CRYSTAL GROWTH & DESIGN
A Simple Strategy for Crystal Engineering Water Clusters
2007 VOL. 7, NO. 12 2649–2653
Benedict C. R. Sansam, Kirsty M. Anderson, and Jonathan W. Steed* Department of Chemistry, Durham UniVersity, South Road, Durham, U.K., DH1 3LE ReceiVed September 25, 2007
ABSTRACT: We report the X-ray crystal structure of the protonated phenazine-2,3-diamine cation (3) salt (3)2SeO4 · 6H2O (4), which contains a discrete water decamer. This material is representative of a broad strategy to bring about the occurrence of solidstate water clusters in ionic structures by the combination of amphiphilic ions with large hydrophobic residues in combination with small, highly charged counterions. The strategy is illustrated by a wide range of examples taken from the Cambridge Structural Database (CSD). Introduction The self-assembled structure of water and the way it interacts with dissolved solutes and with hydrophobic surfaces continue to be highly topical.1–5 Science ranked the study of water among the top 10 breakthroughs in 2004.6 A number of high-quality fundamental solid-state structural studies exist that have described water clusters, chains, and sheets in various crystalline solids with the analysis of water in the single crystal neutron structure of vitamin B12 coenzyme representing a classic in the field.7 In addition, water motifs have been classified systematically,8 and the subject has been reviewed by Nangia.9 There have been a number of recent X-ray structure reports of water in a plethora of environments, of possible relevance to the structure of ice and the nature of water interactions with solutes, particularly biomolecules.10–20 Mascal et al. have sounded a note of caution on claims of new water cluster types, however.21 The formation and structure of solid-state hydrates, and cocrystals22 in general also continues to be a topic of major interest to the pharmaceuticals industry.23–26 From a detailed structural perspective, the key questions to be addressed are what effect do water molecules have on their neighbors and on their surroundings, and how do water–water interactions compete with water-solute (or, in the solid state, hydrate-host) interactions? Hence what effect does hydrate formation have on physical properties such as solubility, dissolution profile, and crystal mechanical strength? Some basic rules have been suggested for the formation of hydrates; they tend to arise from the presence of excess hydrogen bond donors in crystals, and they are more common in ionic compounds and are very rare for hydrophobic compounds (although water diffusion into a “nonporous”, hydrophobic material has been noted recently27).28 A very recent report highlights the particular importance of sum of the average donor and acceptor counts for the functional groups.29 Work by Champness and co-workers has resulted in a strategy for encouraging the formation of extended water arrays in molecules that contain a 1,4-dihydroquinoxaline-2,3-dione core.30 However, comparative studies on water clusters in crystals are hampered by the serendipitous nature of the occurrence of hydrates and the unpredictability of their structures. In this paper,
* To whom correspondence should be sent. E-mail:
[email protected]. Tel: +44 (0)191 334 2085. Fax: +44 (0)191 384 4737.
