion forces leads to an overall energy framework that resembles a ladder, Fig. 6 ▸(c).

Figure 6

Perspective views of the energy frameworks of (I), showing the (a) electrostatic force, (b) dispersion force and (c) total energy. The cylindrical radius is proportional to the relative strength of the corresponding energies and they were adjusted to the same scale factor of 100 with a cut-off value of 8 kJ mol−1 within a 2 × 2 × 2 unit cells.

Database survey

As indicated in the Chemical context, 4 LH2 mol­ecules have long been known to form co-crystals with carb­oxy­lic acids. A list of 4 LH2/carb­oxy­lic acid co-crystals is given in Table 4 ▸, highlighting the symmetry of 4 LH2, the length of the central C—C bond, recognized as being long (Tiekink, 2017 ▸; Tan & Tiekink, 2020 ▸), and the O—H⋯N and NC—H⋯O (involving the C—H atom adjacent to the pyridyl-nitro­gen atom) separations associated with the hy­droxy-O—H⋯N(pyrid­yl) hydrogen bond. The data are separated into 1:1 and 1:2 4 LH2:carb­oxy­lic acid species. In all cases, 4 LH2 adopts an anti-periplanar disposition of the pyridyl rings whereby the pyridyl rings lie to either side of the central C2N2O2 chromophore; often this is crystallographically imposed. This matches the situation in the two known polymorphs of 4 LH2 (Lee & Wang, 2007 ▸; Lee, 2010 ▸), but contrasts with the conformational diversity found in the isomeric 3 LH2 mol­ecules, i.e. in the polymorphs (Jotani et al., 2016 ▸) and multi-component crystals (Tan & Tiekink, 2020 ▸). All but one structure forms hydroxyl-O—H⋯N(pyrid­yl) hydrogen bonds, involving both pyridyl rings, in their crystals. One reason put forward for the stability of hy­droxy-O—H⋯N(pyrid­yl) hydrogen bonds is the close approach of the pyridyl-C—H and carbonyl-O atoms to form a seven-membered {⋯O=COH⋯NCH} pseudo-synthon. In most, but not all examples, the carb­oxy­lic acid and pyridyl ring approach co-planarity, enabling the formation of the aforementioned pseudo-synthon. Among the co-crystals, only one example does not form the anti­cipated hydroxyl-O—H⋯N(pyrid­yl) hydrogen bonds. In this case, the co-former, i.e. 2-[(4-hy­droxy­phen­yl)diazen­yl]benzoic acid, carries a hydroxyl residue and this preferentially forms the hydrogen bonds to the pyridyl-N atoms. This observation is contrary to literature expectation where the carb­oxy­lic acid would be expected to form hydrogen bonds preferentially to pyridyl-N atom in instances where there is a competition with putative hydroxyl-O—H⋯N(pyrid­yl) hydrogen bonds (Shattock et al., 2008 ▸). In this structure, the carb­oxy­lic acid is able to form an intra­molecular hy­droxy-O—H⋯N(azo) hydrogen bond to close an S(6) loop, in accord with Etter’s rules, i.e. ‘six-membered ring intra­molecular hydrogen bonds form in preference to inter­molecular hydrogen bonds’ (Etter, 1990 ▸). Finally, and for completeness, details for a salt are included in Table 4 ▸. Here, proton transfer has occurred, leading to a pyridinium-N—H⋯O(carboxyl­ate) hydrogen bond.

