Thermal Single Crystal to Single Crystal Transformation among

Oct 2, 2013 - In addition, a reversible transformation among polymorphs by the cycle of heating (110 ... Crystal Growth & Design 2015 15 (4), 2017-202...
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Thermal Single Crystal to Single Crystal Transformation among Crystal Polymorphs in 2‑Dimethylamino-5,7-bis(trifluoromethyl)-1,8naphthyridine and in a 1‑Quinoline Analogue Naomi Harada,† Satoru Karasawa,† Taisuke Matsumoto,‡ and Noboru Koga†,* †

Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan Institute for Materials Chemistry and Engineering, Kyushu University, 6-1 Kasuga-koen, Kasuga Fukuoka, 816-8580, Japan

‡

S Supporting Information *

ABSTRACT: 2-Dimethylamino-5,7-bis(trifluoromethyl)-1,8-naphthyridine 1 was prepared as a new solid-state fluorophore. Recrystallization of 1 from CH2Cl2/n-hexane afforded three crystal polymorphs, G, BM, and BO, with the space group (crystal class) C2/c (monoclinic), P21/c (monoclinic), and Pbca (orthorhombic), respectively, at 23 °C. DSC curves for G showed one endothermic peak at 110 °C in the high temperature region and two pairs of endo- and exothermic peaks at ca. 18 and 7 °C in the low temperature region, which were assigned as crystal phase transitions. In the high temperature region, a reversible transformation from G to B (a mixture of BM and BO) by heating at 110 °C and from B to G by grinding was observed with alteration of the emitted color. In the low temperature region, X-ray crystallography suggested that G transformed to G2 (10 °C) and G4 (−50 °C) with a subtle alteration of molecular arrangements through thermal single crystal to single crystal interconversion. Eventually, 1 provided five crystal polymorphs, G, G2, G4, BM, and BO, containing eight crystallographically independent molecules. In contrast, the 1-quinoline analogue, 2, provided two crystal polymorphs, 2α (23 °C) and 2β (−123 °C).

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INTRODUCTION Crystal polymorphs, being the same molecule with different molecular arrangements in the crystalline state, often exhibit different solubilities, bioavailabilities, and stabilities. Therefore, the formation of crystal polymorphs is not desirable in the development of new medicines,1 foods,2 and cosmetics.3 In particular, for the pharmaceutical field, the polymorphs of medicines present an important problem to be solved. Crystal polymorphs have been intensively studied4 using improved Xray crystallography techniques, and organic molecules having many crystal polymorphs have recently been reported.5 In contrast, crystal polymorphs have been employed as useful materials in the field of solid-state emission. Those molecules often demonstrate interconversion between crystal polymorphs due to external stimuli such as heat and pressure. Since the color and intensity of solid-state emissions are generally sensitive to the molecular structure and arrangements in the crystalline state, the use of polymorphs showing solid-state emissions leads to emitting materials that are responsive to external stimuli. Based on this strategy, many molecules and metal complexes6 showing polymorph-dependent emission have been prepared and reported as switchable materials.7 We recently reported the donor−acceptor type of 1-quinoline8a and 1,8-naphthyridine8b derivatives showing reversible emission color and intensity changes by a heating−melting or −grinding cycle. In both compounds, notably, the thermal transformation between the polymorphs took place in single crystal to single crystal (SC-to-SC) form, which was confirmed by X-ray crystallography. This time, the analogous 1-quinoline and 1,8© 2013 American Chemical Society

naphthyridine derivatives were used and the relationship between the chemical structure and the crystal polymorph including a phase transition were investigated. For this purpose, a simple 2-dimethylamino-5,7-bis(trifluoromethyl)-1,8-naphthyridine (1) was selected as the solid-state fluorophore. The corresponding quinoline compound (2) has already been prepared and reported.8a The difference in chemical structure between 1 and 2 was the presence or absence of the nitrogen atom at the 8-position of the ring. We report herein the preparation of a fluorophore 1, the molecular arrangements of crystal polymorphs, and the alteration of molecular arrangements with the change of emittance color through the thermal SC-to-SC transformation. In addition, the molecular arrangements for 1 were compared with those for the corresponding quinoline derivative 2.

