influence of dicarboxylic acid structure on tape networks in co-crystals of 2-pyridone

Crystal Engineering 5 (2002) 25–36www.elsevier.com/locate/cryseng

Influence of dicarboxylic acid structure on tapenetworks in co-crystals of 2-pyridone

M.R. Edwardsa, W. Jonesa,∗, W.D.S. Motherwellb

a Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UKb Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK

Received 29 March 2001; accepted 22 May 2001

Abstract

We report here on the formation of co-crystals of 2-pyridone and several long chain dicar-boxylic acids HO2C(CH2)nCO2H with n an odd number. Supramolecular tapes, illustratingseveral hydrogen bond motifs, were observed. Co-crystals with malonic acid (n � 1) crystallisein the space group P2/n, witha � 19.213,b � 4.031,c � 19.508,b � 114.67°; glutaric acid(n � 3) in P-1, with a � 5.437,b � 9.592,c � 11.797,a � 66.50°, b � 81.64°, g �83.00°; pimelic acid (n � 5) in C2/c, with a � 19.828,b � 5.135,c � 17.401,b �102.98°; and azelaic acid (n � 7) in P21/c, with a � 16.644,b � 5.036,c � 18.213,b �103.09°. Tape compositions of both 1:1 acid:base and 1:2 acid:base were obtained suggesting

that tape stochiometry is independent of the number of constituent carbon atoms in the acidbackbone. The results also suggest that the 2-pyridone dimer may in certain cases act as asupramolecular analogue of phenazine. 2002 Elsevier Science Ltd. All rights reserved.

Keywords: Crystal engineering; Supramolecular tapes; Phenazine analogue; Robust hydrogen bond motifs

1. Introduction

Crystal engineering, the design of crystal structures with predetermined moleculararrangements, is a developing field [1-3]. In particular the use of hydrogen bondinghas received significant attention, leading to the creation of extensive networks ofmolecules with various translational symmetry. These include one dimensional tapes

∗ Corresponding author. Fax:+44-1223-336362.E-mail address: [email protected] (W. Jones).

1463-0184/02/$ - see front matter 2002 Elsevier Science Ltd. All rights reserved.PII: S1463 -0184(02 )00008-4

26 M.R. Edwards et al. / Crystal Engineering 5 (2002) 25–36

(α-networks), two dimensional sheets formed by interactions between tapes (β-networks), or three dimensional networks composed of α and β networks (γ-networks) [4,5]. Our interest lies particularly in the formation of co-crystals com-posed of tape networks (α-networks), and to observe the resulting tape composition,topology and overall arrangement in the crystal. Several authors have demonstratedthe formation of various tape topologies. For example, Whitesides and co-workerssynthesised supramolecular tapes of various acid:base complexes based on cyanuricacids and melamine. Increased steric forces along the tape axis resulted in the forma-tion of crinkled rather than linear tapes [6,7].

Co-crystals composed of tapes built from a hydrogen bond motif consisting of botha relatively strong and relatively weak interaction were investigated by Pedireddi etal. who co-crystallised phenazine with either 3,5-dinitro-4-methylbenzoic acid orwith malonic acid [8]. In the co-crystals, phenazine molecules were linked by acidmolecules, using motif I (Scheme 1). Molecules of 3,5-dinitro-4-methylbenzoic acidwere then linked by weak C–H%O interactions between the methyl and nitro groups.In the case of malonic acid (n � 1), acid dimers (linked by motif II, Scheme 1) werefound to connect the phenazine molecules.

In a further paper, the formation of 1:1 co-crystals of long chain dicarboxylicacids HO2C(CH2)nCO2H containing even and odd numbers of carbon atoms, namelymalonic (n � 1), glutaric (n � 3) and adipic (n � 4) acids, with 4-4’ -bipyridyl hasbeen described [9]. Supramolecular tapes containing acid and base molecules wereagain formed with relatively strong O–H%O and weak C–H%O hydrogen bondswhich link the acid to the base.

Similar investigations performed by Batchelor et al. have shown that co-crystallis-ing succinic acid (n � 2) and glutaric acid (n � 3) with phenazine created co-crystalsbuilt from supramolecular tapes [10,11]. Tapes were grouped as either being 2:1acid:base or 1:1 acid:base, the arrangements are shown in Scheme 2. Tapes of 2:1acid:base composition contained an additional centrosymmetric carboxylic acidmotif. It was concluded that the tape composition was dependent on the number ofconstituent carbon atoms in the acid backbone and its conformation. For example,glutaric acid (n-odd) formed acid dimers (and a 2:1 co-crystal) in the tape arraywhereas succinic acid (n-even) formed a 1:1 complex of acid:base.

