A Model for a Lipid Membrane Stabilized by C-H‚‚‚X Bonds: The Crystal Structure of the Paraffinic Ylide Trimethylammonio n-Hexadecylsulfonamidate CH3(CH2)15SO2N(-)N(+)Me3
CRYSTAL GROWTH & DESIGN 2005 VOL. 5, NO. 1 361-364
David G. Morris,† Karl S. Ryder,‡ and Kenneth W. Muir*,† Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, U.K., and Department of Chemistry, Loughborough University, Loughborough LE11 3TU, U.K. Received April 27, 2004;
Revised Manuscript Received August 24, 2004
W This paper contains enhanced objects available on the Internet at http://pubs.acs.org/crystal. ABSTRACT: The crystal structure of trimethylammonio n-hexadecylsulfonamidate contains antiparallel monolayers stabilized by strong C-H‚‚‚O bonds (C‚‚‚O 3.22 Å). There are also significant C-H‚‚‚X (X ) N, O) bonds linking adjacent layers. The structure suggests that nitrogen ylides have potential as amphoteric surfactants. The crystallography of paraffinic monolayers is discussed and the crystal structures of n-C16H33X compounds are shown to belong to three distinct types. Introduction The first successful synthesis of an artificial membrane1 was based on the principle that the molecular structure of an amphiphile largely predetermines its modes of self-assembly. This principle has been used with much success in the preparation of new bilayer membranes.2,3 Moreover, it has led to renewed interest in the crystal structures of amphiphiles, since the formation of membranes and crystals involves similar processes of self-recognition.4 The title compound CH3(CH2)15SO2N(-)N(+)Me3, 1, has a hydrophobic hydrocarbon tail linked to a dipolar ylide head. The head contains nucleophilic oxygen and nitrogen atoms which can act as the acceptor sites of hydrogen bonds but is devoid of groups capable of behaving as conventional hydrogen bond donors. Instead, only C-H bonds, activated by an electrondeficient nitrogen atom, are available as possible donors. It has recently been argued that C-H‚‚‚X interactions can be important in stabilizing supramolecular assemblages.5 On this view, molecules of 1 have some of the characteristics required for an amphoteric surfactant,6 being capable of self-assembly into a monolayer lipid membrane structure. Figure 1. Types of mono- and bilayer molecular stacking based on the classification of Masuda and Shimuzu.4
The availability of single crystals of 1 whose quality is just sufficient for a diffraction analysis has allowed us to determine whether its solid-state structure is indeed similar to those reported for other amphiphilic n-CH3(CH2)15X molecules, where X is a hydrophilic group capable of conventional hydrogen bond formation, * Corresponding author: Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, U.K. Tel: (44) 330 5345. Fax: (44) 0141 4888. E-mail:
[email protected]. † University of Glasgow. ‡ Loughborough University.
such as n-CH3(CH2)15CO2H and n-CH3(CH2)15OH.7-9 Although both the acid and alcohol are polymorphic, full structure analyses have been reported only for a single polymorph. In each case, the crystal contains sheets two molecules thick, with the X groups pointing outward, and O-H‚‚‚O hydrogen bonds are responsible for binding between, as well as within, sheets. These sheets can be described using the descriptors Masuda and Shimuzu have recently introduced for lipid membranes (see Figure 1).4 Crystals of the acid and alcohol are built from monolayers of type 1 (Figure 1) in which the molecules are packed parallel rather than antiparallel (type 2); head-to-head assembly of two such layers forms a type
10.1021/cg049851z CCC: $30.25 © 2005 American Chemical Society Published on Web 10/09/2004
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Morris et al. Table 1. Selected Bond Lengths [Å] and Angles [°] for 1 C(1)-S(1) C(17)-N(2) C(18)-N(2) C(19)-N(2) N(2)-N(1)-S(1) C(18)-N(2)-N(1) C(18)-N(2)-C(19) N(1)-N(2)-C(19) C(18)-N(2)-C(17) N(1)-N(2)-C(17) C(19)-N(2)-C(17)
1.782(7) 1.510(8) 1.493(8) 1.504(8) 117.2(4) 103.1(5) 109.5(5) 111.7(5) 107.7(5) 115.6(5) 108.8(5)
N(1)-N(2) N(1)-S(1) O(1)-S(1) O(2)-S(1) O(1)-S(1)-O(2) O(1)-S(1)-N(1) O(2)-S(1)-N(1) O(1)-S(1)-C(1) O(2)-S(1)-C(1) N(1)-S(1)-C(1)
1.502(7) 1.579(5) 1.451(5) 1.467(4) 117.5(3) 103.3(3) 114.5(3) 105.8(3) 103.8(3) 111.8(3)
Table 2. Hydrogen Bondsa
Figure 2. Molecular structure of 1 showing 50% probability ellipsoids and atom numbering. The atoms of the hexadecyl chain are numbered sequentially C1-C16. Also shown is the translational repeat along the short a-axis which involves O2‚‚‚H-C17 hydrogen bonds (dotted lines). The perpendicular distance between adjacent alkyl chains, a sin φa where φa is the angle between the a cell edge and the chain axis, is 3.97 Å. W A 3D rotatable image in XYZ format is available.