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EXPERIMENTAL SECTION

General Methods. Infrared spectra were recorded on a JASCO 420 FT-IR spectrometer. 1H NMR spectra were measured on a JEOL Received: May 16, 2013 Published: October 2, 2013 4705

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270 Fourier transform spectrometer using CDCl3 as the solvent and referenced to TMS. Powder X-ray diffraction crystallographies (PXRD) were performed with a Bruker D2PHASER. PXRD measurements for the crystal and powder samples were carried out at a 2θ angle of 5−50° at 25 °C. Differential scanning calorimetry (DSC) curves were recorded by a SII EXSTAR 7000. DSC was conducted in the temperature range −100 to 150 °C (rate, 10 and 2 °C min−1 for heating and cooling, respectively). DSC measurements with temperature modulation (MDSC) were performed with NETZSCH DSC200 F3 in the temperature range −170 to 150 °C (10 °C min−1) and temperature amplitude selected by the instrument according to the “heating only” mode (no cooling of the sample during temperature modulation). ESI mass spectra (ESI MS) were recorded on a Bruker Daltonics microTOF spectrometer. Melting points were obtained with a MEL-TEMP heating block and are uncorrected. Elemental analyses were performed at the Analytical Center of the Faculty of Science at Kyushu University. Absorption and Emission Spectra and Fluorescence Quantum Yield Measurements. In the measurement of solution samples, the compounds were dissolved in the solvents and nitrogen gas was bubbled through the needle. Roughly crushed crystals were used as crystal samples. UV−vis spectra were recorded on a JASCO V570 spectrometer. The absorption spectra of the powder samples diluted with KBr were obtained by measurements of the diffractive reflection spectra followed by Kubelka−Munk conversion using a JASCO ISN-470 integrating sphere assembly. The fluorescence spectra were recorded on a PerkinElmer LS 50B spectrometer. The fluorescence quantum yields were determined with Hamamatsu C9920-01 instruments equipped with a CCD by using a calibrated integrating sphere system. X-ray Molecular and Crystal Structure Analyses. Recrystallization of 1 from CH2Cl2/n-hexane gave pale blue (B) and green (G) color emitting crystals under UV light. The former crystals (B) were found to be a mixture of crystal BM and BO by single-crystal X-ray diffraction crystallography (SXRD). Suitable single crystals were glued onto a glass fiber using epoxy resin. All X-ray data were collected on Bruker APEX-II and Rigaku FR-E diffractometers with graphite monochromated Mo Kα radiation (λ = 0.71069 Å). Reflections were collected at various temperatures. In the G series, data were collected at 296 K for G, 283 K for G2, and 223 K for G4. In the B series, data for BM and BO were collected at 296 K. Reflections for 2α and 2β were collected at 296 and 150 K, respectively. Crystallographic data and experimental details for crystals G, G2, G4, BM, BO, 2α, and 2β are summarized in Tables 1 and 2. The molecular structures were solved by direct methods (SIR2004, 92, and SHELX97).9 The refinements were carried out using the full-matrix least-squares method from the Crystal Structure software package.10 All non-hydrogen atoms were refined anisotropically, and hydrogen atoms were refined isotropically. Crystallographic data for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Center as supplementary publications CCDC 931156, 931160− 931163, and 957303 for crystals, BM, BO, G, G2, G4, and 2α, respectively. The software programs for R/E (distance−energy) plots11 and Hirshfeld fingerprint (di−de) plots12 were Mercury CSD 3.113 and CrystalExplorer 3.0,14 respectively. Materials. A starting compound, 2-chloro-5,7-bis(trifluoromethyl)1,8-naphthyridine, 1,8-naph-Cl,8b and 28a were prepared by the procedure reported previously. 2-Dimethylamino-5,7-bis(trifluoromethyl)-1,8-naphthyridine, 1. 1,8-Naph-Cl (1.0 g, 3.3 mmol), 50% dimethylamine aqueous solution (1.7 mL, 16.6 mmol), copper powder (0.01 g, 0.17 mmol), and water (4 mL) were placed in a sealed tube and heated at 70 °C for 5 h. The reaction mixture was cooled to rt and was extracted with ethyl acetate three times. The ethyl acetate layer was washed with water and dried on sodium sulfate. After filtration, the filtrate was evaporated. The obtained crude mixture was chromatographed on silica gel using n-hexane/ethyl acetate = 5:1−1:1 as eluents to afford 1 as yellowish solids up to 95% yield. The recrystallization from CH2Cl2/n-hexane gave yellow single crystals. Mp 130−133 °C. 1H NMR (270 MHz,

Table 1. Crystallographic Data Collection and Structural Refinement Information for G, G2, and G4 empirical formula formula weight crystal class space group a, Å b, Å c, Å α, deg β, deg γ, deg V, Å3 μ, cm−1 Z (Z′) crystal size, mm3 Dcalcd, g cm−3 F(000) radiation T, K no. reflns measured no. reflns obsd no. params R1a wR2b GOF a

G

G2

G4

C12H9N3F6 309.21 monoclinic C2/c (no. 15) 15.455(3) 15.377(3) 10.876(2) 90 102.385(2) 90 2524.5(9) 1.62 8 (1) 0.5 × 0.5 × 0.4 1.627 1248.00 Mo−Kα 296 6462 2596 217 0.0499 0.1468 1.056

C12H9N3F6 309.21 triclinic P1̅ (no. 2) 10.775(2) 10.872(2) 11.032(2) 81.525(3) 89.898(3) 81.386(3) 1263.4(5) 1.62 4 (2) 0.5 × 0.5 × 0.4 1.625 624.00 Mo−Kα 283 6934 5262 506 0.0636 0.1771 1.035

C12H9N3F6 309.21 triclinic P1̅ (no. 2) 10.8134(15) 15.288(2) 15.328(2) 86.723(2) 89.963(2) 78.969(2) 2483.0(6) 1.65 8 (4) 0.5 × 0.5 × 0.4 1.654 1248.00 Mo−Kα 223 13 094 9924 1027 0.0483 0.1447 1.065

R1 = ∑||Fo| − |Fc||/∑|Fo|. bwR2 = {∑w(Fo2 − Fc2)2/∑w(Fo2)2}1/2.

CDCl3) δ 8.19 (d, J = 8.1 Hz, 1H), 7.68 (s, 1H), 7.17 (d, J = 9.4 Hz, 1H), 3.36 (s, 6H). ESI-MS (MeOH), calcd for [C12H9N3F6Na]+ 332.0598; found 332.0528. Anal. Calcd for C12H9N3F6: C 46.61, H 2.93, N 13.59%. Found: C 46.87, H 2.91, N 13.55%.

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RESULTS AND DISCUSSION Preparation. A donor−acceptor type simple fluorophore, 2dimethylamino-5,7-bis(trifluoromethyl)-1,8-naphthyridine, 1, was prepared in a manner similar to the procedure for 2methylamino-5,7-bis(trifluoromethyl)-1,8-naphthyridine 8b using dimethylamine aqueous solution in place of methylamine aqueous solution. Recrystallization for 1 from a mixture of nhexane and CH2Cl2 afforded single crystals as yellowish blocks and plates, which were denoted as crystals G and B, respectively. Crystals G and B under light at 365 nm emitted greenish blue and pale blue, respectively, and could be visually distinguished by the subtle difference of their emittance colors. Furthermore, crystal B was found to be a mixture of crystals BM and BO by subsequent SXRD. Careful optical examination of B revealed no noticeable differences in the morphologies of crystals BM and BO. To investigate the relationship between the chemical structure and the molecular arrangements, an analogous molecule, 2, which had a quinoline ring in place with a naphthyridine ring, was also prepared by the procedure reported previously.8a Recrystallization for 2 from a mixture of n-hexane and CH2Cl2 afforded only one single crystal as yellowish blocks. Molecular and Crystal Structures. The crystal structures of G, BM, and BO were investigated by single-crystal X-ray diffraction crystallography (SXRD) at 23 °C. SXRD for 2α at 23 °C was also measured, while the data at −123 °C were already reported in the previous study.8a The molecules 4706

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Table 2. Crystallographic Data Collection and Structural Refinement Information for BM, BO, 2α, and 2β empirical formula formula weight crystal class space group a, Å b, Å c, Å α, deg β, deg γ, deg V, Å3 μ, cm−1 Z (Z′) crystal size, mm3 Dcalcd, g cm−3 F(000) radiation T, K no. reflns measured no. reflns obsd no. params R1a wR2b GOF a

BM

BO

2α

2βc

C12H9N3F6 309.21 monoclinic P21/c (no. 14) 15.39(2) 9.709(14) 8.871(13) 90 92.27(2) 90 1325(3) 1.54 4 (1) 0.4 × 0.3 × 0.2 1.550 624.00 Mo Kα 296 5939 2469 253 0.0604 0.1846 1.027

C12H9N3F6 309.21 orthorhombic Pbca (no. 61) 8.2744(8) 10.0481(9) 31.309(3) 90 90 90 2603.1(5) 1.57 8 (1) 0.5 × 0.3 × 0.1 1.578 1248.00 Mo Kα 296 12 696 2711 253 0.0486 0.1550 1.055

C13H10N2F6 308.23 orthorhombic Pnma (no. 62) 11.560(3) 7.4129(17) 15.161(4) 90 90 90 1299.2(5) 1.55 4 (0.5) 0.4 × 0.2 × 0.1 1.576 624.00 Mo Kα 296 6442 1449 151 0.0558 0.1730 1.112

C13H10N2F6 308.23 monoclinic P21/c (no. 14) 7.2714(12) 14.910(3) 11.537(2) 90 95.439(5) 90 1245.2(4) 1.62 4 (1) 0.4 × 0.2 × 0.1 1.644 624.00 Mo Kα 150 11 995 2843 231 0.0692 0.2396 1.142

R1 = ∑||Fo| − |Fc||/∑|Fo|. bwR2 = {∑w(Fo2 − Fc2)2/∑w(Fo2)2}1/2. cReference 8a.

crystallized in the space group (crystal class), C2/c (monoclinic), P21/c (monoclinic), and Pbca (orthorhombic), for G, BM, and BO of 1, respectively. In contrast, 2α was crystallized in the space group (crystal class) of Pnma (orthorhombic) and showed a higher molecular symmetry compared with 1. In G, BM, and BO, the CF3 group at the only 7-position of 1,8naphthyridne ring in two CF3 groups showed disorder. In contrast, the molecule of 2α had no disorder of the CF3 groups. The ORTEP drawings of the molecular structures are shown in Figure 1 for G and 2α and Figure S1, Supporting Information, for BM and BO.

The molecular arrangements for the crystals of 1 were classified into two groups, head-to-tail columnar (HTC) and herringbone (HB) structures. G had a head-to-tail pseudocolumnar (HT-p-C) structure in which face-to-face dimers formed an alternately and partially layered structure with rotation by ca. 40−50° (Figure S2, Supporting Information). BM had herringbone (t-HB) structures with a translation symmetry between the chains, while BO had a herringbone (gHB) structure15 with a glide symmetry between the chains (see Figure S3, Supporting Information). The molecular arrangement of 2α was a head-to-tail columnar (HTC) structure. The molecular arrangements for G, BM, and BO are shown in Figure 2 together with that for 2α. The differences of columnar structure between G and 2α are shown in Figure S2, Supporting Information. In the HT-p-C columns for G, the intra- (rC2−C7; distances a−d in Figure 2a) and interdimer distances (rC7−C7) were 3.71 and 3.48−3.51 Å, respectively, indicating a weak π−π interaction. The distances (rN1,8−H(Me1Me2), A−H in Figure 2a and Table S2, Supporting Information) between the nitrogen atoms (N1 and N8) of naphthyridine and the methyl hydrogens of Me(1) and Me(2) of the neighboring molecule were 2.83 and 3.10 Å, respectively, indicating typical CH−N hydrogen bonds.16 In HB structures for BM and BO, the intermolecular short distance (rN1−H(nap); A in Figure 2b,c) between the hydrogen (H(naph)) at the 5- and 6-position of naphthyridine and the nitrogen atom (N1 and N8) of the neighboring one and that (rN1orN8−H(Me); B in Figure 2b,c) between the methyl hydrogen (H(Me)) and the nitrogen atoms (N1 and N8) of naphthyridine were observed. The former and the latter short distances might cause CH−π interactions17 and the CH−N hydrogen bond, respectively (see Figure S4, Supporting Information), which stabilized the HB structures.15 In BM, the values of rN1−H(naph) and rN1,N8−H(Me)

Figure 1. ORTEP drawings of the molecular structure of crystal G (a) and 2α (b) at 50% probability level.

The molecular structures of the three crystals G, BM, and BO were similar to each other. The bond lengths, rC7−Na, of C7 and Na of amine were 1.33−1.36 Å and were somewhat short, suggesting double bond character. The naphthyridine rings and the planes defined as CMe−Na−CMe were nearly coplanar, and the dihedral angles, ∠Naph−CMe−Na−CMe, were 3.0−7.7°. In 2α, the molecular structure with rC7−Na = 1.37 Å and ∠Qui− CMe−Na−CMe = 0.0° was observed. The small dihedral angles for both molecules were expected to cause strong donor− acceptor interaction. 4707

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Figure 2. Molecular arrangements for G (a), BM (b), BO (c), and 2α (d). Right sides show figures rotated by 27°, 90°, 90°, and 27°, respectively, around the b axis for parts a−c and the a axis for part d. The colored lines indicate the a (red), b (green), and c (blue) axes.

were 2.84 and 3.13 Å and 2.68 and 3.19 Å, respectively, and the HB angles (θ) shown in Figure S4′, Supporting Information, were 78.6°. In BO, those values were rN1−H(nap) = 2.96 and 3.18 Å, rN1,N8−H(Me) = 2.83 and 2.83 Å, and θ = 84.5°. Although those values for BO were close to the corresponding ones for BM, the mode of hydrogen bonds differed from BM. In the hydrogen bond, the two nitrogen atoms (N1 and N8) of 1,8naphthyridine for BM had short contacts, rN1orN8−H(Me), with two hydrogen atoms of three methyl hydrogens, while those for BO had ones with one hydrogen atom of three methyl hydrogens. In the HTC structure for 2α, the interplane distances (rC2−C7; a in Figure 2d) for the π−π interaction were 3.76 Å and the short contacts between the HTC columns for the CH− N hydrogen bonds were 2.96 Å in the distances, rN1−H(Me) (A in Figure 2d), between the nitrogen atoms (N1) of quinoline and the methyl hydrogen of the neighboring molecule (Figure S5, Supporting Information). The difference in the modes of CH− N hydrogen bonds for G, BM, BO, and 2α is drawn in Figure S6, Supporting Information. The selected bond lengths, dihedral angles, and intermolecular distances and angles for G, BM, and BO are listed in Table 3 together with those for 2α. Absorption and Emission Spectra. The absorption and emission properties of 1 were investigated in various solvents and in the solid state. In solution, the steady−state absorption and emission spectra in n-hexane, CHCl3, AcOEt, and MeOH,