Recently, Aackeroy et al. have reported the formation of co-crystals of 2-pyridonewith a series of long chain dicarboxylic acids with n � 0, 2, 4, 6 and 8 [12]. Thesestructures consisted of supramolecular tapes containing 2-pyridone dimers (formed

Scheme 1.

27M.R. Edwards et al. / Crystal Engineering 5 (2002) 25–36

Scheme 2.

via N–H%O interactions) linked by an acid molecule, the acid interacting with thebase dimer through strong O–H%O, and weak C–H%O interactions (motif III,Scheme 1). These hydrogen bond motifs were apparently robust in that they werepresent in all structures and were unaffected by the change in acid length. It is knownthat 2-pyridone undergoes tautomerisation to 2-hydroxypyridine in solution, but onlythe pyridone tautomer was found in the solid state [13,14]

We decided to continue the investigations of Aackeroy et al. for two reasons. Firstto test whether 2-pyridone could satisfactorily be considered as a robust analogueof phenazine—both phenazine and the 2-pyridone dimer are planar and of approxi-mately the same dimensions (Scheme 3). The intermolecular interactions between2-pyridone and phenazine with carboxylic acids are similar, with both bases formingC–H%O interactions with the acid. The additional hydrogen bond formed by phena-zine is the O–H%N bond, whereas O–H%O is formed by 2-pyridone [10-12]. Boththe O–H%N and O–H%O interactions are set at roughly the same position relativeto ring 1, with similar values of hydrogen bond lengths. Secondly, it was clearly of

Scheme 3.


interest to know whether 2-pyridone could co-crystallise with a series of dicarboxylicacids consisting of an odd number of carbon atoms, and to determine whether asimilar odd/even effect operates for the 2-pyridone dimer similar to that reported byBatchelor et al. for phenazine.

2. Experimental

The starting materials, approximately 98% pure, were obtained from Aldrich andwere used without further purification. Equimolar mixtures of 2-pyridone and dicar-boxylic acids were prepared in sample vials and dissolved in ethanol. Each solutionwas slowly evaporated at room temperature. X-ray diffraction data were collectedusing a Nonius Kappa CCD diffractometer equipped with an Oxford CryosystemsCryostream. Data reduction and cell refinement were performed with the programsDENZO [15] and COLLECT [16] and multi-scan absorption corrections were appliedto all intensity data with the program SORTAV [17]. Structures were solved andrefined with the programs SHELX97 and SHELXL97, respectively (Table 1) [18].Carboxylic group H-atoms were located in the final difference maps: the coordinatesof these protons were refined successfully. All other hydrogen atoms were placedin calculated positions. RPLUTO [19,20] was then used to visualise the structuresand to quantify interatomic distances and angles.

Table 1Single crystal data for the co-crystals A (n � 1) to D (n � 7)

Co-crystal A (n � 1) B (n � 3) C (n � 5) D (n � 7)

CCDC Deposit No. 1294/221 1294/222 1294/223 1294/224Chemical formulae C26H28N4O12 C10H13NO5 C17H22N2O6 C14H21NO5

Formula weight 588.52 227.21 350.37 283.32Crystal system Monoclinic Triclinic Monoclinic MonoclinicSpace group P2/n P1 C2/c P21/cT, oC �93 (2) �93 (2) �93 (2) �93 (2)a, A 19.2130 (9) 5.437 (2) 19.8276 (10) 16.6443 (7)b, A 4.0306 (3) 9.592 (2) 5.1350 (3) 5.0355 (4)c, A 19.5084 (12) 11.797 (2) 17.4007 (10) 18.2134 (12)a, deg 90.00 66.500 (10) 90.00 90.00b, deg 114.668 (4) 81.640 (10) 102.983 (3) 103.085 (4)g, deg 90.00 83.000 (10) 90.00 90.00V, A3 1372.86 (15) 556.8 (3) 1726.36 (17) 1486.87 (17)Z 2 2 4 4rcalcd. g, cm�3 1.424 1.355 1.348 1.266m, mm�1 0.114 0.110 0.103 0.096R[F2�2s(F2)] 0.0562 0.0628 0.0419 0.0491wR(F2) 0.1529 0.1242 0.0989 0.1056


3. Results

All the odd carbon length acids chosen were successfully co-crystallised with 2-pyridone, and their structures are summarised below. Each consisted of supramolecu-lar infinite tapes composed of 2-pyridone dimers separated by acid spacers with motifI, similar to those reported by Aackeroy et al. (Table 1).

3.1. Co-crystal structure with malonic acid (A, n � 1)

A 1:2 acid:base co-crystal was isolated in the P2/n space group with two crystallo-graphically independent asymmetric units in the unit cell, both made from a malonicacid and a 2-pyridone residue (Fig. 1a). Interestingly, the 2-pyridone residues aredisordered such that the atom site occupancy of N1 and N1A are both 50% and N2and N2A are 75% and 25%, respectively. Both malonic acid residues interact with2-pyridone dimers, through motif III (Scheme 1), to form buckled tapes that reflectthe geometry around the central methylene carbon atom of the acid.

