Imagination Materializes with Serendipity: Third Polymorph of N-Amino 1,8-Naphthalimide

Imagination Materializes with Serendipity: Third Polymorph of N-Amino 1,8-Naphthalimide | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Imagination Materializes with Serendipity: Third Polymorph of N-Amino 1,8-Naphthalimide Satyendra Verma, Jubaraj B. Baruah This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7535669/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Synthon polymorphs are less encountered in the literature. It is challenging to prepare synthon polymorphs same synthon organized in different manners. We describe here the third polymorph of N-amino 1,8-naphthalimide that has R 2 2 (10) synthon of symmetry-related molecules assembled as a chain similar to a reported polymorph, which had symmetry-independent molecules; this made the difference in the self-assembled structure of the two polymorphs. The assemblies of three polymorphs of the compound, as well as the DFT-optimized energies of the dimeric assemblies of the two polymorphs, were also determined and compared. The new polymorph was obtained through the decomposition of 1-(2,4-dichlorophenyl)-3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)thiourea (DTU) in dimethylformamide solution that was kept at 80°C. When the solution was cooled, crystals of the concomitant polymorphs of two closely related forms were obtained, providing a new methodology for preparing the polymorph. Besides these, the structure of DTU was analysed to show the prerequisites for the alignments of the stacked naphthalimide rings in the starting compound to easily transform to the alignments of the stacking rings observed in the concomitant polymorphs. Naphthalimide Synthon polymorph Self-assembly Energy Calculation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Same compound or assembly of a particular composition but with dissimilar solid-state structures are polymorphs [ 1 – 4 ]. They influence the efficacy of drugs [ 5 – 9 ], Color [ 10 – 12 ], and magnetic properties [ 13 – 15 ]. The polymorphs have also established roles in utility-oriented materials such as electronic materials [ 16 ], fertilizers [ 17 ] etc. Conformation [ 18 – 19 ] as well as packing polymorphs [ 20 – 22 ] are observed in assemblies of a single conformation of a molecule extending to three dimensions. Due to tightly held ions or molecules in a crystal lattice of a crystalline solid, conformers or energetically less preferred geometry gets stabilized. Though the infinite numbers of polymorphs from one system may be imagined but the question remains how many forms can be obtained in reality, or to make a prediction when one of the forms will be formed. Polymorphs with variations of supramolecular synthons termed as synthon polymorph [ 23 – 27 ] are fewer in number also have a significant role in modulating properties [ 28 ]. Concomitant polymorphs [ 29 ] and disappearing polymorphs [ 30 ]. Different methodologies such as solution crystallization [ 31 – 32 ], solvent drop grinding [ 33 ], capillary [ 34 ], nano-confinement [ 35 ], ball-milling [ 36 ], etc, are routinely adopted to crystallize a polymorph. As per the literature, polymorph design has many questions to answer, starting from predictive forms and rationale in crystallization [ 37 ]. However, there are many processes, such as cross-nucleation of multiple forms [ 38 ], thermal transformations [ 39 ], and facial growth leading to morphological differences [ 40 ], which add complications in understanding polymorphs. Thus, there is a search for newer methodologies to prepare polymorphs. For example, two polymorphs of N-amino 1,8-naphthalimide are reported in the literature [ 41 – 42 ]. They are synthon polymorphs, one having hydrogen-bonded dimers, with R 1 2 (5), and the other having R 2 2 (10) types of dimers constituting a chain as illustrated in Figures 1a and 1b. A preliminary look at the second polymorphs shows that there are two sets of symmetry-independent hydrogen-bonded dimers A and B, as marked in Fig. 1 b at alternate places of a chain-like structure. So, there is a possibility of another polymorph that would have the chain with all symmetry-related molecules. Serendipitously, we obtained the new polymorph of N-amino 1,8-naphthalimide from the decomposition of 1-(2,4-dichlorophenyl)-3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)thiourea in dimethyl formamide solution, in a consistently reproducible manner. We report the characteristics of the new polymorph of the N-amino-1,8-naphthalimide by bringing out the distinguishable features from the other two forms. Experimental General: The hot-stage microscopic studies were carried out on a polarizing optical microscope (Nikon Eclipse LV100POL) equipped with a programmable hot stage (Mettler Toledo FP90). For this purpose, a clean glass slide with a coverslip to place the sample in between to record the polarizing optical microscopic images (heating rate = 10°C/min). Thermogravimetric analysis was done on a PerkinElmer thermogravimetric analyzer TGA 4000 (heating rate = 10°C/min). The differential scanning calorimetry was performed on Mettler Toledo DSC1 equipment, and measurements were carried out under a nitrogen atmosphere. The transition temperatures obtained from calorimetric measurements of the first heating and cooling cycles, conducted at a rate of 10°C/min. Infrared spectra of the solid samples were obtained with a PerkinElmer Spectrum FT-IR spectrophotometer (USA) by using the ATR method. Powder X-ray diffraction patterns were recorded using a Bruker powder X-ray diffractometer D2-phaser. DFT calculations were performed by Gaussian 09 software, and calculations were performed at the B3LYP level and using the 631-G++(d,p) basis set. Synthesis The compound 1-(2,4-dichlorophenyl)-3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)thiourea (DTU) was prepared by following the literature procedure [ 43 ]. It was prepared by reacting a 2,4-dichlorophenyl isothiocyanate (202.4 mg, 1 mmol) and N -amino-1,8-naphthalimide (212 mg, 1 mmol) in DMF (15 mL). After stirring the reaction mixture for 8 hs, the solution was kept for crystallization by slow evaporation in an undisturbed condition. After 3–4 days, the crystals of DTU were formed and were collected by decantation of the supernatant layer. Approximately 20% of pure crystals were obtained. The compound was characterized by recording NMR, IR mass, and finally determined by single crystal structure. Yield % 84. 1 HNMR (600 MHz, CDCl 3 , ppm): 8.63–8.8.62 (d, J = 6Hz, 2H), 8.24–8.22 (d, J = 8Hz, 2H), 7.78–7.76 (J = 8 Hz, t, 2H), 5.54 (s, 2H). Formation of concomitant polymorphs: DTU (0.4 g, mmol) was dissolved in DMF (15 mL, ≤ 0.10% water), the solution was placed in an oil bath maintained at 80°C by using a variac for 2 hs, and then the hot solution was allowed to cool to reach room temperature in undisturbed conditions and left for crystallisation. After 30 minutes, the crystals of Polymorph-3 along with Polymorph-2 were crystallised out. Yield: 84%. 