1b bilayer reminiscent of that found in membranes. We were curious to see whether C-H‚‚‚N or C-H‚‚‚O bonding in 1 would lead to a similar mode of molecular aggregation. Experimental Procedures Compound 1 was synthesized from the corresponding sulfonyl chloride ClSO2(CH2)15CH3 by the method of Kameyama et al.,10 itself patterned on those of Wawzonek and Mayer11 and Berry and Brocklehurst.12 Single crystals of indifferent quality for X-ray analysis were grown by slow evaporation of ethanol from a solution of 1; mp 137-8 °C (lit.10 137 °C). A number of structure determinations using different specimens were carried out at room and low temperature. We report only the best of these: it was made using a Nonius KappaCCD diffractometer with Mo KR radiation, λ ) 0.70173 Å, at 100 K. The structure does not appear to change significantly in the temperature range 100-293 K. Absorption corrections were not deemed necessary. All available unique reflections were used in the least-squares refinements, which were on F2 with weights chosen to give a goodness-of-fit near unity. The positions of methylene hydrogen atoms were initially calculated using stereochemical and crystallographic criteria (C-H ) 0.98 Å), while the orientations of methyl groups were determined from difference syntheses. All hydrogen atoms were then refined with riding constraints.13 Crystal Data. Empirical formula C19H42N2O2S, formula weight 362.61, monoclinic, space group P21/n, a ) 5.6334(5), b ) 39.286(3), c ) 9.6819(6) Å, β ) 91.276(7)°, V ) 2142.2(3) Å3, Z ) 4, Dcalc ) 1.124 g/cm3, µ ) 0.164 mm-1, F(000) ) 808, crystal size 0.40 × 0.18 × 0.05 mm, θ for data collection 2.125.6°, -6 e h e 6, 0 e k e 47, 0 e l e 11. 11262 reflections collected, 3647 unique reflections, Rint ) 0.153, completeness to θ ) 25.6° ) 91.0%, data/parameters 3647:218, goodnessof-fit on F2 1.100, R(F) [1798 with I > 2σ(I)] 0.112, wR(F2) (all data) 0.35. ∆F between 0.71 and -0.57 e‚Å-3.
Results In the solid the shape taken up by each molecule of 1 resembles that of a golf club (Figure 2). The shaft consists of a planar, staggered C16H33 zigzag chain, while the club head is formed from the dipolar Me3N(+)N(-)-SO2 nitrogen ylide function. The intramolecu-
D-H‚‚‚A
D‚‚‚A
H‚‚‚A
D-H‚‚‚A
C17-H17A‚‚‚O2i
3.219(11) 3.399(12) 3.562(12) 3.531(11) 3.301(11)
2.34 2.53 2.60 2.74 2.41
149 148 168 138 151
C18-H18B‚‚‚O1ii C17-H17B‚‚‚N1ii C17-H17B‚‚‚O1ii C19-H19B‚‚‚O1ii
a In angstroms and degrees. Symmetry code: (i) x - 1, +y, +z; (ii) x - 1/2, -y + 1/2, +z + 1/2.
