Self-Assembling of Zwitterionic Squaramides through Electrostatically

Communication pubs.acs.org/crystal

Self-Assembling of Zwitterionic Squaramides through Electrostatically Compressed Face-to-Face π‑Stacking: A New Supramolecular Synthon Anna Portell,† Mercè Font-Bardia,‡ and Rafel Prohens*,† †

Unitat de Polimorfisme i Calorimetria, ‡Unitat de Difracció de Raigs X, Centres Científics i Tecnològics, Universitat de Barcelona, Baldiri Reixac 10, 08028 Barcelona, Spain S Supporting Information *

ABSTRACT: We report, herein, a novel supramolecular synthon based on the electrostatic compression phenomenon. A zwitterionic squaric acid/squaramide compound serves as a model for the design of new face-to-face π-stacked architectures in the crystalline state which, in combination with charge-assisted hydrogen bonds, can be used to synthesize multicomponent crystals.

C

rystal engineering1 has received much attention in the past few decades, but most particularly during the past

Figure 1. Synthesis of the zwitterionic squaramide 1 and the schematic self-assembling through electrostatic compression.

few years. This is due, in part, to the fact that new crystalline materials can have applications in related areas such as supramolecular chemistry2 and pharmaceutical sciences3 but especially to the impact in terms of improved drug properties and intellectual property.4 The rational design of new crystalline supramolecular architectures is typically based on supramolecular synthons. This probabilistic model only considers the degree of occurrence of a particular pattern of intermolecular interaction. Thus, supramolecular synthons are defined as arrangements of intermolecular noncovalent interactions frequently observed in crystal structures. This model is applied in supramolecular synthesis in such a manner as synthons do in covalent synthesis.5 Therefore, understanding the preference of a functional group for a particular synthon is mandatory in order to design new crystalline materials. In this sense, the research conducted in the past on many different supramolecular arrangements has provided a deep understanding of the nature and mechanisms of the intermolecular interactions that govern their formation and it can help to © 2013 American Chemical Society

Figure 2. Different assembling motifs for 1 expected through chargeassisted H-bonding.

design strategies in order to obtain novel supramolecular structures. Specifically, hydrogen bonding which combines directionality with strength, π-stacking and their mutual Received: July 31, 2013 Revised: September 2, 2013 Published: September 9, 2013 4200

dx.doi.org/10.1021/cg401161d | Cryst. Growth Des. 2013, 13, 4200−4203

Crystal Growth & Design

Communication

Table 1. Crystal Data and Structure Refinement for All the Forms of 118 crystal data

form A

form B

hydrate

cocrystal

formula Mw crystal system space group a, b, c (Å) β (°) V (Å3) Z, Z′ density (Mg/m3) T (K) Mu (mm−1) F(000) reflections collected independent reflections R(int) GOF R1a [I > 2σ(I)] wR2b [I > 2σ(I)]

C8 H12 N2 O3 184.20 monoclinic P21/c 6.249(4), 12.774(6), 11.848(5) 111.29(3) 881.2(8) 4, 1 1.388 293(2) 0.107 392 6771 2152 0.0362 1.117 0.0526 0.1762

C8 H12 N2 O3 184.20 monoclinic P21/c 9.356(6), 9.541(5), 11.672(6) 121.72(4) 886.3(9) 4,1 1.380 293(2) 0.107 392 6714 2160 0.0403 1.122 0.0610 0.1587

C8H12N2O3,H2O 202.21 monoclinic P21/c 6.563(7), 10.844(9), 14.095(11) 103.17(5) 972.7(14) 4, 1 1.381 105(2) 0.111 432 6841 2673 0.0917 0.907 0.0459 0.1135

C8H13N2O3, C4HO4 298.25 monoclinic P21/c 7.470(3), 16.818(4), 11.912(5) 121.09(3) 1281.5(8) 4, 1 1.546 293(2) 0.129 624 12424 3448 0.0332 1.115 0.0603 0.1633

a

R1 = | Fo| − |Fc| /Σ|Fo| bwR2 = {Σ[w(Fo2 − Fc2)2]/Σw(Fo2)2}1/2

Figure 3. Stacked dimers showing dcentroid‑centroid for anhydrous forms I and II.

Figure 5. Supramolecular synthons observed in (a) form I and (b) form II connecting the electrostatically compressed dimers in the crystal. Figure 4. Molecular electrostatic potential surface at the DFT level of computation of isolated geometry from form I crystal structure.

combinations play a key role and have been long and successfully used in supramolecular chemistry.6 In particular, charge-assisted hydrogen bonds have been exploited to build periodical supramolecular structures.7 The electrostatic nature of this type of hydrogen bond usually strengthens the interaction because of the presence of ionic charges on the hydrogen bonding donor/acceptor interacting groups. This charge assistance preserves the hydrogen-bonding directionality while reinforcing the interaction with the help of Coulombic forces.8 In this paper, we intend to explore the combination between the electrostatic compression phenomenon9 together with charge-assisted hydrogen bond in zwitterionic squaramides to design novel supramolecular synthons with the objective of building new crystal architectures. In the last years, there has been an increasing interest in squaramides because of their broad applications in many

