Dielectrically Controlled Priority of Interactions in Molecular Recognition

Article pubs.acs.org/crystal

Dielectrically Controlled Priority of Interactions in Molecular Recognition Agata Białońska* and Zbigniew Ciunik Faculty of Chemistry, University of Wrocław, 14. F. Joliot-Curie, 50-383 Wrocław, Poland S Supporting Information *

ABSTRACT: It was shown previously that formation of brucinium double salts during attempts of racemic resolution of N-(3,5-dinitrobenzoyl)amino acid (alanine or serine) by fractional crystallization of brucinium diastereomeric salts is related to the self-recognition of anions of the amino acid derivatives into dimeric units stabilized by a set of hydrogen bonds (Białońska, A. and Ciunik, A. Why Is the Resolution of Certain Racemic Modifications Inefficient? Formation of Diastereomeric Double Salts of Brucinium. Cryst. Growth Des. 2013, 13, 111−120). Similar dimeric units were observed in brucinium diastereomeric salts precipitated from methanol solutions containing brucine and one enantiomer of the amino acid derivative. To test if the ability of the anions to form dimeric units can be weakened, an increase of dielectric constant of solutions from which the brucinium salts precipitated was applied. In this approach, three new crystalline forms of brucinium salts with enantiomeric N-(3,5-dinitrobenzoyl)serine were obtained. Two of them belong to Z’ > 1 structure, and occurrence of the Z’ > 1 structures is discussed. In the new crystalline forms, a set of hydrogen bonds that stabilizes the dimeric units is replaced by interactions of the anions with solvent molecules, and the anions are linked to each other at most by lone hydrogen bonds. Recognition between cationic and anionic species by ionic N−H+···O− hydrogen bonds, observed in the previously reported crystal structures of brucinium N-(3,5dinitrobenzoyl)-L-serinate 3.88-hydrate and in the new form, brucinium N-(3,5-dinitrobenzoyl)-L-serinate brucine 11.5-hydrate, is precluded by formation of π···π stacking interactions between the anions and brucine molecules as well as by separation of the anions and cations by the extended net of hydrogen-bonded water molecules.

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INTRODUCTION Crystallization is a process that involves, at a high degree of reliability, the phenomenon of molecular self-recognition or molecular recognition depending on whether the asymmetric unit consists of one or more symmetry-independent molecules. The majority of molecular organic crystals result from selfrecognition and are made up of one symmetry-independent molecule. A small proportion of cocrystals, usually resulting from recognition of carefully selected compounds to interact specifically with one another, contains two or more chemically different molecules in the asymmetric unit. Similar to crystallization of cocrystals, crystallization of organic salts results from multicomponent recognition. The appropriate stoichiometry of ions for electroneutrality and some sort of charge ordering combined with the dense packing requirement are responsible for packing differences between salts and cocrystals.1,2 Long-range Coulombic forces exerted by charged particles in every direction are the main factors that stabilize the structure of organic salts. Behind the Coulombic forces there are other, directional-like hydrogen bonds and more diffuse interactions involved in recognition of the particles. Their priority in molecular recognition may have an influence on the resulted crystal structure and its properties. Intermolecular cohesions can be determined by the quantitative evaluation of crystal potentials and forces.3,4 © XXXX American Chemical Society

Presence of characteristic structural motifs in a given group of compounds may indicate a priority of their formation during molecular recognition. By studying mechanisms of molecular recognition during fractional crystallization of diastereomeric salts, the useful method for racemic resolution of organic acids or bases,5 we noticed that the nature of recognition depends upon the resolving agent.6,7 In most crystals of diastereomeric salts of commonly used resolving agent for separation of racemic carboxylic acids, characteristic N−H+···O− hydrogen bonds systems between ions of resolving agent and resolved compound, defined by a single graph set, are present.8−14 In this respect, brucine and strychnine are unique because common self-assemblies of ions of the alkaloids, governed by weak-like C−H···O/π and vdW interactions only, usually are not significantly affected by incorporation of ions of a resolved compound. Therefore, contrary to many diastereomeric salts of the other resolving agents, weak interactions play a crucial role in molecular recognition in brucinium or strychninium diastereomeric salts. Anions of resolved acid or anions together with their solvation sphere have been recognized on the surface of the brucinium or strychninium self-assembly.7 However, Received: September 29, 2014 Revised: November 12, 2014