Table 4

Selected geometric data, i.e. central C—C bond length, O—H⋯N and NC—H⋯O(carbon­yl) separations (Å) for 4 LH2 in its co-crystals with carb­oxy­lic acids and salt with a carboxyl­ate anion

Carb­oxy­lic acid (CA)	Symmetry of 4 LH2	C—C	O—H⋯N(pyrid­yl)	NC—H⋯O(carbon­yl)	REFCODE	Reference
1:1 co-crystal
bis­(carb­oxy­meth­yl)urea	–	1.53 (2)	1.73	2.54	CAJRAH	Nguyen et al. (2001 ▸)
			1.75	4.21
diglycineoxamide		1.514 (5)	1.74	3.11	SEPSIP01	Nguyen et al. (2001 ▸)
poly(1,2-bis­(2-carb­oxy­eth­yl)tetra-1-en-3-yn-1,4-di­yl		1.537 (13)	1.80	2.98	DOVSIR	Curtis et al. (2005 ▸)
2:1 co-crystal
(4-nitro­phen­yl)acetic acid		1.543 (2)	1.57	2.72	NAXMEG	Arman, Kaulgud et al. (2012 ▸)
benzoic acid	–	1.5401 (14)	1.67	2.59	–	This work
			1.72	3.46
2-methyl­benzoic acid		1.5356 (19)	1.79	2.60	WADXUX	Syed et al. (2016 ▸)
acetic acida		1.5397 (17)	1.75	2.81	GOQQIP	Tan & Tiekink (2019b ▸)
2-[(4-hy­droxy­phen­yl)diazen­yl]benzoic acidb		1.542 (2)	1.89	–	AJEZEV	Arman et al. (2009 ▸)
2,6-di­nitro­benzoatec		1.543 (3)	1.96c	2.51	TIPGUW	Arman, Miller et al. (2012 ▸)

Notes: (a) Characterized as a di-hydrate; (b) hy­droxy-O—N(pyrid­yl) hydrogen bond; (c) salt with a pyridinium-N—H⋯O(carboxyl­ate) hydrogen bond.

Synthesis and crystallization

The precursor, N,N′-bis­(pyridin-4-ylmeth­yl)oxalamide (4 LH2), was prepared according to the literature; M.p.: 486.3–487.6 K; lit. 486–487 K (Nguyen et al., 1998 ▸). Reagent-grade benzoic acid (Merck) was used as received without further purification. Solid 4 LH2 (0.271 g, 0.001 mol) was mixed with benzoic acid (0.122 g, 0.001 mol) and the physical mixture was then ground for 15 min in the presence of a few drops of methanol. The procedures were repeated three times. Colourless blocks were obtained through careful layering of toluene (1 ml) on an N,N-di­methyl­formamide (1 ml) solution of the ground mixture. M.p.: 435.4–436 K. IR (cm−1): 3321 ν(N—H), 3070–2999 ν(C—H), 1702–1662 ν(C=O), 1506 ν(C=C), 1417 ν(C—N).

Similar experiments with 4 LH2:benzoic acid in molar ratios of 1:2, 1:3 and 1:4 were also attempted but only the 2:1 co-crystal (I) was isolated after recrystallization of the powders.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 5 ▸. The carbon-bound H atoms were placed in calculated positions (C—H = 0.95–0.99 Å) and were included in the refinement in the riding-model approximation, with U iso(H) set to 1.2U eq(C). The oxygen- and nitro­gen-bound H atoms were located from a difference Fourier map and refined with O—H = 0.84±0.01 Å and N—H = 0.88±0.01 Å, respectively, and with U iso(H) set to 1.5U eq(O) or 1.2U eq(N).

Table 5

Experimental details

Crystal data
Chemical formula	C14H14N4O2·2C7H6O2
M r	514.53
Crystal system, space group	Triclinic, P
Temperature (K)	100
a, b, c (Å)	9.6543 (2), 9.9235 (2), 14.1670 (3)
α, β, γ (°)	100.755 (2), 108.318 (2), 95.617 (2)
V (Å3)	1247.90 (5)
Z	2
Radiation type	Cu Kα
μ (mm−1)	0.81
Crystal size (mm)	0.12 × 0.07 × 0.05
Data collection
Diffractometer	Rigaku XtaLAB Synergy Dualflex AtlasS2
Absorption correction	Gaussian (CrysAlis PRO; Rigaku OD, 2018 ▸)
T min, T max	0.832, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	31534, 5220, 4736
R int	0.031
(sin θ/λ)max (Å−1)	0.630
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.034, 0.093, 1.02
No. of reflections	5220
No. of parameters	359
No. of restraints	4
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.21, −0.28