we discuss some preliminary observations toward a more general strategy to design and control hydrate formation. Results and Discussion The general solid-state structure of amphiphilic molecules tends to be of a layered or bilayer type in which the hydrophobic portions of the molecule aggregate separately from the hydrophilic ends. Examples include pillared organic sulfonates,31 surfactants,32 or the claylike bilayer arrangement of calix[4]arenesulfonate.33 In ionic systems, there is typically a hydrophilic layer comprising the ionic end(s) or regions of the molecule, counterions, and solvent–water. We reasoned that, as in pillared sulfonates, the spacing between counterions in systems exhibiting contact ion pairing is a direct mirror of the spacing between the ionic portions of the organic molecule, which is in turn dependent on the length and shape of the hydrophobic portion. Furthermore, we observe that in cases where the organic portion of the molecule is large the result is a gap between counterions that is typically filled by water molecules that solvate the counterions. This is particularly true in the case of highly charged hydrophilic counterions such as SO42- or HPO42-. The key hypothesis is that in charged hydrophilic systems, in the absence of suitable large guest molecules, the gap that must be filled by water molecules and hence the size of the water cluster within the crystal can be controlled by the choice of an organic spacer unit. It should prove possible to achieve particularly good control (although not perhaps rigorous predictability) by spacing a number of ionic, hydrophilic groups along a hydrophobic chain. The general concept is illustrated schematically in Figure 1. Specific examples come from our previous work on salts of aliphatic polyamines,34 particularly oxyanion salts.35 The triammonium hydrogen phosphate salt [NH3(CH2)6NH2(CH2)6NH3]2(HPO4)3 · 12H2O (1) crystallizes in an arrangement with two independent triprotonated polyamines and three independent dianions. The double negative charge of the anion and the length of the hexyl spacer results in a significant interanion cavity that is filled by water (Figure 2a). The charge balance arrangements are such that the length of the spacer is slightly too short to accommodate two water molecules, and hence the HPO42- · · · H2O · · · H2O · · · HPO42- repeating unit (Figure 2b) is at a slight diagonal to the major axis of the polyammonium cation. We postulate that this kind of arrangement occurs frequently by serendipity whenever a salt comprising a large organic ion and small, multiply charged counterion crystallizes in the
10.1021/cg700932s CCC: $37.00 2007 American Chemical Society Published on Web 11/20/2007
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Figure 1. Design hypothesis - the size of the water clusters between counterions should parallel the length of the organic spacer. It will also depend on the number and size of the counterions. Fewer, more highly charged ions will leave more space for water inclusion.
presence of water. Or, more generally, water clusters fill hydrophobic voids within ionic structures. To test this hypothesis, we undertook a qualitative Cambridge Structural Database (CSD)36 survey of the X-ray structures of organic amine sulfates containing at least one water–water hydrogen bond. The search revealed a plethora of examples that fit this model (see Supporting Information). A typical example is the structure of cyclo(H-streptolutyl-H-streptolutyl) sulfate pentahydrate (ANTSUL10).37 The small SO42- anions leave large void spaces between them because of the size of the hydrophobic portions of the cyclo(H-streptolutyl-H-streptolutyl) dications. The void space is the width of four water molecules that form a continuous sheet running through the structure, Figure 3. Another example is agmatine sulfate dihydrate (BINWUQ) in which the hydrophobic fragment is about the width of a single water molecule giving rise to a one-dimensional chain, Figure 4.38 Particularly striking is the structure of melemium sulfate dihydrate (MAYGEZ) in which the voids between the large, flat melemium cations are spanned by pairs of discrete water molecules that link sulfate anions together. The length correspondence between the H2O · · · H2O · · · SO42- combination and the aromatic dication is evident, Figure 5.39 An interesting case study is the o-phenylenediammonium
cation 2, which contains the combination of the hydrophobic aryl ring and hydrophilic ammonium groups. As a sulfate salt, it forms a sesquihydrate in which a so-called “flip-flop” water chain of squares bridges the hydrophobic space between pairs of back-to-back cations.40 As an aside, the non-hydrogen bonded SO42- · · · O4S2- O · · · O contacts in this work seem to stem from the fact that pairs of anions are bridged by pairs of dications and are hence brought into a presumably repulsive short contact rather than any stabilizing “strong, non-covalent O · · · O interaction”. Depending on crystallization pH, a closely related mixed anion salt {C6H4(NH3+)2}8(SO4)6(HSO4)4 · 8H2O with eight crystallographically independent dications (albeit with a formal41–43 Z′ ) 2) can also be isolated.44 Once again the water molecules, this time as a discrete (H2O)4 unit, bridge the gap between back-to-back aryl rings,while the anions are concentrated in the hydrophilic region close to the ammonium functionalities. The hydrogen bonded distances within the
Sansam et al.