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dx.doi.org/10.1021/cg501456n | Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

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sample with parafilm results in precipitation of previously reported brucinium N-(3,5-dinitrobenzoyl)-D-serinate methanol 2.5-solvate (BDNBDS) and brucinium N-(3,5-dinitrobenzoyl)-L-serinate 3.88hydrate (BDNBLS). In turn, addition of water instead of methanol leads to formation of the new crystalline form, brucinium N-(3,5dinitrobenzoyl)-D-serinate 4.28-hydrate (BDNBDS1). The thermogravimetric analysis of BDNBDS1 is presented in Figure S1 of the Supporting Information. In turn, solvent evaporation from 10 mL of aqueous solution containing an equimolar amount of brucine, N-(3,5dinitrobenzoyl)-D-serine, and a few drops of methanol results in crystallization of another crystalline form, brucinium N-(3,5dinitrobenzoyl)- D -serinate methanol 0.5-solvate 2.125-hydrate (BDNBDS2). Solvent evaporation from 10 mL of methanol solution containing an equimolar amount of brucine, N-(3,5-dinitrobenzoyl)-Lserine, and a few drops of water leads to crystallization of brucinium N-(3,5-dinitrobenzoyl)-L-serinate brucine 11.5-hydrate (BDNBLS_B). The thermogravimetric analysis of BDNBLS_B is presented in Figure S2 of the Supporting Information. The X-ray diffraction data for all of the brucinium salts were collected on a Xcalibur diffractometer with Sapphire2 detector (Mo− Kα radiation; λ = 0.71073 Å). The data were collected at 100 K using an Oxford Cryosystem device. Data reduction and analysis were carried out with the CrysAlis “RED” program.18 The space group was determined using the XPREP program.19 Structures were solved by direct methods using the SHELXS program and refined using all F2 data as implemented by the SHELXL program.20 In BDNBDS1, most water molecules (O12W−O26W) are disordered. Their occupancy factor was refined. The hydroxyl group of one of four crystallographically unrelated anions is disordered over two positions in the refined ratio of about 3:1. In BDNBLS_B, the refined occupancy factor of disordered water molecules allowed us to group the water molecules into two groups, O7W−O11W and O71W−O121W with the ratio of about 3:1, assuming that the sum of both groups is equal to one. In BDNBLS_B, there is also a water molecule with a partial occupancy factor of 0.26, which regarding distances to neighboring water molecules, belongs to the major group. In BDNBDS2, the arene ring together with the nitro group of one of two crystallographically unrelated N-(3,5-dinitrobenzoyl)-D-serinate anions are disordered over multiple positions. However, we were able to model two-positioned disorder of the arene ring (with refined ratio of 1:1) and fourpositioned disorder of the nitro group (with refined ratio of ca. 1:1:1:1) only. Non-hydrogen atoms were refined with anisotropic displacement parameters. SIMU and ISOR restraints for partially overlapping disordered atoms and for atoms with occupancy factors smaller than 0.5, respectively, were applied during refinement of all structures. H atoms were found in Δρ maps or placed at calculated positions. Before the last cycle of refinement, all H atoms were fixed and were allowed to ride on their parent atoms. The absolute structures were chosen on the basis of the known absolute configuration of brucine.21 Crystallographic details are summarized in Table 1.

anions of an acid can also undergo self-recognition and resulting homo- or heterochiral anionic self-assembly can conduce or preclude racemic resolution.15−17 Formation of homo- or heterochiral hydrogen-bonded dimeric units by anions of N-(3,5-dinitrobenzoyl)amino acid (alaninate or serinate) precluded their racemic resolution by fractional crystallization of brucinium diastereomeric salts.17 Instead of fractional crystallization of diastereomeric salts, double salts precipitated. Similar homochiral dimeric units were observed in crystals of brucinium salts with enantiomeric N(3,5-dinitrobenzoyl)amino acid (alanine or serine) obtained from solutions containing an equimolar amount of brucine and one enantiomer of the amino acid derivative. We wondered if the ability of the anions to form the hydrogen-bonded dimeric units by the anions can be weakened. Such control of a nature of molecular recognition would give a better insight into mechanisms that govern the molecular recognition. After successful dielectrically-controlled spontaneous separation of N-(3,5-dinitrobenzoyl)asparagine,16 a similar approach was applied to weaken the ability of N-(3,5-dinitrobenzoyl)serinate anions to form the hydrogen-bonded dimeric units. An increase in the dielectric constant of the solution containing an equimolar amount of brucine and enantiomeric N-(3,5dinitrobenzoyl)serine by addition of some portion of water resulted in precipitation of new crystalline forms of brucinium N-(3,5-dinitrobenzoyl)-D and of brucinium N-(3,5-dinitrobenzoyl)-L-serinate solvates (Scheme 1). Scheme 1