Computer programs: CrysAlis PRO (Rigaku OD, 2018 ▸), SHELXS (Sheldrick, 2015a ▸), SHELXL2017/1 (Sheldrick, 2015b ▸), ORTEP-3 for Windows (Farrugia, 2012 ▸), DIAMOND (Brandenburg, 2006 ▸) and publCIF (Westrip, 2010 ▸).

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S2056989019016840/hb7875sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989019016840/hb7875Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989019016840/hb7875Isup3.cml

CCDC reference: 1972449

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

C14H14N4O2·2C7H6O2	Z = 2
Mr = 514.53	F(000) = 540
Triclinic, P1	Dx = 1.369 Mg m−3
a = 9.6543 (2) Å	Cu Kα radiation, λ = 1.54184 Å
b = 9.9235 (2) Å	Cell parameters from 16947 reflections
c = 14.1670 (3) Å	θ = 3.3–76.2°
α = 100.755 (2)°	µ = 0.81 mm−1
β = 108.318 (2)°	T = 100 K
γ = 95.617 (2)°	Prism, colourless
V = 1247.90 (5) Å3	0.12 × 0.07 × 0.05 mm

Rigaku XtaLAB Synergy Dualflex AtlasS2 diffractometer	5220 independent reflections
Radiation source: micro-focus sealed X-ray tube	4736 reflections with I > 2σ(I)
Detector resolution: 5.2558 pixels mm-1	Rint = 0.031
ω scans	θmax = 76.4°, θmin = 3.4°
Absorption correction: gaussian (CrysAlis PRO; Rigaku OD, 2018)	h = −12→12
Tmin = 0.832, Tmax = 1.000	k = −12→12
31534 measured reflections	l = −17→17

