Zwitterionic 4-bromo-6-methoxy-2-{[tris(hydroxymethyl)methyl]iminiumylmethyl}phenolate: crystal structure and Hirshfeld surface analysis

The title compound exists in the keto–amine tautomeric form. In the crystal, supramolecular layers are formed by O—H⋯O hydrogen bonding.


Chemical context
Interest in molecules related to the title Schiff base compound derived from tris(hydroxymethyl)aminomethane (see Scheme) rests largely with the biological activity exhibited by their metal complexes. Thus, various species have been studied for their anticancer potential, e.g. vanadium (Back et al., 2012) and tin (Lee et al., 2015). The insulin-mimetic behaviour of vanadium complexes have been explored (Rehder et al., 2002), as has the catecolase activity of binuclear cobalt complexes (Dey & Mukherjee, 2014). More recently, the adipogenic (cell differentiation) capacity of vanadium  and zinc complexes has been described . Over and above these considerations, magnetochemistry motivates on-going investigations, especially single-molecule (Wu et al., 2007;Chandrasekhar et al., 2013;Dey et al., 2015) and lanthanide-containing species (Zou et al., 2015;Das et al., 2015). It was during on-going biological assays (Lee et al., 2015) that the title compound, (I), became available. Herein, the crystal and molecular structures of (I) are described, as well as a Hirshfeld surface analysis.

Analysis of the Hirshfeld surfaces
The Hirshfeld surface of (I) was mapped over the d norm contact distance within the range of À0.67 to 1.31 Å through calculation of the internal (d i ) and external (d e ) Hirshfeld surface distances to the nearest nucleus (McKinnon et al., 2007;Spackman & Jayatilaka, 2009). Two-dimensional fingerprint plots associated with relevant close contacts were obtained through the plot of d e versus d i (Spackman & McKinnon, 2002). The electrostatic potential (ESP) of the crystal structure was mapped onto the Hirshfeld surface by an ab initio quantum modelling approach at the Hartree-Fock level of theory with the STO-3G basis set (HF/STO-3G) over the range of À0.122 to 0.189 au. All Hirshfeld surface and fingerprints plots were generated using Crystal Explorer (Wolff et al., 2012), while the ESP was calculated by TONTO (Spackman et al., 2008) as implemented in Crystal Explorer.
Distances involving H atoms were normalized to the standard neutron diffraction bond lengths. The Hirshfeld surface map provides a visual summary of any close contacts (shown as red) in contrast to relatively long contacts (shown as white and blue). As displayed in Fig. 3(a), there are several red spots observed on the Hirshfeld surface of (I), particularly around the O atoms, indicating close interactions at distances shorter than the sum of the van der Waals radii. A quantitative analysis of the decomposed twodimensional fingerprint plot of the relevant OÁ Á ÁH/HÁ Á ÁO interactions reveals a distinctive reciprocal spike in the plot of d e versus d i (Fig. 3b), with the sum of contact distances being approximately 1.74 Å , signifying a strong intermolecular interaction. Such strong interactions constitute the second major contribution to the Hirshfeld surface, i.e. 25.4%, between the most prominent HÁ Á ÁH (38.2%) and other major contacts, like CÁ Á ÁH/HÁ Á ÁC (15.2%) and BrÁ Á ÁH/HÁ Á ÁBr   Percentage distribution of the corresponding close contacts to the Hirshfeld surface of (I).

Figure 5
The d norm surface for (I), highlighting the OÁ Á ÁH hydrogen-bonding interactions which connect molecules in the molecular packing. surface notwithstanding, as seen from Figs. 3(c) and 3(d), CÁ Á ÁH and BrÁ Á ÁH contacts are at distances greater than their respective van der Waals radii. Fig. 5 shows the O-HÁ Á ÁO interactions formed between a reference molecule and symmetry-related molecules.
In order to gain a qualitative insight into the electrostatic interaction and rationalize the packing motif of the structure, the ESP was mapped over the Hirshfeld surface. The result illustrated in Fig. 6(a), shows that the electronegative sites are predominantly converged on O atoms and that, upon crystallization, the electronegative and electropositive sites are connected (Fig. 6b). It is noteworthy that despite bromine being an electrophilic element, it did not form a significant non-covalent interaction with neighbouring molecules in the inter-layer region where these atoms are directed. The closest contact in this region occurs with methyl-CÁ Á ÁH12C i , at 3.12 Å , i.e beyond the sum of the respective van der Waals radii (Spek, 2009)

Database survey
There are several closely related structures to (I) in the crystallographic literature (Groom et al., 2016). What might be termed the parent compound, i.e. with no substitution at the phenolate ring other than the imino group in the 2-position, (II), exists in the keto-amine tautomeric form and has been the subject of several investigations (Asgedom et al., 1996;Tatar et al., 2005). Similar zwitterionic structures are found in the 4-bromo, (III) (Martinez et al., 2011), and 6-methoxy, (IV) (Odabasoǧ lu et al., 2003), derivatives, both closely related to (I), suggesting this is the most stable form for these molecules, at least in the solid state. Despite the similar electronic structures, conformational differences exist about the ring between (I) and (IV) as seen in the relative dispositions of the methoxy groups, i.e. C12-O5-C3-C2 is 177.7 (2) in (I) but À165.75 (14) in (IV) (Fig. 7). Differences in conformation of the methylhydroxy groups are also apparent, no doubt due to the different hydrogen-bonding patterns in the respective crystal structures. Overlay diagrams for (I) (red image), (II) (green), (III) (blue) and (IV) (pink). Images have been drawn so the benzene rings overlap.

4-Bromo-2-((1E)-{[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]iminiumyl}methyl)-6-methoxybenzen-1-olate
Crystal data Special details 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.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )