organic compounds Acta Crystallographica Section C

Structural Chemistry ISSN 2053-2296

The self-assembling zwitterionic form of L-phenylalanine at neutral pH

The inter-layer interactions were assumed to be weak van der Waals forces, confirming the work of Gurskaya & Vainshtein (1963). Powder diffraction studies have also been carried out: Khawas (1970) crystallized l-phenylalanine from aqueous solution but had difficulties growing large l-phenylalanine single crystals. The samples were nonetheless highly crystalline and X-ray powder diffraction experiments were carried ˚, out yielding a unit cell of a = 13.13, b = 6.59 and c = 10.348 A  and  = 104.38 , with the space group P21.

Estelle Mossou,a,b Susana C. M. Teixeira,b,d Edward P. Mitchell,c,b Sax A. Mason,d Lihi Adler-Abramovich,e Ehud Gazite and V. Trevor Forsytha,b* a

Partnership for Structural Biology, Institut Laue-Langevin, 38042 Grenoble, France, EPSAM/ISTM, Keele University, Staffordshire, ST5 5BG, England, cEuropean Synchrotron Radiation Facility, 38043 Grenoble, France, dInstitut Laue-Langevin, 38042 Grenoble, France, and eDepartment of Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv 6997801, Israel Correspondence e-mail: [email protected] b

Received 18 October 2013 Accepted 4 February 2014

The title zwitterion (2S)-2-azaniumyl-1-hydroxy-3-phenylpropan-1-olate, C9H11NO2, also known as l-phenylalanine, was characterized using synchrotron X-rays. It crystallized in the monoclinic space group P21 with four molecules in the ˚ resolution structure is assumed to asymmetric unit. The 0.62 A be closely related to the fibrillar form of phenylalanine, as observed by electron microscopy and electron diffraction. The structure exists in a zwitterionic form in which – stacking and hydrogen-bonding interactions are believed to form the basis of the self-assembling properties. Keywords: crystal structure; synchrotron radiation; zwitterion; L-phenylalanine; fibrils; nanotubes; optical microscopy analysis.

1. Introduction l-Phenylalanine is an essential aromatic and hydrophobic amino acid and is one of the 20 amino acids found in proteins. X-ray diffraction studies by Gurskaya & Vainshtein (1963) started with the acidic form of l-phenylalanine. Those authors noted an orthorhombic cell with the space group P212121 and ˚ . Their unit-cell dimensions a = 27.68, b = 6.98 and c = 5.34 A model was derived from a three-dimensional Patterson analysis and described a layered structure in which the groups of hydrogen-bonded phenylalanine molecules are stabilized by van der Waals forces. Some time later, Al-Karaghouli & Koetzle (1975) conducted a single-crystal neutron study of the same molecule, allowing precise determination of the H-atom positions and the hydrogen-bonding network. The space group and unit-cell dimensions were consistent with the X-ray ˚ ). The structure results (a = 27.76, b = 7.07 and c = 5.38 A formed a layered system held together by hydrogen-bonded chloride ions, with each chloride ion linking four molecules.

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l-Phenylalanine is interesting for its importance in human health and implications in conditions such as lethargy, liver damage and phenylketonuria (PKU). PKU is a good example of the consequences of an excess of l-phenylalanine in the brain. High concentrations of phenylalanine are extremely harmful especially during early infancy and, if not diagnosed and treated immediately (with a phenylalanine-reduced diet), result in profound and permanent mental retardation, epilespy and microcephaly (Martynyuk et al., 2005). Recently, l-phenylalanine has attracted interest for its possible link to self-assembly in amyloid type systems. Studies on the minimal recognition module of the islet amyloid polypeptide (IAPP), known to be associated with diabetes type 2, have shown that phenylalanine plays a crucial role in the formation of amyloid fibrils (Tenidis et al., 2000). Experimental support for the key role of the phenylalanine residue in self-assembly associated with amyloid formation was demonstrated (Azriel & Gazit, 2001). Over the past decade, there has been extensive research into the assembly properties of a wide range of peptide systems and their ability to form nanotubes is of potential commercial significance. More recently, a number of groups have reported the assembly properties of simpler systems, such as diphenylalanine, and also a number of amino acid derivative systems. For example, it was shown that diphenylalanine can form discrete nanotubes by the process of selfassembly (Reches & Gazit, 2003) with the same packing as in the porous crystalline form observed by Go¨rbitz (2001). Adler-Abramovich et al. (2006) and Tamamis et al. (2009) have subsequently studied the physical and thermal properties of these nanotubes. Additionally, Adler-Abramovich et al. (2012) have shown that l-phenylalanine, like diphenylalanine, has remarkable properties of self-assembly from aqueous solution, forming stable nanofilaments that have been observed by electron microscopy. Hence, this relatively simple molecule appears to have complex behaviour that may be of relevance for a number of biomedical issues.