1 HNMR (600 MHz, CDCl 3 , ppm): 8.63–8.8.62 (d, J = 6 Hz, 2H), 8.24–8.22 (d, J = 8Hz, 2H), 7.78–7.76 (t, J = 8Hz, 2H), 5.54 (s, 2H). IR (neat, cm − 1 ) 3309 (w), 3232 (w), 1696 (s), 1638 (s), 1614 (s), 1581(s), 1549 (s), 1512 (m), 1412 (s), 1380 (s), 1360 (m), 1234 (s), 1174 (s), 1147(m), 1096 (m), 1067 (m), 1025(w), 981(m), 898 (m), 882 (s), 841(s), 768 (s), 727(s), 693 (w), 636 (w), 538 (s), 404 (s). Structure determination Single-crystal X-ray diffraction data of the DTU and Polymorph-3 were collected at 296 K by using Mo Kα radiation (λ = 0.71073 Å) on a Bruker Nonius SMART APEX CCD diffractometer equipped with a graphite monochromator and an Apex CCD camera. Data reductions and cell refinements were performed using SAINT and XPREP software. Structures were solved by direct methods and were refined by full-matrix least-squares on F 2 using SHELXL-2014 software. All non-hydrogen atoms were refined in an anisotropic approximation against F 2 of all reflections. Hydrogen atoms were placed at their geometric positions by riding and refined in the isotropic approximation. The crystal data and refinement parameters are listed in Table 1 S. Hirshfeld surface analysis Hirshfeld surfaces of all the polymorphs were calculated using CrystalExplorer version 17.5. The Finger-print plots were generated by setting parameters as 𝑑 norm = (𝑑 i −𝑟 i vdW )/𝑟 i vdW +(𝑑 e −𝑟 e vdW )/𝑟 e vdW where d e and d i are the distances from the Hirshfeld surface to the nearest atoms outside and inside the surface. Both d e and d i are normalized by the van der Waals radius of the atoms involved. r i vdW and r e vdW are the van der Waals radii of the atoms. When the d norm value is negative (demarcated by a red spot), then the intermolecular contacts between atoms are shorter than the sum of their van der Waals radii. Results and discussions Structural comparisons among the polymorphs: The crystals of the concomitant polymorphs of N-amino-1,8-naphthalimide were obtained serendipitously from the composition of thiourea derivative 1-(2,4-dichlorophenyl)-3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)thiourea (DTU) at 80°C as illustrated in Scheme 1 . The powder pattern of the bulk crystals of the has all the principal peaks matching the theoretically generated pattern from the crystallographic information files of the two polymorphs as given in Fig. 5 S. Our attempt to get only one form from the mixture was not successful. The crystals of the Polymorph-3 were picked up randomly and manually for structure determination, the crystals belonged to the orthorhombic Pna2 1 space group. The unit cell volumes of the three polymorphs of the N-amino 1,8-naphthalimide were similar. The unit cell parameters and crystal densities of are compared in Table 1 . It may be mentioned that one of the reported polymorphs of N-amino-1,8-naphthalimide, designated here as Polymorph-2, had symmetry-independent molecules within the unit cell. In contrast, the other reported one, designated as Plymorph-1, had all symmetry-related molecules in the unit cell. The third form also contains all symmetry-equivalent molecules in the unit cell. The hydrogen-bonded N-amino-1,8-naphthalimide molecules of this polymorph are arranged as linear chains involving both the NH-NC = O faces of the pairs. The chain has Table 1 Comparative unit-cell data of the three polymorphs Polymorph Polymorph-1 Polymorph-2 Polymorph-3 Space group Orthorhombic Pna2 1 Triclinic P -1 Orthorhombic Pna2 1 Length of cell axis (Å) a = 13.296(2), b = 18.408 (4), c = 3.781 (11) a = 7.307(6), b = 9.364 (7), c = 14.655 (10) a = 7.204(18), b = 16.373 (4), c = 7.996 (19) Angles (°) α = β = γ = 90.00 α = 81.676(3), β = 80.506(3), γ = 69.460(3) α = β = γ = 90.00 Volume (Å 3 ) 925.5 (4) 922.15 (12) 943.1(4) Density (gcm − 3 ) 1.518 1.523 1.495 hydrogen-bonded synthons with R 2 2 (10) graph-set notation as shown in Fig. 2a. The synthons have N2-H … O1{d D…A , 3.0579(8)Å; <DHA, 154°) and N2-H … O2 {d D…A , 3.0671(8)Å, <DHA, 159°} hydrogen bonds. The Polymorph-2 and Polymorph-3 have similarity in assembling, as both have chain-like structure; the difference arises from the two alternative pairs of symmetry independent molecules in the Polymorph-2, each associated as pairs with two independent R 2 2 (10) synthons (Fig. 1 b), held to one another with distinguishable hydrogen bond parameters. The naphthalimide rings of independent neighboring chains of the Polymorph-3 are in parallel stacks. Considering the amino-group as the head and the naphthalene ring part as the tail, such stacking dipoles are aligned oppositely, showing a head-to-tail arrangement with a centroid-to-centroid distance of 3.649 Å. This distance is suggestive of weak interactions among the rings [ 44 ]. The Polymorph-1 had head-to-head arrangements, and Polymorph-2 had head-to-tail stackings in pairs formed among the neighboring naphthalimide rings. In the literature, there are examples of polymorphs with eclipsing 1,8-naphthalimide rings with dipoles aligned oppositely, as well as one having dipoles of rings oriented in the same direction [ 45 ]. On the other hand, different positional isomeric naphthalimide-based compounds having flexible tethers generate large variations in the stacks between the naphthalimide rings [ 46 – 47 ], and many polymorphs of naphthalimide derivatives with different orientations prepared by changing the crystallization process have wide variations in colors [ 48 – 49 ]. In the present example, the conformational adjustment can occur through the rotation of the N-N bond of the N-NH 2 unit, changing the orientations of the hydrogen bond donor N-H bonds. In fact, this was a reason, together with the orientations of the rings in proximity, have caused the distinctions in the scheme of hydrogen bonds in packings of the three polymorphs. Hirshfeld surfaces, total energies and DFT optimized energies: The Hirshfeld surface analyses [ 50 ] of each polymorph were performed to distinguish the type of contacts in each case. The percentage of different interactions within a distance of 3.8 Å of the surface. The atoms in the vicinity of the surface are shown in Fig. 3. Different percentages of contacts are listed in the supporting table and the pie-diagrams as for comparison are shown in Fig. 4a-c. They show that major contributions in the polymorphs were from contacts of hydrogen atoms and are comparable. The All in -O in the three polymorphs was in order 2 > 1 > 3, and the All in -C was 3 > 1 > 2. The Polymorph-1 and Polymorph-3 had identical nitrogen contacts with atoms inside the surface, whereas they had 0.8% less All in -N contacts. This was due to differences in the orientation of the molecules of the symmetry-independent molecules within the lattice. Though the Polymorphs-1 and Polymorph-2 had differences in All in -O and All in -N, the total weight of these two contacts was higher in Polymorph-1 than the Polymorph-3, showing that the former had more amounts of moderate hydrogen bonds. The dispersive and repulsive as well as total energies of the polymorphs by using Crystal Explorer with the B3LYP functional at the 6-31G(d,p) level. The respective dispersive energies are Polymorphs-1 to 3 were − 66.0 kJ/mol, -11.0 kJ/mol, and − 70.3 kJ/mol, whereas the respective repulsive energies were 30.8 kJ/mol, 21.2 kJ/mol, and 38.8 kJ/mol. Whereas the respective total energies − 48.7 kJ/mol, -25.6 kJ/mol, and − 51.2 kJ/mol. This showed that the stability of the polymorphs was of the order Polymorph-3 > Polymorph-2 > Polymorph-1. The energy of each molecule in the conformation as observed in each polymorph was calculated by DFT using the B3LYP functional at the 6–31 + + G(d,p) level. It was found that each conformer has different energies, and the energies of the two symmetry-independent molecules differed by 5.2 kJ/mol from one another, as illustrated in Fig. 5 a.. On the other hand electronic energy of the Polymorph 2 > 3 > 1. But the energy difference between the Polymorph-2 and Polymorph-3 was very small. The energy of each polymorph was also optimized in the gas phase by DFT calculation with B3LYP functional at 6–31 + + G(d,p) level. It was found that the optimized energies of Polymorph-1 and Polymorph-3 were the same; hence, the hydrogen-bonded dimers of Polymorphs-2 and Polymorph-3 were independently determined. This has revealed that polymorph-3 is 35.14 kJ/mol lower than the energy of Polymorph-1, whereas polymorph-2 is stable by 1.21 kJ/mol than Polymorph-3, as shown in Fig. 5 , suggesting stability 2 > 3 > 1. These provided the stability gain by the synthons. A recent theoretical study has revealed that a high value of Z׳ (number of symmetry-independent molecules in unit cell) is not reflective of the stability of polymorphs [ 51 ]. Our observations suggest that the replica units of the assemblies, as well as the electronic energy of individual molecules, provide the trend of electronic stability of the discrete molecules in different conformations. The optimized energies of assembled structures within assemblies reflect to distinction of their relative gain or loss of stability by forming different synthons. But the total energy gain from dispersive and attractive forces provides insight into the overall stability of the polymorphs. In this