Table 3. Selected Bond Lengths, Dihedral Angles, and Intermolecular Distances and Angles for G, BM, BO, and 2α G

BM

BO

Bond Lengths and Dihedral Angles 1.343 1.345 1.349 rC7−Na, Å ∠Naph−CMe−Na−CMe, 5.47 3.03 7.70 deg Intermolecular Distances and Angles rC2−C7, Å 3.71 rN1,8−H(nap), Å 2.88, 3.20 2.96, 3.18 rN1orN8−H(Me), Å 2.83, 3.10 2.90, 3.08 2.83, 2.83 θ, deg 79.4 84.5 a

2α 1.373 0a

3.76 2.96

∠Quinoline−CMe−Na−CMe.

which were selected as nonpolar, medium, medium, and polar solvents, respectively, are shown in Figure S7, Supporting Information. In n-hexane, 1 showed fluorescence emission centered at 418 nm with a fluorescence quantum yield, Φf, of 0.30. The fluorescent emitting maximum, λfmax, shifted to a longer wavelength and the value of Φf decreased with increasing solvent polarity. The values of λfmax and Φf for the four solvents are listed in Table 4, together with the absorption f ab maximum, λab max, Stokes shift, λmax − λmax, and solvent polarity 18 function, Δf. The observed large Stokes shift and fluorescence emission dependent on the solvent polarity19 were characteristic of the charge transfer type fluorophore20 and were similar 4708

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Table 4. Photophysical Values for 1 in Various Solvents and in Solid State at rt, Together with Those for 2 G solvents (Δf) λab max, nm λfmax, nm Δf‑ab,e nm Φf

c

n-hexane (0.001) 367(sh), 387, 408(sh) 418, 442(sh) 10−75 0.30

CHCl3 (0.150) 394 444, 465(sh) 50, 76 0.60

AcOEt (0.200) 394 478 84 0.09

MeOH (0.309) 393 479 86 0.02

396d 484 88 0.13

Ba

473 0.15

2b 434d 507 73 0.21

a

A mixture of BM and BO. bReference 8a. cSolvent polarity function. dThe value obtained by measurements of the diffractive reflection spectra followed by Kubelka−Munk conversion. eλfmax − λab max.

heating and cooling rate) for 1 and in the range of −40 to 150 °C for two cycles (10 °C/min for heating and cooling rate) for 2. DSC curves for G and 2α are shown in Figure 4, and those

to the corresponding quinoline derivative 2. For the solid-state emission spectra measurements, crushed crystals were used as crystal samples. The emission spectra for the crystal samples of G and B are shown in Figure S8, Supporting Information. The emission maxima and fluorescence quantum yield, λfmax and Φf, were 484 and 0.13 and 473 and 0.15 nm for G and B, respectively. These λfmax values were very different from those in n-hexane and were red-shifted by 66 and 55 nm for G and B, respectively. The Φf values were substantially reduced compared with those in n-hexane. The large red shifts of λfmax and reduction of Φf observed in the solid-state emission might be due to the intermolecular π−π interaction, the CH−π interactions, and CH−N hydrogen bonding.21 The difference in the degree of red shift between G and B might also suggest that their interactions caused by molecular arrangements in the crystalline state were different, HT-p-C for G and HB for B. A similar alteration of emission in the solid state was observed in 2. No noticeable difference in the emissions for BM and BO was observed, suggesting that the difference in the molecular arrangement was also small. The obtained λfmax and Φf values for G and B together with 2 are included in Table 4. Interestingly, by heating G at a temperature over 100 °C below the melting point, a change of the emitting color was observed. The emission color (pale green) for G slightly changed to pale blue upon heating at 110 °C, while no change was observed for B under similar conditions. Photographs of single crystals of G before and after heating, taken under a microscope are shown in Figure 3. Subsequently, when the

Figure 4. DSC curves for (a) G in the range of 25−150 °C, the first (red) and the second (blue) cycle, and −40 to 30 °C, the first (black) and the second (green) cycle, and (b) 2α in the range of −40 to 150 °C, the first (red) and the second (blue) cycle. Insets for panels a and b indicate the expansion ranges of −5 to 25 and 90−130 °C for G and −4 to 4 °C for 2α. The arrows indicate cooling and heating process.

for B (a mixture of crystals BM and BO) are shown in Figure S9, Supporting Information. To confirm the crystal phase transition in detail, a modulated differential scanning calorimetry (MDSC),22 which provides information about reversing and nonreversing characteristics of thermal events, was also conducted in the range of −170 to 150 °C. MDSC curves for G in the warming process are shown in Figure S9′, Supporting Information. In the high temperature region, the first cycle for G showed weak and intense endothermic peaks at 110 and 132 °C, respectively, in the heating process and an intense exothermic peak at 108 °C in the cooling process. The intense endothermic and exothermic peaks were assigned as the melting and solidification points, Tm and Ts, respectively. The weak endothermic peak, Tp, at 110 °C might be due to the thermal phase transition, suggesting enantiotropic transformation23 to a polymorph from G. The second cycle showed a DSC curve similar to that for the first cycle. In the low temperature region of 30 to −40 °C, two pairs (I and II) of weak and broad peaks

Figure 3. Photographs of a single crystal of G before (left) and after (right) heating. Upper and lower show under light at 365 nm and room light, respectively.

obtained crystal after heating was ground with an agate mortar and pestle, the pale blue emission returned to pale green, suggesting that G was recovered by grinding. Thermal Properties. To investigate the thermal properties for 1 and 2, differential scanning calorimetry (DSC) was conducted in two temperature ranges, 25−150 and −40 to 30 °C, for two cycles of heating and cooling (10 and 2 °C/min for 4709

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were observed; the maximum and minimum of the exo- and endothermic peaks were at 15 and 18 °C for I and at 5 and 7 °C for II on cooling and heating, respectively. The two pairs of exo- and endothermic peaks in cooling and heating might be due to the crystal phase transition at ca. 18 and 7 °C, suggesting that a thermal enantiotropic transition took place.23 In MDSC measurement for G, although the peak corresponding to pair I could not be observed, the reversing components in the peaks at 110 and 5 °C were observed, supporting the crystal phase transition (Figure S9′, Supporting Information). The DSC curve for 2α having a molecular arrangement similar to G of 1 showed endothermic and exothermic peaks at 111−112 and 94−96 °C, assigned as the melting and solidifying points, respectively, in the high temperature region and a weak exothermic peak at 0 °C in the low temperature region. The peak at 0 °C was observed only in the warming process, which was opposite to that for G, while the corresponding endothermic peak was not observed in the cooling process. A weak exothermic peak might be due to a phase transition of the crystal 2α. The DSC curve for B in the first cycle showed endothermic and exothermic peaks at 132 and 110−111 °C, assigned as the melting and solidifying points, respectively, in the high temperature region (Figure S9, Supporting Information). The Tm value of 132 °C for B was consistent with that observed in G, suggesting that the thermal transformation from G to B took place before melting. In the second cycle, a weak endothermic peak at 122 °C in addition to the peaks due to the melting and solidifying points was observed, suggesting that crystal G or crystals containing G formed at Ts after melting. In the low temperature region of −100 to 50 °C, no significant peaks were observed. The results of DSC measurements in the range of −100 to 150 °C suggested that G had three phase transitions, at 110 °C in high temperature and at ca. 18 and 7 °C in low temperature, while 2α had one at 0 °C. Determination of SC-to-SC Transformation. To confirm the thermal SC-to-SC transformation in high and low temperature regions suggested by DSC experiments of G, the molecular arrangements of G were investigated by X-ray diffraction crystallography. A. High Temperature Region. A.1. SXRD Measurements. Single crystal samples for SXRD were prepared as follows. A large sized single crystal (5 × 3 × 3 mm3) of crystal G was heated at 110 °C and then lightly crushed at room temperature. The obtained small sized crystals were randomly selected and then measured by SXRD crystallography. Two kinds of crystallographic data (BM′ and BO′) were obtained, which were consistent with those for BM and BO, respectively. This result obviously indicated that G gave crystal polymorphs, BM and BO, through thermal SC-to-SC transformation at 110 °C. Crystallographic data and experimental details for BM′ and BO′ are listed in Table S1, Supporting Information. A.2. PXRD Measurements. In order to confirm the reversible transformation between G and B, the PXRD patterns after heating G and then after grinding were investigated. The samples for PXRD measurements after heating were prepared as follows: the powder samples were placed on cover glasses and heated on a heating block for melting point measurement. The PXRD measurements were carried out in the order of (1) before heating, (2) after heating at 110 °C, and (3) after grinding. The alterations of PXRD patterns by heating and grinding are shown in Figure 5, together with the simulation for G and the summation of BM and BO.

Figure 5. PXRD patterns of G before (ii) and after heating at 110 °C (iii), and then after grinding for 30 min (iv). The simulation patterns of G and the summation of simulation of BM and BO are shown at as pattern i and v, respectively.

Before heating, all diffraction peaks for crystal G were consistent with those simulated from the results of SXRD (Figure 5, i and ii). After heating the powder samples of G, the PXRD patterns drastically changed (Figure 5, iii) and were consistent with those (Figure 5v) for the summation of simulation of BM and BO. Subsequently, grinding gave the patterns (Figure 5, iv) for the starting crystal G. These PXRD patterns clearly indicated that crystal G was converted to crystal BM and BO by heating at 110 °C and then returned to the initial molecular arrangement for crystal G after grinding. B. Low Temperature Region. To investigate SC-to-SC interconversion in the low temperature region, SXRD was carried out at the various low temperatures. Taking the DSC results into account, Tt = 18 and 7 °C for G and Tt = 0 °C for 2α, SXRD for G were measured at 10 and −50 °C for G2 and G4, respectively, and that for 2α was also measured at −123 °C for 2β. The obtained crystallographic data for G2 and G4 and for 2β are summarized in Tables 1 and 2, respectively. On cooling, the space group (crystal class) changed from C2/c (monoclinic) for G to P1̅ (triclinic) for G2 and G4. In addition, the number of molecules in the asymmetry unit (Z′) increased; Z′ = 1, 2, and 4 for G, G2, and G4, respectively, indicating that the symmetry of the molecules in the crystals decreased as the temperature decreased. The values of thermal displacement parameter (Ueq) of F atoms at the 7-position were 0.139, 0.131, and 0.095 Å for G, G2, and G4, respectively, indicating that the disorder of CF3 groups decreased with decreasing temperature. A similar alteration of crystal structure was observed in 2α. On cooling, the space group (crystal class) of Pnma (orthorhombic) with the Z′ value of 0.5 for 2α changed to P21/c (triclinic) with Z′ value of 1.0 for 2β. The symmetry of the molecules in the crystal also decreased with decreasing temperature. The molecular and crystal structures of G2 and G4 and 2β were similar to those for the starting crystals G and 2α, respectively. The intradimer distance, rC2−C7, for the π−π interaction and the distances, rN1or8−H(Me), between the HT-p-C columns for the CH−N hydrogen bond slightly decreased in order of G, G2, and G4 (Table S2, Supporting Information). Similarly, in 2β, the distance, rN1−H(Me), of 2.96 Å for the hydrogen bond in 2α decreased to 2.85 Å with increasing dihedral angle ∠Q−CMe−Na−CMe = 3.54°. The ORTEP drawings for G2, G4, and 2β are shown in Figure S10, Supporting Information, and the molecular arrangements for G, G2, and G4 and for 2α and 2β are shown in Figures S11 and S11′, respectively, Supporting Information. The intermolecular 4710

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Table 5. Selected Bond Lengths, Dihedral Angles, and Intermolecular Distances for G2, G4, and 2β, together with G and 2α G rC7−Na, Å ∠Naph−CMe−Na−CMe, deg rC2−C7, Å rN1orN8−H(Me), Å a

G2

G4

Bond Lengths and Dihedral Angles 1.343 1.347, 1.347 1.343, 1.344, 1.345, 1.350 5.47 5.60, 5.28 3.51, 4.10, 5.59, 7.06 Intermolecular Distances for π−π Interactions and CH−N Hydrogen Bonds 3.71 3.70, 3.73 3.64, 3.65, 3.67, 3.83 2.83, 3.10 2.76, 2.88, 3.06, 3.08 2.74, 2.77, 2.79, 2.97, 2.99

2α

2β

1.373 0a

1.372 3.54a

3.76 2.96

3.68 2.85

∠Quinoline−CMe−Na−CMe.

distances for G2, G4, and 2β together with G and 2α are summarized in Table 5 in addition to the selected bond lengths and dihedral angles. Compared with the difference of molecular arrangements between G, BM, and BO, the alterations of molecular arrangements for G at the low temperatures were significantly smaller. Similarly, 2α having no disorder at the CF3 group became 2β with a different space group and cell parameters below 0 °C, and the alteration of molecular arrangement was also subtle. Discrimination of Polymorphs. To evaluate the intermolecular interaction caused by the structure alteration observed in high and low temperature regions, the two analyses, distance−energy (R/E) plots11,13 and the examination of the Hirshfeld surfaces for the structures,12,14 which were used for the determination of the existence of polymorphism, were performed. A. R/E (Distance−Energy) Plots. The UNI force field calculation implemented in the software program Mercury CSD 3.1 was used, and the intermolecular energy obtained by summing over the atom−atom energy contribution between the two molecules was plotted as a function of the distances between the centers of mass of molecules. The obtained distance−energy (R−E) plots for G, G2, and G4 are shown in Figure 6, together with G, BM, and BO.

