Chelidamic acid monohydrate: the proton complex of a multidentate ligand

Chelidamic acid, 4-hydroxy­pyridine-2,6-di­carboxyl­ic acid, is found to be zwitterionic in its solid monohydrate form, C₇H₅NO₅·H₂O, with the aryl­oxide and one carboxyl­ate group remaining protonated, but the other carboxyl­ate group losing its proton to the pyridine N atom. In this, it is unlike its parent, dipicolinic acid (pyridine-2,6-di­carboxyl­ic acid), which also crystallizes as a monohydrate, but one in which the acidic H atoms remain bound to the carboxyl­ate groups. In both structures, the water mol­ecule is a component of an extended hydrogen-bonded network.

S1. Comment

Anions derived from weak protic acids form a very extensive family of metal-coordinating agents. In this regard, the acids themselves can be considered as precursive proton complexes, providing useful reference points in analyzing the various effects that complexation may have on both metal and ligand properties. We have discussed this issue in recent structural studies of polynitrophenols and their derivatives (Harrowfield, Sharma, Shand et al., 1998; Harrowfield, Sharma, Skelton & White, 1998; Harrowfield, Sharma, Skelton, Venugopalam & White, 1998), where aromatic π-stacking interactions seem to play an important role in determining coordination modes in the solid state. In extending this work to the study of heteroaromatic polycarboxylates, we have found the need to determine the crystal structure of chelidamic acid, 4-hydroxypyridine-2,6-dicarboxylic acid, H₃chel, the source of a potentially trianionic chelating agent, though, in fact, only rather limited information is available on the nature of metal-bound chelidamate (Bag et al., 1962; Thich et al., 1976; Cline et al., 1979; Pike et al., 1983). We report here the structure of chelidamic acid, (I), comparing it with that known for the closely related dipicolinic acid (pyridine-2,6-dicarboxylic acid; Takusagawa et al., 1973), also the parent of an important chelating anion (Harrowfield et al., 1995, and references therein), in order to draw conclusions as to the sites and effects of proton residency within such molecules, as well as to assess the nature of factors influencing their solid-state structures.

The results of the low-temperature (ca 153 K) single-crystal X-ray study of chelidamic acid are consistent in overall stoichiometry and connectivity with formulation as the monohydrate, C₇H₅NO₅·H₂O, one formula unit devoid of crystallographic symmetry comprising the asymmetric unit of the structure. Data quality permitted location and refinement of H atoms, showing the distribution of these is at variance with the conventional description of the acid as 4-hydroxypyridine-2,6-dicarboxylic acid, since it is in fact zwitterionic, with a cationic pyridinium centre balanced by the (under the present numbering) 2-carboxylate anion. Detailed molecular geometry is given in Table 1 in comparison with pyridine-2,6-dicarboxylic acid (Takusagawa et al., 1973). Structural data for chelidamate derivatives in the literature concern a series of macrocycles in which the two carboxylate groups of chelidamic acid are esterified into an 18-membered ring (ROH = C₁₅H₁₉NO₈) which, in one case, is found with the aryloxide both protonated and deprotonated in separate moieties (PhCH₂NH₃^+.RO^-.ROH) (Bradshaw et al., 1985) and in a further derivative, ROMe, has the aryloxide moiety methylated (Bradshaw et al., 1985).