case, Polymorph 3 has the lowest energy based on attractive and dispersive energies calculated by CrystalExplorer-17.5 version, and has the highest stability as reflected in the melting temperature. On the other hand, the density of polymorph-3 is lower but it has higher stability. Differential scanning calorimetry and hot-stage microscopic study The differential scanning calorimetry (DSC) of the concomitant polymorph was recorded, and it was compared with the DSC of the earlier reported ones. It showed that the Polymorph underwent melting of Polymorph-2 in the mixture at 248°C. Upon further heating, Polymorph-3 melted at 274°C. The first heating and cooling cycle of DSC is shown by the black trace in Fig. 6a. The corroboration of the results with the hot-stage microscopic study showed the melted phase, as shown in the (c) of Fig. 6. Upon cooling after heating up to 300°C, it showed that solidification of the melt at 262°C took place, which, on further cooling, reconverted to an amorphous phase at 221°C corresponding to polymorph-2. The second cycle of heating shown as the red trace of Fig. 6a showed the reversibility of the process, but the solidification at the second cycle took place at 259°C, which was 3°C lower than the first cycle. The images of the cooling samples at two temperatures are shown in Figs. 6b-e. This could be due to defects created within the structures after the first heating cycle, which had affected the colligative properties, affecting the solidification from the melt by forming another form of polymorph. The thermal properties are different from the other two polymorphs. Polymorph-1 melted at 249°C, whereas Polymorph-2 melted at 256°C. While cooling, the Polymorph-1 recrystallized at 233°C, whereas the Polymorph-2 recrystallized at 253°C [ 42 ]. The thermogravimetric analysis shown in Fig. 7 S has no weight loss on heating the concomitant polymorphs till 300°C (below this temperature, DSC plots were recorded), but there was a sharp loss of weight at 325°C, where the sample evaporated. Structural studies on 1-(2,4-dichlorophenyl)-3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)thiourea We analyzed the structure of DTU from which the Polymorphs were formed, by determing the structure by X-ray single-crystal diffraction. The self-assembled structure of DTU is shown in Fig. 7 a. The compound comprises a thiourea part linked to an N-amino 1,8-naphthalimide portion. The packing pattern shows that naphthalimide rings are not stacked but are in a slanted position, with a bisecting angle between the two planes containing such rings was 27.04°, as in (i) of Fig. 7 a. Whereas the rings had occupied positions in an intermittent orientation, neither head to tail, nor head to head, as in (ii) of Fig. 7 b. Hence, formation of the concomitant polymorph (oppositely having dipoles of the napthalimides) from this assembly will require flipping of one of the rings to reorganize to be parallel with the other and a rotation to make a head-tail orientation as suggested in Fig. 7 b. In fact, the same argument would also suggest providing the other polymorphs from such a decomposition. But the Polymorph-2 and Polymorph-3 had the highest comparable energies. Themogravimetry in Fig. 3S has shown that the compound DTU was stable up to 205°C; hence, polymorphs were formed as a result of a chemical decomposition caused by small amounts of water in the solvent or air that led to the formation of N-amino 1,8-napthalimide from DTU at 80°C. Furthermore, there is a literature example on cyclohexyl-derived thiocarbazide undergoing hydrolytic cleavage to produce a rearranged product [ 52 ]. It was also shown that thiocarbazide-based compounds result in different polymorphic solvates by changing crystallization conditions from room temperature to higher temperatures [ 43 ]. These observations have suggested that the specific polymorph crystallization was an outcome of the interplay of weak supramolecular interactions during the course of decomposition. Conclusions The same synthon but with different symmetry relations provided two independent polymorphs (2 and 3) of N-amino 1,8-naphthalimide that have very close electronic energy differences. These examples have established that hydrogen-bonded chains from crystallographically symmetric molecules or from symmetry-independent molecules provide polymorphs. It is also shown that, while in situ decomposition of the DTU it chooses to crystallise the N-amino,1,8-naphthalimide to adopt a head-to-tail arrangement that is observed in stacks among the molecules of the two concomitant polymorphs. So, having an idea of existing polymorphs, searching for closely related forms is essential, and in this case, success was brought in by serendipity. Declarations Ethics approval, and consent to participate: Not applicable. Consent for publication: Both authors give consent for the publication of the manuscript in the Journal of BMC Chemistry. Availability of data and materials: The crystallographic information files of the DUT and Polymorph-3 have the Cambridge Crystallographic Data deposition CCDC numbers 2423507 and 2484027. The supporting materials included with the manuscript are NMR spectra, Thermogravimetry, Crystallographic table, and percentages of contacts from Hirshfeld analysis. Competing interests: The authors declare that they have no competing interests. Funding: This research was not part of a sponsored project to the authors; the work was done with support of the Indian Institute of Technology, Guwahati. Author's contributions: JBB: Conceptualization and writing, theory, and data analysis. SV: Experiments, Structure determination, data management, and spectral interpretation. Acknowledgements: The authors thank the Ministry of Education (India) for providing financial assistance (grant no. F. No. 5-1/2014-TS.VII). 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Yu L, Stephenson GA, Mitchell CA, Bunnell CA, Snorek SV, Bowyer JJ, Borchardt TB, Stowell JG, Byrn SR. Thermochemistry and conformational polymorphism of a hexamorphic crystal system, J Am Chem Soc. 2000; 122: 585– 591. Preston JA, Parisi E, Murray B, Tyler AII, Simone E, Elucidating the polymorphism of xanthone: a crystallization and characterization study, Cryst Growth Des. 2024; 24 : 3256 – 3268. Kovalevsky AY, Ponomarev II, Antipin MY, Ermolenko IG, Shiishkin OV. Influence of steric and electronic effects of substituents on the molecular structures and conformational flexibility of 1,8-naphthalenedicarboximides, Russ. Chem. Bull. 2000; 49: 70 – 76. Sendh J, Baruah JB. Polymorphs, ionic cocrystal and inclusion complex of N -amino-1,8-naphthalimide, CrystEngComm, 2023; 25: 1928 – 1940. Nath J, Baruah JB. Assemblies of sulfathiazole-and sulfamethazine-derived thiourea: polymorphs, solvates, and fluoride detection, Cryst Growth Des. 2024; 24: 1910 – 1925. Chen T, Li M, Liu J, π–π Stacking interaction: a nondestructive and facile means in material engineering for bioapplications, Cryst Growth Des. 2018; 18 : 2765 – 2783. He X, Benniston AC, Saarenpaa H, Lemmetyinen H, Tkchenko NV, Baisch U, Polymorph crystal packing effects on charge transfer emission in the solid state, Chem Sci. 2015; 6: 3525 – 3532. Sarma RJ, Tamuly C, Barooah N, Baruah JB. Role of π-interactions in solid state structures of a few 1,8-naphthalimide derivatives, J Mol Struct. 2007; 829: 29 – 36. Nath JK, Baruah JB. Solvatoemissive dual fluorescence of N-(pyridylmethyl)-3-nitro-1,8-naphthalimides, J. Fluoresc. 2014; 24: 649 – 655. Li N-N, Liu W, Shi N-N, Yang D, Zong Z, Zhang X, Wu R-X, Xu C-G, Bi S-Y, Fan Y-H, Multiple naphthalimide dimers polymorphs triggered solvatofluorochromism, solid-state emission and aggregation-induced emission by different interaction and its application in fluorescence ratiometric sensing of dichloromethane and 1,4-dioxane, Dyes and Pig. 2021; 188: 109172. Chen Z, Wu D, Han X, Nie Y, Yin J, Yu GA, Liu SH, 1,8-Naphthalimide-based highly blue-emissive fluorophore induced by a bromine atom: reversible thermochromism and vapochromism characteristics, RSC Adv. 2014; 4: 63985. Spackman PR, Turner MJ, McKinnon JJ, Wolff SK, Grimwood DJ.; Jayatilaka, D.; Spackman, M. A.; CrystalExplorer: a program for Hirshfeld surface analysis, visualization and quantitative analysis of molecular crystals, J. Appl. Cryst. 