Crystal structure and Hirshfeld surface analysis of 1-carb­oxy-2-(3,4-di­hydroxy­phen­yl)ethan-1-aminium chloride 2-ammonio-3-(3,4-di­hydroxy­phen­yl)propano­ate: a new polymorph of l-dopa HCl and isotypic with its bromide counterpart

Kathiravan, P.; Balakrishnan, T.; Venkatesan, P.; Ramamurthi, K.; Percino, M.J.; Thamotharan, S.

doi:10.1107/S2056989016016789

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ISSN: 2056-9890

Volume 72| Part 11| November 2016| Pages 1628-1632

https://doi.org/10.1107/S2056989016016789

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Crystal structure and Hirshfeld surface analysis of 1-carboxy-2-(3,4-dihydroxyphenyl)ethan-1-aminium chloride 2-ammonio-3-(3,4-dihydroxyphenyl)propanoate: a new polymorph of L-dopa HCl and isotypic with its bromide counterpart

Perumal Kathiravan,^a Thangavelu Balakrishnan,^a ^* Perumal Venkatesan,^b Kandasamy Ramamurthi,^c María Judith Percino ^b and Subbiah Thamotharan ^d ^*

^aCrystal Growth Laboratory, PG and Research Department of Physics, Periyar EVR Government College (Autonomous), Tiruchirappalli 620 023, India, ^bLaboratorio de Polímeros, Centro de Química Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla (BUAP), Complejo de Ciencias, ICUAP, Edif. 103H, 22 Sur y San Claudio, CP 72570 Puebla, Puebla, Mexico, ^cCrystal Growth and Thin Film Laboratory, Department of Physics and Nanotechnology, SRM University, Kattankulathur 603 203, India, and ^dBiomolecular Crystallography Laboratory, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613 401, India
^*Correspondence e-mail: balacrystalgrowth@gmail.com, thamu@scbt.sastra.edu

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 11 October 2016; accepted 19 October 2016; online 25 October 2016)

The title molecular salt, C₉H₁₂NO₄⁺·Cl⁻·C₉H₁₁NO₄, is isotypic with that of the bromide counterpart [Kathiravan et al. (2016 ). Acta Cryst. E72, 1544–1548]. The title salt is a second monoclinic polymorph of the L-dopa HCl structure reported earlier in the monoclinic space group P2₁ [Jandacek & Earle (1971 ). Acta Cryst. B27, 841–845; Mostad & Rømming (1974 ). Acta Chemica Scand. B28, 1161–1168]. In the title compound, monoclinic space group I2, one of the dopa molecules has a positive charge with a protonated α-amino group and the α-carboxylic acid group uncharged, while the second dopa molecule has a neutral charge, the α-amino group is protonated and the α-carboxylic acid is deprotonated. In the previously reported form, a single dopa molecule is observed in which the α-amino group is protonated and the α-carboxylic acid group is uncharged. The invariant and variations of various types of intermolecular interactions present in these two forms of dopa HCl structures are discussed with the aid of two-dimensional fingerprint plots.

Keywords: crystal structure; L-dopa; cyclic N—H⋯Cl hydrogen bonds; Hirshfeld surfaces.

CCDC reference: 1511067

1. Chemical context

The aromatic amino acid enzyme, tyrosine-3-hydroxylase, catalyses the conversion of the amino acid L-tyrosine to L-dopa (L-3,4-dihydroxyphenylalanine). After successful conversion, the L-dopa molecule acts as a precursor for neurotransmitter molecules, such as dopamine, norepinephrine and epinephrine. The L-dopa molecule is found to be an effective drug in the symptomatic treatment of Parkinson's disease (Chan et al., 2012 ). Polymorphism is very common amongst pharamaceutically important molecules and is responsible for differences in many properties (Bernstein, 2002 , 2011 ; Nangia, 2008 ; Guranda & Deeva, 2010 ). The first monoclinic form (I) [space group P2₁ and z′ = 1] of L-dopa HCl was reported in the 1970s (Jandacek & Earle, 1971; Mostad & Rømming, 1974). Herein, we report on the crystal and molecular structure of a second monoclinic polymorph, form (II) (space group I2) of L-dopa HCl. The hydrogen-bonding patterns and the relative contributions of various intermolecular interactions present in forms (I) and (II) are compared.