lar C(16)‚‚‚S(1) and C(18)‚‚‚O(1) distances of 20.6 and 4.7 Å define the lengths of the club shaft and head. The dimensions of the C(1)-C(16) paraffinic chain are unexceptional: C-C ) 1.51-1.54(1) Å, C-C-C 112.6114.8(5)°, |C-C-C-C| ) 176-180(1)°. A second chain, also close to staggered, is defined by the sequence C(18)-N(2)-N(1)-S(1)-O(1) with torsion angles of -166.6(5) and -159.9(4)° across N(2)-N(1) and N(1)S(1). These two chains are approximately normal to one another [N(2)-N(1)-S(1)-C(1) ) 86.9(5)°]. Bond lengths and angles in the Me3N(+)-N(-)-SO2 group (Table 1) agree with those observed in Me3N(+)-N(-)-SO2C6H4CH3-p and in [Ag(Me3N(+)-N(-)-SO2C6H4-Cl-p)2NO3].14,15 They imply a bond of unit order between N(1) and N(2) and some multiple bond character in the N(1)-S(1) bond. The molecules are packed in layers (Figure 3), in each of which the alkyl chains are parallel to one another. One such layer is bounded by the glide planes at y ) 1/4 and 3/4. These layers are built up from ribbons of molecules, related by translations along the short a-axis (Figure 2), which are held together by dispersion forces between the hydrocarbon chains and by quite strong C17-H‚‚‚O2i hydrogen bonds (Table 2). When the cell contents are viewed in projection down the a-axis (Figure 3a) each layer is seen to be built by stacking the ribbons shown in Figure 2. Adjacent ribbons in the stack are antiparallel, being related by inversion centers. The chain axis, defined by the vector between the midpoints of the C(1)-C(2) and C(15)-C(16) bonds, makes angles φa, φb, and φc of 45.2, 49.5, and 74.5° with the cell axes a, b, and c. The resulting arrangement is such that each hydrocarbon chain is surrounded by six others (Figure 4) and ylide groups project out alternately onto the glide planes at y ) +1/4 and y ) +3/4, whereas the methyl ends of the hydrocarbon chains do not quite reach these glide planes. It is apparent from Figure 3 that adjacent layers fit together in a tongue-and-groove fashion derived from the head-to-tail antiparallel bilayer structure type 2a of Figure 1. The ylide heads of molecules in different layers are thereby brought into close proximity. They are linked by C-H‚‚‚N or ‚‚‚O interactions: O1 nestles between three methyl groups attached to the same N2 atom (Table 2, Figure 3b).
Lipid Membrane Stabilized by C-H‚‚‚X Bonds
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Figure 3. (a) The cell contents viewed in projection down the a-axis. Hydrogen atoms are omitted. (b) Magnified detail of the previous figure showing the C-H‚‚‚X (X ) N or O) hydrogen bonds (as dotted lines) which link molecules in different layers. Only the start of each alkyl chain is shown. For symmetry codes see Table 2. W A 3D rotatable image in XYZ format is available. Table 3. Monolayer Structures Present in Crystals of n-C16H33R Compoundsa angles between chain axis and cell edges
cell dimensionsb ref
R
a
b
γ
ab sin γ
φa
φb
A
B
26.7 26.7
87.3 88.1 88.4 62.6 62.6 62.8 89.9 89.5 45.3 45.2
45.2 45.6 45.4 61.1 70.2 70.5 55.9 55.0 77.1 74.5
4.7 4.7 4.8 4.7 4.9 4.9 4.9 5.1 4.1 4.0
4.1 4.1 4.1 4.2 7.5 7.6 7.3 7.2 9.2 9.3
20 20
C3H8PO4 C3H8PO4
4.746 4.752
5.720 5.722
21 7
C8H12NO6 CO2H
5.288 5.561
4.807 8.018
94.37 80.22
25.3 43.9
8 22 23 this work
OH C11H13N2O3 C5H16NS3
4.93 5.122 5.702 5.633
8.85 8.729 9.404 9.682
90 90 104.27 91.276
43.6 44.7 52.0 54.5
100.5 100.8
space group
Z′
monolayer
cell type
P1 h P21
1 2
P(HH) P(HH)
P21 P1 h
1 2
P(HT)) P(HH)
A2/a P212121 P1 h P21/n
1 1 1 1
P(HH) AP AP AP
1 1 1 1 3 3 3c 3c 2 2
a Distances and angles in angstroms and degrees. Abbreviations: A ) a sin φ and B ) b sin φ are perpendicular distances between a b chains; P(HH) parallel head-to-head; P(HT) parallel head-to-tail; AP antiparallel; cell types 1 -3 are defined in the text. b In some cases, c this is a modification of the indexing used by the original authors. Alkyl chain within 1° of coincidence with a crystallographic axis.