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)] = 0.034	Hydrogen site location: mixed
wR(F2) = 0.093	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	w = 1/[σ2(Fo2) + (0.0539P)2 + 0.3396P] where P = (Fo2 + 2Fc2)/3
5220 reflections	(Δ/σ)max = 0.001
359 parameters	Δρmax = 0.21 e Å−3
4 restraints	Δρmin = −0.28 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
O1	0.11169 (8)	0.35585 (8)	0.52445 (6)	0.02229 (17)
O2	0.49733 (8)	0.39415 (8)	0.58292 (6)	0.02091 (16)
N1	−0.09947 (10)	0.21060 (9)	0.09622 (7)	0.02157 (19)
N2	0.25702 (9)	0.46333 (9)	0.45149 (6)	0.01791 (18)
H2N	0.3484 (10)	0.4904 (14)	0.4548 (10)	0.024 (3)*
N3	0.35581 (9)	0.31253 (9)	0.66765 (6)	0.01757 (18)
H3N	0.2664 (11)	0.2971 (14)	0.6716 (11)	0.025 (3)*
N4	0.75967 (10)	0.62970 (10)	0.97336 (7)	0.0225 (2)
C1	−0.14959 (11)	0.32758 (11)	0.12456 (8)	0.0211 (2)
H1	−0.240536	0.343746	0.080891	0.025*
C2	−0.07474 (11)	0.42577 (11)	0.21457 (8)	0.0198 (2)
H2	−0.113267	0.507935	0.231404	0.024*
C3	0.05805 (11)	0.40266 (11)	0.28035 (8)	0.0178 (2)
C4	0.11019 (11)	0.28206 (11)	0.25088 (8)	0.0209 (2)
H4	0.200412	0.262855	0.293315	0.025*
C5	0.02905 (12)	0.18954 (11)	0.15858 (8)	0.0226 (2)
H5	0.066421	0.107775	0.138881	0.027*
C6	0.13776 (11)	0.50952 (11)	0.37960 (8)	0.0190 (2)
H6A	0.178912	0.594422	0.363694	0.023*
H6B	0.064816	0.535030	0.412815	0.023*
C7	0.23279 (11)	0.39410 (10)	0.51848 (7)	0.0168 (2)
C8	0.37639 (11)	0.36670 (10)	0.59305 (7)	0.0165 (2)
C9	0.47933 (11)	0.27763 (11)	0.74404 (8)	0.0198 (2)
H9A	0.539689	0.227162	0.709171	0.024*
H9B	0.439995	0.214321	0.779400	0.024*
C10	0.57768 (11)	0.40374 (10)	0.82273 (7)	0.0179 (2)
C11	0.51872 (12)	0.50271 (12)	0.87410 (9)	0.0261 (2)
H11	0.414595	0.494664	0.858090	0.031*
C12	0.61289 (13)	0.61374 (12)	0.94915 (9)	0.0274 (2)
H12	0.571438	0.680499	0.984407	0.033*
C13	0.81637 (12)	0.53568 (12)	0.92284 (8)	0.0242 (2)
H13	0.920690	0.547791	0.938956	0.029*
C14	0.73011 (12)	0.42117 (12)	0.84793 (8)	0.0224 (2)
H14	0.774771	0.355655	0.814404	0.027*
O3	0.55315 (9)	1.14822 (8)	0.95498 (6)	0.02525 (18)
O4	0.72142 (9)	1.01211 (8)	0.94323 (6)	0.02496 (18)
H4O	0.778 (2)	1.0790 (17)	0.9921 (12)	0.073 (6)*
C15	0.58610 (11)	1.04164 (11)	0.91631 (8)	0.0187 (2)
C16	0.47533 (12)	0.93433 (11)	0.82989 (8)	0.0190 (2)
C17	0.32865 (12)	0.95458 (11)	0.79630 (8)	0.0212 (2)
H17	0.299289	1.032279	0.830770	0.025*
C18	0.22525 (12)	0.86117 (12)	0.71238 (9)	0.0251 (2)
H18	0.125298	0.875244	0.689406	0.030*
C19	0.26769 (13)	0.74743 (12)	0.66210 (9)	0.0277 (2)
H19	0.197060	0.684161	0.604343	0.033*
C20	0.41328 (14)	0.72607 (12)	0.69617 (9)	0.0285 (3)
H20	0.442188	0.648021	0.661755	0.034*
C21	0.51726 (12)	0.81880 (11)	0.78076 (9)	0.0234 (2)
H21	0.616527	0.803107	0.804782	0.028*
O5	−0.16140 (8)	0.74669 (8)	0.22439 (6)	0.02307 (17)
O6	−0.03885 (9)	0.80244 (9)	0.12317 (6)	0.02892 (19)
H6O	−0.1140 (19)	0.747 (2)	0.0769 (14)	0.088 (8)*
C22	−0.05202 (11)	0.80401 (10)	0.21249 (8)	0.0187 (2)
C23	0.08033 (11)	0.88364 (10)	0.30063 (8)	0.0180 (2)
C24	0.20594 (11)	0.94266 (11)	0.28499 (8)	0.0192 (2)
H24	0.209182	0.931865	0.217699	0.023*
C25	0.32654 (12)	1.01739 (11)	0.36799 (8)	0.0220 (2)
H25	0.412647	1.056907	0.357507	0.026*
C26	0.32108 (12)	1.03425 (11)	0.46627 (8)	0.0238 (2)
H26	0.402958	1.086590	0.522807	0.029*
C27	0.19693 (13)	0.97515 (12)	0.48208 (8)	0.0263 (2)
H27	0.193811	0.986854	0.549439	0.032*
C28	0.07667 (12)	0.89864 (12)	0.39969 (8)	0.0234 (2)
H28	−0.007838	0.856648	0.410794	0.028*

	U11	U22	U33	U12	U13	U23
O1	0.0163 (3)	0.0268 (4)	0.0250 (4)	0.0018 (3)	0.0078 (3)	0.0085 (3)
O2	0.0161 (3)	0.0251 (4)	0.0224 (4)	0.0018 (3)	0.0071 (3)	0.0073 (3)
N1	0.0217 (4)	0.0236 (4)	0.0177 (4)	0.0029 (3)	0.0053 (3)	0.0035 (3)
N2	0.0144 (4)	0.0222 (4)	0.0158 (4)	0.0011 (3)	0.0041 (3)	0.0041 (3)
N3	0.0153 (4)	0.0199 (4)	0.0159 (4)	0.0001 (3)	0.0042 (3)	0.0037 (3)
N4	0.0231 (4)	0.0248 (5)	0.0158 (4)	−0.0006 (4)	0.0035 (3)	0.0036 (3)
C1	0.0189 (5)	0.0246 (5)	0.0190 (5)	0.0039 (4)	0.0040 (4)	0.0072 (4)
C2	0.0193 (5)	0.0200 (5)	0.0205 (5)	0.0045 (4)	0.0064 (4)	0.0055 (4)
C3	0.0171 (5)	0.0206 (5)	0.0168 (5)	0.0014 (4)	0.0068 (4)	0.0058 (4)
C4	0.0189 (5)	0.0245 (5)	0.0188 (5)	0.0056 (4)	0.0050 (4)	0.0058 (4)
C5	0.0241 (5)	0.0230 (5)	0.0207 (5)	0.0072 (4)	0.0072 (4)	0.0039 (4)
C6	0.0187 (5)	0.0203 (5)	0.0171 (5)	0.0039 (4)	0.0045 (4)	0.0046 (4)
C7	0.0166 (5)	0.0166 (4)	0.0151 (4)	0.0012 (4)	0.0048 (4)	0.0008 (4)
C8	0.0166 (4)	0.0147 (4)	0.0154 (4)	0.0005 (3)	0.0041 (4)	0.0005 (4)
C9	0.0199 (5)	0.0194 (5)	0.0178 (5)	0.0021 (4)	0.0033 (4)	0.0051 (4)
C10	0.0193 (5)	0.0200 (5)	0.0138 (4)	0.0020 (4)	0.0038 (4)	0.0061 (4)
C11	0.0174 (5)	0.0309 (6)	0.0248 (5)	0.0033 (4)	0.0044 (4)	−0.0005 (5)
C12	0.0249 (5)	0.0285 (6)	0.0241 (5)	0.0046 (4)	0.0065 (4)	−0.0020 (4)
C13	0.0171 (5)	0.0319 (6)	0.0211 (5)	0.0005 (4)	0.0041 (4)	0.0058 (4)
C14	0.0213 (5)	0.0258 (5)	0.0199 (5)	0.0044 (4)	0.0077 (4)	0.0035 (4)
O3	0.0264 (4)	0.0233 (4)	0.0216 (4)	0.0062 (3)	0.0047 (3)	−0.0006 (3)
O4	0.0220 (4)	0.0262 (4)	0.0213 (4)	0.0050 (3)	0.0038 (3)	−0.0017 (3)
C15	0.0226 (5)	0.0211 (5)	0.0139 (4)	0.0036 (4)	0.0071 (4)	0.0057 (4)
C16	0.0239 (5)	0.0191 (5)	0.0151 (5)	0.0011 (4)	0.0077 (4)	0.0062 (4)
C17	0.0250 (5)	0.0207 (5)	0.0196 (5)	0.0028 (4)	0.0091 (4)	0.0067 (4)
C18	0.0233 (5)	0.0277 (6)	0.0231 (5)	−0.0008 (4)	0.0054 (4)	0.0095 (4)
C19	0.0312 (6)	0.0246 (5)	0.0219 (5)	−0.0066 (4)	0.0061 (4)	0.0030 (4)
C20	0.0346 (6)	0.0211 (5)	0.0271 (6)	−0.0005 (5)	0.0121 (5)	−0.0009 (4)
C21	0.0249 (5)	0.0216 (5)	0.0238 (5)	0.0025 (4)	0.0096 (4)	0.0042 (4)
O5	0.0201 (4)	0.0254 (4)	0.0238 (4)	0.0009 (3)	0.0082 (3)	0.0061 (3)
O6	0.0266 (4)	0.0374 (5)	0.0158 (4)	−0.0093 (3)	0.0058 (3)	−0.0004 (3)
C22	0.0203 (5)	0.0175 (5)	0.0187 (5)	0.0035 (4)	0.0070 (4)	0.0045 (4)
C23	0.0203 (5)	0.0158 (4)	0.0174 (5)	0.0041 (4)	0.0055 (4)	0.0038 (4)
C24	0.0216 (5)	0.0196 (5)	0.0171 (5)	0.0048 (4)	0.0067 (4)	0.0049 (4)
C25	0.0192 (5)	0.0218 (5)	0.0233 (5)	0.0023 (4)	0.0053 (4)	0.0050 (4)
C26	0.0234 (5)	0.0226 (5)	0.0194 (5)	0.0054 (4)	0.0010 (4)	0.0011 (4)
C27	0.0315 (6)	0.0310 (6)	0.0156 (5)	0.0068 (5)	0.0072 (4)	0.0042 (4)
C28	0.0251 (5)	0.0267 (5)	0.0205 (5)	0.0034 (4)	0.0102 (4)	0.0066 (4)

