Two modifications of L-alanyl-L-tyrosyl-L-alanine with different solvent mol­ecules in the crystal lattice

The low-temperature crystal and mol­ecular structure analyses of two modifications of L-alanyl-L-tyrosyl-L-alanine with water, C₁₅H₂₁N₃O₅·2.63H₂O [(I), at 9 K], and ethanol, C₁₅H₂₁N₃O₅·C₂H₅O [(II), at 20 K], solvent mol­ecules in the crystal lattice show that the overall conformations of both modifications of the title tripeptide are practically the same. Moreover, despite the presence of different solvent mol­ecules in the crystal lattice, the specific inter­molecular inter­actions characteristic for individual tripeptide mol­ecules of (I) and (II) are conserved. The crystal packing of the two modifications of Ala-Tyr-Ala differ from each other only in the solvent region. The tight arrangements of tripeptide mol­ecules seem to be responsible for similar displacement parameters for all non-H atoms, despite the different distances from the mol­ecular centre of mass. Comparison of the displacement parameters between the room- and low-temperature structures shows that an average U_eq value decrease of about 80% takes place at 9 K [for (I)] and 20 K [for (II)] with respect to room temperature.

S1. Comment

In our ongoing comparative charge-density studies of oligopeptides, we became interested in the structures of tripeptides of the type L-Ala-Xxx-L-Ala, where Xxx is one of the 20 naturally encoded amino acids. First results have recently been obtained for Xxx = L-Ala (Rödel et al., 2006) and Xxx = Gly (Förster et al., 2005). In this paper, we describe the crystal and molecular structures of two modifications of L-alanyl-L-tyrosyl-L-alanine [L-Ala-L-Tyr-L-Ala, AYA; symbol according to the one-letter notation for amino acid sequences (IUPAC–IUB Commission on Biochemical Nomenclature, 1968)] with water, (I), and ethanol, (II), solvent molecules in the crystal structure. The different solvates were obtained using two crystallization routes for the title tripeptide (see Experimental).

The measurement temperature of 9 K [for (I)], realised by the recently installed He gas stream low-temperature set-up (Helijet) at beamline D3 of Hasylab (DESY, Hamburg, Germany), is infrequently observed in the literature. It prompted us to compare the equivalent isotropic displacement parameters of non-H atoms for the title tripeptide molecule at room temperature and at low temperature. Moreover, special attention has been focused on the molecular conformations of L-Ala-L-Tyr-L-Ala in comparison with the crystal structures of the analogous tripeptides previously reported (Förster et al., 2005; Padiyar & Seshadri, 1996; Fawcett et al., 1975). We are also interested in the crystal packing arrangements which are influenced by the presence of different solvent molecules in the crystal lattice.

The molecular structures, with the atom-numbering schemes, of both modifications of Ala-Tyr-Ala, (I) and (II), are shown in Figs. 1 and 2. The asymmetric unit of (I) consists of one tripeptide molecule and an average 2.6 water molecules (1 + 1 + 0.6), while for (II), the solvent consists of one ethanol molecule. In both cases, the Ala-Tyr-Ala molecules exist as zwitterions. Selected bond lengths and angles are given in Tables 1 and 3. The bond distances observed for both modifications are in good agreement and need no detailed disccussion. Table 5 presents the torsion angles, which characterize the backbone conformation of the tripeptide molecules. Among these, the C4—N3—C5—C6 and C4—N3—C5—C8 angles differ by slightly more than 15°, whereas the rest agree to within 10°. Hence, the molecular conformations are basically alike for both modifications. This means that the presence of different solvent molecules does not significantly disturb the overall conformation of the L-Ala-L-Tyr-L-Ala tripeptide.

Considering all published crystal structures of the type Ala-Xxx-Ala (where Xxx is one of the 20 naturally encoded amino acids), our special interest is focused on the conformation of the main peptide chain. It was found that the principal difference, in the conformation of two independent molecules of trialanine, is seen at the carboxyl terminal groups. Such a deformation is attributed to the requirements of hydrogen bonds and is reflected in the two values of the ψ₃ angle (symbols in agreement with IUPAC–IUB Commission on Biochemical Nomenclature, 1970). The substantial variations (about 90° and more) between two forms of L-alanylglycyl-L-alanine, namely the hydrate and the solvent-free form, are visible for the ψ₁ and ϕ₃ torsion angles. Taking into consideration all the above-mentioned tripeptide structures, it seems that the essential conformational differences are noticeable for the N_pep—C_α bonds, described by the ϕ₂ and ϕ₃ torsion parameters (Table 5), while all remaining backbone torsion angles are conserved and differ at most by 30–35°.

Fig. 3 presents equivalent displacement parameters (U_eq values) of all non H-atoms plotted versus their distances (r) from the molecular centre of mass for both modifications of Ala-Tyr-Ala, for the data sets measured at room temperature (Chęcińska et al., 2006) and at temperatures of 9 K [(I)] and 20 K [(II)]. The diagram reveals the influence of temperature on the refined model. It is interesting to note that, at all temperatures, there is no significant tendency for the U_eq values to increase for the outer atoms [with the exception of two outliers, C8 and O3, of the room-temperature structure of (II)], as is frequently observed for room-temperature structures (Meserschmidt et al., 2003; Wagner et al., 2002). The reason is obviously the tight integration of all tripeptide molecular fragments in intermolecular hydrogen bonding, as will be discussed later. The average U_eq values calculated for all non H-atoms at room temperature are 0.044 (9) and 0.055 (20) Ų for (I) and (II), respectively; the corresponding averages at 9 K and 20 K are 0.0086 (14) and 0.0098 (20) Ų for (I) and (II), respectively. Thus, compared with room temperature, an average decrease in U_eq of 80% has taken place at the lower temperatures. Similar reductions of displacement parameters when going to ultra-low temperatures of 10–20 K have frequently been observed, for example in our studies on an ergoline derivative (~80%; Luger & Zobel, 1993) and for an 18-crown-6–KClO₄ complex (85–90%; Luger et al., 1992).