Within H₃chel itself, two sources of asymmetry exist. The aryloxide O atom is protonated and, as is the case with OR' substituents appended to phenyl rings, the R' (including H) groups tend to lie coplanar with the ring, with consequent asymmetry in the angles exocyclic at the point of attachment. Here we find C4—O4 of a length comparable with counterpart values in the ROH and ROMe species; in the latter, a considerable asymmetry in the associated exocyclic angles is observed which is unusually diminished in the present. It is of interest to note that in the RO^- species, without any R' substituent, the angular asymmetry is greater, suggesting hydrogen-bonding and other lattice forces to be appreciable, while the C4—O4 bond is appreciably shorter, with a greatly diminished endocyclic angle opposite it, in keeping with some enhancement of its double-bond character. The angle C3—C4—C5 is little different amongst the substituted phenoxide arrays relative to the unsubstituted dipicolinic acid, though associated C4—C3,5 distances may be slightly shorter in the latter. The other source of asymmetry, not found in the other arrays, is the dissimilarity in the carboxylate groups, one being deprotonated and the other not. This appears to be of little consequence within the region bounded by the carboxylate C atoms other than some asymmetry in the exocyclic angles at C2; angular differences between C21 and C61 are minor, despite the difference in associated protonation and some differences in counterpart C—O bond lengths. Relative to the ROR' arrays, however, large differences are noted in the latter in respect of Cn—Cn1—On1,2 angles, Cn1—On2 being appreciably shorter, and almost purely double bond in these species. In dipicolinic acid, interesting variations are also observed in the carboxylates: despite the protonation of both, the COH dispositions are relatively cis and trans to the ring nitrogen about the Cn—Cn1 bond, with concomitant changes in Cn—-Cn1—On1,2 comparability. In all these systems, as is usual, the carboxylate groups tend to lie coplanar with the aromatic ring, despite predominantly single bond character in Cn—Cn1, but deviations from coplanarity are large, C₂O₂/C₅N interplanar dihedral angles often rising above 20° in the above systems. Protonation of the pyridine N atom in H₃chel is accompanied by enlargement of C2—N1—C6 relative to the unprotonated arrays; associated C—N are slightly lengthened. It is of interest to note that both H₂dipic and H₃chel crystallize as monohydrates, as also does ROH in isolation (Bradshaw et al., 1985). In all cases, the water molecule is intimately involved in the hydrogen-bonding array but there appears to be no distinctive feature common to these systems explaining the monohydrate status. The siting of the water molecule in chelidamic acid hydrate directly above the centroid of an aromatic ring, for example, is not duplicated in dipicolinic acid hydrate. Hydrogen bonds found in the present array are described in Table 2, showing interactions from all NH or OH entities, those from the water H atoms, presumably the least acidic, being weakest; within the water molecule, H—O—H is 114 (2)°. Within the lattice, the H₃chel molecules lie quasi-normal to the a axis. Relatively close (3.3–3.6 Å) approaches between atoms within formally separate aromatic rings are found in all chelidamate and dipicolinate structures known and may be indicative of significant `face-to-face' (π-stacking) and/or `edge/vertex-to-face' aromatic group interactions (Harrowfield, 1996; Dance & Scudder, 1998, and references therein). In the hydrates of the acids in particular, hydrogen-bonded arrays form sheets which lie parallel to one another, approximately 3.4 Å apart.

S2. Experimental

Crystals suitable for diffraction measurements were obtained by forming a saturated solution of chelidamic acid monohydrate (Aldrich) in boiling water, filtering out the solid rapidly precipitated on cooling to room temperature and then allowing the filtrate to slowly evaporate under ambient conditions. Small colourless tablets were readily obtained.

Computing details

Data collection: SMART (Siemens, 1995); cell refinement: SAINT (Siemens, 1995); data reduction: SAINT; program(s) used to solve structure: Xtal3.5 GENTAN (Hall et al., 1995); program(s) used to refine structure: Xtal3.5 CRYLSQ; molecular graphics: Xtal3.5 PIG ORTEP; software used to prepare material for publication: Xtal3.5 BONDLA CIFIO.

Figures

Fig. 1. Projection of a single molecule normal to the ring plane, showing non-H atoms with 50% ellipsoids and the atom-labelling scheme.

(I)

Crystal data

C7H5NO5·H2O	F(000) = 416
Mr = 201.13	Dx = 1.737 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 3552 reflections
a = 6.8832 (6) Å	θ = 1–28°
b = 9.0568 (8) Å	µ = 0.16 mm^−1
c = 12.4376 (11) Å	T = 153 K
β = 97.219 (2)°	Block, colourless
V = 769.21 (12) Å^3	0.1 × 0.1 × 0.1 mm
Z = 4

Data collection

Bruker AXS CCD area detector diffractometer	1639 reflections with F > 4σ(F)
Radiation source: sealed tube	Rint = 0.031
Graphite monochromator	θmax = 28.9°, θmin = 2.8°
ω scans	h = −9→9
8642 measured reflections	k = 0→12
1962 independent reflections	l = 0→16

Refinement

Refinement on F	0 restraints
Least-squares matrix: full	0 constraints
R[F^2 > 2σ(F^2)] = 0.038	All H-atom parameters refined
wR(F^2) = 0.049	w = 1/σ^2(F) + 0.004F^2]
S = 1.62	(Δ/σ)max = 0.041
1639 reflections	Δρmax = 0.31 e Å^−3
156 parameters	Δρmin = −0.26 e Å^−3