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EXPERIMENTAL SECTION

Evaporation of solvent from 10 mL of methanol solution containing an equimolar amount of brucine and N-(3,5-dinitrobenzoyl)-D- or N-(3,5dinitobenzoyl)-L-serine leads to formation of an additional liquid phase.17 Careful addition of an extra portion of methanol (1 mL) to that additional liquid phase (without blending) and covering of the

Table 1. Crystallographic Data for Brucinium Salts with N-(3,5-Dinitrobenzoyl)-D- and N-(3,5-Dinitrobenzoyl)-L-serine chemical formulaa chemical fw cell setting, space group a, b, c (Å) β (deg) V (Å3) Z Dc (mg m−3) cryst form, color cryst size (mm) R[F2 > 2σ(F2)], wR(F2), S

BDNBDS1

BDNBDS2

BDNBLS_B

B+A− · 4.28H2O 781.57 monoclinic, P21 8.338(2), 24.218(4), 34.991(4) 91.43(3) 7064(2) 8 1.470 plate, orange 0.46 × 0.43 × 0.15 0.096, 0.184, 0.927

B+A− · 0.5CH4O 2.125H2O 747.96 monoclinic, P21 12.488(3), 9.092(2), 31.175(4) 97.39(3) 3510.2(13) 4 1.415 plate, pale-yellow 0.23 × 0.20 × 0.05 0.054, 0.080, 0.758

B+A− · 11.5H2O 1299.83 monoclinic, P21 20.962(3), 7.304(2), 21.824(3) 114.79(3) 3033.5(12) 2 1.423 needle, orange 0.34 × 0.26 × 0.12 0.055, 0.064, 0.766

B A = C23H27N2O4+ · C10H8N3O8−.

a + −

B



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Figure 1. Common (left) and atypical (right) corrugated layers39 presented in BDNBDS2 and in BDNBDS1, respectively, and a schematic representation of their corrugation and of orientation of brucinium cations in the layers. Positions of the amide O atom from both sides of the layers are marked by black and red triangles.

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RESULTS

In crystals of BDNBDS1, four crystallographically unrelated ion pairs and 26 partially disordered water molecules are in an asymmetric part of the unit cell. Brucinium cations form corrugated layers. The corrugated layers are made up of two crystallographically unrelated brucinium cations. There are two crystallographically unrelated brucinium layers, oriented antiparallel in relation to each other. The layers reveal some features of the common brucinium corrugated layers.22,23 In the common brucinium corrugated layer, the brucinium cation donates to and accepts C−H···O(methoxy) and C−H···π(arene) hydrogen bonds with four neighboring brucinium cations. The amide O atom of the brucinium cation and of its four neighbors is located in concave parts of the opposite sides of the sheet. In the corrugated layer in BDNBDS1, one of two crystallographically unrelated brucinium cations is a donor, and the other is an acceptor of similar hydrogen bonds just as in the common corrugated layer. However, they accept and donate to C−H···O(methoxy) and C−H···π(arene) interactions, respectively, two neighboring brucinium cations, which, contrary to brucinium cations in the common corrugated layer, have the amide O atom in the concave part of the same side of the sheet. Therefore, in BDNBDS1, rows and ridges of the corrugated layer are wider than in the common corrugated layer and have two different amide O- and amine N-sites, respectively (Figure 1). The 3,5-dinitrobenzoyl group of two crystallographically unrelated N-(3,5-dinitrobenzoyl)-D-serinate anions is located in the same row and is involved in C−H···O and N···O interactions with the brucinium layer. The amino acid residue of the anions is directed outward from the layer. Anions located in the same rows of the brucinium layers form dimers stabilized by N−H···O− and O−H···O−(carboxylate) hydrogen bonds or chains stabilized by O−H···O(hydroxyl) and N−H···O− hydrogen bonds. Among anions located in the same row, one has the carboxylate group involved in ionic N−H+···O− hydrogen bonds with brucinium cations of the neighboring corrugated layer, and the carboxylate group of the others is involved in O−H···O− hydrogen bonds with water molecules only. Resulting cationic−anionic structure abounds with two kinds of channels, narrow and wide, that extend along the rows of the brucinium corrugated layer (Figure 2). The narrow channel is occupied by water molecules that form branched discrete eight-membered water chains. The water chains are