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organic compounds Table 1 Experimental details. Crystal data Chemical formula Mr Crystal system, space group Temperature (K) ˚) a, b, c (A  ( ) ˚ 3) V (A Z Radiation type  (mm1) Crystal size (mm) Data collection Diffractometer No. of measured, independent and observed [I > 2(I)] reflections Rint ˚ 1) (sin /)max (A Refinement R[F 2 > 2(F 2)], wR(F 2), S No. of reflections No. of parameters No. of restraints H-atom treatment ˚ 3) max, min (e A Absolute structure Absolute structure parameter

C9H11NO2 165.19 Monoclinic, P21 100 6.0010 (5), 30.8020 (17), 8.7980 (4) 90.120 (4) 1626.24 (17) 8 ˚ Synchrotron,  = 0.61995 A 0.10 0.20  0.10  0.07

MD2M mini diffractometer 45788, 12740, 10932 0.064 0.820

0.064, 0.170, 1.15 12740 389 1 H-atom parameters constrained 0.91, 0.75 Flack x determined using 4805 quotients (Parsons & Flack, 2004) 0.0 (4)

Computer programs: MxCuBE (Gabadinho et al., 2010), XDS (Kabsch, 1993), SHELXS97 (Sheldrick, 2008), SHELXL2013 (Sheldrick, 2008), PLATON (Spek, 2003, 2009) and publCIF (Westrip, 2010).

Figure 2

2. Experimental

The monoclinic unit cell of l-phenylalanine.

2.1. Synthesis and crystallization

aqueous drops of 20 ml volume containing 10 mg ml1 of l-phenylalanine in 15% polyethylene glycol (PEG) 4 K, 15% propan-2-ol and 0.05 M NaCl. No pH measurements were

l-Phenylalanine was purchased from Sigma–Aldrich. The best crystals were obtained in crystallization screenings using

Figure 1 The four independent molecules A to D from the zwitterionic l-phenylalanine structure. Displacement ellipsoids are drawn at the 50% probability level. Acta Cryst. (2014). C70, 326–331

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organic compounds made on the final solution, which was assumed to be at approximately neutral pH. Crystals formed over a period of one week. They were then cryocooled straight from the drop without the addition of cryoprotectant. X-ray diffraction data were collected to a resolution of ˚ on beamline ID23-1 (Nurizzo et al., 2006) at the 0.62 A European Synchrotron Radiation Facility (ESRF). 2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. H atoms were positioned geometrically and refined as riding, with C—H = 0.95 ˚ (NCR2) and N—H = (aromatic), 0.99 (methylene) or 1.0 A ˚ 0.91 A (tertiary amine), and with Uiso(H) = 1.5Ueq(N) for the the ammonium H atoms and 1.2Ueq(C) for all others. Nine

non-H atoms (C1A, N1A, C2A, C1C, C2C, O1C, C1D, N1D and C2D) were refined with isotropic displacement parameters to avoid nonpositive definite (NPD) displacement parameters.

3. Results and discussion As part of a set of X-ray diffraction experiments designed to characterize phenylalanine fibril self-assembly, a new crystalline form of zwitterionic l-phenylalanine [systematic name: (2S)-2-azaniumyl-1-hydroxy-3-phenylpropan-1-olate] has been identified (Fig. 1 and Table 2). This structure was indexed as a primitive unit cell exhibiting pseudo-B-face-centering geometry, as can be seen in Fig. 2. A layered structure stabilized by alternating hydrophobic (aromatic environment) and hydrophilic interactions is observed in the crystal packing.

Figure 3 Diagram showing the layers of phenylalanine residues.

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organic compounds Table 2 ˚ ,  ). Hydrogen-bond geometry (A D—H  A

D—H

H  A

D  A

D—H  A

N1A—H11A  O2B N1A—H12A  O1C i N1A—H13A  O2C ii N1B—H11B  O1D N1B—H12B  O2Diii N1B—H13B  O2A N1C—H11C  O2D N1C—H12C  O1Aiv N1C—H13C  O2A N1D—H11D  O1Bv N1D—H12D  O2Bvi N1D—H13D  O2C

0.91 0.91 0.91 0.91 0.91 0.91 0.91 0.91 0.91 0.91 0.91 0.91

1.99 1.79 2.06 1.80 1.99 2.00 1.98 1.79 1.99 1.80 2.07 1.98

2.840 (3) 2.695 (3) 2.950 (3) 2.707 (3) 2.883 (3) 2.854 (3) 2.839 (3) 2.694 (3) 2.884 (3) 2.694 (3) 2.963 (3) 2.829 (3)

155 174 166 177 168 156 158 176 168 167 168 156

Symmetry codes: (i) x; y; z þ 1; (ii) x  1; y; z þ 1; (iii) x  1; y; z; (iv) x þ 1; y; z; (v) x þ 1; y; z  1; (vi) x; y; z  1.

Figure 4 The two-dimensional hydrogen-bond network in the l-phenylalanine structure.

Each layer is composed of two rows of phenylalanine molecules held together by hydrogen bonds, whereas the interlayer interactions between the hydrophobic rings are thought to be related to – stacking (Figs. 3 and 5). Previous studies on aromatic interactions between phenyl rings implicated – stacking interactions as playing a critical role in self-assembly (Gillard et al., 1997). Olsztynska et al. (2006) suggested that the presence of hydrophobic interactions in l-phenylalanine dissolved in water leads to self-assembly of the molecules via – stacking. Our structure adopts laterally displaced rings involving residues B and D, and A and C. Furthermore, edgeto-face ring interactions (Jennings et al., 2001) are noted between layers, with the rings forming an angle of approximately 45 with respect to each other. Both l-phenylalanine– l-phenylalanine malonate (Go¨rbitz & Etter, 1992) and l-phenylalanine hydrochloride (Al-Karaghouli & Koetzle, 1975) adopt a similar structure to the one published here, with a combination of edge-to-face and parallel-displaced conformations. However, in both these studies, the rings are all in register, as opposed to the four different conformations adopted by the molecules presented here. To the best of our knowledge, this is the only l-phenylalanine structure showing four distinct conformations of the amino acid. The existence of two types of -stacking interactions within this structure is also consistent with the structure of the amyloid-forming peptide KFFEAAAKKFFE solved by Makin et al. (2005). This configuration corresponds to an energetically favoured stacking arrangement (McGaughey et al., 1998). Within the individual asymmetric units, hydrogen bonding occurs between the carboxylate and amine groups (Fig. 4) forming a two-dimensional hydrogen-bond network parallel to the ac plane. Each molecule takes part in four intermolecular N—H  O hydrogen bonds (Table 2), three of which are illustrated in Fig. 4. The fourth N—H  O interActa Cryst. (2014). C70, 326–331