It is worth mentioning the unusually high fraction of significant reflections with I > 2σ(I), which is between 98 and 99% for both data sets. This is of course the result of the very favourable experimental conditions, especially the low data-collection temperature, which favours an intensity increase of the high-order reflections.

The structures of oligopeptides offer the possibility of a wide variety of potential intermolecular interactions. Additionally, the number of hydrogen bonds increases due to the presence of the solvent molecules (water and ethanol) in the crystal lattice. To facilitate better understanding of the similarities and differences in the crystal packing of (I) and (II), we now describe the hydrogen-bonding networks, first separately for the tripeptide molecules and then together with solvent. The hydrogen-bonding geometries are presented in Tables 2 and 4, for (I) and (II), respectively. Examining the specific intermolecular interactions characteristic for individual tripeptide molecules of (I) and (II) indicates that they are very similar in both cases. Ala-Tyr-Ala possesses six potential hydrogen-bonding donors (–NH or –OH) and five O atoms (–OH, C═O or –COO⁻), which are acceptors. As a result, the crystal structures of (I) and (II) contain three N_amm—H···O intermolecular hydrogen bonds. Based on geometric criteria, the N1—H11C···O2^iv hydrogen bond (see Table 4 for symmetry code) seems to be the strongest, with a donor···acceptor distance of 2.748 (1) Å for structure (II). The remaining N_amm—H···O interactions are characterized by somewhat longer N···O distances, which are in the range 2.786 (1)–2.873 (1) Å. The amide N—H bonds form the next set of interactions, which are typical for tripeptide molecules. Their geometries are roughly comparable for the water and ethanol modifications. In conclusion, it is worth mentioning that, considering only interactions between the tripeptide molecules, the hydrogen-bonded motifs are the same in both structures. The hydroxyl group (O5—H15) of the tyrosine fragment acts as a hydrogen-bond donor to O atoms of the solvent molecule, water and ethanol in (I) and (II), respectively. These O—H···O hydrogen bonds appear to be the strongest of all non-covalent interactions in the present structures.

In the crystal structure of Ala-Tyr-Ala, (I), there are two fully occupied water molecules. Each of them is involved in two interactions as a donor; atom O7 is an acceptor twice, whereas atom O6 is an acceptor only once. The third water molecule, which appears approximately twice every three unit cells, participates in only one (O8—H81···O7) hydrogen bond. In contrast, the hydrogen-bonding network of (II), with ethanol as the solvent, is rather simple. Atom O6 of the ethanol molecule participates in the above-mentioned interaction with the tyrosine hydroxyl group (O5—H15···O6ⁱ), as well as in O6—H16···O3ⁱⁱ interactions. Figs. 4 and 5 present the crystal packing of the reported structures projected onto the ac plane.

In closing, it can be seen from the figures that the arrangements of the molecules of these two modifications of Ala-Tyr-Ala, (I) and (II), differ from each other only in the solvent region.

S2. Experimental

The title tripeptide L-alanyl-L-tyrosyl-L-alanine was obtained from Bachem (Germany). Crystallization from water by slow evaporation yielded crystals of modification (I). Crystals of modification (II) were prepared by diffusion of ethanol into an aqueous solution of the tripeptide at room temperature.

S3. Refinement

One water molecule appears to be partially occupied in the crystal structure of (I). A common occupancy factor for the O atom (O8) and the two H atoms (H81 and H82) was refined freely to 0.628 (4) without any restraints. Due to the absence of significant anomalous scattering effects, 4464 and 4366 Friedel pairs were merged for (I) and (II), respectively. The absolute configuration of the purchased material was known.

Computing details

Data collection: MarCCD (Paulmann & Morgenroth, 2006) for (I); SMART (Bruker, 1997–2001) for (II). Cell refinement: XDS (Kabsch, 1993) for (I); SMART for (II). Data reduction: XDS for (I); SAINT (Bruker, 1997–2001) and SADABS (Bruker, 1997–2001) for (II). For both compounds, program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: PLATON.

Figures

	Fig. 1. The molecular structure of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. The molecular structure of (II), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 3. Equivalent isotropic displacement parameters Ueq (Å^2) plotted versus the corresponding atomic distances r (Å) from the molecular centre of mass for the water and ethanol modifications of AYA at room temperature and at 9 K [(I)] and 20 K [(II)].
	Fig. 4. Part of the crystal structure of (I), showing the hydrogen-bonding network, projected on to the ac plane. N and O atoms are shaded. For clarity, H atoms bonded to C atoms have been omitted.
	Fig. 5. Part of the crystal structure of (II), showing the hydrogen-bonding network, projected on to the ac plane. and O atoms are shaded. For clarity, H atoms bonded to C atoms have been omitted.

(I) L-alanyl-L-tyrosyl-L-alanine 2.63-hydrate

Crystal data

C15H21N3O5·2.628H2O	F(000) = 397
Mr = 370.69	Dx = 1.301 Mg m^−3
Monoclinic, P21	Synchrotron radiation, λ = 0.50 Å
Hall symbol: P 2yb	Cell parameters from 1613 reflections
a = 8.121 (3) Å	θ = 1.9–19.4°
b = 9.299 (4) Å	µ = 0.06 mm^−1
c = 12.532 (5) Å	T = 9 K
β = 91.21 (2)°	Needle, colourless
V = 946.2 (7) Å^3	0.54 × 0.25 × 0.13 mm
Z = 2

Data collection

Huber diffractometer with MarCCD detector	4945 reflections with I > 2σ(I)
Radiation source: synchrotron	Rint = 0.044
Graphite monochromator	θmax = 25.0°, θmin = 1.1°
ϕ scans	h = −13→13
9540 measured reflections	k = −15→15
5019 independent reflections	l = −21→21

Refinement

Refinement on F^2	Secondary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.024	All H-atom parameters refined
wR(F^2) = 0.068	w = 1/[σ^2(Fo^2) + (0.0499P)^2 + 0.0316P] where P = (Fo^2 + 2Fc^2)/3
S = 1.11	(Δ/σ)max = 0.001
5019 reflections	Δρmax = 0.45 e Å^−3
344 parameters	Δρmin = −0.24 e Å^−3
1 restraint	Absolute structure: rm
Primary atom site location: structure-invariant direct methods

