Crystal structures of three halide salts of l-asparagine: an isostructural series.

The structures of three monohydrated halide salt forms of l-asparagine are presented, viz. l-asparaginium chloride monohydrate, C4H9N2O3 +·Cl-·H2O, (I), l-asparaginium bromide monohydrate, C4H9N2O3 +·Br-·H2O, (II), and l-asparaginium iodide monohydrate, C4H9N2O3 +·I-·H2O, (III). These form an isomorphous and isostructural series. The C-C-C-C backbone of the amino acid adopts a gauche conformation in each case [torsion angles for (I), (II) and (III) = -55.4 (2), -55.6 (5) and -58.3 (7)°, respectively]. Each cation features an intra-molecular N-H⋯O hydrogen bond, which closes an S(6) ring. The extended structures feature chains of cations that propagate parallel to the b-axis direction. These are formed by carb-oxy-lic acid/amide complimentary O-H⋯O + N-H⋯O hydrogen bonds, which generate R 2 2(8) loops. These chains are linked by further hydrogen bonds mediated by the halide ions and water mol-ecules to give a layered structure with cation and anion layers parallel to the ab plane. Compound (III) was refined as an inversion twin.

Chemical context

Changing the salt form of an organic material is a well known way of altering the material’s physical properties whilst retaining many of the chemical properties inherent to the organic fragment. Selection of the salt form with the most suitable properties is thus an important consideration in the development of pharmaceutical materials and indeed of other fine chemicals (Stahl & Wermuth, 2008 ▸; Bastin et al., 2000 ▸; Kennedy et al., 2012 ▸). Often, the main property of inter­est is solubility, but salt selection may also be used to alter properties such as crystal morphology, hygroscopicity or stability, as well as mechanical properties such as hardness and strength (Stahl & Wermuth, 2008 ▸; Sun & Grant, 2001 ▸; Hao & Iqbal, 1997 ▸; de Moraes et al., 2017 ▸). In short, any bulk property that depends in some way on the packing or on the inter­molecular forces within the crystalline array structure may be altered by changing the salt-forming counter-ion. Despite the common usage of salt selection strategies, our understanding of what effect on properties any particular change of counter-ion will have is extremely limited. This means, for example, that it is not currently possible to predict which salt form of an active pharmaceutical ingredient (API) will be the most soluble or have the best compaction properties. In this area, isostructural series of structures are especially inter­esting as they allow changes in properties to be related to changes in inter­molecular inter­action strength or type without the complication of changes to the overall gross structure (Galcera & Molins, 2009 ▸; Allan et al., 2018 ▸). Here we present the structures of three isostructural halide salts of l-asparagine, namely the monohydrates [HAsp][Cl]·H2O, (I), [HAsp][Br]·H2O, (II) and [HAsp][I]·H2O, (III), (HAsp = C4H9N2O3 cation). l-aspara­gine is a non-essential amino acid, the bioavailability of which is associated with altered rates of breast cancer progression (Knott et al., 2018 ▸).

Structural commentary

The crystals isolated from all three reactions of l-asparagine with HX (X = Cl, Br, I) solutions were found to be hydrated compounds with the formula [HAsp][X]·H2O with protonation occurring at N1 as well as at the carb­oxy­lic acid. The starting material used was labelled l-asparagine and in all cases the refined Flack parameter confirmed that, as expected, this is S-asparagine.

Crystals (I), (II) and (III) were found to adopt the same space group and to have similar unit-cell dimensions. They thus represent an isostructural series, with the unit-cell dimensions increasing as expected in line with increasing halide ion size. The HAsp cations are found to have near identical geometries. All equivalent bond lengths are statistically similar and all cations adopt the same general conformation with both C=O units syn with respect to the NH3 group, see Figs. 1 ▸–3 ▸ ▸. There are some small differences within this general conformation. The largest of these differences occurs between the iodide salt and the others, as indicated by the torsion angles involving the NH3 group [N1—C2—C1—O1 (acid C=O) = 24.6 (2), 20.2 (5) and 12.5 (8) and N1—C2—C4—O3 (amide) 27.1 (2), 27.73 (5) and 33.38 (8)°, for Cl, Br and I respectively].

Figure 1

View of the contents of the asymmetric unit of (I). Non-H atoms are drawn as 50% probability ellipsoids and H atoms as spheres of arbitrary size.

Figure 2

View of the contents of the asymmetric unit of (II). Non-H atoms are drawn as 50% probability ellipsoids and H atoms as spheres of arbitrary size.

Figure 3

View of the contents of the asymmetric unit of (III). Non-H atoms are drawn as 50% probability ellipsoids and H atoms as spheres of arbitrary size.

Supra­molecular features

Isostructurality is also indicated by examination of the hydrogen bonding, Tables 1 ▸–3 ▸ ▸ and Fig. 4 ▸. The three compounds all make the same number and type of hydrogen bonds, with the main difference being the increasing D⋯A distances caused by the different anion sizes. Where A = X there is a 7.4 to 11.5% increase in D⋯A distance from Cl to I, whereas where A = O there is a smaller 0.6 to 4.0% increase. The only exception is the sole intra­molecular inter­action. The D⋯A distance of this NH3 to amide contact decreases by about 1.5% from Cl to I.