2. Structural commentary

The asymmetric unit of the title compound, (II), is illustrated in Fig. 1. It consists of two dopa molecules, and a Cl⁻ anion located on a twofold rotation axis. As observed in the isotypic L-dopa HBr molecular salt (III) (Kathiravan et al., 2016), one of the dopa molecules is in the zwitterionic form and the other in the cationic form. In the cationic dopa molecule, the α-amino group is protonated and carries a positive charge and the hydrogen atom (H4O) of the α-carboxylic acid group is located in a general position and was refined with 50% occupancy.

Figure 1
The molecular structure of the title molecular salt, (II), showing the atom labelling scheme [symmetry code: ($) −x + 3, y, −z + 1]. Displacement ellipsoids are drawn at the 50% probability level.

The crystal structures of L-dopa (Mostad et al., 1971 ), its hydrochloride form (I) (Jandacek & Earle, 1971; Mostad & Rømming, 1974), the hydrobromide form (III) (Kathiravan et al., 2016) and the dihydrate form (André & Duarte, 2014 ), have been reported. The dihydrate form of dopa crystallizes in the orthorhombic space group P2₁2₁2₁ with a single dopa molecule in its zwitterionic form. The free dopa molecule and its hydrochloride form (I) crystallized in the monoclinic space group P2₁. In the L-dopa structure, the dopa molecule is in the zwitterionic form, while in the latter the α-amino group is protonated and the α-carboxylic acid is neutral. As mentioned earlier (Kathiravan et al., 2016), the deposited coordinates of the L-dopa HCl structure belong to the R configuration. Therefore, the L-dopa HCl structure was inverted and the inverted model used for superposition. As shown in Fig. 2, one of the dopa molecules of the title molecular salt (II) is superimposed with the inverted model of L-dopa HCl (I) and one of the dopa molecules of the isotypic Br compound (III). The r.m.s. deviation of the former pair is 0.105 Å while for the latter pair it is calculated to be 0.094 Å.

Figure 2
Structural superimposition of cationic dopa molecules in (II) (red), bromide counterpart (green) and form (I)

L-dopa HCl (blue).

3. Supramolecular features

The crystal structure of the title molecular salt (II) displays a network of intermolecular N—H⋯Cl, N—H⋯O and O—H⋯O hydrogen bonds (Table 1), producing a three-dimensional framework (Fig. 3). It is of interest to note that the N—H⋯O and O—H⋯O hydrogen-bonding geometries in the title compound are slightly different when compared to its isotypic bromide counterpart (III) (Kathiravan et al., 2016). A short intermolecular O—H⋯O hydrogen bond links the carboxylic acid group of a dopa molecule with the carboxylate group of an adjacent dopa molecule. This interaction produces dopa dimers that are arranged as ribbons propagating along the b axis (Fig. 3). As observed in the bromide counterpart (III), the protonated amino group acts as a threefold donor for three intermolecular hydrogen bonds, two of them with Cl⁻ anions and one with the carbonyl oxygen atom, O3, of the dopa acid group. One of the characteristic features observed in many amino acid–carboxylic acid/metal complexes (Sharma et al., 2006 ; Selvaraj et al., 2007 ; Balakrishnan, Ramamurthi & Thamotharan et al., 2013 ; Balakrishnan, Ramamurthi, Jeyakanthan et al., 2013 ; Sathiskumar et al., 2015a ,b ,c ; Revathi et al., 2015 ) is that the amino acid molecules aggregate in head-to-tail sequences of the type ⋯NH₃⁺—CHR—COO⁻⋯NH₃⁺—CHR—COO⁻⋯ in which α-amino and α-carboxylate groups are brought into periodic hydrogen-bonded proximity in a peptide-like arrangements. Similar arrangements (as layers) are observed in the title compound, in which α-amino (atom N1) and α-carboxylate (atom O3) groups interact via an N—H⋯O hydrogen bond. Adjacent layers are interconnected by strong O—H⋯O hydrogen bonds. The former N—H⋯O and the latter O—H⋯O interactions collectively form an R₄⁴(18) ring motif (Fig. 4). Similar interactions are presented in dopa and the HCl form (I).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1O⋯O3ⁱ	0.82	1.98	2.746 (2)	155
O2—H2O⋯O1ⁱⁱ	0.82	2.33	2.999 (2)	140
O2—H2O⋯O2ⁱⁱ	0.82	2.16	2.8730 (8)	146
O4—H4O⋯O4ⁱⁱⁱ	0.90 (3)	1.50 (3)	2.373 (2)	161 (8)
N1—H1A⋯Cl1^iv	0.91 (3)	2.35 (4)	3.249 (2)	167 (3)
N1—H1B⋯Cl1	0.89 (3)	2.31 (3)	3.178 (2)	166 (2)
N1—H1C⋯O3^v	0.90 (3)	1.93 (3)	2.7901 (19)	160 (3)
Symmetry codes: (i) x-1, y+1, z; (ii) $[-x+{\script{1\over 2}}, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (iii) -x+3, y, -z+1; (iv) x, y+1, z; (v) x-1, y, z.

Figure 3
Crystal packing of the title molecular salt, (II), viewed along the b axis. The hydrogen bonds are shown as dashed lines (see Table 1

), and C-bound H atoms have been omitted for clarity.

Figure 4
Part of the crystal structure of (II) showing the R₄⁴(18) motifs formed through N—H⋯O and O—H⋯O hydrogen bonds (see Table 1

As shown in Table 1, the amino group (via H1A and H1B) of the dopa molecule participates in N—H⋯Cl interactions with two different Cl⁻ anions. As observed in the bromide counterpart (III), these interactions interconnect the cations and anions into a chain of cyclic motifs that enclose R₂⁴(8) rings and runs parallel to the b axis (Fig. 5a). Forms (I) and (II) of the dopa HCl structures differ in the formation of cyclic motifs. In form (I), two N—H⋯Cl hydrogen bonds link the cations and anions into a chain. Adjacent chains are interconnected through O—H⋯Cl interactions (carboxylic acid⋯Cl). Collectively, these interactions generate cyclic motifs (Fig. 5b).

Figure 5
(a) Part of the crystal structure of (II) showing the R₂⁴(8) motif formed by intermolecular N—H⋯Cl hydrogen bonds (see Table 1

), and (b) part of the crystal structure of form (I)

dopa HCl showing the cyclic motif formed by N—H⋯Cl and O—H⋯Cl hydrogen bonds.

The side-chain hydroxy groups (O1—H1O and O2—H2O) of the dopa molecules are involved in O—H⋯O hydrogen-bonding interactions, the former with the carbonyl oxygen atom (O3) and the latter in a bifurcated mode with two different hydroxy (O1 and O2) oxygen atoms of adjacent dopa layers (Fig. 6). These interactions are invariant in the dopa structures reported earlier.

Figure 6
Adjacent dopa layers are interlinked by side chain–side chain interactions in (II) through intermolecular O—H⋯O hydrogen bonds (see Table 1

4. Hirshfeld surface analysis

The Hirshfeld surfaces (HS) and the decomposed two-dimensional fingerprint plots have been generated, using the program CrystalExplorer (Wolff et al., 2012 ), to investigate the similarities and differences in the crystal packing amongst polymorphs. The two different views of the HS diagram for the complete unit of dopa molecules along with the Cl⁻ anion and the two-dimensional fingerprint plots are shown in Fig. 7.