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.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.06035 (7)	0.37956 (6)	0.47927 (4)	0.00942 (8)
O2	0.00628 (7)	0.73348 (6)	0.76658 (4)	0.00960 (8)
O3	0.17783 (6)	0.59346 (6)	1.02578 (4)	0.00998 (8)
O4	−0.02513 (6)	0.70248 (5)	1.11477 (4)	0.00792 (8)
O5	0.61147 (6)	1.02747 (6)	0.68076 (4)	0.01050 (8)
N1	0.04654 (7)	0.52309 (6)	0.29184 (4)	0.00788 (8)
N2	0.04051 (7)	0.58477 (6)	0.57845 (4)	0.00723 (8)
N3	−0.03024 (7)	0.52213 (6)	0.85565 (4)	0.00704 (8)
C1	−0.02046 (7)	0.59748 (7)	0.38758 (4)	0.00667 (9)
C2	0.03198 (7)	0.51064 (7)	0.48649 (4)	0.00656 (9)
C3	0.08504 (7)	0.51225 (6)	0.67848 (4)	0.00673 (9)
C4	0.01586 (7)	0.60003 (7)	0.77079 (4)	0.00661 (9)
C5	−0.10079 (7)	0.58966 (7)	0.94938 (4)	0.00662 (8)
C6	0.03030 (7)	0.63138 (7)	1.03519 (4)	0.00650 (8)
C7	−0.20806 (8)	0.60620 (8)	0.37742 (5)	0.01114 (10)
C8	−0.23060 (8)	0.49022 (8)	0.99806 (5)	0.01105 (10)
C20	0.27471 (8)	0.48933 (7)	0.69096 (5)	0.00813 (9)
C21	0.37347 (8)	0.62734 (7)	0.69027 (5)	0.00793 (9)
C22	0.40865 (8)	0.70208 (8)	0.78569 (5)	0.00980 (10)
C23	0.49152 (8)	0.83439 (8)	0.78489 (5)	0.01009 (10)
C24	0.53805 (8)	0.89353 (7)	0.68726 (5)	0.00848 (9)
C25	0.50980 (8)	0.81836 (7)	0.59189 (5)	0.00955 (10)
C26	0.42775 (8)	0.68600 (7)	0.59367 (5)	0.00904 (9)
H1	0.0288 (19)	0.688 (2)	0.3896 (12)	0.016 (3)*
H3	0.0330 (17)	0.4168 (16)	0.6823 (11)	0.010 (3)*
H5	−0.154 (2)	0.674 (2)	0.9252 (13)	0.019 (4)*
H7A	−0.253 (2)	0.510 (2)	0.3775 (13)	0.019 (3)*
H7B	−0.253 (2)	0.657 (2)	0.4393 (14)	0.024 (4)*
H7C	−0.243 (2)	0.650 (2)	0.3091 (15)	0.030 (5)*
H8A	−0.182 (2)	0.402 (2)	1.0187 (14)	0.020 (4)*
H8B	−0.280 (2)	0.533 (2)	1.0564 (15)	0.025 (4)*
H8C	−0.318 (2)	0.473 (2)	0.9479 (15)	0.028 (4)*
H11C	0.012 (2)	0.434 (2)	0.2821 (14)	0.022 (4)*
H11B	0.155 (2)	0.519 (2)	0.2969 (13)	0.020 (4)*
H11A	0.018 (2)	0.579 (2)	0.2303 (13)	0.020 (4)*
H12	0.0172 (18)	0.6775 (19)	0.5781 (12)	0.014 (3)*
H13	−0.020 (2)	0.434 (2)	0.8576 (13)	0.021 (4)*
H15	0.585 (2)	1.082 (2)	0.7330 (15)	0.028 (4)*
H20A	0.300 (2)	0.436 (2)	0.7588 (14)	0.021 (4)*
H20B	0.309 (2)	0.425 (2)	0.6326 (14)	0.024 (4)*
H22	0.3720 (18)	0.6618 (18)	0.8511 (12)	0.014 (3)*
H23	0.510 (2)	0.887 (2)	0.8474 (14)	0.021 (4)*
H25	0.5437 (19)	0.866 (2)	0.5280 (12)	0.019 (4)*
H26	0.399 (2)	0.6352 (19)	0.5279 (13)	0.017 (3)*
O6	0.32383 (6)	0.34130 (6)	0.94027 (4)	0.01026 (8)
H61	0.289 (2)	0.420 (2)	0.9633 (14)	0.024 (4)*
H62	0.232 (3)	0.295 (2)	0.9209 (16)	0.032 (5)*