Table 1

Hydrogen-bond geometry (Å, °) for (I)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H1H⋯O3i	0.88 (1)	1.66 (2)	2.533 (2)	172 (4)
N1—H1N⋯Cl1	0.91 (1)	2.27 (1)	3.1663 (17)	166 (2)
N1—H2N⋯Cl1ii	0.89 (1)	2.56 (2)	3.2909 (17)	140 (2)
N1—H2N⋯O3	0.89 (1)	2.19 (2)	2.809 (2)	126 (2)
N1—H3N⋯O1W	0.90 (1)	1.97 (1)	2.867 (2)	172 (2)
N2—H4N⋯Cl1iii	0.90 (1)	2.89 (2)	3.4056 (17)	118 (2)
N2—H4N⋯O1iv	0.90 (1)	2.21 (2)	3.051 (2)	156 (2)
N2—H5N⋯O1W v	0.88 (1)	2.08 (1)	2.949 (2)	167 (2)
O1W—H1W⋯Cl1vi	0.87 (1)	2.41 (1)	3.2650 (18)	169 (2)
O1W—H2W⋯Cl1vii	0.87 (1)	2.40 (2)	3.2184 (17)	157 (2)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) .

Table 2

Hydrogen-bond geometry (Å, °) for (II)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H1H⋯O3i	0.88 (1)	1.68 (2)	2.543 (4)	167 (6)
N1—H1N⋯Br1	0.90 (1)	2.46 (2)	3.314 (5)	159 (4)
N1—H2N⋯Br1ii	0.89 (1)	2.59 (3)	3.408 (5)	153 (4)
N1—H2N⋯O3	0.89 (1)	2.30 (5)	2.787 (6)	114 (4)
N1—H3N⋯O1W	0.90 (1)	1.99 (2)	2.886 (4)	173 (5)
N2—H4N⋯Br1iii	0.90 (1)	2.95 (4)	3.479 (4)	119 (4)
N2—H4N⋯O1iv	0.90 (1)	2.26 (3)	3.081 (5)	152 (4)
N2—H5N⋯O1W v	0.90 (1)	2.07 (2)	2.959 (6)	170 (5)
O1W—H1W⋯Br1vi	0.88 (1)	2.51 (2)	3.362 (4)	167 (5)
O1W—H2W⋯Br1vii	0.88 (1)	2.61 (4)	3.323 (4)	138 (5)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) .

Table 3

Hydrogen-bond geometry (Å, °) for (III)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H1H⋯O3i	0.88 (1)	1.71 (3)	2.549 (6)	160 (9)
N1—H1N⋯I1	0.91	2.65	3.528 (7)	164
N1—H2N⋯I1ii	0.91	2.89	3.591 (8)	135
N1—H2N⋯O3	0.91	2.11	2.766 (8)	129
N1—H3N⋯O1W	0.91	2.03	2.905 (6)	160
N2—H4N⋯I1iii	0.90 (1)	3.07 (6)	3.659 (5)	125 (5)
N2—H4N⋯O1iv	0.90 (1)	2.37 (4)	3.171 (7)	149 (6)
N2—H5N⋯O1W v	0.90 (1)	2.12 (3)	2.983 (9)	160 (7)
O1W—H1W⋯I1vi	0.88 (1)	2.68 (2)	3.526 (8)	164 (5)
O1W—H2W⋯I1vii	0.88 (1)	2.76 (4)	3.504 (7)	143 (6)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) .

Figure 4

View of all the unique hydrogen-bonding contacts made by the contents of the asymmetric unit of (I).

The only HAsp to HAsp hydrogen bonds form the classic carb­oxy­lic acid to amide O—H⋯O + N—H⋯O heterodimer motif [R(8)2 2]. With two such contacts per cation, this motif generates a one-dimensional hydrogen-bonded chain running parallel to the b-axis direction, see Fig. 5 ▸. Additionally, each halide ion accepts five unique hydrogen bonds, two bonds from water mol­ecules, two from NH3 groups and one from NH2. The water mol­ecules donate two hydrogen bonds to the halide ions and accept two from the NH3 and NH2 groups. The water mol­ecules thus form fourfold nodes, as is typical for organic hydrates (Gillon et al., 2003 ▸; Briggs et al., 2012 ▸). These inter­actions combine to give the structure shown in Fig. 6 ▸ with alternating layers of organic cations and halide anions lying parallel to the ab plane.

Figure 5

Chain of cations in (II) propagating parallel to the b-axis direction via O—H⋯O and O—H⋯N carb­oxy­lic acid to amide hydrogen bonds.

Figure 6

Packing diagram of (III) as viewed down the a-axis direction.

Database survey

The only other known structure of a simple salt of S-asparagine is that of the nitrate (Aarthy et al., 2005 ▸). Here both the cations in a Z′ = 2 structure adopt different conformations from that found for the halides: compare N—C—C—O(acid C=O) of −176.9 (6) and 173.2 (5)° and N—C—C—O(amide) of −123.2 (7) and 77.0 (4)° with the equivalent values given above. The structures of two simple salts of racemic asparagine have also been reported. These are the nitrate and the perchlorate forms (Moussa Slimane et al., 2009 ▸; Guenifa et al., 2009 ▸). All these literature forms are anhydrous, but despite this difference and further differences in anion type and cation geometry, all form the same R(8)2 2-based, one-dimensional hydrogen-bonded chain motif seen in the halide salts (I), (II) and (III).

Synthesis and crystallization

Salt forms of l-asparagine were prepared by dissolving 29 mmol of the amino acid in 90 ml of distilled water. The solution was stirred and heated slightly until complete dissolution had occurred. The solution was then equally divided between three vials. To each vial was added 1 ml of concentrated acid, either hydro­chloric acid, hydro­bromic acid or hydro­iodic acid. The first crystals appeared after 24 h of sitting at room temperature. Crystals suitable for analyses [colourless prisms for (I), colourless tablets for (II) and colourless rods for (III)] were obtained directly from the mother liquors and were removed from these solutions just prior to data collection.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 4 ▸. Structure solution for (III) was by substitution from the Br equivalent. All H atoms bound to C were placed in calculated positions and refined in riding modes. C—H distances were 0.99 and 1.00 Å for CH2 and CH groups respectively, with U(H)iso = 1.2U eq(C). With the exception noted below, all other H atoms were observed and positioned as found. For (I) these were refined isotropically, but for (II) restraints were required for the NH3 and OH2 atoms. For (III) all H atoms required restraints to be applied. N—H distances were restrained to 0.90 (1) Å and O—H distances to 0.88 (1) Å. U(H)iso = 1.2U eq of the parent atom. The exception was the NH3 group of (III). The best model involved treating this as a rigid tetra­hedral group and allowing only rotation around the C—N bond. For this group, U iso(H) = 1.5U eq(N). Compound (III) was refined as an inversion twin.

Table 4

Experimental details

	(I)	(II)	(III)
Crystal data
Chemical formula	C4H9N2O3 +·Cl−·H2O	C4H9N2O3 −·Br+·H2O	C4H9N2O3 +·I−·H2O
M r	186.60	231.06	278.05
Crystal system, space group	Monoclinic, P21	Monoclinic, P21	Monoclinic, P21
Temperature (K)	123	123	123
a, b, c (Å)	5.0922 (1), 10.1450 (2), 8.1950 (2)	5.2167 (2), 10.2784 (5), 8.3063 (4)	5.3668 (5), 10.6744 (8), 8.4532 (6)
β (°)	103.834 (2)	103.606 (5)	102.772 (8)
V (Å3)	411.08 (2)	432.88 (4)	472.28 (7)
Z	2	2	2
Radiation type	Mo Kα	Mo Kα	Mo Kα
μ (mm−1)	0.44	4.72	3.37
Crystal size (mm)	0.45 × 0.30 × 0.25	0.5 × 0.3 × 0.12	0.6 × 0.35 × 0.15
Data collection
Diffractometer	Oxford Diffraction Xcalibur E	Oxford Diffraction Xcalibur E	Oxford Diffraction Xcalibur E
Absorption correction	Multi-scan [CrysAlis PRO (Agilent, 2014 ▸), based on expressions derived by Clark & Reid (1995 ▸)]	Analytical [CrysAlis PRO (Agilent, 2014 ▸), based on expressions derived by Clark & Reid (1995 ▸)]	Analytical [CrysAlis PRO (Agilent, 2014 ▸), based on expressions derived by Clark & Reid (1995 ▸)]
T min, T max	0.900, 1.000	0.205, 0.487	0.286, 0.612
No. of measured, independent and observed [I > 2σ(I)] reflections	4053, 2079, 2032	4320, 2232, 2118	5854, 2458, 2288
R int	0.013	0.032	0.039
(sin θ/λ)max (Å−1)	0.698	0.700	0.702
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.022, 0.058, 1.07	0.028, 0.062, 1.03	0.029, 0.058, 1.02
No. of reflections	2079	2232	2458
No. of parameters	128	128	117
No. of restraints	9	9	7
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement	H atoms treated by a mixture of independent and constrained refinement	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.26, −0.20	0.60, −0.38	0.87, −0.65
Absolute structure	Flack x determined using 897 quotients [(I +)−(I −)]/[(I +)+(I −)] (Parsons et al., 2013 ▸)	Flack x determined using 908 quotients [(I +)−(I −)]/[(I +)+(I −)] (Parsons et al., 2013 ▸)	Refined as an inversion twin
Absolute structure parameter	−0.02 (2)	−0.022 (11)	−0.07 (4)

Computer programs: CrysAlis PRO (Agilent, 2014 ▸), SIR92 (Altomare et al., 1994 ▸), SHELXL2014 (Sheldrick, 2015 ▸) and Mercury (Macrae et al., 2008 ▸).