Figure 2. Recognition of N-(3,5-dinitrobenzoyl)-D-serinate anions (yellow surface) on the atypical brucinium corrugated layer (blue surface) and the narrow (left) and wide (right) channels occupied by water molecules in BDNBDS1.40,41

bonded to the O atoms of the amide, carboxylate, and hydroxyl groups of the anions as well as to the brucinium amine N atom. Resulting tape is made up of six- and higher-membered rings (Figure 3). The wide channel is occupied by water molecules, which in majority are disordered. In the wide channel, only water molecules directly hydrogen bonded to the anions are ordered. In crystals of BDNBDS2, two crystallographically unrelated ion pairs, methanol and 4.25 water molecules, are in an asymmetric part of the unit cell. Brucinium cations form the common corrugated layers (see Figure 1).22,23 Neighboring brucinium layers are separated by crystallographically unrelated thick and thin anionic/solvent sheets (Figure 4). The only similarity between the anionic/solvent sheets is presence of ionic N−H+···O− hydrogen bonds with the brucinium layer and O−H···O− hydrogen bonds between the hydroxyl and carboxylate groups, which result in anionic chain formation that extends along the row of the brucinium layer. The same carboxylate O atom is involved in the N−H+···O− and O−H··· O− hydrogen bonds. In the thick anionic/solvent sheet, the other carboxylate O atom is bonded to methanol and water molecules (Figure 5a). The water molecule is also bonded to the amide O atom of the brucinium cation and to another water C



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Figure 3. Hydrogen bonds system between water molecules and anionic self-assemblies in the narrow channel of BDNBDS1.42

Figure 5. Hydrogen-bonded anionic chains and solvent molecules in the thick (a) and thin (b) anionic/solvent sheets in BDNBDS2. In the think anionic/solvent sheets, anions are partially disordered, and the disordered nitro group is likely involved in N···O interactions.42

disordered nitro group of neighboring anionic chains likely is involved in N···O interactions. In this anionic/solvent sheet there is also a water molecule with a partial occupancy. Surrounding of the water molecule suggests that it can be involved in hydrogen bonds with a hydroxyl group and some component of the disordered nitro group. In the thin anionic/ solvent sheet, one water molecule is bonded to the hydroxyl and carboxylate groups of the same anion. The other water molecule is bonded to the just mentioned water molecule and to the amide O atom of a neighboring anion (Figure 5b). The amide N atoms of the anion form a hydrogen bond with the amide O atom of brucinium cations. The nitro groups of the ordered anions are involved in C−H···O hydrogen bonds with brucinium layers, and one of them is additionally involved in N···O interaction with the water molecule. In crystals of BDNBLS_B, one brucinium−N-(3,5-dinitrobenzoyl)-L-serinate ion pair, brucine and 12 partially disordered water molecules are present in an asymmetric part of the unit cell. The brucine molecule and N-(3,5-dinitrobenzoyl)-Lserinate anion are assembled by π···π stacking interactions. The arene ring of brucinium cations is bonded to the stacking assembly by a C−H···π hydrogen bond, and the amide O atom of the cations is involved in C−H···O hydrogen bonds with the neighboring stacking assembly, which results in a mixed bilayer (Figure 6). There are small channels in the bilayer sheets occupied by three crystallographically unrelated water molecules. The water molecules form discrete three-membered water chains, which are bonded to the amine, the ether atoms of neighboring brucine molecules, and the hydroxyl and carboxylate groups of neighboring N-(3,5-dinitrobenzoyl)-Lserinate anions. Consecutive bilayer sheets are separated by partially disordered water molecules (in the ratio of 3:1). By