O7	0.58445 (7)	0.20851 (6)	0.84060 (4)	0.01131 (8)
H71	0.658 (2)	0.179 (2)	0.8852 (15)	0.026 (4)*
H72	0.513 (3)	0.249 (3)	0.8723 (18)	0.041 (6)*
O8	0.71471 (12)	0.37599 (12)	0.66470 (8)	0.0159 (3)	0.628 (4)
H81	0.679 (4)	0.337 (4)	0.716 (3)	0.030 (7)*	0.628 (4)
H82	0.673 (4)	0.451 (5)	0.652 (3)	0.039 (9)*	0.628 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0156 (2)	0.00504 (17)	0.00765 (17)	0.00096 (15)	0.00012 (14)	−0.00056 (14)
O2	0.0152 (2)	0.00476 (17)	0.00892 (18)	0.00081 (15)	0.00213 (14)	0.00034 (14)
O3	0.00860 (17)	0.0104 (2)	0.01095 (18)	0.00120 (15)	0.00054 (14)	−0.00251 (16)
O4	0.01135 (18)	0.00675 (18)	0.00570 (15)	0.00097 (14)	0.00109 (13)	−0.00129 (13)
O5	0.01189 (18)	0.00853 (19)	0.01113 (18)	−0.00185 (15)	0.00158 (14)	−0.00272 (15)
N1	0.01100 (19)	0.00686 (19)	0.00582 (17)	0.00108 (16)	0.00128 (14)	−0.00030 (15)
N2	0.01216 (19)	0.00519 (18)	0.00434 (17)	0.00038 (15)	0.00034 (14)	−0.00018 (14)
N3	0.01139 (19)	0.00499 (18)	0.00483 (17)	0.00035 (15)	0.00218 (14)	−0.00042 (14)
C1	0.0095 (2)	0.0054 (2)	0.00518 (18)	0.00096 (17)	0.00055 (15)	−0.00041 (16)
C2	0.00901 (19)	0.0056 (2)	0.00509 (19)	0.00003 (16)	0.00080 (14)	−0.00009 (15)
C3	0.0102 (2)	0.0053 (2)	0.00473 (18)	0.00031 (17)	0.00125 (15)	0.00009 (15)
C4	0.0089 (2)	0.0060 (2)	0.00497 (18)	0.00029 (16)	0.00099 (15)	−0.00022 (16)
C5	0.00850 (19)	0.0060 (2)	0.00544 (18)	−0.00008 (16)	0.00123 (15)	−0.00094 (16)
C6	0.00891 (19)	0.0050 (2)	0.00558 (19)	−0.00016 (16)	0.00097 (15)	0.00015 (15)
C7	0.0090 (2)	0.0132 (3)	0.0112 (2)	0.00165 (19)	0.00012 (17)	−0.0002 (2)
C8	0.0125 (2)	0.0101 (2)	0.0108 (2)	−0.00381 (19)	0.00457 (18)	−0.00275 (19)
C20	0.0101 (2)	0.0070 (2)	0.0073 (2)	0.00115 (17)	0.00113 (16)	0.00039 (17)
C21	0.0091 (2)	0.0081 (2)	0.00659 (19)	0.00007 (17)	0.00115 (15)	−0.00030 (17)
C22	0.0121 (2)	0.0107 (2)	0.0066 (2)	−0.00095 (19)	0.00069 (16)	−0.00052 (18)
C23	0.0119 (2)	0.0109 (2)	0.0074 (2)	−0.0010 (2)	0.00045 (17)	−0.00190 (18)
C24	0.0087 (2)	0.0083 (2)	0.0084 (2)	−0.00040 (17)	0.00082 (16)	−0.00146 (17)
C25	0.0124 (2)	0.0090 (2)	0.0073 (2)	−0.00179 (18)	0.00233 (16)	−0.00122 (17)
C26	0.0119 (2)	0.0086 (2)	0.0068 (2)	−0.00115 (18)	0.00178 (16)	−0.00114 (17)
O6	0.01022 (18)	0.00865 (19)	0.01197 (19)	0.00046 (15)	0.00143 (14)	−0.00076 (15)
O7	0.01121 (18)	0.0126 (2)	0.01007 (17)	0.00237 (16)	−0.00020 (14)	−0.00210 (16)
O8	0.0152 (4)	0.0180 (5)	0.0147 (4)	−0.0025 (3)	0.0030 (3)	0.0013 (3)

Geometric parameters (Å, º)

O1—C2	1.2442 (9)	C7—H7A	0.961 (19)
O2—C4	1.2444 (9)	C7—H7B	0.983 (18)
O3—C6	1.2568 (9)	C7—H7C	0.985 (19)
O4—C6	1.2859 (8)	C8—H8A	0.946 (18)
O5—C24	1.3840 (10)	C8—H8B	0.930 (19)
O5—H15	0.859 (19)	C8—H8C	0.950 (19)
N1—C1	1.4971 (9)	C20—C21	1.5135 (10)
N1—H11C	0.89 (2)	C20—H20A	1.003 (18)
N1—H11B	0.883 (17)	C20—H20B	0.986 (19)
N1—H11A	0.954 (17)	C21—C26	1.4071 (10)
N2—C2	1.3434 (9)	C21—C22	1.4073 (10)
N2—C3	1.4622 (9)	C22—C23	1.4025 (11)
N2—H12	0.883 (17)	C22—H22	0.955 (16)
N3—C4	1.3463 (9)	C23—C24	1.4006 (10)
N3—C5	1.4598 (9)	C23—H23	0.933 (18)
N3—H13	0.82 (2)	C24—C25	1.3993 (10)
C1—C7	1.5283 (11)	C25—C26	1.4000 (11)
C1—C2	1.5322 (9)	C25—H25	0.962 (16)
C1—H1	0.934 (18)	C26—H26	0.974 (17)
C3—C4	1.5322 (9)	O6—H61	0.838 (19)
C3—C20	1.5595 (11)	O6—H62	0.89 (2)
C3—H3	0.984 (15)	O7—H71	0.855 (19)
C5—C8	1.5381 (10)	O7—H72	0.80 (2)
C5—C6	1.5466 (10)	O8—H81	0.80 (4)
C5—H5	0.943 (18)	O8—H82	0.79 (4)
C24—O5—H15	112.1 (14)	C1—C7—H7A	109.0 (10)
C1—N1—H11C	115.2 (11)	C1—C7—H7B	110.0 (10)
C1—N1—H11B	110.1 (11)	H7A—C7—H7B	107.5 (15)
H11C—N1—H11B	106.1 (17)	C1—C7—H7C	111.3 (11)
C1—N1—H11A	108.1 (11)	H7A—C7—H7C	106.5 (16)
H11C—N1—H11A	109.4 (15)	H7B—C7—H7C	112.4 (16)
H11B—N1—H11A	107.7 (15)	C5—C8—H8A	110.4 (11)
C2—N2—C3	120.41 (6)	C5—C8—H8B	111.2 (12)
C2—N2—H12	119.3 (10)	H8A—C8—H8B	109.9 (16)
C3—N2—H12	120.3 (10)	C5—C8—H8C	110.2 (12)
C4—N3—C5	121.63 (6)	H8A—C8—H8C	109.6 (17)
C4—N3—H13	121.9 (12)	H8B—C8—H8C	105.4 (16)
C5—N3—H13	116.5 (12)	C21—C20—C3	113.95 (5)
N1—C1—C7	109.65 (5)	C21—C20—H20A	109.2 (10)
N1—C1—C2	107.77 (5)	C3—C20—H20A	109.5 (10)
C7—C1—C2	110.79 (5)	C21—C20—H20B	110.4 (11)
N1—C1—H1	106.0 (10)	C3—C20—H20B	107.5 (11)
C7—C1—H1	112.3 (10)	H20A—C20—H20B	105.9 (15)
C2—C1—H1	110.0 (10)	C26—C21—C22	118.55 (6)
O1—C2—N2	123.97 (6)	C26—C21—C20	120.62 (6)
O1—C2—C1	120.42 (5)	C22—C21—C20	120.80 (6)
N2—C2—C1	115.60 (6)	C23—C22—C21	121.07 (6)
N2—C3—C4	108.28 (5)	C23—C22—H22	120.6 (10)
N2—C3—C20	112.02 (5)	C21—C22—H22	118.3 (10)
C4—C3—C20	111.98 (5)	C24—C23—C22	119.28 (6)
N2—C3—H3	111.0 (8)	C24—C23—H23	119.0 (11)
C4—C3—H3	106.2 (9)	C22—C23—H23	121.6 (11)
C20—C3—H3	107.2 (8)	O5—C24—C25	117.54 (6)
O2—C4—N3	123.50 (6)	O5—C24—C23	121.96 (6)
O2—C4—C3	121.52 (5)	C25—C24—C23	120.50 (7)
N3—C4—C3	114.97 (6)	C24—C25—C26	119.68 (6)
N3—C5—C8	110.15 (5)	C24—C25—H25	115.8 (11)
N3—C5—C6	113.04 (6)	C26—C25—H25	124.4 (11)
C8—C5—C6	110.03 (5)	C25—C26—C21	120.82 (6)
N3—C5—H5	106.5 (10)	C25—C26—H26	121.2 (10)
C8—C5—H5	108.4 (10)	C21—C26—H26	117.8 (10)
C6—C5—H5	108.6 (11)	H61—O6—H62	103.3 (18)
O3—C6—O4	124.54 (6)	H71—O7—H72	109 (2)
O3—C6—C5	120.53 (6)	H81—O8—H82	114 (3)
O4—C6—C5	114.91 (6)
C3—N2—C2—O1	−0.09 (9)	C8—C5—C6—O3	116.19 (7)
C3—N2—C2—C1	178.39 (5)	N3—C5—C6—O4	174.16 (5)
N1—C1—C2—O1	−26.26 (8)	C8—C5—C6—O4	−62.25 (7)
C7—C1—C2—O1	93.70 (7)	N2—C3—C20—C21	59.76 (7)
N1—C1—C2—N2	155.20 (5)	C4—C3—C20—C21	−62.11 (7)
C7—C1—C2—N2	−84.84 (7)	C3—C20—C21—C26	−88.59 (7)
C2—N2—C3—C4	−156.19 (5)	C3—C20—C21—C22	89.44 (7)
C2—N2—C3—C20	79.85 (7)	C26—C21—C22—C23	1.94 (10)
C5—N3—C4—O2	1.91 (10)	C20—C21—C22—C23	−176.13 (6)
C5—N3—C4—C3	−179.08 (5)	C21—C22—C23—C24	0.77 (10)
N2—C3—C4—O2	−33.58 (8)	C22—C23—C24—O5	176.18 (6)
C20—C3—C4—O2	90.41 (7)	C22—C23—C24—C25	−3.21 (10)
N2—C3—C4—N3	147.39 (5)	O5—C24—C25—C26	−176.52 (6)
C20—C3—C4—N3	−88.62 (6)	C23—C24—C25—C26	2.89 (10)
C4—N3—C5—C8	145.72 (6)	C24—C25—C26—C21	−0.11 (10)
C4—N3—C5—C6	−90.75 (7)	C22—C21—C26—C25	−2.27 (9)
N3—C5—C6—O3	−7.41 (8)	C20—C21—C26—C25	175.81 (6)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H15···O7^i	0.86 (2)	1.79 (2)	2.629 (1)	165 (2)
O6—H61···O3	0.84 (2)	2.02 (2)	2.847 (1)	172 (2)
O6—H62···O4^ii	0.89 (2)	1.93 (3)	2.821 (1)	176 (2)
O7—H71···O3^iii	0.86 (2)	1.90 (2)	2.746 (1)	173 (2)
O7—H72···O6	0.80 (2)	1.97 (2)	2.771 (1)	175 (3)
O8—H81···O7	0.80 (4)	2.12 (4)	2.916 (1)	173 (4)
N1—H11A···O4^iv	0.96 (2)	1.88 (2)	2.827 (1)	175 (2)
N1—H11B···O5^v	0.88 (2)	1.91 (2)	2.792 (1)	174 (2)
N1—H11C···O2^vi	0.88 (2)	1.97 (2)	2.821 (1)	163 (2)
N2—H12···O1^vii	0.88 (2)	2.10 (2)	2.947 (2)	160 (2)
N3—H13···O4^ii	0.82 (2)	2.21 (2)	3.028 (2)	172 (2)

Symmetry codes: (i) x, y+1, z; (ii) −x, y−1/2, −z+2; (iii) −x+1, y−1/2, −z+2; (iv) x, y, z−1; (v) −x+1, y−1/2, −z+1; (vi) −x, y−1/2, −z+1; (vii) −x, y+1/2, −z+1.