2021; 54: 1006 – 1011. Pradhan AK, Sudheendranath A, Jitesh Arora J, Dahiya R, Thomas SP. Are high- Z ′ polymorphs metastable? Insight from pharmaceutical polymorphs. Phys Chem Chem Phys. 2025; 27: 17779 – 17786. Jaiswal S, Gond MK, Bharty MK, Maiti B, Krishnamoorthi S, Butcher RJ. Manganese(II) catalyzed synthesis of bis (N-cyclohexylthiourea) derived from thiosemicarbazide: Structural characterization, fluorescence, cyclic voltammetry, Hirshfeld surface analysis and DFT calculation, J Mol Struct. 2021; 1246: 131060. Scheme 1 Scheme 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files SupportingInformation3rdseptember.docx floatimage1.jpeg Graphical Abstract Schem1.png Scheme 1: The decomposition of DTU leading to N-amino-1,8-naphthalimide. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 05 Jan, 2026 Reviews received at journal 29 Dec, 2025 Reviewers agreed at journal 20 Dec, 2025 Reviews received at journal 06 Nov, 2025 Reviewers agreed at journal 23 Oct, 2025 Reviewers invited by journal 18 Sep, 2025 Editor assigned by journal 08 Sep, 2025 Submission checks completed at journal 08 Sep, 2025 First submitted to journal 04 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7535669","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":512032270,"identity":"1c9d58b1-b749-49d4-b6af-3b692d585c3b","order_by":0,"name":"Satyendra Verma","email":"","orcid":"","institution":"Indian Institute of Technology Guwahati","correspondingAuthor":false,"prefix":"","firstName":"Satyendra","middleName":"","lastName":"Verma","suffix":""},{"id":512032271,"identity":"51d22561-939c-4d0c-a9fd-22ca1012c317","order_by":1,"name":"Jubaraj B. Baruah","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtElEQVRIiWNgGAWjYBACxgYeBoYPBhJQrgGRWhhnGEhIEK+FgYGHgRlokQRhhTDAPCP34GebAos6eQfmhx8YCu4Q4bAZecnSOUCHGR5gM5ZgMHhGjJYcA4iWBgYzoF8OE6XF+LcFWAv7N6K1mEkzALXIM/AQa0vPuzTLHgMJyQ3MPMUSCcRoMWzPPXzjx586fvn29o0fPvwhRksDlAE2P4GwBgYGeTijAY+qUTAKRsEoGNkAAKLcL7WjXmO8AAAAAElFTkSuQmCC","orcid":"","institution":"Indian Institute of Technology Guwahati","correspondingAuthor":true,"prefix":"","firstName":"Jubaraj","middleName":"B.","lastName":"Baruah","suffix":""}],"badges":[],"createdAt":"2025-09-04 11:38:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7535669/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7535669/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91028170,"identity":"d8ab778e-961e-4611-a778-38dfd7bef89e","added_by":"auto","created_at":"2025-09-10 21:44:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":351874,"visible":true,"origin":"","legend":"\u003cp\u003eLiterature reported synthon polymorphs of N-amino 1,8-naphthalimide, one having (a) R\u003csup\u003e1\u003c/sup\u003e\u003csub\u003e2\u003c/sub\u003e(5) hydrogen bonded synthon and the other (b) having assemblies of symmetry-independent (A and B) hydrogen bonded R\u003csup\u003e2\u003c/sup\u003e\u003csub\u003e2\u003c/sub\u003e(10) synthons.\u0026nbsp;\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7535669/v1/ae64bfd410e6634eb26888cc.png"},{"id":91028320,"identity":"b746d92d-e96c-49ef-bc7b-0ec0ce061539","added_by":"auto","created_at":"2025-09-10 21:52:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":311309,"visible":true,"origin":"","legend":"\u003cp\u003e(a) The hydrogen-bonded chain of the Polymorph-3, and (b) The head-to-tail stacking arrangements of two adjacent rings of the polymorph\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7535669/v1/5fbbda50ecc2f32db6c198fc.png"},{"id":91028171,"identity":"76a14678-866e-42b4-8bba-24f30db80af0","added_by":"auto","created_at":"2025-09-10 21:44:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":693369,"visible":true,"origin":"","legend":"\u003cp\u003eThe Hirshfeld surfaces of the polymorphs showing the molecules within 3.6 Å of the surface of (a) Polymorph-1, (b) Polymorph-2, (c) Polymorph-3.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7535669/v1/a8db3f475c2b596b7ebebc9e.png"},{"id":91028322,"identity":"38773ced-bd8b-4bb2-a8d5-419952d14a96","added_by":"auto","created_at":"2025-09-10 21:52:24","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":177516,"visible":true,"origin":"","legend":"\u003cp\u003ePie diagrams of the different All\u003csub\u003ein\u003c/sub\u003e-atom contacts of atoms from Hirshfeld analysis.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7535669/v1/0857cd4817d004e844f2c33e.png"},{"id":91028177,"identity":"8fbb7075-4534-464b-99dc-dde4e96ecfce","added_by":"auto","created_at":"2025-09-10 21:44:24","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":346938,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Energies of the molecules as obtained in crystallographic information files; (b) Optimized energy of the polymorphs by DFT using with B3LYP functional at the 6-31++G(d,p) level\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7535669/v1/24b01b4ec125271996d90a5a.png"},{"id":91028178,"identity":"aa3fe2f3-1bde-43f0-b80b-268dc20f92b7","added_by":"auto","created_at":"2025-09-10 21:44:24","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":992897,"visible":true,"origin":"","legend":"\u003cp\u003eHeating and cooling cycle of DSC plots of concomitant Polymorph\u003cstrong\u003e. \u003c/strong\u003e(Heating rate = 10 °C/min under nitrogen), Images of the concomitant Polymorph after heating (b) 225 °C and (c) 181 °C, while the images upon cooling after heating to (a) 241 °C and (e) cooling to 158 °C.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7535669/v1/47897243e7abb491e6aaab5a.png"},{"id":91028326,"identity":"869bc735-2321-4089-b00c-7653a8bbc13d","added_by":"auto","created_at":"2025-09-10 21:52:24","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":657242,"visible":true,"origin":"","legend":"\u003cp\u003e(a) The assembly of DTU, (b) The stacks of naphthalimide in (i) DTU and (ii) in Polymorph-3.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-7535669/v1/295cf0644d9b1076174cb1bb.png"},{"id":91028817,"identity":"32beea0f-e1d4-4de6-a551-aa9fb58e1e09","added_by":"auto","created_at":"2025-09-10 22:08:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5053463,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7535669/v1/198c33d2-aa13-4331-a7d2-b144301e0c79.pdf"},{"id":91028578,"identity":"0416b6e7-3e63-4adf-a102-4fa2cf2c3b4a","added_by":"auto","created_at":"2025-09-10 22:00:24","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":3237300,"visible":true,"origin":"","legend":"","description":"","filename":"SupportingInformation3rdseptember.docx","url":"https://assets-eu.researchsquare.com/files/rs-7535669/v1/a6fa6d489547824f6d52f6b8.docx"},{"id":91028175,"identity":"a44ad32c-e205-42cf-841d-612aac1d7613","added_by":"auto","created_at":"2025-09-10 21:44:24","extension":"jpeg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":40633,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical Abstract\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7535669/v1/988f4ff3cd948777a00d52d9.jpeg"},{"id":91028173,"identity":"682dd427-0cd7-4fd3-9a65-b77da7e2c05c","added_by":"auto","created_at":"2025-09-10 21:44:23","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":102267,"visible":true,"origin":"","legend":"\u003cp\u003eScheme 1: The decomposition of DTU leading to N-amino-1,8-naphthalimide.\u003c/p\u003e","description":"","filename":"Schem1.png","url":"https://assets-eu.researchsquare.com/files/rs-7535669/v1/66dedf607abd7709b2f80ce0.