Tapes then stack along the b-axis through C7–H%O3 and C7–H%O3C interac-tions in tape a and C14–H%O5 and C14–H%O5A for tape b (Fig. 1b). Tapes inadjacent stacks form C–H%O interactions between the 2-pyridone ring and the oxy-gen atoms of the acid, to form buckled β-sheets (Fig. 1c).

3.2. Co-crystal structure with glutaric acid (B, n � 3)

The 1:1 complex crystallises in the triclinic space group P-1 (Fig. 2a). The crystalsare composed of flat tapes formed by motif III, through O3–H%O1 interactions andC5–H%O2 interactions, with additional O5–H%O4 interactions to form the aciddimer. The conformation of glutaric acid within the co-crystal is different to thatfound for the case of pure malonic acid in that the terminal acid groups are synperi-planar. Tapes are stacked along the a-axis, and interact through C9–H%O2 hydrogenbonds (Fig. 2b). Tapes, in adjacent stacks, interact through weak C2–H%O5 andC3–H%O4 interactions to form flat β-sheets (Fig. 2c), which have the same structureas those formed from glutaric acid and phenazine [10,11].

3.3. Co-crystal structure with pimelic acid (C, n � 5)

Monoclinic co-crystals (acid:base ratio 1:2) were formed in the space group C2/c(Fig. 3a). Crystals are composed of buckled tapes that accommodate the acid groupsin a cis orientation and allows for the formation of the observed tape topology. Tapesare maintained by motif III through C5–H%O2, and O3–H%O1 interactions, whichare longer than found in the previous two co-crystals (Table 2). Tapes are stackedalong the b-axis through two hydrogen bonds; C7–H%O3 and C7–H%O1. The for-mation of β-sheets is made through C3–H%O2 interactions between the neighbour-ing 2-pyridone ring and carbonyl group of the acid (Fig. 3c). Comparison of Fig. 3cwith Fig. 1c shows the similar packing, where both patterns are viewed down thecrystallographic axis in P2/c and C2/c, respectively.


Fig. 1. (a) Structure A. (b) Tapes stack along the b-axis with the C–H%O interactions between the acidmethylene group and neighbouring acid carboxyl groups. (c) β-Sheet formed by C–H%O interactionsbetween tapes.


Fig. 2. (a) Structure B. (b) Tapes stack along the a-axis with the C–H%O interactions between neigh-bouring acid molecules. (c) A planar β-sheet is generated through edge-to-edge packing of tapes.

3.4. Co-crystal Structure with Azelaic Acid (D, n=7)

Crystals of a 1:1 composition were obtained in the space group P21/c (Figure 4a).The co-crystal is composed of tapes that consist of motif III formed by O3-H%O1and C5-H%O2 interactions. Acid dimers are maintained by O5-H%O4 interactions.Tapes adopt the same overall tape structure as for B. Tapes are again stacked alongthe b-axis through C7-H%O1 interactions (Figure 4b). The acid conformation isdifferent to all others presented here, diverging from the normal extended alkanechain by a gauche twist at the C12-C13 bond as exemplified by the different torsionangles at both ends of the acid. One side has a torsion angle, C6-C7-C8-C9, of


Fig. 3. (a) Structure C. (b) Tapes are stacked along the b-axis and interact through C–H%O betweenneighbouring acids. (c) Buckled β-sheet structure formed by C–H%O interactions.


Table 2Summary of intermolecular interactions within tapes

Co-crystal D–H–A H–A/A D–A/A D-H–A/deg

Aa O3–H%O1 1.53 (5) 2.59 (6) 179 (2)C5–H%O2 2.638 3.353 132N1–H%O1 1.93 2.79 (6) 163.2N1A–H%O1A 1.94 2.79 (6) 163.4

Ab O6–H%O4 1.43 (3) 2.57 (4) 168 (2)C12–H%O5 2.532 3.325 141N2–H%O4 1.93 2.80 (4) 171.3N2A–H%O4A 1.95 2.77 (14) 153.9

B O3–H%O1 1.58 (3) 2.600 (3) 175 (3)C5–H%O2 2.439 3.277 147N1–H%O1 1.93 2.809 (3) 172.8O5–H%O4 1.68 (3) 2.619 (3) 172 (3)

C O3–H%O1 1.742 (19) 2.6273 (15) 171.4 (16)C5–H%O2 2.645 3.524 154N1–H%O1 1.87 2.7502 (14) 179.4

D O3–H%O1 1.77(2) 2.611 (2) 174 (2)C5–H%O2 2.462 3.312 149N1–H%O1 1.91 2.7827 (19) 173.8O5–H%O4 1.73 (3) 2.654 (2) 174 (2)

approximately 75o, whereas the other has a torsion angle, C11-C12-C13-C14, ofapproximately 7o. This results in an overall anticlinal conformation of the acid witha 126o angle between the terminal acid groups. Another interesting observation isthat adjacent stacked tapes are packed non-parallel and are twisted relative to eachother. An inter-stack angle of approximately 56o creates a criss-cross arrangementof stacks, which interact through C9-H%O5 and C12-H%O3 interactions betweenadjacent acid molecules (Figure 4c).