action is not visible in Fig. 4 since it occurs between residues in neighbouring layers of the lattice. Collectively, these hydrogen bonds, within and between layers, in combination with the – stacking geometry described above, form a strong set of interactions that hold this structure together and that are likely to be significant in the self-assembly of phenylalanine fibrils (Figs. 3 and 5). Our observations in this structure that the phenylalanine rings are located in the hydrophobic region of the structure can be related to the observations of Chelli et al. (2002) that -stacking interactions between the rings are more frequent in the hydrophobic cores of proteins. As seen in Fig. 6, l-phenylalanine is found by light microscopy to form fibrous structures, reflecting its fundamental tendency to self-assemble into fibrils. The relationship between this water-free structure and the filamentous structure as seen by fibre diffraction and electron microscopy is part of an ongoing study. It appears likely that the – stacking between neighbouring phenyl rings is the basis of the unique specific aggregation properties that lead to the formation of fibrils. In this context it seems likely that the short axis of the unit cell would correspond to the fibril axis. EM was supported through a studentship held at Keele University with EU funding under contract STRP 033256. VTF acknowledges EPSRC support under grant EP/ C015452/1 and from the EU under contract RII3-CT-2003505925. We acknowledge the ESRF for time on beamline ID23-1. Supporting information for this paper is available from the IUCr electronic archives (Reference: SK3518).

References Adler-Abramovich, L., Reches, M., Sedman, V. L., Allen, S., Tendler, S. J. B. & Gazit, E. (2006). Langmuir, 22, 1313–1320. Adler-Abramovich, L., Vaks, L., Carny, O., Trudler, D., Frenkel, D. & Gazit, E. (2012). Nat. Chem. Biol. 8, 701–706. Al-Karaghouli, A. R. & Koetzle, T. F. (1975). Acta Cryst. B31, 2461–2465. Azriel, R. & Gazit, E. (2001). J. Biol. Chem. 276, 34156–34161. Chelli, R., Gervasio, F. L., Procacci, P. & Schettino, V. (2002). J. Am. Chem. Soc. 124, 6133–6143. Gabadinho, J., et al. (2010). J. Synchrotron Rad. 17, 700–707. Mossou et al.



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Figure 5 Diagram showing the interactions holding the l-phenylalanine structure together. The -stacking interactions between the rings within a layer are dominated by so-called nearly parallel-displaced interactions, while the interactions between them are based on edge-to-face interactions between the rings. Hydrogen bonds between the carboxylate and ammonium group contribute to the stacking.

Figure 6 Optical microscopy image showing the filaments formed from l-phenylalanine.

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Gillard, R. E., Raymo, F. M. & Stoddart, J. F. (1997). Chem. Eur. J. 3, 1933– 1940. Go¨rbitz, C. H. (2001). Chem. Eur. J. 7, 5153–5159. Go¨rbitz, C. H. & Etter, M. C. (1992). Acta Cryst. C48, 1317–1320. Gurskaya, G. V. & Vainshtein, B. K. (1963). Sov. Phys. Crystallogr. 8, 288– 291. Jennings, W. B., Farrell, B. M. & Malone, J. F. (2001). Acc. Chem. Res. 34, 885– 894. Kabsch, W. (1993). J. Appl. Cryst. 26, 795–800. Khawas, B. (1970). Acta Cryst. B26, 1919–1922. Makin, O. S., Atkins, E., Sikorski, P., Johansson, J. & Serpell, L. C. (2005). Proc. Natl Acad. Sci. USA, 102, 315–320. Martynyuk, A. E., Glushakov, A. V., Sumners, C., Laipis, P. J., Dennis, D. M. & Seubert, C. N. (2005). Mol. Genet. Metab. 86, S34–S42. McGaughey, G. B., Gagn, M. & Rapp, A. K. (1998). J. Biol. Chem. 273, 15458– 15463. Nurizzo, D., Mairs, T., Guijarro, M., Rey, V., Meyer, J., Fajardo, P., Chavanne, J., Biasci, J.-C., McSweeney, S. & Mitchell, E. (2006). J. Synchrotron Rad. 13, 227–238. Olsztynska, S., Dupuy, N., Vrielynck, L. & Komorowska, M. (2006). Appl. Spectrosc. 60, 1040–1053. Parsons, S. & Flack, H. (2004). Acta Cryst. A60, s61. Reches, M. & Gazit, E. (2003). Science, 300, 625–627. Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Spek, A. L. (2003). J. Appl. Cryst. 36, 7–13. Acta Cryst. (2014). C70, 326–331

organic compounds Spek, A. L. (2009). Acta Cryst. D65, 148–155. Tamamis, P., Adler-Abramovich, L., Reches, M., Marshall, K., Sikorski, P., Serpell, L. C., Gazit, E. & Archontis, G. (2009). Biophys. J. 96, 5020– 5029.