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"Imagination Materializes with Serendipity: Third Polymorph of N-Amino 1,8-Naphthalimide","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSame compound or assembly of a particular composition but with dissimilar solid-state structures are polymorphs [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. They influence the efficacy of drugs [\u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], Color [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and magnetic properties [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The polymorphs have also established roles in utility-oriented materials such as electronic materials [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], fertilizers [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] etc. Conformation [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] as well as packing polymorphs [\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] are observed in assemblies of a single conformation of a molecule extending to three dimensions. Due to tightly held ions or molecules in a crystal lattice of a crystalline solid, conformers or energetically less preferred geometry gets stabilized. Though the infinite numbers of polymorphs from one system may be imagined but the question remains how many forms can be obtained in reality, or to make a prediction when one of the forms will be formed. Polymorphs with variations of supramolecular synthons termed as synthon polymorph [\u003cspan additionalcitationids=\"CR24 CR25 CR26\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] are fewer in number also have a significant role in modulating properties [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Concomitant polymorphs [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] and disappearing polymorphs [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Different methodologies such as solution crystallization [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], solvent drop grinding [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], capillary [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], nano-confinement [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], ball-milling [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], etc, are routinely adopted to crystallize a polymorph. As per the literature, polymorph design has many questions to answer, starting from predictive forms and rationale in crystallization [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. However, there are many processes, such as cross-nucleation of multiple forms [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e], thermal transformations [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], and facial growth leading to morphological differences [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e], which add complications in understanding polymorphs. Thus, there is a search for newer methodologies to prepare polymorphs. For example, two polymorphs of N-amino 1,8-naphthalimide are reported in the literature [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. They are synthon polymorphs, one having hydrogen-bonded dimers, with R\u003csup\u003e1\u003c/sup\u003e\u003csub\u003e2\u003c/sub\u003e(5), and the other having R\u003csup\u003e2\u003c/sup\u003e\u003csub\u003e2\u003c/sub\u003e(10) types of dimers constituting a chain as illustrated in Figures 1a and 1b. A preliminary look at the second polymorphs shows that there are two sets of symmetry-independent hydrogen-bonded dimers A and B, as marked in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb at alternate places of a chain-like structure. So, there is a possibility of another polymorph that would have the chain with all symmetry-related molecules. Serendipitously, we obtained the new polymorph of N-amino 1,8-naphthalimide from the decomposition of 1-(2,4-dichlorophenyl)-3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)thiourea in dimethyl formamide solution, in a consistently reproducible manner. We report the characteristics of the new polymorph of the N-amino-1,8-naphthalimide by bringing out the distinguishable features from the other two forms.\u003c/p\u003e"},{"header":"Experimental","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eGeneral:\u003c/h2\u003e\u003cp\u003eThe hot-stage microscopic studies were carried out on a polarizing optical microscope (Nikon Eclipse LV100POL) equipped with a programmable hot stage (Mettler Toledo FP90). For this purpose, a clean glass slide with a coverslip to place the sample in between to record the polarizing optical microscopic images (heating rate = 10°C/min). Thermogravimetric analysis was done on a PerkinElmer thermogravimetric analyzer TGA 4000 (heating rate = 10°C/min). The differential scanning calorimetry was performed on Mettler Toledo DSC1 equipment, and measurements were carried out under a nitrogen atmosphere. The transition temperatures obtained from calorimetric measurements of the first heating and cooling cycles, conducted at a rate of 10°C/min. Infrared spectra of the solid samples were obtained with a PerkinElmer Spectrum FT-IR spectrophotometer (USA) by using the ATR method. Powder X-ray diffraction patterns were recorded using a Bruker powder X-ray diffractometer D2-phaser. DFT calculations were performed by Gaussian 09 software, and calculations were performed at the B3LYP level and using the 631-G++(d,p) basis set.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSynthesis\u003c/h3\u003e\n\u003cp\u003eThe compound 1-(2,4-dichlorophenyl)-3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)thiourea (DTU) was prepared by following the literature procedure [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. It was prepared by reacting a 2,4-dichlorophenyl isothiocyanate (202.4 mg, 1 mmol) and \u003cem\u003eN\u003c/em\u003e-amino-1,8-naphthalimide (212 mg, 1 mmol) in DMF (15 mL). After stirring the reaction mixture for 8 hs, the solution was kept for crystallization by slow evaporation in an undisturbed condition. After 3–4 days, the crystals of DTU were formed and were collected by decantation of the supernatant layer. Approximately 20% of pure crystals were obtained. The compound was characterized by recording NMR, IR mass, and finally determined by single crystal structure. Yield % 84. \u003csup\u003e1\u003c/sup\u003eHNMR (600 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e, ppm): 8.63–8.8.62 (d, J = 6Hz, 2H), 8.24–8.22 (d, J = 8Hz, 2H), 7.78–7.76 (J = 8 Hz, t, 2H), 5.54 (s, 2H).\u003c/p\u003e\n\u003ch3\u003eFormation of concomitant polymorphs:\u003c/h3\u003e\n\u003cp\u003eDTU (0.4 g, mmol) was dissolved in DMF (15 mL, ≤ 0.10% water), the solution was placed in an oil bath maintained at 80°C by using a variac for 2 hs, and then the hot solution was allowed to cool to reach room temperature in undisturbed conditions and left for crystallisation. After 30 minutes, the crystals of Polymorph-3 along with Polymorph-2 were crystallised out. Yield: 84%. \u003csup\u003e1\u003c/sup\u003eHNMR (600 MHz, CDCl\u003csub\u003e3\u003c/sub\u003e, ppm): 8.63–8.8.62 (d, J = 6 Hz, 2H), 8.24–8.22 (d, J = 8Hz, 2H), 7.78–7.76 (t, J = 8Hz, 2H), 5.54 (s, 2H). IR (neat, cm\u003csup\u003e− 1\u003c/sup\u003e) 3309 (w), 3232 (w), 1696 (s), 1638 (s), 1614 (s), 1581(s), 1549 (s), 1512 (m), 1412 (s), 1380 (s), 1360 (m), 1234 (s), 1174 (s), 1147(m), 1096 (m), 1067 (m), 1025(w), 981(m), 898 (m), 882 (s), 841(s), 768 (s), 727(s), 693 (w), 636 (w), 538 (s), 404 (s).\u003c/p\u003e\n\u003ch3\u003eStructure determination\u003c/h3\u003e\n\u003cp\u003eSingle-crystal X-ray diffraction data of the DTU and Polymorph-3 were collected at 296 K by using Mo Kα radiation (λ = 0.71073 Å) on a Bruker Nonius SMART APEX CCD diffractometer equipped with a graphite monochromator and an Apex CCD camera. Data reductions and cell refinements were performed using SAINT and XPREP software. Structures were solved by direct methods and were refined by full-matrix least-squares on F\u003csup\u003e2\u003c/sup\u003e using SHELXL-2014 software. All non-hydrogen atoms were refined in an anisotropic approximation against F\u003csup\u003e2\u003c/sup\u003e of all reflections. Hydrogen atoms were placed at their geometric positions by riding and refined in the isotropic approximation. The crystal data and refinement parameters are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003eS.\u003c/p\u003e\n\u003ch3\u003eHirshfeld surface analysis\u003c/h3\u003e\n\u003cp\u003eHirshfeld surfaces of all the polymorphs were calculated using CrystalExplorer version 17.5. The Finger-print plots were generated by setting parameters as 𝑑\u003csub\u003enorm\u003c/sub\u003e = (𝑑\u003csub\u003ei\u003c/sub\u003e−𝑟\u003csub\u003ei\u003c/sub\u003e\u003csup\u003evdW\u003c/sup\u003e)/𝑟\u003csub\u003ei\u003c/sub\u003e\u003csup\u003evdW\u003c/sup\u003e+(𝑑\u003csub\u003ee\u003c/sub\u003e−𝑟\u003csub\u003ee\u003c/sub\u003e\u003csup\u003evdW\u003c/sup\u003e)/𝑟\u003csub\u003ee\u003c/sub\u003e\u003csup\u003evdW\u003c/sup\u003e where \u003cem\u003ed\u003c/em\u003e\u003csub\u003ee\u003c/sub\u003e and \u003cem\u003ed\u003c/em\u003e\u003csub\u003ei\u003c/sub\u003e are the distances from the Hirshfeld surface to the nearest atoms outside and inside the surface. Both \u003cem\u003ed\u003c/em\u003e\u003csub\u003ee\u003c/sub\u003e and \u003cem\u003ed\u003c/em\u003e\u003csub\u003ei\u003c/sub\u003e are normalized by the van der Waals radius of the atoms involved. \u003cem\u003er\u003c/em\u003e\u003csub\u003ei\u003c/sub\u003e\u003csup\u003evdW\u003c/sup\u003e and \u003cem\u003er\u003c/em\u003e\u003csub\u003ee\u003c/sub\u003e\u003csup\u003evdW\u003c/sup\u003e are the van der Waals radii of the atoms. When the \u003cem\u003ed\u003c/em\u003e\u003csub\u003enorm\u003c/sub\u003e value is negative (demarcated by a red spot), then the intermolecular contacts between atoms are shorter than the sum of their van der Waals radii.\u003c/p\u003e"},{"header":"Results and discussions","content":"\u003ch2\u003eStructural comparisons among the polymorphs:\u003c/h2\u003e\u003cp\u003eThe crystals of the concomitant polymorphs of N-amino-1,8-naphthalimide were obtained serendipitously from the composition of thiourea derivative 1-(2,4-dichlorophenyl)-3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)thiourea (DTU) at 80°C as illustrated in Scheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The\u003c/p\u003e\u003cp\u003epowder pattern of the bulk crystals of the has all the principal peaks matching the theoretically generated pattern from the crystallographic information files of the two polymorphs as given in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e5\u003c/span\u003eS. Our attempt to get only one form from the mixture was not successful. The crystals of the Polymorph-3 were picked up randomly and manually for structure determination, the crystals belonged to the orthorhombic Pna2\u003csub\u003e1\u003c/sub\u003e space group. The unit cell volumes of the three polymorphs of the N-amino 1,8-naphthalimide were similar. The unit cell parameters and crystal densities of are compared in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. It may be mentioned that one of the reported polymorphs of N-amino-1,8-naphthalimide, designated here as Polymorph-2, had symmetry-independent molecules within the unit cell. In contrast, the other reported one, designated as Plymorph-1, had all symmetry-related molecules in the unit cell. The third form also contains all symmetry-equivalent molecules in the unit cell. The hydrogen-bonded N-amino-1,8-naphthalimide molecules of this polymorph are arranged as linear chains involving both the NH-NC = O faces of the pairs. The chain has\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparative unit-cell data of the three polymorphs\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePolymorph\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePolymorph-1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePolymorph-2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePolymorph-3\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSpace group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOrthorhombic Pna2\u003csub\u003e1\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTriclinic P -1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOrthorhombic Pna2\u003csub\u003e1\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLength of cell axis (Å)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea = 13.296(2), b = 18.408 (4), c = 3.781 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ea = 7.307(6), b = 9.364 (7), c = 14.655 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea = 7.204(18), b = 16.373 (4), c = 7.996 (19)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAngles (°)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eα = β = γ = 90.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eα = 81.676(3), β = 80.506(3), γ = 69.460(3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eα = β = γ = 90.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVolume (Å\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e925.5 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e922.15 (12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e943.1(4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDensity (gcm\u003csup\u003e− 3\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.518\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.523\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.495\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003ehydrogen-bonded synthons with R\u003csup\u003e2\u003c/sup\u003e\u003csub\u003e2\u003c/sub\u003e(10) graph-set notation as shown in Fig.\u0026nbsp;2a. The synthons have N2-H\u003csup\u003e…\u003c/sup\u003eO1{d\u003csub\u003eD…A\u003c/sub\u003e, 3.0579(8)Å; \u0026lt;DHA, 154°) and N2-H\u003csup\u003e…\u003c/sup\u003eO2 {d\u003csub\u003eD…A\u003c/sub\u003e, 3.0671(8)Å, \u0026lt;DHA, 159°} hydrogen bonds. The Polymorph-2 and Polymorph-3 have similarity in assembling, as both have chain-like structure; the difference arises from the two alternative pairs of symmetry independent molecules in the Polymorph-2, each associated as pairs with two independent R\u003csup\u003e2\u003c/sup\u003e\u003csub\u003e2\u003c/sub\u003e(10) synthons (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb), held to one another with distinguishable hydrogen bond parameters. The naphthalimide rings of independent neighboring chains of the Polymorph-3 are in parallel stacks. Considering the amino-group as the head and the naphthalene ring part as the tail, such stacking dipoles are aligned oppositely, showing a head-to-tail arrangement with a centroid-to-centroid distance of 3.649 Å. This distance is suggestive of weak interactions among the rings [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. The Polymorph-1 had head-to-head arrangements, and Polymorph-2 had head-to-tail stackings in pairs formed among the neighboring naphthalimide rings. In the literature, there are examples of polymorphs with eclipsing 1,8-naphthalimide rings with dipoles aligned oppositely, as well as one having dipoles of rings oriented in the same direction [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. On the other hand, different positional isomeric naphthalimide-based compounds having flexible tethers generate large variations in the stacks between the naphthalimide rings [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e–\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e], and many polymorphs of naphthalimide derivatives with different orientations prepared by changing the crystallization process have wide variations in colors [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e–\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. In the present example, the conformational adjustment can occur through the rotation of the N-N bond of the N-NH\u003csub\u003e2\u003c/sub\u003e unit, changing the orientations of the hydrogen bond donor N-H bonds. In fact, this was a reason, together with the orientations of the rings in proximity, have caused the distinctions in the scheme of hydrogen bonds in packings of the three polymorphs.\u003c/p\u003e\u003ch3\u003eHirshfeld surfaces, total energies and DFT optimized energies:\u003c/h3\u003e\u003cp\u003eThe Hirshfeld surface analyses [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e] of each polymorph were performed to distinguish the type of contacts in each case. The percentage of different interactions within a distance of 3.8 Å of the surface. The atoms in the vicinity of the surface are shown in Fig.\u0026nbsp;3. Different\u003c/p\u003e\u003cp\u003epercentages of contacts are listed in the supporting table and the pie-diagrams as for comparison are shown in Fig.