Crystal structure: contains datablock(s) I, II, III, general. DOI: 10.1107/S2056989018014603/hb7779sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989018014603/hb7779Isup2.hkl

Structure factors: contains datablock(s) II. DOI: 10.1107/S2056989018014603/hb7779IIsup3.hkl

Structure factors: contains datablock(s) III. DOI: 10.1107/S2056989018014603/hb7779IIIsup4.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989018014603/hb7779Isup5.cml

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989018014603/hb7779IIsup6.cml

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989018014603/hb7779IIIsup7.cml

CCDC references: 1873483, 1873482, 1873481

Additional supporting information: crystallographic information; 3D view; checkCIF report

C4H9N2O3+·Cl−·H2O	F(000) = 196
Mr = 186.60	Dx = 1.508 Mg m−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 5.0922 (1) Å	Cell parameters from 3444 reflections
b = 10.1450 (2) Å	θ = 3.3–29.7°
c = 8.1950 (2) Å	µ = 0.44 mm−1
β = 103.834 (2)°	T = 123 K
V = 411.08 (2) Å3	Prism, colourless
Z = 2	0.45 × 0.30 × 0.25 mm

Oxford Diffraction Xcalibur E diffractometer	2032 reflections with I > 2σ(I)
Radiation source: sealed tube	Rint = 0.013
ω scans	θmax = 29.8°, θmin = 3.3°
Absorption correction: multi-scan [CrysAlis PRO (Agilent, 2014), based on expressions derived by Clark & Reid (1995)]	h = −7→7
Tmin = 0.900, Tmax = 1.000	k = −14→13
4053 measured reflections	l = −10→10
2079 independent reflections

Refinement on F2	H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full	w = 1/[σ2(Fo2) + (0.0331P)2 + 0.0289P] where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.022	(Δ/σ)max < 0.001
wR(F2) = 0.058	Δρmax = 0.26 e Å−3
S = 1.07	Δρmin = −0.20 e Å−3
2079 reflections	Extinction correction: SHELXL-2014/7 (Sheldrick 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
128 parameters	Extinction coefficient: 0.029 (8)
9 restraints	Absolute structure: Flack x determined using 897 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.02 (2)
Hydrogen site location: mixed

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

	x	y	z	Uiso*/Ueq
Cl1	0.36571 (8)	0.90075 (4)	0.92401 (5)	0.02062 (13)
O1	1.1145 (3)	0.51257 (16)	0.77258 (18)	0.0258 (3)
O2	0.8130 (3)	0.48931 (15)	0.52673 (18)	0.0237 (3)
O3	0.8617 (3)	0.83494 (16)	0.56812 (17)	0.0269 (3)
O1W	1.1611 (3)	0.58702 (15)	1.1607 (2)	0.0242 (3)
H1W	1.275 (4)	0.528 (2)	1.142 (3)	0.029*
H2W	1.034 (4)	0.532 (2)	1.170 (3)	0.029*
N1	0.8288 (3)	0.71004 (16)	0.8685 (2)	0.0162 (3)
H1N	0.699 (4)	0.758 (2)	0.902 (3)	0.019*
H2N	0.936 (4)	0.764 (2)	0.827 (3)	0.019*
H3N	0.927 (4)	0.664 (2)	0.957 (2)	0.019*
N2	0.5625 (4)	0.78473 (17)	0.3247 (2)	0.0218 (4)
C1	0.8969 (4)	0.53507 (18)	0.6792 (2)	0.0153 (3)
C2	0.6864 (4)	0.61977 (17)	0.7318 (2)	0.0140 (3)
H1	0.5703	0.5597	0.7813	0.017*
C3	0.5009 (4)	0.69279 (18)	0.5859 (2)	0.0162 (3)
H2	0.3900	0.6278	0.5091	0.019*
H3	0.3765	0.7499	0.6304	0.019*
C4	0.6548 (4)	0.77587 (19)	0.4888 (2)	0.0170 (4)
H1H	0.936 (6)	0.437 (3)	0.503 (5)	0.067 (11)*
H4N	0.643 (4)	0.8399 (19)	0.266 (3)	0.019 (6)*
H5N	0.423 (4)	0.736 (2)	0.273 (3)	0.023 (6)*

	U11	U22	U33	U12	U13	U23
Cl1	0.01624 (19)	0.0241 (2)	0.0209 (2)	0.00077 (17)	0.00325 (14)	−0.00539 (18)
O1	0.0182 (7)	0.0346 (8)	0.0224 (7)	0.0096 (6)	0.0008 (5)	−0.0059 (6)
O2	0.0211 (7)	0.0281 (8)	0.0204 (7)	0.0067 (6)	0.0020 (5)	−0.0079 (6)
O3	0.0222 (7)	0.0359 (8)	0.0199 (7)	−0.0128 (6)	0.0000 (6)	0.0078 (6)
O1W	0.0252 (8)	0.0200 (7)	0.0270 (8)	−0.0019 (6)	0.0051 (6)	−0.0003 (6)
N1	0.0150 (8)	0.0182 (8)	0.0156 (8)	0.0008 (6)	0.0040 (6)	−0.0019 (6)
N2	0.0265 (9)	0.0217 (8)	0.0163 (7)	−0.0029 (7)	0.0034 (7)	0.0011 (6)
C1	0.0149 (8)	0.0149 (8)	0.0168 (8)	−0.0014 (6)	0.0052 (6)	0.0014 (6)
C2	0.0123 (8)	0.0149 (8)	0.0152 (8)	−0.0006 (6)	0.0039 (6)	−0.0007 (6)
C3	0.0129 (8)	0.0186 (8)	0.0166 (8)	0.0004 (7)	0.0026 (6)	0.0023 (7)
C4	0.0168 (8)	0.0163 (8)	0.0183 (8)	0.0023 (6)	0.0046 (7)	0.0023 (6)