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.94129 (16)	0.46506 (13)	0.22581 (9)	0.0153 (5)
C2	0.8890 (2)	0.56360 (14)	0.14520 (10)	0.0151 (6)
C21	0.77747 (19)	0.50470 (14)	0.04095 (10)	0.0154 (6)
O21	0.68729 (15)	0.38485 (11)	0.04885 (7)	0.0200 (5)
O22	0.78631 (15)	0.58032 (11)	−0.04183 (7)	0.0194 (5)
C3	0.9358 (2)	0.71102 (15)	0.15752 (11)	0.0163 (6)
C4	1.03808 (19)	0.75988 (15)	0.25579 (10)	0.0153 (6)
O4	1.08359 (15)	0.90211 (10)	0.26897 (8)	0.0190 (5)
C5	1.0930 (2)	0.65563 (14)	0.33686 (11)	0.0164 (6)
C6	1.04528 (19)	0.51041 (15)	0.31970 (10)	0.0150 (6)
C61	1.1168 (2)	0.40001 (15)	0.40668 (10)	0.0174 (6)
O61	1.05507 (15)	0.26605 (11)	0.38924 (8)	0.0221 (5)
O62	1.22549 (17)	0.44381 (11)	0.48533 (8)	0.0268 (5)
O01	0.57758 (18)	0.67615 (12)	0.32760 (9)	0.0301 (6)
H1	0.918 (3)	0.361 (3)	0.2095 (16)	0.046 (6)*
H3	0.895 (2)	0.7816 (18)	0.0990 (12)	0.016 (4)*
H4	1.147 (4)	0.918 (3)	0.344 (2)	0.070 (8)*
H5	1.164 (2)	0.6828 (16)	0.4038 (14)	0.020 (4)*
H61	1.119 (3)	0.201 (2)	0.4520 (19)	0.060 (7)*
H01a	0.520 (4)	0.595 (3)	0.289 (2)	0.077 (8)*
H01b	0.644 (4)	0.652 (3)	0.392 (2)	0.072 (8)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0175 (6)	0.0140 (6)	0.0137 (5)	−0.0002 (4)	−0.0010 (4)	0.0003 (4)
C2	0.0156 (6)	0.0167 (7)	0.0125 (6)	0.0012 (5)	0.0001 (5)	0.0008 (5)
C21	0.0161 (6)	0.0136 (6)	0.0157 (6)	0.0030 (5)	−0.0012 (5)	−0.0014 (5)
O21	0.0259 (5)	0.0160 (5)	0.0169 (5)	−0.0037 (4)	−0.0024 (4)	−0.0012 (4)
O22	0.0242 (5)	0.0198 (5)	0.0128 (5)	0.0001 (4)	−0.0033 (4)	0.0021 (4)
C3	0.0179 (7)	0.0164 (7)	0.0138 (6)	0.0007 (5)	−0.0006 (5)	0.0012 (5)
C4	0.0170 (7)	0.0134 (6)	0.0150 (6)	−0.0006 (5)	0.0001 (5)	−0.0007 (5)
O4	0.0265 (5)	0.0133 (5)	0.0154 (5)	−0.0030 (4)	−0.0039 (4)	−0.0002 (4)
C5	0.0182 (7)	0.0171 (7)	0.0129 (6)	−0.0001 (5)	−0.0015 (5)	−0.0010 (5)
C6	0.0155 (6)	0.0163 (6)	0.0127 (6)	0.0005 (5)	−0.0005 (5)	−0.0001 (5)
C61	0.0198 (7)	0.0171 (7)	0.0147 (6)	0.0010 (5)	−0.0004 (5)	0.0006 (5)
O61	0.0309 (6)	0.0145 (5)	0.0184 (5)	−0.0013 (4)	−0.0072 (4)	0.0024 (4)
O62	0.0376 (7)	0.0186 (5)	0.0202 (5)	−0.0037 (4)	−0.0121 (5)	0.0030 (4)
O01	0.0442 (7)	0.0171 (5)	0.0241 (6)	−0.0034 (5)	−0.0142 (5)	0.0023 (4)

Geometric parameters (Å, º)

N1—C2	1.3566 (17)	C4—C5	1.3983 (18)
N1—C6	1.3544 (16)	O4—H4	0.99 (2)
N1—H1	0.98 (2)	C5—C6	1.3659 (19)
C2—C21	1.5182 (17)	C5—H5	0.943 (16)
C2—C3	1.3776 (19)	C6—C61	1.5095 (18)
C21—O21	1.2604 (16)	C61—O61	1.2948 (17)
C21—O22	1.2444 (16)	C61—O62	1.2207 (16)
O21—H61	1.46 (2)	O61—H61	1.03 (2)
O22—H4	1.61 (2)	O01—H01a	0.94 (3)
C3—C4	1.4033 (18)	O01—H01b	0.90 (3)
C3—H3	0.983 (15)	O01—H1	1.73 (2)
C4—O4	1.3309 (16)	H01a—H01b	1.54 (4)
N1···C21	2.4566 (16)	C3···C6	2.7487 (18)
N1···O21	2.7316 (14)	C4···C6	2.3936 (19)
N1···C3	2.3827 (18)	C4···H3	2.082 (14)
N1···C4	2.7659 (18)	C4···H4	1.90 (2)
N1···C5	2.3695 (17)	C4···H5	2.055 (16)
N1···C61	2.4868 (16)	O4···C5	2.3846 (16)
N1···O61	2.7557 (15)	O4···O01	2.9152 (15)
N1···O01	2.6987 (16)	O4···H3	2.581 (15)
C2···O21	2.3593 (16)	O4···H5	2.613 (16)
C2···O22	2.3496 (15)	O4···H01a	1.99 (3)
C2···C4	2.3981 (18)	C5···C61	2.4708 (19)
C2···C5	2.7400 (18)	C5···O62	2.7384 (17)
C2···C6	2.3479 (17)	C5···H4	2.40 (2)
C2···H1	2.00 (2)	C6···O61	2.3740 (17)
C2···H3	2.058 (16)	C6···O62	2.3461 (16)
C21···C3	2.5267 (18)	C6···H1	2.05 (2)
C21···H1	2.55 (2)	C6···H5	1.996 (15)
C21···H4	2.60 (2)	C61···H1	2.678 (19)
C21···H61	2.36 (2)	C61···H5	2.583 (15)
O21···O22	2.2503 (14)	C61···H61	1.89 (2)
O21···O61	2.4866 (13)	O61···O62	2.2459 (14)
O21···O01	2.8157 (15)	O61···O01	2.8550 (15)
O21···H1	2.400 (19)	O61···H1	2.47 (2)
O21···H01b	2.47 (3)	O61···H01a	2.70 (3)
O22···C3	2.8225 (16)	O62···O01	2.7638 (15)
O22···O4	2.5855 (13)	O62···H5	2.406 (15)
O22···H3	2.573 (16)	O62···H61	2.34 (2)
O22···H5	2.372 (15)	O62···H01b	1.88 (3)
C3···O4	2.3658 (16)	H1···H01b	2.29 (3)
C3···C5	2.4065 (18)	H4···H5	2.25 (3)
C2—N1—C6	120.01 (11)	C4—C5—C6	119.98 (12)
C2—N1—H1	117.5 (11)	C4—C5—H5	121.5 (9)
C6—N1—H1	121.9 (11)	C6—C5—H5	118.5 (9)
N1—C2—C21	117.31 (11)	N1—C6—C5	121.15 (12)
N1—C2—C3	121.25 (11)	N1—C6—C61	120.43 (11)
C21—C2—C3	121.44 (11)	C5—C6—C61	118.39 (11)
C2—C21—O21	115.92 (11)	C6—C61—O61	115.47 (11)
C2—C21—O22	116.18 (11)	C6—C61—O62	118.09 (12)
O21—C21—O22	127.90 (12)	O61—C61—O62	126.44 (12)
C21—O21—H61	120.3 (9)	C61—O61—H61	108.1 (12)
C21—O22—H4	130.6 (9)	H01a—O01—H01b	114 (2)
C2—C3—C4	119.16 (12)	H01a—O01—H1	129.6 (17)
C2—C3—H3	120.4 (9)	H01b—O01—H1	116.7 (17)
C4—C3—H3	120.4 (9)	N1—H1—O01	169 (2)
C3—C4—O4	119.80 (11)	O4—H4—O22	168 (2)
C3—C4—C5	118.41 (12)	O61—H61—O21^i	172 (2)
O4—C4—C5	121.78 (11)	O01—H01a—H01b	32.5 (13)
C4—O4—H4	109.0 (14)	O01—H01b—H01a	33.9 (14)

Symmetry code: (i) x+1/2, −y+1/2, z+1/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D—H···A
N1—H1···O01^ii	0.98 (2)	1.74 (2)	169 (2)
O4—H4···O22^iii	0.99 (2)	1.61 (2)	168 (2)
O61—H61···O21^i	1.03 (2)	1.46 (2)	172 (2)
O01—H01a···O4^ii	0.94 (3)	1.99 (3)	169 (2)
O01—H01b···O62^iv	0.90 (3)	1.88 (3)	167 (2)

Symmetry codes: (i) x+1/2, −y+1/2, z+1/2; (ii) −x+3/2, y−1/2, −z+1/2; (iii) x+1/2, −y+3/2, z+1/2; (iv) −x+2, −y+1, −z+1.