(II) L-alanyl-L-tyrosyl-L-alanine ethanol solvate

Crystal data

C15H21N3O5·C2H6O	F(000) = 396
Mr = 369.42	Dx = 1.243 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 1447 reflections
a = 8.845 (2) Å	θ = 1.2–15.8°
b = 9.057 (2) Å	µ = 0.09 mm^−1
c = 12.364 (3) Å	T = 20 K
β = 94.56 (3)°	Prism, colourless
V = 987.3 (4) Å^3	0.4 × 0.25 × 0.2 mm
Z = 2

Data collection

Huber four-circle diffractometer with Bruker SMART Apex CCD area-detector	5178 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.035
Graphite monochromator	θmax = 37.0°, θmin = 1.7°
ϕ scans	h = −14→14
9710 measured reflections	k = −15→14
5258 independent reflections	l = −20→20

Refinement

Refinement on F^2	Secondary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.029	All H-atom parameters refined
wR(F^2) = 0.077	w = 1/[σ^2(Fo^2) + (0.0564P)^2 + 0.0452P] where P = (Fo^2 + 2Fc^2)/3
S = 1.10	(Δ/σ)max = 0.001
5258 reflections	Δρmax = 0.50 e Å^−3
343 parameters	Δρmin = −0.19 e Å^−3
2 restraints	Absolute structure: rm
Primary atom site location: structure-invariant direct methods

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.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.42025 (7)	0.41657 (6)	0.48566 (4)	0.01016 (9)
O2	0.50363 (7)	0.03376 (6)	0.76064 (4)	0.01123 (9)
O3	0.32839 (7)	0.22453 (7)	1.03294 (5)	0.01133 (9)
O4	0.46140 (7)	0.05567 (7)	1.13499 (4)	0.00951 (9)
O5	−0.08155 (7)	−0.22438 (7)	0.67985 (5)	0.01151 (9)
O6	0.08376 (7)	0.13907 (7)	0.13284 (5)	0.01257 (10)
N1	0.40141 (7)	0.25752 (7)	0.29610 (5)	0.00849 (9)
N2	0.46622 (7)	0.20696 (7)	0.58601 (4)	0.00793 (9)
N3	0.52908 (7)	0.22916 (7)	0.87748 (5)	0.00809 (9)
C1	0.49715 (8)	0.19911 (8)	0.39217 (5)	0.00795 (10)
C2	0.45654 (8)	0.28409 (8)	0.49275 (5)	0.00735 (9)
C3	0.43687 (8)	0.27494 (8)	0.68946 (5)	0.00729 (9)
C4	0.49528 (7)	0.16845 (7)	0.77971 (5)	0.00710 (9)
C5	0.56879 (8)	0.14001 (8)	0.97423 (5)	0.00817 (10)
C6	0.44057 (7)	0.14022 (8)	1.05208 (5)	0.00762 (9)
C7	0.66571 (8)	0.21795 (10)	0.37416 (6)	0.01203 (11)
C8	0.71655 (9)	0.19542 (11)	1.03487 (6)	0.01431 (13)
C20	0.26481 (8)	0.30847 (8)	0.69791 (5)	0.00853 (10)
C21	0.16606 (8)	0.17168 (8)	0.69369 (5)	0.00829 (10)
C22	0.13990 (8)	0.09578 (8)	0.78985 (5)	0.00943 (10)
C23	0.05527 (8)	−0.03487 (8)	0.78698 (5)	0.01021 (11)
C24	−0.00400 (8)	−0.09195 (8)	0.68672 (5)	0.00924 (10)
C25	0.01633 (8)	−0.01536 (9)	0.59034 (5)	0.01064 (11)
C26	0.10136 (8)	0.11531 (8)	0.59433 (5)	0.00974 (10)
C31	0.08069 (10)	−0.01990 (10)	0.13299 (7)	0.01596 (13)
C32	0.13330 (10)	−0.08282 (11)	0.24398 (8)	0.01866 (14)
H1	0.4740 (18)	0.102 (2)	0.4028 (14)	0.013 (3)*
H3	0.4955 (17)	0.3668 (19)	0.6988 (12)	0.010 (3)*
H5	0.579 (2)	0.042 (2)	0.9507 (14)	0.017 (4)*
H7A	0.726 (2)	0.182 (2)	0.4322 (15)	0.022 (4)*
H7B	0.688 (2)	0.315 (3)	0.3675 (16)	0.028 (5)*
H7C	0.692 (2)	0.162 (2)	0.3095 (14)	0.018 (4)*
H8A	0.707 (2)	0.292 (2)	1.0593 (15)	0.025 (4)*
H8B	0.742 (2)	0.141 (3)	1.1018 (18)	0.034 (5)*