O1—C1	1.209 (2)	N2—C4	1.317 (2)
O2—C1	1.305 (2)	N2—H4N	0.897 (12)
O2—H1H	0.876 (13)	N2—H5N	0.882 (13)
O3—C4	1.251 (2)	C1—C2	1.515 (2)
O1W—H1W	0.869 (13)	C2—C3	1.527 (2)
O1W—H2W	0.868 (13)	C2—H1	1.0000
N1—C2	1.493 (2)	C3—C4	1.502 (3)
N1—H1N	0.913 (13)	C3—H2	0.9900
N1—H2N	0.891 (13)	C3—H3	0.9900
N1—H3N	0.901 (12)
C1—O2—H1H	110 (3)	N1—C2—C3	112.85 (15)
H1W—O1W—H2W	97 (3)	C1—C2—C3	113.57 (15)
C2—N1—H1N	107.3 (15)	N1—C2—H1	107.3
C2—N1—H2N	108.8 (17)	C1—C2—H1	107.3
H1N—N1—H2N	110 (2)	C3—C2—H1	107.3
C2—N1—H3N	111.2 (16)	C4—C3—C2	112.56 (15)
H1N—N1—H3N	109 (2)	C4—C3—H2	109.1
H2N—N1—H3N	110 (2)	C2—C3—H2	109.1
C4—N2—H4N	119.5 (15)	C4—C3—H3	109.1
C4—N2—H5N	119.9 (17)	C2—C3—H3	109.1
H4N—N2—H5N	121 (2)	H2—C3—H3	107.8
O1—C1—O2	125.44 (17)	O3—C4—N2	123.25 (18)
O1—C1—C2	122.06 (16)	O3—C4—C3	118.34 (16)
O2—C1—C2	112.48 (15)	N2—C4—C3	118.40 (17)
N1—C2—C1	108.17 (14)
O1—C1—C2—N1	24.6 (2)	N1—C2—C3—C4	68.1 (2)
O2—C1—C2—N1	−156.61 (16)	C1—C2—C3—C4	−55.4 (2)
O1—C1—C2—C3	150.72 (17)	C2—C3—C4—O3	−37.7 (2)
O2—C1—C2—C3	−30.5 (2)	C2—C3—C4—N2	143.49 (18)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H1H···O3i	0.88 (1)	1.66 (2)	2.533 (2)	172 (4)
N1—H1N···Cl1	0.91 (1)	2.27 (1)	3.1663 (17)	166 (2)
N1—H2N···Cl1ii	0.89 (1)	2.56 (2)	3.2909 (17)	140 (2)
N1—H2N···O3	0.89 (1)	2.19 (2)	2.809 (2)	126 (2)
N1—H3N···O1W	0.90 (1)	1.97 (1)	2.867 (2)	172 (2)
N2—H4N···Cl1iii	0.90 (1)	2.89 (2)	3.4056 (17)	118 (2)
N2—H4N···O1iv	0.90 (1)	2.21 (2)	3.051 (2)	156 (2)
N2—H5N···O1Wv	0.88 (1)	2.08 (1)	2.949 (2)	167 (2)
O1W—H1W···Cl1vi	0.87 (1)	2.41 (1)	3.2650 (18)	169 (2)
O1W—H2W···Cl1vii	0.87 (1)	2.40 (2)	3.2184 (17)	157 (2)

C4H9N2O3−·Br+·H2O	F(000) = 232
Mr = 231.06	Dx = 1.773 Mg m−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 5.2167 (2) Å	Cell parameters from 3145 reflections
b = 10.2784 (5) Å	θ = 3.2–29.8°
c = 8.3063 (4) Å	µ = 4.72 mm−1
β = 103.606 (5)°	T = 123 K
V = 432.88 (4) Å3	Tablet, colourless
Z = 2	0.5 × 0.3 × 0.12 mm

Oxford Diffraction Xcalibur E diffractometer	2232 independent reflections
Radiation source: fine-focus sealed tube	2118 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.032
ω scans	θmax = 29.8°, θmin = 3.2°
Absorption correction: analytical [CrysAlis PRO (Agilent, 2014), based on expressions derived by Clark & Reid (1995)]	h = −7→6
Tmin = 0.205, Tmax = 0.487	k = −14→14
4320 measured reflections	l = −11→11