Figure 4. N-(3,5-dinitrobenzoyl)-D-serinate anions in thin (black) and thick (red) anionic/solvent sheets between common brucinium corrugated layers (top) in BDNBDS2.39 Various recognitions of the anions on surfaces of the brucinium layer (bottom).40,41

molecule. The latter is bonded to the amide O and N atoms of neighboring anions of the chain. One of the nitro groups of the anion is directed toward the row of the corrugated brucinium layer and together with the amide O atom of brucinium cations forms N···O interaction. The other nitro group and the arene ring of the anions reveal a large degree of disorder. The D



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reported crystal structures, anions form dimeric units stabilized by a set of N−H···O− hydrogen bonds. In BDNBDS1, only two of four crystallographically unrelated anions form dimers. In BDNBDS2, anions form chains in which neighboring anions are linked to each other by lone hydrogen bonds. In BDNBLS_B, anions are completely separated from each other. The tendency of the anions to form the hydrogen bonded dimeric units drastically decreases when some amount of water has been added to the solutions from which the brucinium salts precipitate. Simultaneously, it can be observed that the anions in the above-described crystal structures form expanded networks of hydrogen bonds with water molecules. It manifests that hydration of the anions influences a decreased ability of the anions to form hydrogen-bonded dimeric units. Addition of water to the solutions leads also to a gain of importance of weak interactions such as C−H···O, C−H···π, and vdW. In the previously reported crystal structure of BDNBDS, the brucinium methoxy O atoms are involved in O− H···O hydrogen bonds. In BDNBDS1 and BDNBDS2, the brucinium methoxy O atoms are involved in weak C−H···O hydrogen bonds. The importance of weak interactions is also observed in recognition of N-(3,5-dinitrobenzoyl)-D-serinate anions on the surface of brucinium self-assemblies. Formation of the atypical brucinium corrugated layer in BDNBDS1 allows for a large hydrophobic 3,5-dinitrobenzoyl group of the anions to be hidden, which leaves more hydrophilic parts of the anions exposed to interactions with solvent molecules. It is worth noting that such recognition precludes the ionic N−H+···O− hydrogen bond formation for two of four crystallographically unrelated anions. In BDNBDS2, the atypical for brucinium salts with N-aroylamino acids interaction of the amide N atom of the anions with the amide O atom of brucinium cations is combined with recognition of the 3,5-dinitrobenzoyl group on the surface of the brucinium corrugated layer by weak interactions. BDNBLS_B compared to the previously reported crystal structure of brucinium N-(3,5-dinitrobenzoyl)-L-serinate 3.88-hydrate is probably the most distinguished example (for brucinium salts) of an increased importance of weak interactions in molecular recognition with increased ratio of water to methanol in solution. In BDNBLS_B N-(3,5dinitrobenzoyl)-L-serinate anions, brucinium cations and brucine molecules are linked to each other only by weak hydrogen bonds like C−H···O and C−H···π, π···π stacking, and vdW interactions, which lead to mixed assembly appropriate for hydration. To conclude this paragraph, comparison of the crystal structures of brucinium salts with enantiomeric N-(3,5dinitrobenzoyl)serine obtained by crystallization from methanol solution or methanol solution with the addition of water reveals a direct link of recognition in solution with the resulted solid, where the addition of water to the methanol solution of brucinium N-(3,5-dinitrobenzoyl)-D- or brucinium N-(3,5dinitrobenzoyl)-L-serinate leads to more effective recognition of the hydrophobic moieties, and hydration of the hydrophilic moieties weakens the ability of hydrogen bonds to selfassemble. In a similar way, a change of dielectric constants of solution, achieved by the addition of water, change of solvent, temperature of crystallization, or other factors, can affect the molecular recognition nature of other systems. In our previous paper,15 focused on a recognition in brucinium salts with N-(4nitrobenzoyl)asparagine, we showed that “in low temperature, the system favors hydrophobic recognition, while higher temperature encourages the system to synthon propagation into hydrogen-bonded anionic self-assembly,” which is

Figure 6. Mixed bilayers made up of brucine molecules and brucinium cations (blue surface) and N-(3,5-dinitrobenzoyl)-L-serinate anions (yellow surface) separated by water molecules in BDNBLS_B.40,41

taking into account the major component of the disorder, water molecules form tapes made up of two crystallographically unrelated five-membered rings coupled with one another. Moreover, a chain of three water molecules is bonded to one of the five-membered rings. By taking into account the amide O atom of the anions bonded to the water chain and to the five membered water ring, the type is extended on six-membered rings. In turn, the carboxylate group, bonded to three water chains, links neighboring water tapes into a layer and generates another six- and a ten-membered ring (if only the O atoms are counted, Figure 7). Water molecules of the layer are bonded to the amide O and to the amine N atoms of brucine molecules and brucinium cations, respectively.

