The crystal structure of zwitterionic 2-{[(4-iminiumyl-3-methyl-1,4-dihydropyridin-1-yl)methyl]carbamoyl}benzoate hemihydrate

The molecular and crystal structure of zwitterionic 2-{[(4-iminiumyl-3-methyl-1,4-dihydropyridin-1-yl)methyl]carbamoyl}benzoate hemihydrate is reported. The crystal structure is stabilized by a variety of hydrogen bonds and offset π–π stacking interactions.


Chemical context
Zwitterions are high-performance materials that can be used as drug protein stabilizers without affecting the activity of the drug (Keefe & Jiang, 2012). Drug protein stabilizers not only maintain the native chemical structure, but the native secondary and higher order structures necessary for biological activity and can increase the stability of the therapeutic protein and enhancs protein-substrate hydrophobic interactions without affecting the activity of the drugs. Zwitterionic polymers grafted from polysulfone (PSF) membranes show improved protein anti-fouling properties, together with good blood compatibility and cytocompatibility in comparison with the pristine PSF membrane (Yue et al., 2013). Furthermore, zwitterionic nanocarrier drugs showed excellent biocompatibility and non-fouling properties, and were found to extend blood circulation times in vivo. The study and synthesis of new zwitterions is therefore important in the search for new biomedical applications (Jin et al., 2014). ISSN 2056-9890

Structural commentary
The asymmetric unit of the title compound comprises two crystallographically independent 2-{[(4-iminiumyl-3-methyl-1,4-dihydropyridin-1-yl)methyl]carbamoyl}benzoate zwitterions (molecules A and B) and a cocrystallized water molecule, as shown in Fig. 1. The zwitterions are formed through protonation of the imine substituent on the pyridine ring and deprotonation of the carboxylate substituent on the benzene ring. The bond lengths and angles (Table 1) in the title compound ( Fig. 1) are generally within normal ranges. However, the N3-C3 [1.335 (3) Å in both molecules] are shorter than expected for an NH 2 -C ar single bond [1.38 (3) Å ], but are similar to those found in related compounds with an N + C double bond (Sharmila et al., 2014;Sun et al., 2015). The C-O bonds in the carboxylate units [C15A-O3A = 1.247 (3) Å and C15A-O2A = 1.257 (3) Å ] in molecule A, with comparable values in molecule B, are similar to values found in other deprotonated carboxylate groups (Hemamalini & Fun, 2010).

Supramolecular features
In the crystal, molecules are linked by N-HÁ Á ÁO, C-HÁ Á ÁO and O-HÁ Á ÁO hydrogen bonds (Table 2)  The molecular structure of the title compound, with the atom labelling and 50% probability displacement ellipsoids.

Figure 5
The molecular packing in the title compound with two kinds ofinteractions (dotted lines).
packing diagram, showing the three-dimensional array of parallel sheet of molecules in the ac plane is shown in Fig. 6.
A search for iminopyridine derivatives using 4-( 4 -azanylidene)-4H-1 2 -pyridine as the skeleton gave 15 hits, although none of these were zwitterionic derivatives comparable to the title compound. Of these, only three had aromatic rings in the cation in addition to the iminopoyridine unit (Sharmila et al., 2014;Pei et al., 2013)

Synthesis and crystallization
The title compound was obtained unexpectedly from the reaction of 0.01 mol of N-(bromomethyl)phthalimide and 0.01 mol of 4-amino-3-methylpyridine in 10 ml of dimethylformamide with a catalytic amount of potassium carbonate.
The mixture was stirred in a 50 ml round-bottomed flask at room temperature for about 3 h. The progress of the reaction was monitored by thin-layer chromatography and the mixture was poured into cold water once the reaction was complete. The resulting precipitate was filtered off, washed successively with distilled water, and recrystallized from acetone solution by slow evaporation to obtain colourless block-shaped single crystals.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. The N-and O-bound H atoms were located from difference Fourier maps and the former were refined freely [N-H = 0.88 (2)-0.95 (3) Å ], whereas for the latter, the distances from atom O1W were fixed at 0.86 Å , the HÁ Á ÁH distance was fixed at 1.34 Å and the H atoms were refined with a riding model [U iso (H) = 1.5U eq (O), and O-H = 0.864 and 0.865 Å ]. The C-bound H atoms were positioned geometrically using a riding model, with U iso (H) = 1.2 or 1.5U eq (C) (C-H = 0.93, 0.96 and 0.97 Å ). A rotating-group model was applied to the methyl groups. The overall packing of the title compound, viewed along the b-axis direction, showing parallel sheets in the ac plane linked into a threedimensional network along b.  (Sheldrick, 2015); molecular graphics: SHELXL2013 (Sheldrick, 2015) and Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXL2013 (Sheldrick, 2015) and PLATON (Spek, 2009).

Special details
Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell esds are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement on F 2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The observed criterion of F 2 > 2sigma(F 2 ) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.