O1—C7	1.2270 (12)	C13—H13	0.9500
O2—C8	1.2312 (12)	C14—H14	0.9500
N1—C5	1.3395 (14)	O3—C15	1.2162 (13)
N1—C1	1.3421 (14)	O4—C15	1.3197 (13)
N2—C7	1.3336 (13)	O4—H4O	0.860 (10)
N2—C6	1.4538 (13)	C15—C16	1.4980 (14)
N2—H2N	0.881 (9)	C16—C21	1.3902 (15)
N3—C8	1.3298 (13)	C16—C17	1.3929 (15)
N3—C9	1.4570 (13)	C17—C18	1.3895 (15)
N3—H3N	0.883 (9)	C17—H17	0.9500
N4—C12	1.3346 (15)	C18—C19	1.3867 (17)
N4—C13	1.3338 (15)	C18—H18	0.9500
C1—C2	1.3845 (15)	C19—C20	1.3869 (18)
C1—H1	0.9500	C19—H19	0.9500
C2—C3	1.3968 (14)	C20—C21	1.3935 (16)
C2—H2	0.9500	C20—H20	0.9500
C3—C4	1.3869 (15)	C21—H21	0.9500
C3—C6	1.5157 (14)	O5—C22	1.2237 (13)
C4—C5	1.3906 (15)	O6—C22	1.3084 (13)
C4—H4	0.9500	O6—H6O	0.865 (10)
C5—H5	0.9500	C22—C23	1.4991 (14)
C6—H6A	0.9900	C23—C24	1.3932 (15)
C6—H6B	0.9900	C23—C28	1.3955 (15)
C7—C8	1.5402 (14)	C24—C25	1.3904 (15)
C9—C10	1.5139 (14)	C24—H24	0.9500
C9—H9A	0.9900	C25—C26	1.3893 (16)
C9—H9B	0.9900	C25—H25	0.9500
C10—C11	1.3861 (15)	C26—C27	1.3824 (17)
C10—C14	1.3857 (15)	C26—H26	0.9500
C11—C12	1.3894 (16)	C27—C28	1.3899 (16)
C11—H11	0.9500	C27—H27	0.9500
C12—H12	0.9500	C28—H28	0.9500
C13—C14	1.3857 (15)
C5—N1—C1	117.75 (9)	N4—C13—C14	123.03 (10)
C7—N2—C6	121.82 (9)	N4—C13—H13	118.5
C7—N2—H2N	119.7 (9)	C14—C13—H13	118.5
C6—N2—H2N	118.1 (9)	C13—C14—C10	118.93 (10)
C8—N3—C9	120.98 (9)	C13—C14—H14	120.5
C8—N3—H3N	120.2 (9)	C10—C14—H14	120.5
C9—N3—H3N	118.8 (9)	C15—O4—H4O	108.5 (15)
C12—N4—C13	118.30 (9)	O3—C15—O4	123.81 (9)
N1—C1—C2	122.96 (10)	O3—C15—C16	122.06 (10)
N1—C1—H1	118.5	O4—C15—C16	114.08 (9)
C2—C1—H1	118.5	C21—C16—C17	119.87 (10)
C1—C2—C3	119.25 (10)	C21—C16—C15	121.37 (10)
C1—C2—H2	120.4	C17—C16—C15	118.72 (9)