4. Discussion

The 2-pyridone dimer (R22(8)) is formed by two N–H%O interactions, in agree-

ment with the results of Aakeroy et al. Its persistence in each co-crystal shows thisbimolecular motif to be robust [12]. The planarity of both the R2

2(8) and R23(9) motifs

causes the tape topology to be dictated by the acid backbone conformation. Forexample, tapes in A and C are buckled due to the buckled nature of the correspond-ing acids.

Interestingly, tapes in the co-crystals of glutaric acid (n � 3) with phenazine, andglutaric acid with 2-pyridone are composed of very similar β-sheet structures. Bothsystems crystallise in the same space group with very similar unit cell lengths, butdiffer in the overall packing of the sheets. Significantly, the regular formation oflinear supramolecular tapes when using the more flexible longer acids is observed,in agreement with the work of Aakeroy et al. [12].


Fig. 4. (a) Structure D. (b) Tapes are stacked along the b-axis through C–H%O interactions. (c) Adjacentstacks of tapes are twisted relative to each other.

The packing of adjacent tape stacks in D is particularly interesting as they aretwisted relative to each other. A similar observation was made by Batchelor et al.[11] who found that in co-crystals of succinic acid (n � 2) with phenazine, adjacenttapes were twisted almost normal to each other. An explanation for this observation,


published by Schweibert et al. [21], is that greater acid length will favour the twistingof adjacent tapes so that close packing will be achieved by filling voids.

The co-crystals with malonic acid (n � 1) and pimelic acid (n � 5), in whichboth acids adopt a cis conformation of their terminal acid groups, have the sametape composition as the tapes reported by Aackeroy et al. [12], but produce buckledtapes as opposed to planar tapes. However, the trans conformation of the terminalacid groups, in the co-crystals of glutaric acid (n � 3) and azelaic acid (n � 7),produce tapes with 1:1 composition of acid:base. This implies that tape compositionis independent of whether the acid backbone consists of an even or odd number ofcarbon atoms, but rather is dependent on the conformation of the acid.

The effect of acid length on the structure of tapes reported here can be quantifiedwith the slip-angle used by Hamilton et al. [22]. They co-crystallised a selection ofdicarboxylic acids with n � 4, 6 and 10, for example, with 2-aminopyridone deriva-tives and observed the change in the tape topology, of constant acid:base ratio, asthe acid length or base width was changed. If the acid spacer increased in length orif the base decreased in width, the slip angle changed accordingly. The width of the2-pyridone dimer is approximately constant, and so the slip angle is dependent onthe length of the acid spacer. Additionally the slip angle of tapes composed of oddcarbon length acids may be divided into two groups (Table 3); one for tapes com-posed of 1:2 acid:base (ca 85°) the other for 1:1 acid:base (ca 64°).

5. Conclusion

We have shown that it is possible to co-crystallise 2-pyridone with odd carbonlength dicarboxylic acids. The robust nature of the 2-pyridone dimer is demonstrated.Our strategy of using 2-pyridone as a bimolecular analogue of phenazine is shownto be partially successful for the case of glutaric acid for which similar β-sheets areformed with 2-pyridone and phenazine [11]. In the case of malonic acid (n � 1),however, the tapes formed with 2-pyridone and phenazine are different—with thephenazine tapes involving the formation of acid–acid pairs.

Combined with the work of Aackeroy et al., the formation of supramolecular tapesis observed in all the co-crystals irrespective of whether even or odd carbon lengthacids, ranging in length from n � 0 to n � 8, are used. Tape composition appears

Table 3Summary of slip angle of the tapes

Acid Slip angle, deg

Aa 85Ab 86B 65C 82D 64


to be dependent on the conformation of the acid backbone whereas buckled and flattapes are observed, irrespective of whether they contain even or odd acids.

Acknowledgements

We wish to thank both the EPSRC and the Cambridge Crystallographic DataCentre (CCDC) for a CASE award to M.R.E, and for assistance with the purchaseof the diffractometer. We also acknowledge Dr J.E. Davies, N. Shan, and Dr A.Bond for their help in data collection and structure solution.

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influence of dicarboxylic acid structure on tape networks in co-crystals of 2-pyridone

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