\u0026nbsp;4a-c. They show that major contributions in the polymorphs were from contacts of hydrogen atoms and are comparable. The All\u003csub\u003ein\u003c/sub\u003e-O in the three polymorphs was in order 2 \u0026gt; 1 \u0026gt; 3, and the All\u003csub\u003ein\u003c/sub\u003e-C was 3 \u0026gt; 1 \u0026gt; 2. The Polymorph-1 and Polymorph-3 had identical nitrogen contacts with atoms inside the surface, whereas they had 0.8% less All\u003csub\u003ein\u003c/sub\u003e-N contacts. This was due to differences in the orientation of the molecules of the symmetry-independent molecules within the lattice. Though the Polymorphs-1 and Polymorph-2 had differences in All\u003csub\u003ein\u003c/sub\u003e-O and All\u003csub\u003ein\u003c/sub\u003e-N, the total weight of these two contacts was higher in Polymorph-1 than the Polymorph-3, showing that the former had more amounts of moderate hydrogen bonds.\u003c/p\u003e\u003cp\u003eThe dispersive and repulsive as well as total energies of the polymorphs by using Crystal Explorer with the B3LYP functional at the 6-31G(d,p) level. The respective dispersive energies are Polymorphs-1 to 3 were − 66.0 kJ/mol, -11.0 kJ/mol, and − 70.3 kJ/mol, whereas the respective repulsive energies were 30.8 kJ/mol, 21.2 kJ/mol, and 38.8 kJ/mol. Whereas the respective total energies − 48.7 kJ/mol, -25.6 kJ/mol, and − 51.2 kJ/mol. This showed that the stability of the polymorphs was of the order Polymorph-3 \u0026gt; Polymorph-2 \u0026gt; Polymorph-1.\u003c/p\u003e\u003cp\u003eThe energy of each molecule in the conformation as observed in each polymorph was calculated by DFT using the B3LYP functional at the 6–31 + + G(d,p) level. It was found that each conformer has different energies, and the energies of the two symmetry-independent molecules differed by 5.2 kJ/mol from one another, as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e5\u003c/span\u003ea.. On the other hand electronic energy of the Polymorph 2 \u0026gt; 3 \u0026gt; 1. But the energy difference between the Polymorph-2 and Polymorph-3 was very small. The energy of each polymorph was also optimized in the gas phase by DFT calculation with B3LYP functional at 6–31 + + G(d,p) level. It was found that the optimized energies of Polymorph-1 and Polymorph-3 were the same; hence, the hydrogen-bonded dimers of Polymorphs-2 and Polymorph-3 were independently determined. This has revealed that polymorph-3 is 35.14 kJ/mol lower than the energy of Polymorph-1, whereas polymorph-2 is stable by 1.21 kJ/mol than Polymorph-3, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e5\u003c/span\u003e, suggesting stability 2 \u0026gt; 3 \u0026gt; 1. These provided the stability gain by the synthons. A recent theoretical study has revealed that a high value of Z׳ (number of symmetry-independent molecules in unit cell) is not reflective of the stability of polymorphs [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. Our observations suggest that the replica units of the assemblies, as well as the electronic energy of individual molecules, provide the trend of electronic stability of the discrete molecules in different conformations. The optimized energies of assembled structures within assemblies reflect to distinction of their relative gain or loss of stability by forming different synthons. But the total energy gain from dispersive and attractive forces provides insight into the overall stability of the polymorphs. In this case, Polymorph 3 has the lowest energy based on attractive and dispersive energies calculated by CrystalExplorer-17.5 version, and has the highest stability as reflected in the melting temperature. On the other hand, the density of polymorph-3 is lower but it has higher stability.\u003c/p\u003e\u003ch2\u003eDifferential scanning calorimetry and hot-stage microscopic study\u003c/h2\u003e\u003cp\u003eThe differential scanning calorimetry (DSC) of the concomitant polymorph was recorded, and it was compared with the DSC of the earlier reported ones. It showed that the Polymorph underwent melting of Polymorph-2 in the mixture at 248°C. Upon further heating, Polymorph-3 melted at 274°C. The first heating and cooling cycle of DSC is shown by the black trace in Fig.\u0026nbsp;6a. The corroboration of the results with the hot-stage microscopic study showed the melted phase, as shown in the (c) of Fig.\u0026nbsp;6. Upon cooling after heating up to 300°C, it showed that solidification of the melt at 262°C took place, which, on further cooling, reconverted to an amorphous phase at 221°C corresponding to polymorph-2. The second cycle of heating shown as the red trace of Fig.\u0026nbsp;6a showed the reversibility of the process, but the solidification at the second cycle took place at 259°C, which was 3°C lower than the first cycle. The images of the cooling samples at two temperatures are shown in Figs.\u0026nbsp;6b-e. This could be due to defects created within the structures after the first heating cycle, which had affected the colligative properties, affecting the solidification from the melt by forming another form of polymorph. The thermal properties are different from the other two polymorphs. Polymorph-1 melted at 249°C, whereas Polymorph-2 melted at 256°C. While cooling, the Polymorph-1 recrystallized at 233°C, whereas the\u003c/p\u003e\u003cp\u003ePolymorph-2 recrystallized at 253°C [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. The thermogravimetric analysis shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e7\u003c/span\u003eS has no weight loss on heating the concomitant polymorphs till 300°C (below this temperature, DSC plots were recorded), but there was a sharp loss of weight at 325°C, where the sample evaporated.\u003c/p\u003e\u003ch2\u003eStructural studies on 1-(2,4-dichlorophenyl)-3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)thiourea\u003c/h2\u003e\u003cp\u003eWe analyzed the structure of DTU from which the Polymorphs were formed, by determing the structure by X-ray single-crystal diffraction. The self-assembled structure of DTU is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e7\u003c/span\u003ea. The compound comprises a thiourea part linked to an N-amino 1,8-naphthalimide portion. The packing pattern shows that naphthalimide rings are not stacked but are in a slanted position, with a bisecting angle between the two planes containing such rings was 27.04°, as in (i) of Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e7\u003c/span\u003ea. Whereas the rings had occupied positions in an intermittent orientation, neither head to tail, nor head to head, as in (ii) of Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e7\u003c/span\u003eb. Hence, formation of the concomitant polymorph (oppositely having dipoles of the napthalimides) from this assembly will require flipping of one of the rings to reorganize to be parallel with the other and a rotation to make a head-tail orientation as suggested in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e7\u003c/span\u003eb. In fact, the same argument would also suggest providing the other\u003c/p\u003e\u003cp\u003epolymorphs from such a decomposition. But the Polymorph-2 and Polymorph-3 had the highest comparable energies. Themogravimetry in Fig.\u0026nbsp;3S has shown that the compound DTU was stable up to 205°C; hence, polymorphs were formed as a result of a chemical decomposition caused by small amounts of water in the solvent or air that led to the formation of N-amino 1,8-napthalimide from DTU at 80°C. Furthermore, there is a literature example on cyclohexyl-derived thiocarbazide undergoing hydrolytic cleavage to produce a rearranged product [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. It was also shown that thiocarbazide-based compounds result in different polymorphic solvates by changing crystallization conditions from room temperature to higher temperatures [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. These observations have suggested that the specific polymorph crystallization was an outcome of the interplay of weak supramolecular interactions during the course of decomposition.