C3—C2—H2	120.4	C16—C17—C18	120.01 (10)
C4—C3—C2	117.79 (9)	C16—C17—H17	120.0
C4—C3—C6	123.35 (9)	C18—C17—H17	120.0
C2—C3—C6	118.85 (9)	C19—C18—C17	120.12 (11)
C3—C4—C5	119.32 (10)	C19—C18—H18	119.9
C3—C4—H4	120.3	C17—C18—H18	119.9
C5—C4—H4	120.3	C18—C19—C20	119.98 (10)
N1—C5—C4	122.91 (10)	C18—C19—H19	120.0
N1—C5—H5	118.5	C20—C19—H19	120.0
C4—C5—H5	118.5	C19—C20—C21	120.18 (11)
N2—C6—C3	114.41 (8)	C19—C20—H20	119.9
N2—C6—H6A	108.7	C21—C20—H20	119.9
C3—C6—H6A	108.7	C16—C21—C20	119.82 (11)
N2—C6—H6B	108.7	C16—C21—H21	120.1
C3—C6—H6B	108.7	C20—C21—H21	120.1
H6A—C6—H6B	107.6	C22—O6—H6O	108.4 (17)
O1—C7—N2	125.93 (9)	O5—C22—O6	123.94 (9)
O1—C7—C8	121.14 (9)	O5—C22—C23	122.33 (9)
N2—C7—C8	112.92 (8)	O6—C22—C23	113.73 (9)
O2—C8—N3	124.54 (9)	C24—C23—C28	119.83 (9)
O2—C8—C7	121.86 (9)	C24—C23—C22	121.07 (9)
N3—C8—C7	113.60 (9)	C28—C23—C22	119.10 (9)
N3—C9—C10	113.22 (8)	C25—C24—C23	119.91 (10)
N3—C9—H9A	108.9	C25—C24—H24	120.0
C10—C9—H9A	108.9	C23—C24—H24	120.0
N3—C9—H9B	108.9	C26—C25—C24	119.98 (10)
C10—C9—H9B	108.9	C26—C25—H25	120.0
H9A—C9—H9B	107.7	C24—C25—H25	120.0
C11—C10—C14	117.99 (9)	C27—C26—C25	120.23 (10)
C11—C10—C9	121.18 (9)	C27—C26—H26	119.9
C14—C10—C9	120.79 (9)	C25—C26—H26	119.9
C10—C11—C12	119.57 (10)	C26—C27—C28	120.18 (10)
C10—C11—H11	120.2	C26—C27—H27	119.9
C12—C11—H11	120.2	C28—C27—H27	119.9
N4—C12—C11	122.16 (11)	C27—C28—C23	119.85 (10)
N4—C12—H12	118.9	C27—C28—H28	120.1
C11—C12—H12	118.9	C23—C28—H28	120.1
C5—N1—C1—C2	−0.12 (16)	N4—C13—C14—C10	1.01 (17)
N1—C1—C2—C3	−0.91 (16)	C11—C10—C14—C13	0.07 (16)
C1—C2—C3—C4	1.13 (15)	C9—C10—C14—C13	−177.84 (10)
C1—C2—C3—C6	−178.91 (9)	O3—C15—C16—C21	174.45 (10)