As shown in Figure 6, the plots for G, G2, and G4 and for G, BM, and BO were clearly different from the other two, indicating that they were polymorphous. B. Hirshfeld Fingerprint Plots. The program CrystalExplorer 3.014 was used for calculation of Hirshfeld fingerprint (di−de) plots12 of nine molecules given from cif files of G, G2, G4, BM, and BO, are shown in Figure 7. Those for 2α and 2β are also

Figure 7. Hirshfeld fingerprint (di−de) plots for G, G2, G4, BM, and BO. G2-1 and G2-2, and G4-1, G4-2, G4-3, and G4-4 indicate the individual crystallographic independent molecules in G2 and G4, respectively.

shown in Figure S12, Supporting Information. The symbols de and di indicate distance from a point on the surface to the nearest nucleus outside the surface and to the nearest inside the surface, respectively. In visual comparisons of the Hirshfeld fingerprint plots, the molecule G2-1 of G2 with Z′ = 2 was similar to that of G, which might be identical, while the remaining seven molecules including G, BM, and BO might look different from each other. Therefore, it was judged that 1,8-naphthyridine 1 had five crystal polymorphs containing eight crystallographic independent molecules, G (or G2-1), G2-2, G4-1, G4-2, G4-3, G4-4, BM, and BO. The Hirshfeld fingerprint plots for 2α and 2β were also different, suggesting that the 1-quinoline derivative, 2, had two crystal polymorphs (Figure S12, Supporting Information).

Figure 6. R/E (distance−energy) plots for (a) G (red circle), G2 (blue square), and G4 (black triangle) and (b) G (red circle), BM (blue square), and BO (black triangle). 4711

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Although the alterations of molecular arrangements for G, G2, and G4 were subtle, both the distance−energy (R/E) and the Hirshfeld fingerprint plots suggested the existence of polymorphism. In this study, G2 and G4, having peaks due to the phase transition in DSC, were regarded as polymorphs in addition to G, BM, and BO. Similarly, 2α and 2β were also regarded to be polymorphous.

Article

ASSOCIATED CONTENT

S Supporting Information *

CIF files, absorption and emission spectra in various solvents, molecular and crystal structures, and XRD results for 1. This material is available free of charge via the Internet at http:// pubs.acs.org.

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CONCLUSIONS 1,8-Naphthyridine derivative 1 was prepared as a new fluorophore, and its crystallization afforded three crystal polymorphs, G, BM, and BO. In the high temperature region, the crystal of G showed reversible emittance changes through C-to-C transformations from G to BM and BO by heating at 110 °C and from BM and BO to G by grinding. In the low temperature region, G converted to G2 (10 °C) and G4 (−50 °C) through thermal SC-to-SC interconversions. The observed thermal and mechanical phase transitions among polymorphs of 1 are summarized in Scheme 1.

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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Scheme 1. Thermal and Mechanical Phase Transition of 1

ACKNOWLEDGMENTS This work was partially supported by Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology, Japan. The crystal structure analysis was partially supported by the “Network Joint Research Center for Materials and Devices” Research Program.

The 1,8-naphthyridine derivative 1 provided five crystal polymorphs, G, G2, G4, BM, and BO, containing eight crystallographically independent molecules. In contrast, the analogous 1-quinoline derivative, 2, provided two polymorphs, 2α and 2β, in which 2α converted to 2β below 0 °C through SC-to-SC interconversion. In 2, the molecular arrangements for 2α and 2β were HTC structures similar to G, G2, and G4, and were not HB structures such as BM and BO. The lack of a polymorph with HB structure might be due to the difference in the chemical structure between 1,8-naphthyridine and 1quinoline. In the 1,8-naphthyridine molecule, the nitrogen atoms at 1- and 8-positions formed intermolecular short contacts for the CH−π interaction and the CH−N hydrogen bond to stabilize the HB structure. In contrast, 1-quinoline having no nitrogen atom at the 8-position could not stabilize the HB structure and provided no polymorph having an HB structure. It is worth noting that naphthyridine derivative 1, having two nitrogen atoms, was favorable to provide crystal polymorphs, compared with quinoline derivative, 2, having one nitrogen atom in a ring. In the crystalline state, the crystal structures are controlled by the formation of hydrogen bonds and intermolecular interactions such as the π−π and CH−π interactions, the dipole−dipole interaction, and van der Waals interaction. Fluorophores 1 and 2 have no substituents effective for strong hydrogen bonds and intermolecular interaction. Actually, the hydrogen bonding and intermolecular interactions observed in the polymorphs were relatively weak. The results obtained in this study might suggest that the formation of crystal polymorphs rests on a subtle balance of the weak intermolecular interactions including hydrogen bonds in the crystalline state.

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