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Tenidis, K., Waldner, M., Bernhagen, J., Fischle, W., Bergmann, M., Weber, M., Merkle, M. L., Voelter, W., Brunner, H. & Kapurniotu, A. (2000). J. Mol. Biol. 295, 1055–1071. Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.

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supplementary materials Acta Cryst. (2014). C70, 326-331

[doi:10.1107/S2053229614002563]

The self-assembling zwitterionic form of L-phenylalanine at neutral pH Estelle Mossou, Susana C. M. Teixeira, Edward P. Mitchell, Sax A. Mason, Lihi AdlerAbramovich, Ehud Gazit and V. Trevor Forsyth Computing details Data collection: MxCuBE (Gabadinho et al., 2010); cell refinement: XDS (Kabsch, 1993); data reduction: XDS (Kabsch, 1993); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2003, 2009); software used to prepare material for publication: publCIF (Westrip, 2010). (I) Crystal data C9H11NO2 Mr = 165.19 Monoclinic, P21 a = 6.0010 (5) Å b = 30.8020 (17) Å c = 8.7980 (4) Å β = 90.120 (4)° V = 1626.24 (17) Å3 Z=8

F(000) = 704 Dx = 1.349 Mg m−3 Synchrotron radiation, λ = 0.61995 Å Cell parameters from 841 reflections θ = 1–20° µ = 0.10 mm−1 T = 100 K Polygon, colourless 0.20 × 0.10 × 0.07 mm

Data collection MD2M mini diffractometer Radiation source: synchrotron profile from θ /2θ scans 45788 measured reflections 12740 independent reflections

10932 reflections with I > 2σ(I) Rint = 0.064 θmax = 30.5°, θmin = 2.0° h = −9→9 k = −47→47 l = −13→12

Refinement Refinement on F2 Least-squares matrix: full R[F2 > 2σ(F2)] = 0.064 wR(F2) = 0.170 S = 1.15 12740 reflections 389 parameters 1 restraint Hydrogen site location: inferred from neighbouring sites

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H-atom parameters constrained w = 1/[σ2(Fo2) + (0.0808P)2 + 1.0335P] where P = (Fo2 + 2Fc2)/3 (Δ/σ)max < 0.001 Δρmax = 0.91 e Å−3 Δρmin = −0.75 e Å−3 Absolute structure: Flack x determined using 4805 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons and Flack (2004), Acta Cryst. A60, s61). Absolute structure parameter: 0.0 (4)

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supplementary materials Special details Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

O2A O1A C1A N1A H11A H12A H13A C2A H21A C3A H31A H32A C4A C5A H51A C6A H61A C7A H71A C8A H81A C9A H91A O2B O1B N1B H11B H12B H13B C2B H21B C3B H31B H32B C4B C1B C5B H51B C9B H91B

x

y

z

Uiso*/Ueq

0.5490 (3) 0.2463 (3) 0.4529 (4) 0.5090 (3) 0.5181 0.5929 0.3645 0.5939 (4) 0.7538 0.5733 (4) 0.6520 0.4138 0.6634 (4) 0.5310 (5) 0.3845 0.6109 (7) 0.5191 0.8230 (7) 0.8761 0.9577 (6) 1.1042 0.8794 (5) 0.9746 0.5510 (3) 0.2387 (3) 0.5026 (3) 0.5811 0.3548 0.5265 0.5773 (4) 0.7402 0.5340 (4) 0.6239 0.3750 0.5883 (4) 0.4455 (4) 0.4241 (4) 0.2777 0.8012 (5) 0.9159

0.02363 (6) 0.01989 (7) 0.01845 (7) 0.03736 (6) 0.0658 0.0329 0.0305 0.00934 (7) 0.0163 −0.03755 (8) −0.0401 −0.0438 −0.07162 (8) −0.08962 (9) −0.0788 −0.12319 (10) −0.1350 −0.13945 (10) −0.1629 −0.12114 (11) −0.1319 −0.08719 (9) −0.0744 0.11439 (6) 0.11734 (7) 0.10167 (7) 0.1075 0.1058 0.0736 0.13141 (8) 0.1273 0.17805 (8) 0.1835 0.1808 0.21249 (8) 0.12022 (8) 0.24153 (9) 0.2388 0.21697 (9) 0.1976

0.7803 (2) 0.9286 (2) 0.9055 (3) 1.1741 (2) 1.1463 1.2590 1.1939 1.0478 (3) 1.0271 1.1029 (3) 1.2015 1.1214 0.9970 (3) 0.8829 (3) 0.8668 0.7923 (4) 0.7144 0.8148 (4) 0.7547 0.9263 (5) 0.9421 1.0148 (4) 1.0885 0.9990 (2) 0.8591 (2) 0.6082 (2) 0.5222 0.5901 0.6366 0.7326 (3) 0.7519 0.6786 (3) 0.5863 0.6498 0.7953 (3) 0.8765 (3) 0.8420 (3) 0.8018 0.8562 (3) 0.8259