Figure 5. Packing of parallel alkyl chains. Assuming typical covalent and contact radii, a parallel monolayer is generated by the translations of an oblique cell with A ) 4.8, B ) 4.0 Å, Γ ) 115° (cell type 1). In an antiparallel monolayer, the chains in successive rows point in opposite directions and one cell axis is doubled (type 2). Figure 4. The packing of adjacent alkyl chains in 1. The direction of view is such that the chain axis points toward the viewer. The a-axis is horizontal and c-axis points upward. The ORTEP-type symmetry descriptor of the central molecule is 1555. Starting at the top right and going clockwise, its nearest neighbors are derived by the operations 2455, 1655, 2354, 2254, 1455, and 2355 (1: x, y, z; 2: -x, -y, -z). The corresponding perpendicular distances from the central chain to those of its nearest neighbors are 4.95, 3.97, 4.77, 5.28, 3.97, and 4.57 Å.
Discussion The crystal structure of 1 contains antiparallel monolayers. The only identifiable intermolecular interactions are C-H‚‚‚O and C-H‚‚‚N hydrogen bonds which link
molecules in the same monolayer and also help to bind together adjacent monolayers. Evidently, the ability of ylide functional groups to form such bonds could be exploited in the design of amphoteric surfactants. The structure also reveals that the classification of monolayers using the scheme outlined in Figure 1 has some inadequacies when applied to an antiparallel head-to-tail type 2a structure like that of 1. Although crystals of 1 contain antiparallel monolayers, in that equal numbers of molecules point in opposite directions, the shortest intermolecular contacts within each monolayer involve ribbons of parallel molecules running along the a-axis (Figure 2). Furthermore, though Figure 3a suggests a head-to-tail junction between monolayers,
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R ) C3H8PO4 each monolayer is crystallographically ordered but adjacent layers are independent. The two chain orientations in the type 3 cell of heptadecanoic acid are also independent of one another. Finally, we note that both faces of an antiparallel monolayer are identical and that, where the heads are much larger than the tails as in 1, their junction involves a region that involves predominantly headhead interactions which might be better described as tongue-in-groove (Figure 6). Figure 6. Tongue-in-grove junction of two identical, antiparallel monolayers. The precise nature of the interactions between the heads from adjacent layers will depend on the layer type (see text).
the important interactions between layers are C-H‚‚‚ X bonds connecting ylide heads (Figure 3b). We offer some comments on crystallographically ordered monolayers based on Kataigorodsky’s analysis17 of n-alkane structures,18 which has recently been brought up to date by Mak and Zhou.19 In a monolayer of the type considered by Masuda and Shimuzu, the parallel chains are usually stacked obliquely and the angle between the axis of each n-alkyl chain and the normal to the monolayer plane is arbitrary. When this is so, as it is in crystals of 1, the only crystallographic symmetry operations that can relate molecules within the layer are pure lattice translations and inversion centers. Proper and improper axes of order greater than one, whether parallel or perpendicular to the layer normal, would lead to angles other than 0 or 180° between chain axes. It follows that crystallographic ordering within an obliquely stacked monolayer must be based on an oblique Bravais net. If the crude assumption is made that alkyl chains have a rectangular cross-section 4.0 × 4.4 Å, a parallel monolayer with each chain touching six others, as in Figure 4, is generated by plane group p1 and a two-dimensional unit cell with A ) 4.8, B ) 4.0 Å, Γ ) 115° (cell type 1; see Figure 5). An antiparallel monolayer can be generated by plane group p2 with a doubling of one of the axes (cell type 2). These considerations apply only if the planes defined by the carbon atom backbones of the alkyl chains are all oriented identically. An alternative structure, exemplified by polyethylene,18 has A ) 7.5, B ) 5.0 Å, Γ ) 90°, and the carbon planes of alternate ribbons oriented differently; this arrangement is accessible to both parallel and antiparallel sheets (cell type 3). A survey of the few known structures with identically oriented n-C16H33 hexadecyl chains9 is consistent with this analysis (Table 3) in that it leads to the following conclusions. (a) All three cell types are found. In general, the perpendicular distances between alkyl chains, A ) a sin φa and B ) b sin φb, must be recovered from the three-dimensional lattice parameters and from the angles, φa and φb, between the cell edges and the axis of the paraffin chain, before the cell type is obvious. (b) Each monolayer is based on an oblique net except on the rare occasion when the alkyl chain axis coincides (to within 1°) with a crystallographic axis: operations such as 21 axes or glide planes are then consistent with parallel or antiparallel chain stacking. (c) In two structures, crystallographically independent chains (Z′ ) 2) occur but the independent φ angles are nearly identical. In the monoclinic form of the compound with
Acknowledgment. We thank EPSRC and the University of Glasgow for financial support. Supporting Information Available: An X-ray crystallographic information file and a complete set of crystallographic tables are available for compound 1. This material is available free of charge via the Internet at http:// pubs.acs.org. The CIF has also been deposited with the Cambridge Crystallographic Data Centre as CCDC 236978.