Figure 7
(a) Two different views of Hirshfeld surfaces of dimeric dopa molecules along with a Cl⁻ anion, (b) two-dimensional fingerprint plots for complete unit of dopa and (c) anionic Cl⁻. Various types of contacts are indicated.

The analysis suggests that the O⋯H contacts contribute more (41.6%) to the crystal packing when compared to other contacts with respect to the dopa molecules in the title compound. The relative contributions of H⋯H, C⋯H and H⋯Cl contacts are 29, 18.6 and 6.2%, respectively, with respect to the complete unit of dopa molecule. These contacts are nearly identical in the case of the bromide counterpart. The H⋯Cl and O⋯Cl contacts contributions to the Hirshfeld surface area for the Cl ion are 71.9 and 13.7%, respectively. In the bromide counterpart (III), the corresponding contacts are found to be 64.1 (H⋯Br) and 10.2% (O⋯Br). It is clearly seen that these contacts are lower in the bromide counterpart (III) when compared to the title salt (II).

In form (I) of the dopa HCl structure, the relative contributions of O⋯H, H⋯H, C⋯H and H⋯Cl contacts are 40.5, 25.2, 17.1 and 14.1%, respectively, with respect to the cationic dopa molecule. It is worthy to note that O⋯H and H⋯H contacts are reduced by 1.1–3.8% when compared to form (II). The H⋯Cl contact is increased by 7.9% in (I) when compared to (II) of the dopa HCl structure. In (I) anionic Cl⁻, the relative contribution of H⋯Cl contacts is found be 90.4%. This is approximately 18.5 and 26% higher when compared to (II) and its bromide counterpart (III). These contacts are used to discriminate between forms (I) and (II).

5. Synthesis and crystallization

L-dopa and HCl (1:1 molar ratio) were dissolved in double-distilled water and stirred well for 6 h. The mixture was filtered and the filtrate left to evaporate slowly. Colourless block-shaped crystals of the title molecular salt (II) were obtained after a growth period of 15 days.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. Since the title molecular salt (I) is isotypic with its bromide counterpart (III) (Kathiravan et al., 2016), it was refined with the coordinates of the dopa molecule of the latter as a starting model. The Cl⁻ anion was located from a difference Fourier map. The amino and carboxylic acid H atoms were located from a difference Fourier map and freely refined. The OH groups of the dopa side chain and C-bound H atoms were treated as riding atoms and included in geometrically calculated positions: C—H = 0.93–0.98 and O—H = 0.82 Å, with U_iso(H) = 1.2U_eq(C) and 1.5U_eq(O). The carboxylic acid O—H bond length was restrained to 0.90 (2) Å, using a DFIX option.

Table 2
Experimental details

Crystal data
Chemical formula	C₉H₁₂NO₄⁺·Cl⁻·C₉H₁₁NO₄
M_r	430.83
Crystal system, space group	Monoclinic, I2
Temperature (K)	293
a, b, c (Å)	6.1768 (3), 5.4349 (3), 28.7651 (16)
β (°)	98.140 (4)
V (Å³)	955.92 (9)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.25
Crystal size (mm)	0.30 × 0.25 × 0.20

Data collection
Diffractometer	Bruker Kappa APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2004 )
T_min, T_max	0.927, 0.959
No. of measured, independent and observed [I > 2σ(I)] reflections	14303, 2982, 2623
R_int	0.024
(sin θ/λ)_max (Å⁻¹)	0.777

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.035, 0.094, 1.05
No. of reflections	2982
No. of parameters	151
No. of restraints	2
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.57, −0.21
Absolute structure	Flack x determined using 1021 quotients [(I⁺) − (I⁻)]/[(I⁺) + (I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	0.033 (17)
Computer programs: APEX2, SAINT and XPREP (Bruker, 2004), Mercury (Macrae et al., 2006 ), SHELXL2014/7 (Sheldrick, 2015 ) and publCIF (Westrip, 2010 ). Structure solution – isomorphous replacement.