Refinement on F2	H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full	w = 1/[σ2(Fo2) + (0.0274P)2] where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.028	(Δ/σ)max = 0.001
wR(F2) = 0.062	Δρmax = 0.60 e Å−3
S = 1.03	Δρmin = −0.38 e Å−3
2232 reflections	Extinction correction: SHELXL2014 (Sheldrick, 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
128 parameters	Extinction coefficient: 0.019 (3)
9 restraints	Absolute structure: Flack x determined using 908 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.022 (11)
Hydrogen site location: mixed

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

	x	y	z	Uiso*/Ueq
Br1	0.36490 (6)	0.90306 (8)	0.92345 (4)	0.01479 (13)
O1	1.1176 (6)	0.5163 (3)	0.7609 (4)	0.0196 (7)
O2	0.8106 (6)	0.4779 (3)	0.5270 (4)	0.0187 (7)
O3	0.8665 (6)	0.8262 (3)	0.5653 (4)	0.0226 (7)
O1W	1.1602 (8)	0.5964 (4)	1.1565 (6)	0.0196 (9)
H1W	1.274 (8)	0.536 (4)	1.147 (7)	0.024*
H2W	1.059 (10)	0.541 (5)	1.193 (7)	0.024*
N1	0.8287 (9)	0.7034 (5)	0.8580 (6)	0.0124 (9)
H1N	0.716 (8)	0.749 (4)	0.903 (6)	0.015*
H2N	0.951 (8)	0.757 (4)	0.836 (6)	0.015*
H3N	0.932 (8)	0.663 (5)	0.947 (4)	0.015*
N2	0.5699 (7)	0.7822 (4)	0.3244 (4)	0.0169 (8)
C1	0.8998 (8)	0.5314 (4)	0.6731 (5)	0.0124 (8)
C2	0.6900 (8)	0.6143 (4)	0.7242 (5)	0.0109 (8)
H1	0.5765	0.5549	0.7729	0.013*
C3	0.5124 (8)	0.6858 (4)	0.5811 (5)	0.0130 (8)
H2	0.4071	0.6215	0.5044	0.016*
H3	0.3884	0.7411	0.6243	0.016*
C4	0.6627 (8)	0.7697 (4)	0.4866 (5)	0.0132 (8)
H1H	0.938 (9)	0.428 (5)	0.509 (8)	0.046 (18)*
H4N	0.645 (9)	0.837 (4)	0.265 (5)	0.016 (12)*
H5N	0.431 (7)	0.733 (4)	0.276 (6)	0.016 (14)*

	U11	U22	U33	U12	U13	U23
Br1	0.01205 (18)	0.01658 (19)	0.01513 (18)	0.0006 (2)	0.00197 (12)	−0.0034 (2)
O1	0.0120 (15)	0.0263 (18)	0.0185 (16)	0.0072 (13)	−0.0002 (13)	−0.0061 (13)
O2	0.0148 (14)	0.0238 (17)	0.0159 (15)	0.0046 (13)	0.0003 (12)	−0.0062 (13)
O3	0.0176 (16)	0.0309 (19)	0.0159 (15)	−0.0127 (13)	−0.0031 (13)	0.0076 (14)
O1W	0.015 (2)	0.018 (2)	0.025 (2)	−0.0018 (17)	0.0022 (16)	0.0001 (17)
N1	0.013 (2)	0.012 (2)	0.012 (2)	0.0026 (18)	0.0035 (17)	−0.0018 (17)
N2	0.0205 (19)	0.0169 (18)	0.0123 (17)	−0.0031 (16)	0.0013 (15)	0.0014 (14)
C1	0.014 (2)	0.0102 (18)	0.0142 (19)	−0.0021 (15)	0.0056 (16)	0.0019 (15)
C2	0.0072 (18)	0.0129 (19)	0.0124 (18)	−0.0021 (15)	0.0020 (15)	−0.0005 (15)
C3	0.0092 (18)	0.014 (2)	0.016 (2)	−0.0008 (16)	0.0018 (16)	0.0003 (16)
C4	0.0135 (19)	0.0099 (19)	0.0158 (19)	0.0025 (16)	0.0024 (16)	0.0017 (15)

O1—C1	1.207 (5)	N2—C4	1.326 (5)
O2—C1	1.314 (5)	N2—H4N	0.898 (14)
O2—H1H	0.879 (14)	N2—H5N	0.897 (14)
O3—C4	1.252 (5)	C1—C2	1.524 (6)
O1W—H1W	0.875 (14)	C2—C3	1.515 (6)
O1W—H2W	0.879 (14)	C2—H1	1.0000
N1—C2	1.490 (6)	C3—C4	1.504 (6)
N1—H1N	0.900 (14)	C3—H2	0.9900
N1—H2N	0.894 (14)	C3—H3	0.9900
N1—H3N	0.904 (14)
C1—O2—H1H	106 (4)	N1—C2—C1	107.3 (3)
H1W—O1W—H2W	93 (5)	C3—C2—C1	113.5 (3)
C2—N1—H1N	112 (3)	N1—C2—H1	107.7
C2—N1—H2N	118 (3)	C3—C2—H1	107.7
H1N—N1—H2N	109 (5)	C1—C2—H1	107.7
C2—N1—H3N	115 (4)	C4—C3—C2	113.0 (3)
H1N—N1—H3N	102 (4)	C4—C3—H2	109.0
H2N—N1—H3N	98 (5)	C2—C3—H2	109.0
C4—N2—H4N	121 (3)	C4—C3—H3	109.0
C4—N2—H5N	118 (3)	C2—C3—H3	109.0
H4N—N2—H5N	121 (5)	H2—C3—H3	107.8
O1—C1—O2	125.7 (4)	O3—C4—N2	123.2 (4)
O1—C1—C2	122.6 (4)	O3—C4—C3	118.4 (4)
O2—C1—C2	111.7 (4)	N2—C4—C3	118.4 (4)
N1—C2—C3	112.8 (3)
O1—C1—C2—N1	20.2 (5)	N1—C2—C3—C4	66.7 (5)
O2—C1—C2—N1	−161.4 (4)	C1—C2—C3—C4	−55.6 (5)
O1—C1—C2—C3	145.4 (4)	C2—C3—C4—O3	−35.7 (5)
O2—C1—C2—C3	−36.1 (5)	C2—C3—C4—N2	145.6 (4)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H1H···O3i	0.88 (1)	1.68 (2)	2.543 (4)	167 (6)
N1—H1N···Br1	0.90 (1)	2.46 (2)	3.314 (5)	159 (4)
N1—H2N···Br1ii	0.89 (1)	2.59 (3)	3.408 (5)	153 (4)
N1—H2N···O3	0.89 (1)	2.30 (5)	2.787 (6)	114 (4)
N1—H3N···O1W	0.90 (1)	1.99 (2)	2.886 (4)	173 (5)
N2—H4N···Br1iii	0.90 (1)	2.95 (4)	3.479 (4)	119 (4)
N2—H4N···O1iv	0.90 (1)	2.26 (3)	3.081 (5)	152 (4)
N2—H5N···O1Wv	0.90 (1)	2.07 (2)	2.959 (6)	170 (5)
O1W—H1W···Br1vi	0.88 (1)	2.51 (2)	3.362 (4)	167 (5)
O1W—H2W···Br1vii	0.88 (1)	2.61 (4)	3.323 (4)	138 (5)

C4H9N2O3+·I−·H2O	F(000) = 268
Mr = 278.05	Dx = 1.955 Mg m−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 5.3668 (5) Å	Cell parameters from 4015 reflections
b = 10.6744 (8) Å	θ = 3.8–29.9°
c = 8.4532 (6) Å	µ = 3.37 mm−1
β = 102.772 (8)°	T = 123 K
V = 472.28 (7) Å3	Fragment cut from long rod, colourless
Z = 2	0.6 × 0.35 × 0.15 mm

Oxford Diffraction Xcalibur E diffractometer	2288 reflections with I > 2σ(I)
Radiation source: sealed tube	Rint = 0.039
ω scans	θmax = 29.9°, θmin = 3.8°
Absorption correction: analytical [CrysAlis PRO (Agilent, 2014), based on expressions derived by Clark & Reid (1995)]	h = −7→7
Tmin = 0.286, Tmax = 0.612	k = −14→14
5854 measured reflections	l = −11→11
2458 independent reflections

Refinement on F2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.029	w = 1/[σ2(Fo2) + (0.0215P)2] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.058	(Δ/σ)max = 0.001
S = 1.02	Δρmax = 0.87 e Å−3
2458 reflections	Δρmin = −0.65 e Å−3
117 parameters	Absolute structure: Refined as an inversion twin
7 restraints	Absolute structure parameter: −0.07 (4)
Primary atom site location: structure-invariant direct methods

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refined as a two-component inversion twin.

	x	y	z	Uiso*/Ueq
I1	0.36921 (6)	0.90844 (10)	0.91430 (3)	0.01907 (10)
O1	1.1192 (8)	0.5186 (4)	0.7440 (5)	0.0243 (10)
O2	0.8070 (8)	0.4561 (4)	0.5384 (5)	0.0258 (11)
H1H	0.936 (10)	0.415 (8)	0.516 (7)	0.031*
O3	0.8904 (9)	0.7986 (4)	0.5464 (5)	0.0282 (11)
O1W	1.1491 (15)	0.6160 (6)	1.1460 (9)	0.0274 (16)
H1W	1.253 (10)	0.553 (4)	1.143 (9)	0.033*
H2W	1.029 (9)	0.575 (5)	1.181 (8)	0.033*
N1	0.8348 (14)	0.6975 (7)	0.8380 (8)	0.0165 (16)
H3N	0.9372	0.6546	0.9205	0.025*
H1N	0.7172	0.7420	0.8773	0.025*
H2N	0.9315	0.7508	0.7926	0.025*
N2	0.5817 (11)	0.7743 (5)	0.3201 (6)	0.0224 (12)
H5N	0.428 (7)	0.740 (6)	0.277 (8)	0.027*
H4N	0.636 (13)	0.835 (5)	0.262 (7)	0.027*
C1	0.9010 (11)	0.5232 (5)	0.6669 (7)	0.0161 (12)
C2	0.7013 (12)	0.6073 (5)	0.7127 (7)	0.0155 (12)
H2	0.5882	0.5537	0.7640	0.019*
C3	0.5321 (12)	0.6737 (6)	0.5676 (7)	0.0177 (12)
H3A	0.4349	0.6100	0.4937	0.021*
H3B	0.4074	0.7271	0.6067	0.021*
C4	0.6816 (11)	0.7537 (6)	0.4743 (7)	0.0181 (12)

	U11	U22	U33	U12	U13	U23
I1	0.01668 (17)	0.01986 (16)	0.01982 (16)	0.0013 (3)	0.00223 (11)	−0.0036 (2)
O1	0.018 (2)	0.029 (2)	0.024 (2)	0.009 (2)	−0.0010 (17)	−0.006 (2)
O2	0.016 (2)	0.031 (2)	0.029 (2)	0.0061 (18)	0.0031 (18)	−0.0140 (18)
O3	0.023 (3)	0.034 (3)	0.024 (2)	−0.011 (2)	−0.0023 (18)	0.011 (2)
O1W	0.025 (4)	0.022 (4)	0.034 (3)	−0.006 (3)	0.003 (3)	0.001 (3)
N1	0.013 (4)	0.019 (4)	0.018 (3)	0.007 (3)	0.005 (2)	0.001 (3)
N2	0.025 (3)	0.022 (3)	0.019 (3)	−0.003 (2)	0.002 (2)	0.002 (2)
C1	0.017 (3)	0.013 (3)	0.018 (3)	0.001 (2)	0.004 (2)	0.003 (2)
C2	0.015 (3)	0.015 (3)	0.016 (2)	−0.002 (2)	0.003 (2)	−0.001 (2)
C3	0.014 (3)	0.018 (3)	0.020 (3)	0.002 (3)	0.002 (2)	0.001 (2)
C4	0.016 (3)	0.016 (3)	0.022 (3)	0.002 (2)	0.004 (2)	0.001 (2)

O1—C1	1.209 (7)	N2—C4	1.314 (7)
O2—C1	1.305 (7)	N2—H5N	0.900 (14)
O2—H1H	0.876 (14)	N2—H4N	0.896 (14)
O3—C4	1.247 (7)	C1—C2	1.513 (8)
O1W—H2W	0.880 (14)	C2—C3	1.529 (8)
O1W—H1W	0.877 (14)	C2—H2	1.0000
N1—C2	1.492 (9)	C3—C4	1.509 (9)
N1—H3N	0.9100	C3—H3A	0.9900
N1—H1N	0.9100	C3—H3B	0.9900
N1—H2N	0.9100
C1—O2—H1H	106 (5)	N1—C2—C3	112.1 (5)
H1W—O1W—H2W	98 (3)	C1—C2—C3	113.5 (5)
C2—N1—H3N	109.5	N1—C2—H2	107.7
C2—N1—H1N	109.5	C1—C2—H2	107.7
H3N—N1—H1N	109.5	C3—C2—H2	107.7
C2—N1—H2N	109.5	C4—C3—C2	113.1 (5)
H3N—N1—H2N	109.5	C4—C3—H3A	109.0
H1N—N1—H2N	109.5	C2—C3—H3A	109.0
C4—N2—H5N	118 (5)	C4—C3—H3B	109.0
C4—N2—H4N	124 (5)	C2—C3—H3B	109.0
H4N—N2—H5N	117 (7)	H3A—C3—H3B	107.8
O1—C1—O2	125.2 (6)	O3—C4—N2	123.1 (6)
O1—C1—C2	122.9 (5)	O3—C4—C3	119.1 (5)
O2—C1—C2	111.9 (5)	N2—C4—C3	117.8 (5)
N1—C2—C1	107.9 (5)
O1—C1—C2—N1	12.5 (8)	N1—C2—C3—C4	64.3 (7)
O2—C1—C2—N1	−168.8 (5)	C1—C2—C3—C4	−58.3 (7)
O1—C1—C2—C3	137.5 (6)	C2—C3—C4—O3	−27.3 (8)
O2—C1—C2—C3	−43.9 (7)	C2—C3—C4—N2	153.8 (6)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H1H···O3i	0.88 (1)	1.71 (3)	2.549 (6)	160 (9)
N1—H1N···I1	0.91	2.65	3.528 (7)	164
N1—H2N···I1ii	0.91	2.89	3.591 (8)	135
N1—H2N···O3	0.91	2.11	2.766 (8)	129
N1—H3N···O1W	0.91	2.03	2.905 (6)	160
N2—H4N···I1iii	0.90 (1)	3.07 (6)	3.659 (5)	125 (5)
N2—H4N···O1iv	0.90 (1)	2.37 (4)	3.171 (7)	149 (6)
N2—H5N···O1Wv	0.90 (1)	2.12 (3)	2.983 (9)	160 (7)
O1W—H1W···I1vi	0.88 (1)	2.68 (2)	3.526 (8)	164 (5)
O1W—H2W···I1vii	0.88 (1)	2.76 (4)	3.504 (7)	143 (6)