(H2O)4 units are such as to suggest possibly dynamic proton transfer from HSO4- to give at least one oxonium ion per eight water molecules, and this is the subject of further current study in our group. As with compound 1, the principle is not limited to sulfate or sulfonate salts. A search for selenates reveals the more complicated example of the structure of streptomycin oxime selenate tetrahydrate.45 The complex, multifunctional nature of the streptomycin derivative results in significant interactions between the cationic molecules, anions, and to some extent the water molecules. However, the large size of the cation and small size of the 2- anion leaves a gap in the structure that is bridged by a discrete water hexameric chain that bridges a hydrophobic region in the packing of the cations and parallel the spacing of two adjacent SeO42- anions, Figure 6. Following our work on o-phenylenediamine (2) sulfate derivatives,44 we attempted to prepare selenate analogues. In fact, H2SeO4 is a sufficiently strong oxidizing agent that on reaction of o-phenylenediamine with H2SeO4 in aqueous solution we obtained a hexahydrate selenate salt of the protonated phenazine-2,3-diamine cation (3), namely, (3)2SeO4 · 6H2O (4). Cation 3 has been previously reported as a monohydrate salt with the univalent perchlorate anion, and as a trihydrate with the smaller chloride.46,47 The water is arranged in an infinite 1D chain in the former case, while the latter contains broader infinite channels several water molecules wide. It is interesting to note that the smaller chloride anion salt requires more water to bridge the cations than the perchlorate analogue, although this is not always the case in comparing related salts in more conformationally versatile systems. The structure of 4 comprises two crystallographically unique monocations and a selenate dianion. In comparison with the 1:1 perchlorate and chloride salts, the presence of half the number of the more highly charged SeO42- counteranions results in the incorporation of additional water to bridge the hydrophobic regions of the structure. The water is arranged into a discrete water decamer, encapsulated within the hydrophobic cations and selenate dianions, Figure 7. The classification of the decamer in the Infantes and Motherwell nomenclature is not obvious to us.8 It is based on the common R6 motif but with four water molecules in the 1, 2, 4, and 5 positions each hydrogen bonding to an additional water molecule. The structure is thus a discrete, two-dimensional (2D) sheetlike fragment. A further water molecule (per formula unit) unconnected to the decamer bridges between pairs of SeO42anions allowing them to span the length of the cations. The structure of 4 is a nice illustration of the principles discussed herein and shows how the loss of a tetrahedral anion, in this case replacing two ClO4- ions with one SeO42-, leads to additional water incorporation within a crystal containing a cation with a significant hydrophobic residue. Given the two very different types of water in the structure of 4, we examined the material by thermogravimetric analysis (TGA). The TGA trace revealed three distinct weight loss stages. The first with an onset temperature ca. 45 °C corresponds to 15.0% mass loss, or loss of essentially all six water molecules in a single step. A second step with an onset at 175 °C and 9.2% mass loss corresponds with the loss of a further 3–4 water molecules and may represent oxidation of the protonated phenazine-2,3-diamine cation by the selenate to give a benzoselenadiazole derivative.48 2,1,3Benzoselenadiazole is also isolated as a byproduct in the synthesis of 4. Further mass loss occurs beyond 300 °C and can be assigned to decomposition of the compound. The
Crystal Engineering Water Clusters
Crystal Growth & Design, Vol. 7, No. 12, 2007 2651
Figure 2. (a) Crystal packing in triammonium hydrogen phosphate salt [NH3(CH2)6NH2(CH2)6NH3]2(HPO4)3 · 12H2O (1) showing the water-filled voids; (b) the hexamethylene spacer requires two water molecules to span the gap between the hydrogen phosphate anions.
Figure 5. Matching of the length of the H2O · · · H2O · · · SO42- combination and the aromatic dication in melemium sulfate dihydrate.39 Figure 3. X-ray crystal structure of cyclo(H-streptolutyl-H-streptolutyl) sulfate pentahydrate (ANTSUL10)37 showing how the size mismatch between large, hydrophobic cations and small, highly charged sulfate anions results in the space-filing inclusion of a water sheet four water molecules wide.