Supporting information

CCDC reference: 1511067

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989016016789/su5331sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989016016789/su5331Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989016016789/su5331Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2004); cell refinement: APEX2/SAINT (Bruker, 2004); data reduction: SAINT/XPREP (Bruker, 2004); program(s) used to solve structure: structure solution – isomorphous replacement; program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXL2014/7 (Sheldrick, 2015) and publCIF (Westrip, 2010).

1-Carboxy-2-(3,4-dihydroxyphenyl)ethan-1-aminium chloride 2-ammonio-3-(3,4-dihydroxyphenyl)propanoate top

Crystal data top

C₉H₁₂NO₄⁺·Cl⁻·C₉H₁₁NO₄	F(000) = 452
M_r = 430.83	D_x = 1.497 Mg m⁻³
Monoclinic, I2	Mo Kα radiation, λ = 0.71073 Å
a = 6.1768 (3) Å	Cell parameters from 7161 reflections
b = 5.4349 (3) Å	θ = 3.8–31.1°
c = 28.7651 (16) Å	µ = 0.25 mm⁻¹
β = 98.140 (4)°	T = 293 K
V = 955.92 (9) Å³	Block, colourless
Z = 2	0.30 × 0.25 × 0.20 mm

Data collection top

Bruker Kappa APEXII CCD diffractometer	2623 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.024
ω and φ scan	θ_max = 33.5°, θ_min = 2.9°
Absorption correction: multi-scan (SADABS; Bruker, 2004)	h = −8→9
T_min = 0.927, T_max = 0.959	k = −7→7
14303 measured reflections	l = −39→40
2982 independent reflections

Refinement top

Refinement on F²	2 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.035	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.094	w = 1/[σ²(F_o²) + (0.0541P)² + 0.236P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max < 0.001
2982 reflections	Δρ_max = 0.57 e Å⁻³
151 parameters	Δρ_min = −0.21 e Å⁻³

Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
O1	0.3951 (2)	1.2691 (3)	0.33134 (6)	0.0290 (3)
H1O	0.4509	1.3678	0.3510	0.044*
O2	0.3026 (2)	0.9556 (3)	0.26334 (5)	0.0299 (3)
H2O	0.2767	0.8411	0.2448	0.045*
O3	1.4771 (2)	0.5509 (3)	0.41112 (5)	0.0329 (4)
O4	1.32315 (19)	0.6323 (4)	0.47766 (4)	0.0276 (3)
H4O	1.467 (5)	0.623 (16)	0.489 (3)	0.07 (2)*	0.5
N1	0.9230 (2)	0.6219 (4)	0.44032 (5)	0.0192 (3)
H1A	0.937 (4)	0.751 (7)	0.4608 (11)	0.038 (8)*
H1B	0.933 (3)	0.498 (5)	0.4608 (8)	0.013 (5)*
H1C	0.784 (5)	0.629 (7)	0.4261 (10)	0.043 (7)*
C1	0.8763 (3)	0.8689 (4)	0.34670 (6)	0.0203 (4)
C2	0.7324 (3)	1.0590 (4)	0.35439 (7)	0.0216 (4)
H2	0.7691	1.1672	0.3793	0.026*
C3	0.5418 (3)	1.0860 (3)	0.32596 (6)	0.0202 (4)
C4	0.4932 (3)	0.9175 (4)	0.29009 (6)	0.0207 (4)
C5	0.6340 (3)	0.7289 (4)	0.28237 (7)	0.0237 (4)
H5	0.5961	0.6194	0.2577	0.028*
C6	0.8254 (3)	0.7042 (4)	0.31046 (7)	0.0238 (4)
H6	0.9217	0.5784	0.3056	0.029*
C7	1.0881 (3)	0.8448 (4)	0.37635 (7)	0.0231 (4)
H7A	1.1137	0.9888	0.3963	0.028*
H7B	1.2030	0.8373	0.3566	0.028*
C8	1.0974 (2)	0.6136 (4)	0.40704 (6)	0.0170 (3)
H8	1.0707	0.4692	0.3866	0.020*
C9	1.3196 (3)	0.5949 (4)	0.43384 (6)	0.0193 (4)
Cl1	1.0000	0.12970 (14)	0.5000	0.0428 (2)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0242 (7)	0.0254 (7)	0.0347 (8)	0.0052 (6)	−0.0053 (6)	−0.0063 (6)
O2	0.0210 (6)	0.0325 (8)	0.0314 (8)	0.0000 (6)	−0.0127 (5)	−0.0043 (6)
O3	0.0148 (5)	0.0560 (11)	0.0263 (7)	0.0060 (6)	−0.0025 (5)	−0.0092 (7)
O4	0.0137 (5)	0.0486 (9)	0.0186 (6)	0.0019 (7)	−0.0049 (4)	−0.0034 (7)
N1	0.0122 (6)	0.0258 (8)	0.0185 (7)	−0.0008 (6)	−0.0015 (5)	0.0018 (8)
C1	0.0176 (7)	0.0246 (9)	0.0175 (8)	−0.0016 (7)	−0.0022 (6)	0.0054 (7)
C2	0.0201 (7)	0.0237 (9)	0.0192 (8)	−0.0031 (7)	−0.0028 (6)	−0.0007 (7)
C3	0.0180 (7)	0.0205 (10)	0.0210 (8)	−0.0009 (7)	−0.0007 (6)	0.0025 (7)
C4	0.0178 (7)	0.0240 (9)	0.0188 (8)	−0.0028 (7)	−0.0029 (6)	0.0025 (7)
C5	0.0240 (9)	0.0258 (10)	0.0197 (9)	−0.0012 (8)	−0.0021 (7)	−0.0029 (7)
C6	0.0216 (8)	0.0265 (10)	0.0224 (9)	0.0041 (7)	0.0003 (7)	0.0007 (7)
C7	0.0151 (7)	0.0291 (10)	0.0233 (9)	−0.0042 (7)	−0.0038 (6)	0.0065 (8)
C8	0.0122 (6)	0.0215 (8)	0.0161 (7)	−0.0002 (7)	−0.0022 (5)	−0.0005 (7)
C9	0.0130 (6)	0.0237 (10)	0.0197 (8)	0.0003 (7)	−0.0033 (5)	−0.0012 (7)
Cl1	0.0677 (5)	0.0189 (3)	0.0390 (4)	0.000	−0.0016 (4)	0.000

Geometric parameters (Å, º) top

O1—C3	1.369 (2)	C1—C7	1.463 (2)
O1—H1O	0.8200	C2—C3	1.343 (2)
O2—C4	1.329 (2)	C2—H2	0.9300
O2—H2O	0.8200	C3—C4	1.380 (3)
O3—C9	1.269 (2)	C4—C5	1.382 (3)
O4—C9	1.274 (2)	C5—C6	1.341 (3)
O4—H4O	0.90 (3)	C5—H5	0.9300
N1—C8	1.540 (2)	C6—H6	0.9300
N1—H1A	0.91 (3)	C7—C8	1.532 (3)
N1—H1B	0.89 (3)	C7—H7A	0.9700
N1—H1C	0.90 (3)	C7—H7B	0.9700
C1—C6	1.376 (3)	C8—C9	1.479 (2)
C1—C2	1.401 (3)	C8—H8	0.9800

