Three New Compounds Derived from Nitrofurantoin : X-Ray Structures and Hirshfeld Surface Analyses

The polymorphism of nitrofurantoin (NF), 1), the cocrystals of NF:2,2’-bipyridyl = 2:1, 2) and NF: 1,10-phenanthroline = 1:1, 3) have been prepared and characterized. The crystal structure analyses show that there are various weak forces among the molecules, such as C/N-H···O, N-H···N hydrogen bond interactions and π···π/lone pair stacking interactions, which play a key role in the assembly of supramolecular networks. A thorough analysis of Hirshfeld surfaces and fingerprint plots facilitates a comparison of intermolecular interactions in 1 3, which are crucial in building supramolecular architectures.


Introduction
Noncovalent weak intermolecular interactions have gained much attention due to their unquestionable role in various chemical, physical, and biological processes [1]- [6].Among these interactions, the hydrogen bonds are the most important in view of their energy and directionality [7].Nitrofurantoin (NF) is an antibacterial drug and widely used for the treatment of urinary tract infections [8], however, a series of potential problems that occur in using such drugs, such as photosensitive [9], low solubility and low permeability [10].In recent years, some progresses in improving these insufficient have been made according to crystal engineering through exploring the molecular recognition between NF and co-formers [11]- [13].Considering the planar structure of NF, the molecules with delocalization П bonds, such as 2,2'-bipyridyl (bipy) and 1,10-phenanthroline (phen), were selected to form cocrystals with NF through molecular recognition.Fortunately, one new polymorphism [14] of NF and two new cocrystals, NF:bipy = 2:1 (2) and NF:phen = 1:1 (3), were obtained.As anticipated, singlecrystal X-ray structural analyses of compounds 1-3 revealed the generation of extended supramolecular networks by means of hydrogen bond interactions, π•••π interactions and lone pair•••π interactions.
The Hirshfeld surface [15] [16] provides a remarkable way of exploring intermolecular interactions in molecular crystals using a partitioning of crystal space in a novel visual manner.The surfaces encode information about all intermolecular interactions and offer a facile way of obtaining information on crystal packing.The breakdown of the associated fingerprint plots [17] explores quantitatively the types of intermolecular contacts experienced by molecules and presents this information in a convenient color plot.This plot provides a useful means of revealing significant similarities and differences between related structures by analyzing the packing motifs.The size and shape of the Hirshfeld surface are intimately related to the chemical environment surrounding the molecule, making it ideal for use in comparing different crystal structures incorporating the same molecule.In the context of crystal structure prediction, Hirshfeld surface base tools shows a major advance in analyzing intermolecular interactions [18] [19] and should be considered by the crystal engineers in building molecular architectures.The Hirshfeld surface and associated fingerprint plots of the three compounds have been presented to explore the nature of intermolecular interactions and their relative contributions in building the solid-state architecture.In addition, the thermal stability of the compounds has been investigated associated with the noncovalent interactions observed in the crystal structures.

Materials and Physical Measurements
Nitrofurantoin, were obtained from Alfa Aesar corporation, ZnCl 2 , 2,2'-dipyridyl and 1,10-phenanthroline were obtained from Sinopharm Chemical Reagent corporation, all available chemicals were of reagent grade and used without further purification.Elemental analyses were performed on a Thermo 1112 elemental analyzer.Infrared spectra were recorded on a Bruker-Tensor 27 FT-IR spectrometer with the samples prepared as KBr pellets.Thermogrvimetric analyses were performed using a SDT Q600 V8.3 Build101 thermal analyzer at a heating rate of 10˚C/min under an atmosphere of N 2 .

X-Ray Crystallography
Single crystal X-ray diffraction intensity data were collected using a Bruker SMART APEX CCD diffractometer equipped with graphite monochromated MoKα radiation (λ = 0.71073 Å).The data reduction was carried out using the program Bruker SAINT [20] and corrected for absorption using SADABS [21].The structures were solved by directed methods using SHELXTL [22] and refined by full matrix least-squares on F 2 with SHELXL-97 [23].Data collection and refinement parameters for compounds 1-3 are summarized in Table 1.

Hirshfeld Surfaces Analysis
Molecular Hirshfeld surfaces and the associated fingerprint information of 1-3 were calculated using the Crystal Explorer 3.0 software [24].All bond lengths to hydrogen were automatically modified to typical standard neutron values [25] (C-H = 1.083Å, N-H = 1.009Å and O-H = 0.983 Å), while the CIF.files of crystals 1-3 were read into the Crystal Explorer software program for calculations.

Crystal Structures Description
Compound 1 crystallizes in monoclinic space group P21/c with β = 109.68˚,which is one new polymorphism of nitrofurantoin [26] [27].The structural parameters about the polymorphism reported including compound 1 are summarized in Table S1.The selected bond lengths and angles about NF molecule in compounds 1-3 are listed in Table 2, and perspective views of the structures for compounds 1-3 are shown in Figure 1.The bond lengths   and angles of NF molecule in compounds 1-3 are similar, except that the lengths of the C-C bonds in furan ring and the N-O bonds of nitryl are slightly longer in compounds 2 and 3 than those in 1, which might attribute to the weak interactions between NF and bipy (or phen) molecules.As is illustrated in Table S2, the dihedral angle between the furan ring and the hydantoin ring in 3 is 10.98˚, much larger than that in 1 (5.35˚) and 2 (3.26˚), due to the electron repulsion and steric hindrance of phen molecule in 3.

Hirshfeld Surfaces Analysis
Herein, the Hirshfeld surfaces of compounds 1-3 are illustrated in Figure 5, showing the surfaces that have been mapped over d norm and shape-index.The information given in Table 3 is summarized effectively in the Hirshfeld surfaces as the large circular red areas marked with N•••H and O•••H, respectively.The other small extents of visible red spots and light-white regions in the d norm surfaces are indicative of weaker and longer contacts other than hydrogen bonds (Figure 5, d norm ).The hydrogen bonds interactions are also evident in shape-index by a red concave region around the acceptor atom and a complementary blue convex region around the hydrogen bond donor.Apart from hydrogen bonds, the π•••π interactions stacks for 2-3 are also observed on the same region of the shape index as the pattern of red and blue triangles highlighted by black dashed circles (Figure 5, right).
Meanwhile, the 2D fingerprint plots that decomposed to highlight particular atoms pair close contacts are provided in Figure 6, and the relative contributions of individual intermolecular interactions to the Hirshfeld surfaces area are depicted in

Thermal Analysis
The thermal behaviors of compounds 1-3 have been investigated, and the TGA curves are shown in Figure 8.In compound 1, the NF molecule decomposed at 230˚C with the weight loss of 46.2% (calc.47.4%), which is slightly lower than that of β-NF (240˚C) [28].For compound 2, the bipy molecule decomposed before the NF molecule at about 154.0˚C with the weight loss of 25.1%, which is in a good agreement with the calculated value of 24.7%.While to compound 3, the NF molecule decomposed before the phen molecule at 175˚C with the weight loss of 26.2% (calc.27.0%).

Conclusion
In summary, the crystal structures, Hirshfeld surfaces and thermal behaviors of the title compounds 1-3 are studied.With the construction of hydrogen bond interaction, along with π•••π/lone pair stacking interactions (for 2 and 3), the supramolecular structures are formed, 1D parallel ribbon structure of 1, 3D grid network of 2, and 1D square column of 3. The Hirshfeld surfaces and 2D fingerprint plots analyses make the understanding of the intermolecular interactions easily.In addition, the thermal stable studies show that the intermolecular interactions play a key role in the thermal properties of the compounds.

Table S1
listing unit cell parameters of nitrofurantoin crystal structures reported in the CSD and in this study.
Table S2 listing the dihedral angle between the furan and the hydantoin ring designated by α.Crystallographic data (excluding structure factors) for compounds 1-3 have been deposited with the Cambridge Crystallographic Data Centre (CCDC) as supplementary publication numbers CCDC 1035025, 1035026 and 1035027, respectively.Copies of the data can be obtained on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: +441223336033; e-mail:deposit@ccdc.cam.ac.uk.

Figure 7 .
In 1, the O•••H/H•••O intermolecular interactions appear as a pair of symmetrical large sharp spikes in the fingerprint plots in the region of (1.10 Å, 0.76 Å), which comprise 50.4% of the total Hirshfeld surfaces area.The N•••H/H•••N interactions comprise 3.9% of the total Hirshfeld surfaces and represent two small wings with d i + d e = 3.08 Å, which is longer than the r vdW separation and suggests the absence of any C/N-H•••N.Furthermore, the H•••H interactions are displayed in the distribution of scattered points in the fingerprint plots, which spread up to d i = d e = 1.39 Å and comprise 10.0% of the total Hirshfeld surfaces.Unlike 1, the O•••H/H•••O intermolecular interactions are longer in 2 (d i + d e = 2.27 Å) and 3 (d i + d e = 2.24 Å), respectively, with the smaller percentage of 45.6% and 36.1% to the total Hirshfeld surfaces, respectively.However, the N•••H/H•••N interactions are displayed in two sharp spikes in the fingerprint plots, which spread up to the shorter distance of d i + d e = 1.98 Å and d i + d e = 2.16 Å for 2 and 3, respectively, and contribute 8.7% and 13.2% to the total Hirshfeld surfaces, respectively.The H•••H interactions have more significant contribution to the total Hirshfeld surfaces in 2 (20.2%) and 3 (20.7%)when compared with 1, which spread up to

Figure 3 .
Figure 3. (a) View of the hydrogen bond interactions in 2; (b) The 3D grid-like supramolecular structure viewed down the c-axis in 2; (c) A diagrammatic representation of the 3D supramolecular architecture.

Figure 4 .
Figure 4. (a) View of the hydrogen bond interactions in 3; (b) A space-filling model of 1D structure in 3. d i = d e = 1.08 Å and d i = d e = 0.9 Å, respectively.The most significant difference amongst 1-3 is the presence of π•••π/lone pair stacking interactions only in 2 and 3, while introduce the Bipy and Phen molecules.The π•••π stacking interactions is closer in 3 (d i + d e = 3.16 Å) than in 2 (d i + d e = 3.28 Å), and the proportions of the total Hirshfeld surfaces are 4.0% and 2.4%, respectively.The O•••C/C•••O contacts associated with lone pair•••π stacking interactions are closer and maximum in 3 (d i + d e = 3.08 Å, 7.0%) than that in 2 (d i + d e = 3.14 Å, 4.7%), respectively.

Figure 5 .
Figure 5. Hirshfeld surfaces mapped with d norm (front view, left), d norm (back view, middle) and shape index (right) of NF in compounds 1-3, respectively.The π•••π stacking interactions are highlighted by black dashed circles.

Figure 6 .
Figure 6.Fingerprint plots of compounds 1-3: Full (left) and resolved into N•••H/H•••N (middle) and O•••H/H•••O (right) contacts, showing the percentages of contacts contributed to the total Hirshfeld surface area of molecules.

Figure 7 .
Figure 7. Relative contributions of various intermolecular contacts to the Hirshfeld surfaces area in compounds 1-3.

Table S1 .
Unit cell parameters of Nitrofurantoin crystal structures reported in the CSD and in this study.

Table S2 .
The dihedral angle between the furan and the hydantoin ring designated by α (˚).