C2—C3—C4—C5	−0.39 (15)	O4—C15—C16—C21	−3.20 (14)
C6—C3—C4—C5	179.65 (10)	O3—C15—C16—C17	−3.13 (15)
C1—N1—C5—C4	0.91 (16)	O4—C15—C16—C17	179.22 (9)
C3—C4—C5—N1	−0.66 (17)	C21—C16—C17—C18	−1.48 (15)
C7—N2—C6—C3	−87.36 (12)	C15—C16—C17—C18	176.13 (9)
C4—C3—C6—N2	−12.00 (14)	C16—C17—C18—C19	0.20 (16)
C2—C3—C6—N2	168.05 (9)	C17—C18—C19—C20	0.61 (17)
C6—N2—C7—O1	3.86 (16)	C18—C19—C20—C21	−0.12 (18)
C6—N2—C7—C8	−175.03 (8)	C17—C16—C21—C20	1.96 (16)
C9—N3—C8—O2	−1.50 (15)	C15—C16—C21—C20	−175.59 (10)
C9—N3—C8—C7	178.88 (8)	C19—C20—C21—C16	−1.17 (17)
O1—C7—C8—O2	173.94 (9)	O5—C22—C23—C24	177.14 (10)
N2—C7—C8—O2	−7.10 (13)	O6—C22—C23—C24	−3.01 (14)
O1—C7—C8—N3	−6.43 (13)	O5—C22—C23—C28	−2.98 (16)
N2—C7—C8—N3	172.52 (8)	O6—C22—C23—C28	176.87 (10)
C8—N3—C9—C10	75.45 (12)	C28—C23—C24—C25	−0.63 (15)
N3—C9—C10—C11	50.59 (14)	C22—C23—C24—C25	179.25 (9)
N3—C9—C10—C14	−131.57 (10)	C23—C24—C25—C26	−0.63 (16)
C14—C10—C11—C12	−0.84 (17)	C24—C25—C26—C27	1.00 (16)
C9—C10—C11—C12	177.05 (10)	C25—C26—C27—C28	−0.10 (17)
C13—N4—C12—C11	0.40 (18)	C26—C27—C28—C23	−1.16 (17)
C10—C11—C12—N4	0.64 (19)	C24—C23—C28—C27	1.52 (16)
C12—N4—C13—C14	−1.24 (17)	C22—C23—C28—C27	−178.36 (10)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N···O2	0.88 (1)	2.36 (1)	2.7192 (12)	105 (1)
N3—H3N···O1	0.88 (1)	2.36 (1)	2.7154 (12)	104 (1)
O4—H4O···N1i	0.86 (2)	1.78 (2)	2.6366 (12)	177 (2)
O6—H6O···N4ii	0.86 (2)	1.72 (2)	2.5731 (13)	169 (2)
N2—H2N···O2iii	0.88 (1)	2.05 (1)	2.8618 (12)	152 (1)
N3—H3N···O5iv	0.88 (1)	2.12 (1)	2.8516 (12)	140 (1)
C1—H1···O3v	0.95	2.58	3.2009 (14)	124
C2—H2···O5	0.95	2.47	3.3602 (14)	155
C6—H6B···O1iv	0.99	2.41	3.3826 (14)	166
C12—H12···O3vi	0.95	2.36	3.3025 (15)	171