C3—O1—H1O	109.5	C6—C5—C4	119.90 (18)
C4—O2—H2O	109.5	C6—C5—H5	120.0
C9—O4—H4O	103 (5)	C4—C5—H5	120.0
C8—N1—H1A	114.6 (18)	C5—C6—C1	118.60 (18)
C8—N1—H1B	113.7 (14)	C5—C6—H6	120.7
H1A—N1—H1B	99 (2)	C1—C6—H6	120.7
C8—N1—H1C	115.1 (18)	C1—C7—C8	111.52 (15)
H1A—N1—H1C	105 (3)	C1—C7—H7A	109.3
H1B—N1—H1C	108 (3)	C8—C7—H7A	109.3
C6—C1—C2	121.15 (15)	C1—C7—H7B	109.3
C6—C1—C7	118.24 (18)	C8—C7—H7B	109.3
C2—C1—C7	120.58 (17)	H7A—C7—H7B	108.0
C3—C2—C1	120.37 (17)	C9—C8—C7	108.25 (15)
C3—C2—H2	119.8	C9—C8—N1	110.92 (13)
C1—C2—H2	119.8	C7—C8—N1	111.19 (16)
C2—C3—O1	123.21 (17)	C9—C8—H8	108.8
C2—C3—C4	117.50 (17)	C7—C8—H8	108.8
O1—C3—C4	119.29 (15)	N1—C8—H8	108.8
O2—C4—C3	114.24 (17)	O3—C9—O4	129.22 (14)
O2—C4—C5	123.27 (17)	O3—C9—C8	117.83 (15)
C3—C4—C5	122.47 (16)	O4—C9—C8	112.93 (14)

C6—C1—C2—C3	−0.8 (3)	C2—C1—C6—C5	0.0 (3)
C7—C1—C2—C3	177.45 (18)	C7—C1—C6—C5	−178.29 (19)
C1—C2—C3—O1	−179.42 (18)	C6—C1—C7—C8	−69.7 (2)
C1—C2—C3—C4	1.3 (3)	C2—C1—C7—C8	112.0 (2)
C2—C3—C4—O2	−179.88 (17)	C1—C7—C8—C9	176.83 (16)
O1—C3—C4—O2	0.8 (3)	C1—C7—C8—N1	−61.1 (2)
C2—C3—C4—C5	−1.1 (3)	C7—C8—C9—O3	−67.7 (2)
O1—C3—C4—C5	179.57 (18)	N1—C8—C9—O3	170.10 (19)
O2—C4—C5—C6	179.00 (19)	C7—C8—C9—O4	110.8 (2)
C3—C4—C5—C6	0.4 (3)	N1—C8—C9—O4	−11.4 (3)
C4—C5—C6—C1	0.2 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···O3ⁱ	0.82	1.98	2.746 (2)	155
O2—H2O···O1ⁱⁱ	0.82	2.33	2.999 (2)	140
O2—H2O···O2ⁱⁱ	0.82	2.16	2.8730 (8)	146
O4—H4O···O4ⁱⁱⁱ	0.90 (3)	1.50 (3)	2.373 (2)	161 (8)
N1—H1A···Cl1^iv	0.91 (3)	2.35 (4)	3.249 (2)	167 (3)
N1—H1B···Cl1	0.89 (3)	2.31 (3)	3.178 (2)	166 (2)
N1—H1C···O3^v	0.90 (3)	1.93 (3)	2.7901 (19)	160 (3)

Symmetry codes: (i) x−1, y+1, z; (ii) −x+1/2, y−1/2, −z+1/2; (iii) −x+3, y, −z+1; (iv) x, y+1, z; (v) x−1, y, z.

Acknowledgements

TB acknowledges the Council of Scientific and Industrial Research (CSIR), India for providing financial support [Project ref. No. 03 (1314)/14/EMR – II dt.16-04-14]. ST is highly grateful to the management of SASTRA University for their encouragement and financial support (Prof. TRR fund), and also thanks the DST–SERB (SB/YS/LS-19/2014) for research funding.

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