Figure 6. Supramolecular synthons observed together with the stacked dimer in the hydrate form.

fields,10 and we have recently described the crystal structures of a family of disecondary squaramides and observed a preference for chains versus ribbons in the solid state as a consequence of a cooperative induction effect.11 On the other hand, squarate salts have been extensively studied in the solid state,12 and a πstacking is observed as a consequence of an electrostatic 4201



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This different interaction motif has important consequences on the connection of the electrostatically compressed dimers in the crystal, producing completely different supramolecular synthons for both polymorphs: R22(10) rings in form I and C(5) chains in form II (Figure 5). On the other hand, in the hydrate form, a different supramolecular synthon is observed. Each compressed dimer interacts with the neighboring dimer in a C(6) motif with water molecules stabilizing the structure through H-bonding interactions with the free carbonyls. The electrostatically compressed dimer that is formed is very similar to the one in form I, with a centroid−centroid distance of 3.52 Å (Figure 6). Since the condensation reaction between squaric acid and the N,N-dimethylethylendiamine is not complete, mixtures of nonreacted squaric acid and 1 are present in the synthesis crude and, unexpectedly, crystals of a different phase were isolated from the reaction mass. The solved crystal structure20 revealed that a new monosquarate/1 salt was obtained. Interestingly, the structure shows another electrostatically compressed motif, which is formed through a combination of a monosquarate anion and two different moieties of 1 in a similar stacked way, as in the anhydrous and hydrate forms of 1, with a centroid−centroid distance of 3.51 Å (Figure 7). The most remarkable feature of this structure is that peripheral Hbonding squaric/squaric interactions are established with the same R22(10) motif previously reported by Mathew et al.,12a suggesting that self-assembled zwitterionic squaramides could be used as efficient coformers for cocrystallization of a variety of donor/acceptor compounds, such as carboxylic acids, ureas, amides, etc. Further investigation in this direction is underway. In summary, guided by a poorly studied phenomenon in chemistry, such as the electrostatic compression, we have designed a new supramolecular synthon based on zwitterionic squaramides. We have studied four crystal structures containing our model compound 1 using X-ray crystallography, and in all four cases, the formation of similar electrostatically compressed π-stacked assemblies is confirmed, which demonstrates the robustness of the synthon. Moreover, these results highlight the potential of this new supramolecular synthon as a tool to synthesize new cocrystals with both H-bond donor and acceptor coformers.

Figure 7. Crystal structure of monosquarate/1 salt.

compression phenomenon. The distances observed between stacked squarate anions are shorter than those in neutral systems; however, this is not the result of a cohesive π interaction, being the interaction electrostatically repulsive,9 but an electrostatic compression from attractive anion−cation interactions.13 With these antecedents, we decided to exploit the strong tendency of squaramides for hydrogen bonding combined with the electrostatic compression phenomenon to design a new supramolecular synthon. Thus, the zwitterionic squaramide/squarate compound 1 was designed as the building block of a new family of supramolecular assemblies and was synthesized in one single step from squaric acid and N,Ndimethylethylendiamine in water.14 The strong acidity of the squaric acid moiety ensures the zwitterionic character of 1, which in combination with a geometrical complementarity can result in self-assembling dimers (Figure 1). In principle, two different supramolecular synthons are geometrically possible through charge-assisted hydrogen-bond interactions if the electrostatically compressed assemblies are formed in the solid state: an R22(10) motif in a self-assembling manner (Figure 2a) and a head-to-tail C motif (Figure 2b) can be established. In order to study this hypothesis, a polymorph screening was conducted. Crystals of three different phases were obtained through crystallization of 1 by slow diffusion of dioxane in dimethylsulfoxide, of toluene in dimethylsulfoxide, and of dichloromethane in water. The structures of two anhydrate polymorphs (forms I and II)15,16 and a hydrate17 were solved by single-crystal XRD (Table 1). Form II crystallized concomitantly with form I in all experiments; however, we were able to isolate flat needles of form II from the crystallization mixture. In the two anhydrous crystal structures similar electrostatically compressed dimers establish complementary N−H···O interactions with adjacent dimers in a ring fashion (Figure 2a). However, squaramide rings in form I are closer to each other than in form II with centroids distances of 3.47 Å and 3.70 Å, respectively (Figure 3). The most important difference lies on the carbonylic oxygen, which is involved in the intermolecular hydrogen bond. While in form I the carbonylic oxygen in anti with respect to the NH is forming the hydrogen bond, in form II this interaction is established by the oxygen in syn. This is the consequence of two geometrically possible H-bond donor/acceptor combinations, since the H-bond acceptor ability of the two available carbonyl oxygen atoms are similar (molecular electrostatic potential minima19 of −330 and −349 kJ/mol, Figure 4).

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ASSOCIATED CONTENT

S Supporting Information *

This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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REFERENCES

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Self-Assembling of Zwitterionic Squaramides through Electrostatically

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