0.0063 (3) 0.0081 (3) 0.0034 (4)* 0.0049 (3)* 0.007* 0.007* 0.007* 0.0038 (4)* 0.005* 0.0083 (4) 0.010* 0.010* 0.0077 (4) 0.0135 (5) 0.016* 0.0215 (7) 0.026* 0.0232 (7) 0.028* 0.0219 (7) 0.026* 0.0138 (5) 0.017* 0.0069 (3) 0.0088 (3) 0.0043 (3) 0.006* 0.006* 0.006* 0.0038 (4) 0.005* 0.0072 (4) 0.009* 0.009* 0.0065 (4) 0.0040 (4) 0.0103 (5) 0.012* 0.0108 (5) 0.013*

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supplementary materials C7B H71B C8B H81B C6B H61B O1C O2C N1C H11C H12C H13C C2C H21C C4C C9C H91C C3C H31C H32C C5C H51C C6C H61C C8C H81C C1C C7C H71C O1D O2D C3D H31D H32D C2D H21D N1D H11D H12D H13D C4D C5D H51D C9D H91D C8D H81D C6D H61D

0.6817 (5) 0.7137 0.8480 (5) 0.9941 0.4693 (5) 0.3552 0.7424 (3) 1.0545 (3) 1.0008 (3) 1.0162 1.0814 0.8545 1.0835 (4) 1.2452 1.1204 (4) 1.3395 (4) 1.4494 1.0525 (4) 1.1411 0.8938 0.9634 (5) 0.8140 1.0202 (5) 0.9102 1.3957 (5) 1.5442 0.9501 (4) 1.2387 (5) 1.2797 0.7469 (3) 1.0503 (3) 1.0828 (4) 1.1711 0.9258 1.0964 (4) 1.2550 1.0083 (3) 1.0965 0.8669 1.0077 1.1644 (4) 1.0215 (5) 0.8748 1.3814 (4) 1.4830 1.4493 (5) 1.5964 1.0893 (5) 0.9902

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0.27839 (9) 0.3005 0.24964 (9) 0.2523 0.27442 (10) 0.2941 0.01836 (6) 0.02108 (6) 0.03647 (7) 0.0646 0.0320 0.0308 0.00685 (7) 0.0125 −0.07435 (8) −0.07789 (9) −0.0577 −0.03957 (8) −0.0432 −0.0438 −0.10435 (9) −0.1021 −0.13751 (10) −0.1576 −0.11105 (10) −0.1131 0.01616 (7) −0.14121 (9) −0.1641 0.11726 (7) 0.11366 (6) 0.17255 (8) 0.1749 0.1790 0.12565 (7) 0.1179 0.09752 (6) 0.1003 0.1058 0.0693 0.20645 (8) 0.22383 (9) 0.2126 0.22282 (9) 0.2108 0.25671 (10) 0.2679 0.25721 (10) 0.2685

1.0067 (3) 1.0788 0.9611 (3) 1.0019 0.9461 (4) 0.9754 0.4276 (2) 0.2877 (2) 0.6786 (2) 0.6484 0.7648 0.6971 0.5555 (3) 0.5368 0.5024 (3) 0.4487 (3) 0.4807 0.6140 (3) 0.7083 0.6406 0.4522 (4) 0.4869 0.3527 (4) 0.3197 0.3487 (4) 0.3121 0.4101 (3) 0.3013 (4) 0.2346 0.3557 (2) 0.5056 (2) 0.1799 (3) 0.0853 0.1538 0.2371 (3) 0.2593 0.1121 (3) 0.0287 0.0885 0.1432 0.2902 (3) 0.3992 (3) 0.4084 0.2807 (4) 0.2095 0.3754 (4) 0.3673 0.4944 (4) 0.5686

0.0127 (5) 0.015* 0.0120 (5) 0.014* 0.0150 (5) 0.018* 0.0087 (3)* 0.0068 (3) 0.0047 (3) 0.007* 0.007* 0.007* 0.0032 (4)* 0.004* 0.0070 (4) 0.0114 (5) 0.014* 0.0074 (4) 0.014 (10)* 0.017* 0.0125 (5) 0.015* 0.0169 (6) 0.020* 0.0148 (5) 0.018* 0.0036 (4)* 0.0157 (5) 0.019* 0.0082 (3) 0.0062 (3) 0.0075 (4) 0.009* 0.009* 0.0040 (4)* 0.005* 0.0043 (3)* 0.006* 0.006* 0.006* 0.0065 (4) 0.0115 (5) 0.014* 0.0115 (5) 0.014* 0.0147 (5) 0.018* 0.0157 (5) 0.019*

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supplementary materials C1D C7D H71D

0.9534 (4) 1.3045 (5) 1.3509

0.11820 (7) 0.27409 (9) 0.2975

0.3788 (3) 0.4805 (4) 0.5434

0.0036 (4)* 0.0148 (5) 0.018*

Atomic displacement parameters (Å2)

O2A O1A C3A C4A C5A C6A C7A C8A C9A O2B O1B N1B C2B C3B C4B C1B C5B C9B C7B C8B C6B O2C N1C C4C C9C C3C C5C C6C C8C C7C O1D O2D C3D C4D C5D C9D C8D C6D C7D

U11

U22

U33

U12

U13

U23

0.0057 (7) 0.0020 (7) 0.0111 (10) 0.0094 (10) 0.0174 (12) 0.0405 (19) 0.040 (2) 0.0177 (14) 0.0094 (11) 0.0061 (7) 0.0032 (7) 0.0022 (7) 0.0016 (8) 0.0107 (10) 0.0074 (9) 0.0033 (8) 0.0070 (10) 0.0086 (10) 0.0175 (13) 0.0113 (11) 0.0162 (12) 0.0074 (7) 0.0028 (8) 0.0096 (10) 0.0086 (10) 0.0101 (10) 0.0108 (11) 0.0198 (13) 0.0126 (12) 0.0213 (14) 0.0030 (7) 0.0061 (7) 0.0108 (10) 0.0068 (9) 0.0102 (11) 0.0069 (10) 0.0097 (11) 0.0204 (13) 0.0192 (13)