References (1) Kunitake, T.; Okahata, Y. J. Am. Chem. Soc. 1977, 99, 3860. (2) Ringsdorf, H.; Schlarb, B.; Venzmer, J. Angew. Chem., Int. Ed. Engl. 1988, 27, 113. (3) Kunitake, T. Angew. Chem., Int. Ed. Engl. 1992, 31, 709. (4) Masuda, M.; Shimuzu, T. Chem. Commun. 2001, 2442. (5) Broder, C. K.; Davidson, M. G.; Forsyth, V. T.; Howard, J. A. K.; Lamb, S.; Mason, S. A. Cryst. Growth Des. 2002, 2, 163. (6) Hargreaves, T. Chem. Br. 2003, 38. (7) Goto, M.; Asada, E. Bull. Chem. Soc. Jpn. 1984, 57, 1146. (8) Abrahamsson, S.; Larsson, G.; von Sydow, E. Acta Crystallogr. 1960, 13, 770. (9) Allen, F. H.; Kennard, O. Chem. Des. Autom. News 1993, 8, 1, 31-37. All structural searches were carried out locally using the QUEST and CONQUEST search programs with Version 5.25 (November 2003) of the Cambridge Structural Database (CSD). (10) Kameyama, E.; Inokuma, S.; Akagawa, A.; Kuwamura, T. Yukagaku 1973, 22, 434. (11) Wawzonek, S.; Meyer, D. J. Am. Chem. Soc. 1954, 76, 2918. (12) Berry, R. W. H.; Brocklehurst, P. J. Chem. Soc. 1964, 2264. (13) Programs used: Sheldrick, G. M. SHELX97, Programs for Crystal Structure Analysis (Release 97-2); Institut fu¨r Anorganische Chemie der Universita¨t: Tammanstrasse 4, D-3400 Go¨ttingen, Germany, 1998. WinGX, A Windows Program for Crystal Structure Analysis; Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837. DENZO-SCALEPACK, Otwinowski Z.; Minor, W. Processing of X-ray Diffraction Data Collected in Oscillation Mode, Methods in Enzymology; Carter, C. W., Jr., Sweet, R. M., Eds.; Academic Press: 1997; Vol. 276, pp 307-326. (14) Cameron, A. F.; Duncanson, F. D.; Morris, D. G. Acta Crystallogr. 1976, B32, 1987. (15) Morris, D. G.; Muir, K. W.; Chii, C. O. W. Polyhedron 2003, 22, 3345. (16) Spek, A. L. Acta Crystallogr. 1990, A46, C34. (b) PLATON, A Multipurpose Spek, A. L. Crystallographic Tool; Utrecht University: Utrecht, The Netherlands, 1998. (17) Kitaigorodsky, A. I. Molecular Crystal and Molecules; Academic Press: New York, 1973. (18) Norman, N.; Mathisen, H. Acta Chem. Scand. 1972, 26, 3913 and references therein. (19) Mak, T. C. W.; Zhou, G.-D. Crystallography in Modern Chemistry; J. Wiley & Sons: New York, 1992; p 750. (20) Pascher, I.; Sundell, S.; Elbl, H.; Harlos, K. Chem. Phys. Lipids 1984, 35, 103. (21) Andre, C.; Luger, P.; Gutberlet, T.; Volhardt, D.; Fuhrhop, J.-H. Carbohydr. Res. 1995, 272, 129. (22) Sharma, S.; Radhakrishnan, T. P. J. Phys. Chem. A 2003, 107, 147. (23) Hjorth, M.; Thorup, N.; Jorgensen, M.; Bechgard, K. Acta Crystallogr. 1991, C47, 1548.
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