H8C	0.7979 (19)	0.191 (2)	0.9897 (14)	0.017 (4)*
H11A	0.409 (2)	0.189 (3)	0.2391 (16)	0.029 (5)*
H11B	0.3103 (18)	0.264 (2)	0.3084 (13)	0.013 (3)*
H11C	0.428 (2)	0.338 (2)	0.2779 (14)	0.019 (4)*
H12	0.490 (2)	0.117 (2)	0.5838 (15)	0.019 (4)*
H13	0.5212 (18)	0.3221 (10)	0.8816 (12)	0.011 (3)*
H15	−0.070 (2)	−0.263 (3)	0.7389 (17)	0.029 (5)*
H16	0.160 (3)	0.167 (3)	0.098 (2)	0.041 (6)*
H23	0.039 (2)	−0.088 (2)	0.8538 (14)	0.019 (4)*
H22	0.183 (2)	0.137 (2)	0.8566 (15)	0.025 (4)*
H26	0.118 (2)	0.172 (2)	0.5247 (14)	0.018 (4)*
H25	−0.0235 (19)	−0.054 (2)	0.5227 (13)	0.015 (4)*
H20A	0.261 (2)	0.363 (2)	0.7651 (14)	0.019 (4)*
H20B	0.2321 (19)	0.373 (2)	0.6419 (13)	0.013 (3)*
H31A	−0.028 (2)	−0.046 (3)	0.1128 (17)	0.032 (5)*
H31B	0.147 (2)	−0.055 (3)	0.0776 (16)	0.026 (5)*
H32A	0.065 (2)	−0.042 (2)	0.3013 (15)	0.023 (4)*
H32B	0.235 (2)	−0.057 (3)	0.2663 (18)	0.033 (5)*
H32C	0.130 (2)	−0.193 (3)	0.2403 (16)	0.029 (5)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0158 (2)	0.00629 (19)	0.00853 (18)	0.00100 (16)	0.00179 (15)	0.00002 (15)
O2	0.0181 (2)	0.0060 (2)	0.00944 (18)	0.00156 (17)	0.00032 (16)	−0.00076 (16)
O3	0.0115 (2)	0.0121 (2)	0.01054 (19)	0.00330 (17)	0.00190 (15)	0.00217 (17)
O4	0.0142 (2)	0.0081 (2)	0.00635 (17)	0.00010 (17)	0.00166 (14)	0.00161 (15)
O5	0.0132 (2)	0.0096 (2)	0.0116 (2)	−0.00326 (17)	0.00072 (16)	0.00106 (17)
O6	0.0124 (2)	0.0111 (2)	0.0146 (2)	0.00058 (18)	0.00362 (17)	−0.00234 (18)
N1	0.0112 (2)	0.0079 (2)	0.00635 (18)	−0.00008 (17)	0.00031 (15)	0.00020 (16)
N2	0.0126 (2)	0.0064 (2)	0.00491 (18)	0.00045 (17)	0.00144 (15)	0.00025 (16)
N3	0.0124 (2)	0.0067 (2)	0.00515 (18)	0.00008 (17)	0.00054 (15)	0.00015 (16)
C1	0.0107 (2)	0.0074 (2)	0.0057 (2)	0.00046 (19)	0.00069 (17)	0.00003 (18)
C2	0.0093 (2)	0.0071 (2)	0.0057 (2)	−0.00064 (18)	0.00112 (16)	0.00003 (17)
C3	0.0103 (2)	0.0061 (2)	0.0056 (2)	−0.00023 (18)	0.00111 (16)	−0.00010 (17)
C4	0.0090 (2)	0.0065 (2)	0.0059 (2)	−0.00006 (18)	0.00113 (16)	0.00012 (17)
C5	0.0105 (2)	0.0084 (2)	0.00565 (19)	0.00068 (19)	0.00108 (17)	0.00104 (18)
C6	0.0099 (2)	0.0069 (2)	0.00608 (19)	−0.00043 (19)	0.00106 (16)	−0.00002 (18)
C7	0.0102 (2)	0.0150 (3)	0.0111 (2)	0.0010 (2)	0.00210 (19)	−0.0001 (2)
C8	0.0113 (3)	0.0204 (3)	0.0109 (2)	−0.0030 (2)	−0.0012 (2)	0.0044 (2)
C20	0.0095 (2)	0.0071 (2)	0.0090 (2)	0.00014 (18)	0.00099 (17)	0.00002 (18)
C21	0.0093 (2)	0.0077 (2)	0.0078 (2)	−0.00023 (18)	0.00078 (17)	0.00047 (18)
C22	0.0111 (2)	0.0096 (2)	0.0075 (2)	−0.0017 (2)	0.00075 (18)	0.00049 (19)
C23	0.0119 (3)	0.0105 (3)	0.0081 (2)	−0.0017 (2)	0.00065 (18)	0.0009 (2)
C24	0.0097 (2)	0.0086 (3)	0.0094 (2)	−0.00161 (19)	0.00074 (18)	0.0006 (2)
C25	0.0124 (3)	0.0111 (3)	0.0083 (2)	−0.0022 (2)	−0.00029 (19)	0.0005 (2)
C26	0.0120 (2)	0.0095 (3)	0.0077 (2)	−0.0017 (2)	0.00027 (18)	0.00099 (19)
C31	0.0160 (3)	0.0116 (3)	0.0207 (3)	−0.0014 (2)	0.0041 (2)	−0.0049 (3)
C32	0.0156 (3)	0.0130 (3)	0.0277 (4)	−0.0009 (3)	0.0037 (3)	0.0034 (3)