0.0107 (8) 0.0187 (9) 0.0099 (10) 0.0067 (9) 0.0118 (11) 0.0116 (12) 0.0094 (12) 0.0130 (12) 0.0111 (11) 0.0119 (8) 0.0203 (9) 0.0085 (9) 0.0086 (9) 0.0082 (10) 0.0075 (9) 0.0083 (9) 0.0117 (11) 0.0102 (11) 0.0089 (10) 0.0131 (11) 0.0117 (11) 0.0114 (8) 0.0089 (9) 0.0068 (10) 0.0122 (11) 0.0087 (10) 0.0134 (11) 0.0136 (12) 0.0148 (12) 0.0108 (11) 0.0203 (9) 0.0103 (8) 0.0074 (9) 0.0062 (9) 0.0107 (11) 0.0122 (11) 0.0138 (12) 0.0136 (12) 0.0098 (11)

0.0026 (8) 0.0035 (8) 0.0041 (11) 0.0068 (12) 0.0112 (13) 0.0124 (15) 0.0206 (18) 0.035 (2) 0.0210 (15) 0.0028 (8) 0.0028 (9) 0.0023 (9) 0.0010 (10) 0.0027 (11) 0.0045 (11) 0.0005 (10) 0.0123 (13) 0.0134 (13) 0.0117 (13) 0.0115 (13) 0.0171 (15) 0.0018 (8) 0.0025 (9) 0.0045 (11) 0.0133 (13) 0.0033 (11) 0.0132 (14) 0.0173 (16) 0.0170 (15) 0.0150 (15) 0.0015 (8) 0.0022 (8) 0.0042 (11) 0.0065 (11) 0.0135 (14) 0.0153 (14) 0.0205 (15) 0.0132 (15) 0.0152 (14)

0.0018 (6) −0.0010 (6) 0.0028 (8) 0.0008 (8) 0.0000 (9) −0.0031 (12) 0.0034 (12) 0.0065 (11) 0.0030 (9) −0.0003 (6) 0.0004 (6) 0.0002 (6) 0.0002 (7) −0.0002 (8) −0.0018 (8) 0.0007 (7) 0.0002 (8) −0.0006 (8) −0.0069 (9) −0.0051 (9) −0.0004 (10) 0.0014 (6) 0.0000 (6) 0.0016 (8) 0.0005 (8) 0.0015 (8) −0.0007 (9) −0.0036 (10) 0.0057 (9) 0.0031 (10) 0.0026 (6) 0.0003 (6) 0.0004 (8) 0.0006 (7) −0.0024 (8) −0.0008 (8) −0.0036 (9) 0.0000 (10) −0.0029 (10)

0.0002 (6) −0.0015 (6) 0.0001 (8) −0.0004 (8) −0.0082 (10) −0.0041 (13) 0.0120 (14) 0.0084 (13) −0.0036 (10) −0.0023 (6) 0.0007 (6) 0.0008 (6) 0.0003 (7) 0.0002 (8) −0.0005 (8) 0.0006 (7) 0.0006 (8) −0.0015 (9) 0.0022 (10) −0.0040 (9) 0.0048 (10) 0.0004 (6) −0.0020 (6) 0.0008 (8) 0.0004 (9) −0.0002 (8) 0.0029 (9) 0.0016 (11) 0.0050 (10) 0.0017 (11) 0.0009 (6) −0.0017 (6) 0.0016 (8) 0.0007 (8) 0.0058 (9) 0.0031 (9) −0.0028 (10) 0.0038 (11) −0.0044 (11)

0.0016 (6) 0.0018 (7) 0.0020 (8) 0.0024 (8) 0.0018 (9) −0.0009 (10) −0.0010 (11) 0.0013 (12) 0.0005 (10) 0.0014 (6) 0.0031 (7) −0.0003 (6) −0.0003 (7) 0.0027 (7) 0.0019 (7) 0.0005 (7) −0.0005 (9) 0.0021 (9) 0.0006 (9) 0.0037 (9) −0.0036 (10) 0.0023 (6) −0.0001 (7) 0.0016 (7) −0.0001 (9) 0.0020 (8) −0.0008 (9) −0.0042 (10) 0.0007 (10) −0.0027 (10) 0.0023 (6) 0.0012 (6) 0.0032 (7) 0.0029 (7) −0.0016 (9) 0.0034 (9) 0.0036 (10) −0.0034 (10) 0.0009 (9)

Acta Cryst. (2014). C70, 326-331

sup-4

supplementary materials Geometric parameters (Å, º) O2A—C1A O1A—C1A C1A—C2A N1A—C2A N1A—H11A N1A—H12A N1A—H13A C2A—C3A C2A—H21A C3A—C4A C3A—H31A C3A—H32A C4A—C9A C4A—C5A C5A—C6A C5A—H51A C6A—C7A C6A—H61A C7A—C8A C7A—H71A C8A—C9A C8A—H81A C9A—H91A O2B—C1B O1B—C1B N1B—C2B N1B—H11B N1B—H12B N1B—H13B C2B—C1B C2B—C3B C2B—H21B C3B—C4B C3B—H31B C3B—H32B C4B—C9B C4B—C5B C5B—C6B C5B—H51B C9B—C8B C9B—H91B C7B—C6B C7B—C8B C7B—H71B C8B—H81B C6B—H61B