Figure 6. Hexameric water chain bridging the hydrophobic region of streptomycin oxime selenate tetrahydrate. The chain length parallels the space taken up by the two SeO42- anions and hence equally the size of the hydrophobic backbone of the molecules.45
their hydrated pseudopolymorphs, and in addition to the empirical structural observations made herein, crystallization and nucleation factors related to the very significant hydration energies of ions such as sulfate and selenate must also play a significant part. Conclusions Figure 4. One-dimensional water chain in agmatine sulfate dihydrate.38
existence of a region between ca. 90 and 175 °C in which a dehydrated form of 4 is stable suggests that anhydrous phases are not impossible in these systems, merely less stable than
In this paper, we present and summarize some straightforward observations on a qualitative way to bring about the inclusion of relatively large water clusters in certain crystalline salts. In brief, this strategy comprises the combination of amphiphile type ions containing large hydrophobic regions balanced by small, multiply charged counterions. The space
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Sansam et al.
Figure 7. Two views showing the discrete water decameric sheet in (3)2SeO4 · 6H2O spanning the hydrophobic region. A further water molecule (two repeats shown) unconnected to the decamer bridges selenate anion pairs. Hydrogen bonded distances of O · · · O 2.77–2.97 Å all fall within the normal range.
spanned by the hydrophobic region is then filled by water molecules that bridge between the counterions. We can also note that even in the case of larger, singly charged counterions structural voids in hydrophobic portions of the molecule can also be filled with water. A particularly nice special case is where the void is part of a hydrophobic cryptand, as in the structure of cryptand 5 (CSD refcode YAJNON) that contains a cluster of three water molecules as the p-toluene sulfonate salt. Even though they are singly charged, the tosylate anions are too large to enter the cryptand cavity in this instance.
Our strategy may be of interest to workers wishing to study the increasingly topical area of water clusters in condensed phases. The ever-present difficulties in predicting the nuances in crystal packing mean that this approach is in no way quantitative. We cannot as yet predict the size of a water cluster nor its shape; however, the fact that there is a relationship to the size of the hydrophobic residue of the matrix suggests that
some control over the amount of water included should be possible, particularly in closely related series. Experimental Procedures Crystals of 4 were prepared by dissolving o-phenylenediamine (0.380 g, 0.043 mmol) in 30 mL of water and adding 45 drops of H2SeO4. The reaction was carried out anerobically. Small red crystals of 4 formed concomitantly with colorless crystals corresponding to 2,1,3-benzoselenadiazole (unit cell determined by X-ray diffraction: a ) 12.5069(52), b ) 12.3847(41), c ) 3.8565(12) Å, δ ) 90, β ) 90, γ ) 90°, corresponding to CSD refcodes BESEAZ and BESEAZ01). Anal. Calc for C24H34N8O10Se: C, 42.62; H, 4.99; N, 16.07%. Found: C, 42.67; H, 5.37; N, 16.59%. Crystal data for 4: C24H34N8O10Se, M ) 673.55, red plate, 0.20 × 0.10 × 0.10 mm3, triclinic, space group P1j (No. 2), a ) 11.1428(15) Å, b ) 11.8561(16) Å, c ) 12.5867(17) Å, δ ) 78.650(4), β ) 70.040(4)°, γ ) 63.599(4)°, V ) 1397.9(3) Å3, Z ) 2, Dc ) 1.600 g/cm3, F000 ) 696, SMART 6k, Mo KR radiation, λ ) 0.71073 Å, T ) 120(2) K, 2θmax ) 58.2°, 21 868 reflections collected, 7494 unique (Rint ) 0.1787). Final GOF ) 0.945, R1 ) 0.0776, wR2 ) 0.1151, R indices based on 3569 reflections with I > 2σ(I) (refinement on F2), 444 parameters, 12 restraints. Lp and absorption corrections applied, µ ) 1.415 mm-1.
Acknowledgment. We are grateful to the EPSRC and the Nuffield Foundation (summer bursary) for financial support of this work. Supporting Information Available: A crystallographic information file for the structure of 4 (in .cif format). Results of a CSD search on
Crystal Engineering Water Clusters sulfate hydrates with at least one water-water hydrogen bond. This material is available free of charge via the Internet at http://pubs.acs.org.
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