Crystal structures and Hirshfeld surface analyses of (E)-N′-benzylidene-2-oxo-2H-chromene-3-carbohydrazide and the disordered hemi-DMSO solvate of (E)-2-oxo-N′-(3,4,5-trimethoxybenzylidene)-2H-chromene-3-carbohydrazide: lattice energy and intermolecular interaction energy calculations for the former

The structures and Hirshfeld surface analyses of the title compounds are reported.


Chemical context
Tuberculosis (TB) is one of the world's most infectious killer diseases, claiming 4,500 lives each day (https://www.who.int/ en/news-room/fact-sheets/detail/tuberculosis). The development of drug resistance to the first-line drugs seriously compounds the dangers of the disease. The latest multidrugresistant TB data analysis shows that 4.1% of new and 19% of previously treated TB cases in the world are estimated to have rifampicin-or multidrug-resistant tuberculosis (MDR/RR-TB) and about 6.2% of the MDR-TB cases have additional drug resistance, extensively drug-resistant TB (XDR-TB) (www.who.int/tb/challenges/mdr/MDR-RR_TB_factsheet_ 2017.pdf). As a result of the increase of MDR-TB/XDR-TB and AIDS cases worldwide, associated with the lack of efficacy of available drugs, the discovery of new potent and safer drugcandidate prototypes able to treat this disease has become an urgent challenge.
We have continued studies of the Mycobacterial activities of compounds of type 4 (Capelini et al., 2019) against various strains, namely M. tuberculosis H37Rv ATCC 27294 INHresistant Mtb, multidrug-resistant Mtb and wild INH/RIFresistant Mtb isolates: [4: R = (3,4,5-MeO) 3 C 6 H 2 ] exhibited significant activity against the INH resistant/RIP resistant strain, M. tuberculosis SR 5110/1116. We now wish to report the crystal structures and the Hirshfeld surface analyses of a DMSO hemi-solvate of this compound and also that of the parent compound, (4: R = C 6 H 5 ), an inactive compound. In addition, lattice energy and intermolecular interaction energy calculations are reported for 4 (R = C 6 H 5 ). This article also continues our reporting of the structures of nitrogencontaining 2-oxo-2H-chromene derivatives (Gomes et al., 2016a).

Figure 2
Compound (4: R = C 6 H 5 ). (a) Molecular structure and numbering scheme with displacement ellipsoids drawn at the 50% level and (b) side-on view of the conformation. C31 O31Á Á Á(1) into undulating sheets, see Fig. 3b. A further structural subset is formed from a series of C-HÁ Á Á interactions: C431-H43BÁ Á Á(3) and C451-H51BÁ Á Á(3) separately form chains of [4: R = (3,4,5-MeO) 3 C 6 H 2 ] propagating in the b-axis direction, while the C451-H51CÁ Á Á2 interaction generates a spiral chain of molecules; together these three interactions form a tube, into which the disordered DMSO molecule is cocooned, held there by a number of C-HÁ Á ÁX (X = O, N and S) hydrogen bonds. A view of the channels in which the the disordered DMSO sits is shown in Fig. 3c. These channels run along the crystallographic twofold axis.
The -i interaction is considered to be the stronger, both from the CgÁ Á ÁCg separation [3.8417 (6) compared to 4.1750 (6) Å ] and from its greater overlap, average slippages being 1.820 and 2.325 Å (the rings are inclined to each other). Further confirmation of the relative importance of the two interactions comes from the energy calculations, see Section 3.3. The combination of all the intermolecular interactions provides a three-dimensional arrangement.

Lattice energy and intermolecular interaction energy calculations
Lattice energies and intermolecular interaction energies were calculated using the PIXEL routine implemented in the CLP package (Gavezzotti, 2003(Gavezzotti, , 2008 which allows the calculation of intermolecular energies by distributed charge description on the basis of a preliminary evaluation of charge density from GAUSSIAN at the MP2/6-311G** level of theory (CUBE option). The PIXEL mode calculates the total stabilization energies of the crystal packing, E tot , distributed as coulombic, (E coul ), polarization (E pol ), dispersion (E disp ) and repulsion (E rep ) terms between separate, rigid molecules. Coulombic terms are treated on the basis of Coulombic law, polarization terms are calculated as a linear dipole approximation, dispersion terms are based on London's inverse sixpower approximation involving ionization potentials and polarizabilities and the repulsion term comes from a modulated function of the wave-function overlap.
The presence of a half molecule of DMSO lying at a symmetry centre in [4: R = (3,4,5-MeO) 3 C 6 H 2 Á0.5DMSO], precludes the PIXEL analysis for this structure. Partial analysis of the PIXEL calculations, however, was carried out on (4: R = C 6 H 5 ). The six molecule pairs that contribute most to the total energy of the packing of (4: R = C 6 H 5 ) are shown in Fig. 8.
The various energies for these six significant molecule pairs are also listed in Fig. 8. As such energy values pertain to both the reference molecule at x, y, z and its partner in the molecule pair, the energies thus associated with the reference molecule at x, y, z are half of these sums. The total PIXEL energy calculated for the complete lattice is À157.9 kJ.mol À1 . Of that, À123.9 kJ.mol À1 (78.5%) is derived from the six molecule pairs shown in Fig. 8. The percentage contribution of pairs involved in O-HÁ Á ÁO hydrogen bonds is 29.4% while pairs making CÁ Á ÁC close contacts contribute 26.6% to the total stabilization energy. Two views of the Hirshfeld surface of (4: R = C 6 H 5 )ÁThe red areas on the surfaces correspond to the designated close contacts. FP plots for (a) [4: R = 3,4,5-(MeO) 3 C 6 H 2 Á0.5DMSO] and (b) (4: R = C 6 H 5 ) in which the blue spikes ending at (1.2; 0.9) and (0.9;1.1) relate to OÁ Á ÁH/HÁ Á ÁO contacts and the high intensity of pixels, green and red areas relate to CÁ Á ÁC contacts. 0.094  and was briefly mentioned in a submitted article (Capelini et al., 2019). The molecule of (4: R = 4-MeOC 6 H 4 ) has a near-planar conformation and possesses equivalent intramolecular hydrogen bonds to those shown by the compounds reported in this article. A database search revealed other types of nitrogen-containing 2-oxo-2H-chromene derivatives, including amido derivatives (Gomes et al., 2016a,b); see also: DOLYEK (Borges et al., 2014a), DOLYIO (Cagide et al., 2015) and DOLYOU (Borges et al., 2014b(Borges et al., , 2016. Angelova et al. (2017) reported the structures of (1: R 1 = Me, R = C 6 H 5 ) and (1: R 1 = Me, R = pyridine-4-yl).

Synthesis and crystallization
5.1. General procedure for the synthesis of compounds 4 To a suspension of coumarinic acid (cis-o-hydroxycinammic acid, C 9 H 3 OH) (29 mmol, 1.0 equiv.) in CH 3 CN (100 ml) at room temperature, was added HOBt (34.64 mmol, 1.2 equiv.), followed by EDC (65.40 mmol, 2.25 equiv). The reaction was stirred at room temperature for 2 h, and slowly added to a solution of hydrazine hydrate (58.20 mmol, 2.0 equiv.) in CH 3 CN (100 mL) maintaining the temperature below 283 K. Water (70ml) was added to the reaction mixture, which was extracted successively with chloroform (3 Â 95 mL) and aqueous 5% sodium bicarbonate (3 Â 120 mL). The organic phases were collected and rotary evaporated to yield the coumarinic hydrazide (5), as a yellow solid. Crystallization of compound [4: R = (3,4,5-(MeO) 3 C 6 H 2 ] from DMSO solution produced the hemi-DMSO solvate, which on heating slowly decomposed to a dark residue. Attempts to gain suitable crystals for the structural study by slow recrystallization from ethanol solution at room temperature failed.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 5    where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.31 e Å −3 Δρ min = −0.30 e Å −3 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 )
x y z U iso */U eq Occ. (     where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.23 e Å −3 Δρ min = −0.19 e Å −3 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.