1.255 (3) 1.258 (3) 1.535 (3) 1.498 (3) 0.9100 0.9100 0.9100 1.528 (3) 1.0000 1.505 (4) 0.9900 0.9900 1.390 (4) 1.394 (4) 1.392 (5) 0.9500 1.381 (6) 0.9500 1.390 (6) 0.9500 1.386 (5) 0.9500 0.9500 1.262 (3) 1.253 (3) 1.496 (3) 0.9100 0.9100 0.9100 1.533 (3) 1.535 (3) 1.0000 1.511 (4) 0.9900 0.9900 1.392 (4) 1.393 (4) 1.392 (4) 0.9500 1.394 (4) 0.9500 1.386 (4) 1.394 (4) 0.9500 0.9500 0.9500

O1C—C1C O2C—C1C N1C—C2C N1C—H11C N1C—H12C N1C—H13C C2C—C3C C2C—C1C C2C—H21C C4C—C5C C4C—C9C C4C—C3C C9C—C8C C9C—H91C C3C—H31C C3C—H32C C5C—C6C C5C—H51C C6C—C7C C6C—H61C C8C—C7C C8C—H81C C7C—H71C O1D—C1D O2D—C1D C3D—C4D C3D—C2D C3D—H31D C3D—H32D C2D—N1D C2D—C1D C2D—H21D N1D—H11D N1D—H12D N1D—H13D C4D—C5D C4D—C9D C5D—C6D C5D—H51D C9D—C8D C9D—H91D C8D—C7D C8D—H81D C6D—C7D C6D—H61D C7D—H71D

1.258 (3) 1.256 (3) 1.501 (3) 0.9100 0.9100 0.9100 1.531 (3) 1.534 (3) 1.0000 1.391 (4) 1.402 (4) 1.510 (4) 1.390 (4) 0.9500 0.9900 0.9900 1.389 (4) 0.9500 1.393 (5) 0.9500 1.387 (4) 0.9500 0.9500 1.256 (3) 1.264 (3) 1.506 (4) 1.532 (3) 0.9900 0.9900 1.496 (3) 1.532 (3) 1.0000 0.9100 0.9100 0.9100 1.395 (4) 1.399 (4) 1.387 (4) 0.9500 1.396 (4) 0.9500 1.379 (5) 0.9500 1.398 (4) 0.9500 0.9500

O2A—C1A—O1A

126.3 (2)

C2C—N1C—H11C

109.5

Acta Cryst. (2014). C70, 326-331

sup-5

supplementary materials O2A—C1A—C2A O1A—C1A—C2A C2A—N1A—H11A C2A—N1A—H12A H11A—N1A—H12A C2A—N1A—H13A H11A—N1A—H13A H12A—N1A—H13A N1A—C2A—C3A N1A—C2A—C1A C3A—C2A—C1A N1A—C2A—H21A C3A—C2A—H21A C1A—C2A—H21A C4A—C3A—C2A C4A—C3A—H31A C2A—C3A—H31A C4A—C3A—H32A C2A—C3A—H32A H31A—C3A—H32A C9A—C4A—C5A C9A—C4A—C3A C5A—C4A—C3A C6A—C5A—C4A C6A—C5A—H51A C4A—C5A—H51A C7A—C6A—C5A C7A—C6A—H61A C5A—C6A—H61A C6A—C7A—C8A C6A—C7A—H71A C8A—C7A—H71A C9A—C8A—C7A C9A—C8A—H81A C7A—C8A—H81A C8A—C9A—C4A C8A—C9A—H91A C4A—C9A—H91A C2B—N1B—H11B C2B—N1B—H12B H11B—N1B—H12B C2B—N1B—H13B H11B—N1B—H13B H12B—N1B—H13B N1B—C2B—C1B N1B—C2B—C3B C1B—C2B—C3B N1B—C2B—H21B C1B—C2B—H21B

Acta Cryst. (2014). C70, 326-331

119.1 (2) 114.6 (2) 109.5 109.5 109.5 109.5 109.5 109.5 106.3 (2) 108.17 (18) 112.74 (19) 109.8 109.8 109.8 115.7 (2) 108.4 108.4 108.4 108.4 107.4 118.2 (3) 120.5 (2) 121.2 (2) 120.8 (3) 119.6 119.6 120.4 (3) 119.8 119.8 119.2 (3) 120.4 120.4 120.3 (3) 119.8 119.8 121.0 (3) 119.5 119.5 109.5 109.5 109.5 109.5 109.5 109.5 108.17 (19) 107.22 (19) 112.3 (2) 109.7 109.7

C2C—N1C—H12C H11C—N1C—H12C C2C—N1C—H13C H11C—N1C—H13C H12C—N1C—H13C N1C—C2C—C3C N1C—C2C—C1C C3C—C2C—C1C N1C—C2C—H21C C3C—C2C—H21C C1C—C2C—H21C C5C—C4C—C9C C5C—C4C—C3C C9C—C4C—C3C C8C—C9C—C4C C8C—C9C—H91C C4C—C9C—H91C C4C—C3C—C2C C4C—C3C—H31C C2C—C3C—H31C C4C—C3C—H32C C2C—C3C—H32C H31C—C3C—H32C C6C—C5C—C4C C6C—C5C—H51C C4C—C5C—H51C C5C—C6C—C7C C5C—C6C—H61C C7C—C6C—H61C C7C—C8C—C9C C7C—C8C—H81C C9C—C8C—H81C O2C—C1C—O1C O2C—C1C—C2C O1C—C1C—C2C C8C—C7C—C6C C8C—C7C—H71C C6C—C7C—H71C C4D—C3D—C2D C4D—C3D—H31D C2D—C3D—H31D C4D—C3D—H32D C2D—C3D—H32D H31D—C3D—H32D N1D—C2D—C3D N1D—C2D—C1D C3D—C2D—C1D N1D—C2D—H21D C3D—C2D—H21D

109.5 109.5 109.5 109.5 109.5 106.5 (2) 108.36 (18) 113.04 (19) 109.6 109.6 109.6 118.5 (2) 119.6 (2) 121.9 (2) 120.0 (3) 120.0 120.0 114.2 (2) 108.7 108.7 108.7 108.7 107.6 121.4 (3) 119.3 119.3 119.8 (3) 120.1 120.1 121.1 (3) 119.4 119.4 126.5 (2) 118.5 (2) 115.1 (2) 119.2 (3) 120.4 120.4 115.1 (2) 108.5 108.5 108.5 108.5 107.5 106.61 (19) 108.26 (18) 112.3 (2) 109.9 109.9

sup-6

supplementary materials C3B—C2B—H21B C4B—C3B—C2B C4B—C3B—H31B C2B—C3B—H31B C4B—C3B—H32B C2B—C3B—H32B H31B—C3B—H32B C9B—C4B—C5B C9B—C4B—C3B C5B—C4B—C3B O1B—C1B—O2B O1B—C1B—C2B O2B—C1B—C2B C4B—C5B—C6B C4B—C5B—H51B C6B—C5B—H51B C4B—C9B—C8B C4B—C9B—H91B C8B—C9B—H91B C6B—C7B—C8B C6B—C7B—H71B C8B—C7B—H71B C9B—C8B—C7B C9B—C8B—H81B C7B—C8B—H81B C7B—C6B—C5B C7B—C6B—H61B C5B—C6B—H61B

109.7 114.2 (2) 108.7 108.7 108.7 108.7 107.6 118.2 (2) 121.8 (2) 120.0 (2) 126.1 (2) 115.3 (2) 118.6 (2) 121.6 (3) 119.2 119.2 120.7 (3) 119.7 119.7 119.4 (3) 120.3 120.3 120.4 (3) 119.8 119.8 119.7 (3) 120.2 120.2

C1D—C2D—H21D C2D—N1D—H11D C2D—N1D—H12D H11D—N1D—H12D C2D—N1D—H13D H11D—N1D—H13D H12D—N1D—H13D C5D—C4D—C9D C5D—C4D—C3D C9D—C4D—C3D C6D—C5D—C4D C6D—C5D—H51D C4D—C5D—H51D C8D—C9D—C4D C8D—C9D—H91D C4D—C9D—H91D C7D—C8D—C9D C7D—C8D—H81D C9D—C8D—H81D C5D—C6D—C7D C5D—C6D—H61D C7D—C6D—H61D O1D—C1D—O2D O1D—C1D—C2D O2D—C1D—C2D C8D—C7D—C6D C8D—C7D—H71D C6D—C7D—H71D

109.9 109.5 109.5 109.5 109.5 109.5 109.5 118.4 (2) 120.6 (2) 120.9 (2) 121.4 (3) 119.3 119.3 120.3 (3) 119.8 119.8 120.5 (3) 119.8 119.8 119.5 (3) 120.2 120.2 126.3 (2) 115.2 (2) 118.5 (2) 119.9 (3) 120.1 120.1

Hydrogen-bond geometry (Å, º) D—H···A

D—H

H···A

D···A

D—H···A

N1A—H11A···O2B N1A—H12A···O1Ci N1A—H13A···O2Cii N1B—H11B···O1D N1B—H12B···O2Diii N1B—H13B···O2A N1C—H11C···O2D N1C—H12C···O1Aiv N1C—H13C···O2A N1D—H11D···O1Bv N1D—H12D···O2Bvi N1D—H13D···O2C

0.91 0.91 0.91 0.91 0.91 0.91 0.91 0.91 0.91 0.91 0.91 0.91

1.99 1.79 2.06 1.80 1.99 2.00 1.98 1.79 1.99 1.80 2.07 1.98

2.840 (3) 2.695 (3) 2.950 (3) 2.707 (3) 2.883 (3) 2.854 (3) 2.839 (3) 2.694 (3) 2.884 (3) 2.694 (3) 2.963 (3) 2.829 (3)

155 174 166 177 168 156 158 176 168 167 168 156

Symmetry codes: (i) x, y, z+1; (ii) x−1, y, z+1; (iii) x−1, y, z; (iv) x+1, y, z; (v) x+1, y, z−1; (vi) x, y, z−1.

Acta Cryst. (2014). C70, 326-331

sup-7

The self-assembling zwitterionic form of L-phenylalanine at neutral pH.

The title zwitterion (2S)-2-azaniumyl-1-hydroxy-3-phenylpropan-1-olate, C9H11NO2, also known as L-phenylalanine, was characterized using synchrotron X...
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