Geometric parameters (Å, º)

O1—C2	1.2434 (9)	C5—H5	0.94 (2)
O2—C4	1.2457 (9)	C7—H7A	0.921 (19)
O3—C6	1.2594 (9)	C7—H7B	0.91 (2)
O4—C6	1.2811 (9)	C7—H7C	0.989 (18)
O5—C24	1.3809 (10)	C8—H8A	0.93 (2)
O5—H15	0.81 (2)	C8—H8B	0.98 (2)
O6—C31	1.4400 (11)	C8—H8C	0.947 (16)
O6—H16	0.87 (2)	C20—C21	1.5142 (10)
N1—C1	1.4993 (10)	C20—H20A	0.970 (18)
N1—H11A	0.94 (2)	C20—H20B	0.935 (17)
N1—H11B	0.834 (16)	C21—C22	1.4083 (10)
N1—H11C	0.80 (2)	C21—C26	1.4091 (10)
N2—C2	1.3451 (9)	C22—C23	1.3991 (11)
N2—C3	1.4612 (9)	C22—H22	0.954 (19)
N2—H12	0.85 (2)	C23—C24	1.4056 (10)
N3—C4	1.3399 (9)	C23—H23	0.978 (18)
N3—C5	1.4627 (9)	C24—C25	1.4026 (10)
N3—H13	0.847 (9)	C25—C26	1.4010 (11)
C1—C2	1.5293 (10)	C25—H25	0.949 (17)
C1—C7	1.5344 (11)	C26—H26	1.022 (18)
C1—H1	0.919 (19)	C31—C32	1.5241 (14)
C3—C4	1.5331 (10)	C31—H31A	1.00 (2)
C3—C20	1.5635 (10)	C31—H31B	0.99 (2)
C3—H3	0.982 (17)	C32—H32A	1.031 (19)
C5—C8	1.5382 (11)	C32—H32B	0.95 (2)
C5—C6	1.5448 (10)	C32—H32C	1.00 (2)
C24—O5—H15	107.2 (16)	H7A—C7—H7C	106.7 (16)
C31—O6—H16	107.6 (18)	H7B—C7—H7C	110.7 (18)
C1—N1—H11A	106.9 (13)	C5—C8—H8A	111.6 (12)
C1—N1—H11B	112.0 (11)	C5—C8—H8B	112.1 (14)
H11A—N1—H11B	108.0 (17)	H8A—C8—H8B	103.0 (18)
C1—N1—H11C	112.3 (13)	C5—C8—H8C	110.8 (11)
H11A—N1—H11C	110.3 (18)	H8A—C8—H8C	109.0 (17)
H11B—N1—H11C	107.3 (18)	H8B—C8—H8C	110.1 (17)
C2—N2—C3	121.87 (6)	C21—C20—C3	113.62 (6)
C2—N2—H12	118.3 (12)	C21—C20—H20A	112.7 (12)
C3—N2—H12	119.9 (12)	C3—C20—H20A	105.0 (11)
C4—N3—C5	122.22 (6)	C21—C20—H20B	110.1 (10)
C4—N3—H13	116.7 (10)	C3—C20—H20B	108.6 (10)
C5—N3—H13	121.0 (10)	H20A—C20—H20B	106.5 (15)
N1—C1—C2	108.19 (6)	C22—C21—C26	118.46 (6)
N1—C1—C7	109.87 (6)	C22—C21—C20	120.22 (6)
C2—C1—C7	110.84 (6)	C26—C21—C20	121.30 (6)
N1—C1—H1	109.5 (10)	C23—C22—C21	120.99 (6)
C2—C1—H1	107.4 (11)	C23—C22—H22	121.5 (13)
C7—C1—H1	111.0 (10)	C21—C22—H22	117.5 (13)
O1—C2—N2	124.06 (6)	C22—C23—C24	119.65 (6)
O1—C2—C1	120.29 (6)	C22—C23—H23	120.7 (11)
N2—C2—C1	115.64 (6)	C24—C23—H23	119.6 (11)
N2—C3—C4	107.40 (6)	O5—C24—C25	118.29 (6)
N2—C3—C20	112.46 (6)	O5—C24—C23	121.49 (6)
C4—C3—C20	110.30 (6)	C25—C24—C23	120.22 (7)
N2—C3—H3	109.3 (9)	C26—C25—C24	119.51 (6)
C4—C3—H3	107.7 (9)	C26—C25—H25	120.3 (11)
C20—C3—H3	109.6 (9)	C24—C25—H25	120.1 (11)
O2—C4—N3	124.07 (6)	C25—C26—C21	121.09 (6)
O2—C4—C3	119.99 (6)	C25—C26—H26	120.4 (11)
N3—C4—C3	115.88 (6)	C21—C26—H26	118.5 (11)
N3—C5—C8	110.98 (6)	O6—C31—C32	111.75 (7)
N3—C5—C6	111.62 (6)	O6—C31—H31A	104.9 (14)
C8—C5—C6	109.47 (6)	C32—C31—H31A	110.7 (13)
N3—C5—H5	106.8 (10)	O6—C31—H31B	107.8 (13)
C8—C5—H5	111.3 (11)	C32—C31—H31B	110.5 (12)
C6—C5—H5	106.6 (11)	H31A—C31—H31B	111.1 (17)
O3—C6—O4	125.01 (7)	C31—C32—H32A	109.5 (11)
O3—C6—C5	119.36 (6)	C31—C32—H32B	112.5 (14)
O4—C6—C5	115.58 (6)	H32A—C32—H32B	107.5 (17)
C1—C7—H7A	111.0 (12)	C31—C32—H32C	109.0 (12)
C1—C7—H7B	110.0 (13)	H32A—C32—H32C	111.6 (17)
H7A—C7—H7B	107.4 (18)	H32B—C32—H32C	106.7 (19)
C1—C7—H7C	111.0 (10)
C3—N2—C2—O1	−1.18 (11)	C8—C5—C6—O3	115.71 (8)
C3—N2—C2—C1	177.49 (6)	N3—C5—C6—O4	174.91 (6)
N1—C1—C2—O1	−33.98 (9)	C8—C5—C6—O4	−61.83 (9)
C7—C1—C2—O1	86.55 (8)	N2—C3—C20—C21	62.90 (7)
N1—C1—C2—N2	147.31 (6)	C4—C3—C20—C21	−56.95 (7)
C7—C1—C2—N2	−92.17 (8)	C3—C20—C21—C22	89.00 (8)
C2—N2—C3—C4	−166.37 (6)	C3—C20—C21—C26	−89.50 (8)
C2—N2—C3—C20	72.11 (8)	C26—C21—C22—C23	1.76 (11)
C5—N3—C4—O2	−4.73 (11)	C20—C21—C22—C23	−176.78 (7)
C5—N3—C4—C3	172.63 (6)	C21—C22—C23—C24	0.35 (11)
N2—C3—C4—O2	−25.65 (9)	C22—C23—C24—O5	176.68 (7)
C20—C3—C4—O2	97.22 (8)	C22—C23—C24—C25	−2.55 (11)
N2—C3—C4—N3	156.88 (6)	O5—C24—C25—C26	−176.67 (7)
C20—C3—C4—N3	−80.25 (7)	C23—C24—C25—C26	2.58 (11)
C4—N3—C5—C8	129.52 (7)	C24—C25—C26—C21	−0.42 (11)
C4—N3—C5—C6	−108.07 (7)	C22—C21—C26—C25	−1.73 (11)
N3—C5—C6—O3	−7.56 (9)	C20—C21—C26—C25	176.79 (7)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H15···O6^i	0.81 (2)	1.83 (2)	2.627 (1)	169 (2)
O6—H16···O3^ii	0.87 (3)	1.82 (3)	2.689 (1)	176 (3)
N1—H11A···O4^ii	0.95 (2)	1.85 (2)	2.786 (1)	170 (2)
N1—H11B···O5^iii	0.83 (2)	2.04 (2)	2.873 (1)	174 (2)
N1—H11C···O2^iv	0.80 (2)	1.95 (2)	2.748 (1)	178 (2)
N2—H12···O1^v	0.85 (2)	2.18 (2)	2.975 (1)	156 (2)
N3—H13···O4^vi	0.85 (1)	2.13 (1)	2.963 (1)	167 (2)

Symmetry codes: (i) −x, y−1/2, −z+1; (ii) x, y, z−1; (iii) −x, y+1/2, −z+1; (iv) −x+1, y+1/2, −z+1; (v) −x+1, y−1/2, −z+1; (vi) −x+1, y+1/2, −z+2.