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe same synthon but with different symmetry relations provided two independent polymorphs (2 and 3) of N-amino 1,8-naphthalimide that have very close electronic energy differences. These examples have established that hydrogen-bonded chains from crystallographically symmetric molecules or from symmetry-independent molecules provide polymorphs. It is also shown that, while in situ decomposition of the DTU it chooses to crystallise the N-amino,1,8-naphthalimide to adopt a head-to-tail arrangement that is observed in stacks among the molecules of the two concomitant polymorphs. So, having an idea of existing polymorphs, searching for closely related forms is essential, and in this case, success was brought in by serendipity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval, and consent to participate:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Both authors give consent for the publication of the manuscript in the Journal of BMC Chemistry.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The crystallographic information files of the DUT and Polymorph-3 have the Cambridge Crystallographic Data deposition CCDC numbers 2423507 and 2484027. The supporting materials included with the manuscript are NMR spectra, Thermogravimetry, Crystallographic table, and percentages of contacts from Hirshfeld analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This research was not part of a sponsored project to the authors; the work was done with support of the Indian Institute of Technology, Guwahati.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026apos;s contributions:\u003c/strong\u003e JBB: Conceptualization and writing, theory, and data analysis.\u003c/p\u003e\n\u003cp\u003eSV: Experiments, Structure determination, data management, and spectral interpretation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the Ministry of Education (India) for providing financial assistance (grant no. F. No. 5-1/2014-TS.VII). The authors also acknowledge the Central Instrumentation Facilities, IIT Guwahati, for instrument facilities. Thanks are due to the Department of Science and Technology, New Delhi, for the use of the SCXRD facility (sanction no. SR/FST/CS-11/2017/23C). \u0026nbsp; Authors also thank Prof. A. Achalkumar for extending help to use the hot-stage microscope and Mr. Sarvar Parvez for recording the higher temperature images of the polymorph.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBernstein J, Polymorphism. In: Domenicano A, Hargittai I. (eds) Strength from weakness: structural consequences of weak interactions in molecules, supermolecules, and crystals. NATO Science Series, 2002; vol 68. Springer, Dordrecht. \u003c/li\u003e\n\u003cli\u003eCruz-Cabeza AJ, Reutzel-Edens SM, Bernstein, J. 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Solvatoemissive dual fluorescence of N-(pyridylmethyl)-3-nitro-1,8-naphthalimides, J. Fluoresc. 2014; 24: 649 \u0026ndash; 655. \u003c/li\u003e\n\u003cli\u003eLi N-N, Liu W, Shi N-N, Yang D, Zong Z, Zhang X, Wu R-X, Xu C-G, Bi S-Y, Fan Y-H, Multiple naphthalimide dimers polymorphs triggered solvatofluorochromism, solid-state emission and aggregation-induced emission by different interaction and its application in fluorescence ratiometric sensing of dichloromethane and 1,4-dioxane, Dyes and Pig. 2021; 188: 109172.\u003c/li\u003e\n\u003cli\u003eChen Z, Wu D, Han X, Nie Y, Yin J, Yu GA, Liu SH, 1,8-Naphthalimide-based highly blue-emissive fluorophore induced by a bromine atom: reversible thermochromism and vapochromism characteristics, RSC Adv. 2014; 4: 63985.\u003c/li\u003e\n\u003cli\u003eSpackman PR, Turner MJ, McKinnon JJ,\u003csup\u003e \u003c/sup\u003eWolff SK, Grimwood DJ.; Jayatilaka, D.; Spackman, M. A.; CrystalExplorer: a program for Hirshfeld surface analysis, visualization and quantitative analysis of molecular crystals, J. Appl. Cryst. 2021; 54: 1006 \u0026ndash; 1011.\u003c/li\u003e\n\u003cli\u003ePradhan AK, Sudheendranath A, Jitesh Arora J, Dahiya\u003cem\u003e R,\u003c/em\u003e Thomas SP. Are high-\u003cem\u003eZ\u003c/em\u003e\u0026prime; polymorphs metastable? Insight from pharmaceutical polymorphs. Phys Chem Chem Phys. 2025; 27: 17779 \u0026ndash; 17786.\u003c/li\u003e\n\u003cli\u003eJaiswal S, Gond MK, Bharty MK, Maiti B, Krishnamoorthi S, Butcher RJ. Manganese(II) catalyzed synthesis of bis (N-cyclohexylthiourea) derived from thiosemicarbazide: Structural characterization, fluorescence, cyclic voltammetry, Hirshfeld surface analysis and DFT calculation, J Mol Struct. 2021; 1246: 131060.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Scheme 1","content":"\u003cp\u003eScheme 1 is available in the Supplementary Files section.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-chemistry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ccjo","sideBox":"Learn more about [BMC Chemistry](https://bmcchem.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ccjo/default.aspx","title":"BMC Chemistry","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Naphthalimide, Synthon polymorph, Self-assembly, Energy Calculation","lastPublishedDoi":"10.21203/rs.3.rs-7535669/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7535669/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSynthon polymorphs are less encountered in the literature. It is challenging to prepare synthon polymorphs same synthon organized in different manners. We describe here the third polymorph of \u0026nbsp;N-amino 1,8-naphthalimide that has R\u003csup\u003e2\u003c/sup\u003e\u003csub\u003e2\u003c/sub\u003e(10) synthon of symmetry-related molecules assembled as a chain similar to a reported polymorph, which had symmetry-independent molecules; this made the difference in the self-assembled structure of the two polymorphs. The assemblies of three polymorphs of the compound, as well as the DFT-optimized energies of the dimeric assemblies of the two polymorphs, were also determined and compared. The new polymorph was obtained through the decomposition of 1-(2,4-dichlorophenyl)-3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)thiourea (DTU) in dimethylformamide solution that was kept at 80°C. When the solution was cooled, crystals of the concomitant polymorphs of two closely related forms were obtained, providing a new methodology for preparing the polymorph. Besides these, the structure of DTU was analysed to show the prerequisites for the alignments of the stacked naphthalimide rings in the starting compound to easily transform to the alignments of the stacking rings observed in the concomitant polymorphs.\u0026nbsp;\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Imagination Materializes with Serendipity: Third Polymorph of N-Amino 1,8-Naphthalimide","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-10 21:44:19","doi":"10.21203/rs.3.rs-7535669/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-05T11:36:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-29T07:26:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"4714260801683720913793517017221855334","date":"2025-12-20T10:27:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-06T06:34:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"141180859706168469876087395229254586155","date":"2025-10-23T10:01:03+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-18T10:41:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-08T15:04:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-08T15:04:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Chemistry","date":"2025-09-04T11:28:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-chemistry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ccjo","sideBox":"Learn more about [BMC Chemistry](https://bmcchem.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ccjo/default.aspx","title":"BMC Chemistry","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"08f1758b-55f2-4eee-af8f-463a43d54c8a","owner":[],"postedDate":"September 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-27T10:41:21+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-10 21:44:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7535669","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7535669","identity":"rs-7535669","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}