Figure 7. Hydrogen bonds network between water molecules and N(3,5-dintrobenzoyl)-serinate anions in BDNBLS_B. For clarity, minor components of disordered water molecules are omitted.42

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DISCUSSION The above results combined with the previously reported crystal structures of diastereomeric brucinium salts with enantiomeric N-(3,5-dinitrobenzoyl)serine17 show that a nature of molecular recognition in these systems is very sensitive to conditions under which the salts precipitate. In the previously E



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disordered N-(3,5-dinitrobenzoyl)-D-serinate anions in the thick anionic/solvent sheets are recognized on the surface of the brucinium layer in a similar way to the disordered N-(3,5dinitrobenzoyl)-D-alaninate anions in the previously reported crystal structure of brucinium N-(3,5-dinitrobenzoyl)-D-alaninate methanol 0.83-solvate 2.17-hydrate.17 However, there is only one kind of anionic/solvent sheet in the latter; therefore, the differentiation of surfaces of the brucinium corrugated layers in BDNBDS2 must be induced by recognition of the ordered anions. The ordered anions, by bonding to three brucinium cations of the same corrugated layer by N−H+···O−, N−H···O, and C−H···O(nitro) hydrogen bonds (and vdW interactions), stabilize the brucinium corrugated layer and bring on a reorientation of the brucinium cations. Formation of the N−H+···O− and N−H···O interactions causes a decrease in the distance between the amide O and methoxy C atoms of brucinium cations bonded to the anions in the recognized surface and an increase in the suitable distance in the opposite surface (the O(amide)···C(methoxy) distances were chosen as the indicator of a surface differentiation because both of the atoms are located in the row of the corrugated layer and are relatively colinear). In turn, the O(amide)···C(methoxy) distance between brucinium cations bonded to the anions by N−H···O and C−H···O(nitro) interactions increases and decreases in the recognized and opposite surfaces, respectively. The difference of the O···C distances in both surfaces is equal to about 0.4 Å (>10%). The changes caused by the recognition of the ordered anions on one surface preclude similar recognition of anions on the opposite surface. Therefore, the opposite surface is recognized by the anions in another way. The resulting surface of the recognized ordered anions on the brucinium layer is relatively flat, and it was previously reported for fractional crystallization of diastereomeric salts that formation of anionic/cationic supramolecular structures with relatively flat surface advantages faster crystallization.10

consistent with the above conclusion. Dependent on dielectric constants, a change of molecular recognition nature also has been manifested in crystals as the results of crystallization from solution prepared by dissolvation of anhydrous components and of recrystallization of resulted hydrate. Crystals of distrychninium N-(4-nitrobenzoyl)-D-glutamate hydrates are one such example where the 4-nitrobenzoyl group of the anions is directed outward in a surface of the strychninium selfassembly (in the product of crystallization) or is hidden in a deep row in a surface of the strychninium self-assembly (in the product of recrystallization).24 Sakai et al.25,26 showed that a change of dielectric constant of solvent can affect fractional crystallization order during racemic resolution of some amines in which N-tosyl-(S)-phenylalanine, (S)-mandelic acid, or (R,R)-tartaric acid were used as the resolving agents. A less soluble diastereomeric salt that crystallizes from one solvent/ mixture of solvents is more soluble than diastereomeric salt that crystallizes from another solvent/mixture of solvents. Among brucinium, strychninium, quininium, and cinchonidinium salts, there are also known examples of a change of fractional crystallization order that depends on an applied solvent or mixture of solvents.5 It is likely that the change of dielectric constant affected molecular recognition and hence the order of fractional crystallization in those systems. Recently we showed that separation of hydrophobic from hydrophilic parts of N(3,5-dinitrobenzoyl)asparagine molecules depends on the dielectric constant of the solvent used for crystallization.16 The above-mentioned examples show that dielectrically controlled molecular recognition can be applied to a wide range of ionic as well as molecular compounds. Information on intermolecular interactions can also facilitate the synthesis of suitable polymorphs predicted in techniques of crystal structure prediction. For a long time, crystals containing multiple molecules in the asymmetric unit (Z’ > 1 structures) have been of interest in many areas of crystal engineering.27−29 Various reasons for their occurrence have been proposed, for example, synthon frustraction,30 conformational flexibility,31,32 self-inclusion,33 or kinetic trapping in the metastable state.34 Twenty-one of 94 (ca. 22%) crystal structures of brucinium salts for which crystal data is deposited in the Cambridge Structural Database35 are Z’ > 1 structures. The percentage of Z’ > 1 structures in this group of compounds is higher than for all organic structures deposited in the CSD (ca. 11.5%).36 Brucinium cations often form layered structures, and in the Z’ > 1 structures crystallographically unrelated anions are located in the same anionic/solvent sheets between the brucinium layers. By taking into account cationic substructures, BDNBDS1 is one of two exceptions of Z’ > 1 structures of brucinium salts37 in which crystallographically unrelated brucinium cations are differently surrounded by neighboring brucinium cations. BDNBDS1 could belong to Z’ = 2 structures and to the space group P2 12 1 2 1 . Comparison of BDNBDS1 with isostructural brucinium N-(3,5-dinitrobenzoyl)-D-alaninate hydrate38 shows that the presence of four crystallographically unrelated ion pairs instead of two is related to interactions of the anions and especially of their hydroxyl group with water molecules. By taking into account crystallographically unrelated anionic/solvent sheets, BDNBDS2 is unique. It is intriguing that the anionic/solvent sheets in BDNBDS2 are completely different (see Figure 5). Surfaces from both sides of the brucinium corrugated layer must undergo differentiation during the recognition of N-(3,5dinitrobenzoyl)-D-serinate anions. The

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CONCLUSIONS By crystallization of three new crystalline forms of brucinium salts with enantiomeric N-(3,5-dinitrobenzoyl)serine, brucinium N-(3,5-dinitrobenzoyl)- D -serinate 4.28-hydrate (BDNBDS1), brucinium N-(3,5-dinitrobenzoyl)-D-serinate methanol 0.5-solvate 2.125-hydrate (BDNBDS2), and brucinium N-(3,5-dinitrobenzoyl)-L-serinate brucine 11.5-hydrate (BDNBLS_B) and comparison of their crystal structures with the previously reported crystal structures of brucinium salts with enantiomeric N-(3,5-dinitrobenzoyl)serine, we showed that the nature of recognition in these systems is sensitive to the condition under which the recognition occurs. By an increase of the dielectric constant of the solutions, selfrecognition of N-(3,5-dinitrobenzoyl)serinate anions, observed in the previously reported crystal structures of brucinium N(3,5-dinitrobenzoyl)-D-serinate methanol 2.5-solvate and brucinium N-(3,5-dinitrobenzoyl)-L-serinate 3.88-hydrate, is replaced by recognition of solvent molecules by the anions. Additionally, recognition between cationic and anionic species by ionic N−H+···O− hydrogen bonds, observed in the previously reported crystals of brucinium N-(3,5-dinitrobenzoyl)-L-serinate 3.88-hydrate, in BDNBLS_B, is precluded by formation of π···π stacking interactions between the anions and brucine molecules as well as by separation of the anions and cations by the extended net of hydrogen-bonded water molecules. F



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In BDNBDS2, recognition of N-(3,5-dinitrobenzoyl)-Dserinate anions on a surface of the brucinium corrugated layer induces a differentiation of both surfaces of the layer. The induced differentiation of the surfaces of the brucinium layer precludes similar recognition of the anions from both sides of the layer, which leads to the formation of the Z’ = 2 structure in which two completely different anionic/solvent sheets are present.

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ASSOCIATED CONTENT

S Supporting Information *

Crystal data for BDNBDS1, BDNBDS2, BDNBLS_B, and TGA curves. 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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ACKNOWLEDGMENTS We thank the Ministry of Science and Higher Education of Poland for their financial support and Grant No. 1486/M/ WCH/11.

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REFERENCES

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Dielectrically Controlled Priority of Interactions in Molecular Recognition

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