Crystal structure and Hirshfeld surface analysis of 1-carboxy-2-(3,4-dihydroxyphenyl)ethan-1-aminium bromide 2-ammonio-3-(3,4-dihydroxyphenyl)propanoate

In the title salt, one of the dopa molecules is in the cationic form, in which the α-amino group is protonated and the α-carboxylic acid group is uncharged, while the second dopa molecule is in the zwitterionic form, and the Br− anion is located on a twofold rotation axis.

In the title molecular salt, C 9 H 12 NO 4 + ÁBr À ÁC 9 H 11 NO 4 , one of the dopa molecules is in the cationic form in which the -amino group is protonated and the -carboxylic acid group is uncharged, while the second dopa molecule is in the zwitterion form. The Br À anion occupies a special position and is located on a twofold rotation axis. The two dopa molecules are interconnected by short O-HÁ Á ÁO hydrogen bonds. In the crystal, the various units are linked by O-HÁ Á ÁO, N-HÁ Á ÁBr and N-HÁ Á ÁO hydrogen bonds, forming a three-dimensional framework. The title compound was refined as an inversion twin with an absolute structure parameter of 0.023 (8).

Chemical context
An aromatic amino acid enzyme hydroxylase converts l-tyrosine into l-dopa (l-3,4-dihydroxyphenylalanine). After conversion, l-dopa acts as a precursor for the neurotransmitters dopamine, norepinephrine and epinephrine. The l-dopa molecule is also effectively used in the symptomatic treatment of Parkinson's disease (Chan et al., 2012). In view of this interest, we have crystallized the title salt and report herein on its crystal structure. The hydrogen-bonding pattern and the relative contributions of various intermolecular interactions present are compared with the closely related chloride counterpart reported on earlier (Jandacek & Earle, 1971; Mostad & Rømming, 1974). ISSN 2056-9890

Structural commentary
The asymmetric unit of the title salt, Fig. 1, is composed of a Br À anion located on a twofold rotation axis, a dopa molecule in the zwitterionic form and a cationic dopa molecule. In the latter, the -amino group is protonated and carries a positive charge and the hydrogen atom (H4O) of the -carboxylic acid group is located on a general position and was refined with 50% occupancy.
The crystal structures of l-dopa (Mostad et al., 1971) and its hydrochloride form (Jandacek & Earle, 1971;Mostad & Rømming, 1974) have been reported. Both of these compounds crystallized in the monoclinic space group P2 1 . In the crystal structure of l-dopa HCl, the -amino group is protonated and the -carboxylic acid is neutral. The stoichiometry between the cation and the Cl À anion is 1:1. The authors of these structures concluded that l-dopa exists as the S enantiomer, based on the R factor and the effects of anomalous scattering. However, the deposited coordinates for these structures belong to the R configuration. Therefore, the l-dopa HCl structure was inverted and used for superposition with one of the dopa molecules of the title compound. These structures superimpose well, with an r.m.s. deviation of 0.045 Å (Fig. 2).

Supramolecular features
The structure of the title compound features a network of intermolecular N-HÁ Á ÁBr, N-HÁ Á ÁO and O-HÁ Á ÁO hydrogen bonds (Table 1), forming a three-dimensional framework. The cationic dopa molecules form dimers in which the carboxylic acid groups (O4) of the dopa molecules are interconnected via a short O-HÁ Á ÁO hydrogen bond and the dimers are arranged as ribbons propagating along the b axis (Fig. 3). The protonated amino group forms three hydrogen bonds; two of them with the Br À anions and one with the carbonyl oxygen atom, O3, of the carboxylic acid group. The dopa molecules aggregate in a head-to-tail sequence of the type Á Á ÁNH 3 + -CHR-COO À Á Á ÁNH 3 + -CHR-COO À Á Á Á, in which the -amino atom, N1, and the -carboxylate atom O3 form a hydrogen-bonded peptide-like arrangement (layers), as observed in many amino acid-carboxylic acid complexes (Sharma et al., 2006;Selvaraj et al., 2007). Adjacent layers are interconnected by short O-HÁ Á ÁO hydrogen bonds. These two interactions combine to form an R 4 4 (18) ring motif (Fig. 4). Similar interactions are observed in dopa and its HCl form (Mostad et al., 1971;Jandacek & Earle, 1971;Mostad & Rømming, 1974).
The amino group (via H1A and H1B) of the cationic dopa molecule participates in intermolecular N-HÁ Á ÁBr interactions with two different Br À anions (Table 1) The molecular structure of the title molecular salt, showing the atom labelling [symmetry code: (#) Àx + 3, y, Àz + 1]. Displacement ellipsoids are drawn at the 50% probability level.

Figure 3
The crystal packing of the title molecular salt, viewed along the b axis. H atoms have been omitted for clarity. that can be described as an R 4 2 (8) ring and it runs parallel to the b axis (Fig. 5). This pattern is also observed in the crystal structure of l-dopaÁHCl, where two intermolecular N-HÁ Á ÁCl hydrogen bonds link the cations and anions into a chain. There, adjacent chains are interconnected through O-HÁ Á ÁCl hydrogen bonds (carboxylic acidÁ Á ÁCl).
One of the hydroxy groups (O1-H1O) is involved in an intermolecular O-HÁ Á ÁO hydrogen bond with the carbonyl oxygen (O3) of the dopa molecule. This interaction links the dopa molecules into a C(9) chain. The other hydroxy (O2-H2O) group participates in bifurcated hydrogen bonds with two different hydroxy O atoms (O1 and O2) of adjacent dopa layers. The side chain of the dopa molecules in one layer is interconnected by the side chain of the dopa molecules in the adjacent layer through these interactions (Fig. 6). These interactions are also observed in the dopa hydrochloride structure.

Hirshfeld surface analysis
The Hirshfeld surfaces (HS) mapped with d norm and 2D fingerprint plots were generated using the program Crystal-Explorer    The side chainÁ Á Áside chain interactions of the dopa molecules in the title molecular salt, through intermolecular O-HÁ Á ÁO hydrogen bonds.
anion are shown in Fig. 7. The two-dimensional fingerprint plots are illustrated in Fig. 8. The HS analysis suggests that the intermolecular OÁ Á ÁH contacts contribute most (41.4%) to the crystal packing compared to other contacts. For example, the relative contributions of HÁ Á ÁH, CÁ Á ÁH and HÁ Á ÁBr contacts are 29, 18.6 and 6.1%, respectively, with regard to the complete unit of the dopa molecule. Concerning the Br À anion, the relative contributions of HÁ Á ÁBr and OÁ Á ÁBr contacts are 64.1 and 10.2%, respectively.
In the dopa HCl structure, the relative contributions of OÁ Á ÁH, HÁ Á ÁH, CÁ Á ÁH and HÁ Á ÁCl contacts are 40.5, 25.2, 17.1 and 14.1%, respectively, with respect to the cationic dopa molecule. It is of interest to note that OÁ Á ÁH and HÁ Á ÁH contacts are reduced by 1.1 and 3.8%, respectively, when compared to the title salt. Concerning the Cl À anion, the relative contribution of HÁ Á ÁCl contacts is 90.4%. This is approximately 26% higher compared to the relative contributions of HÁ Á ÁBr contacts in the title salt.

Synthesis and crystallization
l-dopa and HBr (1:1 molar ratio) were dissolved in doubledistilled water and stirred well for 4 h. The homogeneous solution was filtered and the filtrate allowed to evaporate slowly. Colourless block-like crystals were harvested after a growth period of two weeks. Two different views of the Hirshfeld surfaces of the dimeric dopa molecules along with a Br À anion.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The amino and carboxylic acid H atoms were located in a difference Fourier map and freely refined. The OH and C-bound H atoms were included in calculated positions and treated as riding atoms: C-H = 0.93-0.98 Å , O-H = 0.82 Å with U iso (H) = 1.2U eq (C) and U iso (H) = 1.5U eq (O). The title compound was refined as an inversion twin; absolute structure parameter = 0.023 (8).