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Syntheses and characterizations of two curcumin-based cocrystals
Inorganic Chemistry Communications 55 (2015) 92–95
Contents lists available at ScienceDirect
Inorganic Chemistry Communications journal homepage: www.elsevier.com/locate/inoche
Feature article
Syntheses and characterizations of two curcumin-based cocrystals Hongmin Su a, Hongming He b, Yuyang Tian b, Nian Zhao b, Fuxing Sun b, Xiaoming Zhang b, Qing Jiang a,⁎, Guangshan Zhu b,⁎ a b
Key Laboratory of Automobile Materials, Ministry of Education and School of Materials Science and Engineering, Jilin University, Changchun 130022, China State Key Laboratory of Inorganic Synthesis & Preparative Chemistry, Jilin University, Changchun 130012, China
a r t i c l e
i n f o
Article history: Received 15 January 2015 Received in revised form 11 March 2015 Accepted 14 March 2015 Available online 16 March 2015 Keywords: Curcumin Pharmaceutical cocrystal Single crystal X-ray diffraction Powder X-ray diffraction Differential scanning calorimetry
a b s t r a c t Two pharmaceutical cocrystals, named Jilin University China–Cocrystal-14 (JUC-C14) and Jilin University China– Cocrystal-15 (JUC-C15), which were composed of curcumin and 4, 4′-bipyridine-N, N′-dioxide, were successfully prepared by crystal engineering strategy. The crystal structures of the two cocrystals were solved and refined by single crystal X-ray diffraction. It is indicated that the crystal structures are assembled via intermolecular interactions including hydrogen bonds and π⋯π stacking. Additionally, in the structure of JUC-C15 curcumin existed in a di-keto form which is rare in other reported curcumin polymorphs. Power X-ray diffraction, Fouriertransform infrared spectra, thermogravimetric analyses and differential scanning calorimetry were executed as well to confirm the formation of the cocrystals. © 2015 Published by Elsevier B.V.
Contents Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 Appendix A. Supplementary material . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
During the past decade, cocrystallization has rapidly developed as an emerging approach to design and prepare pharmaceutical materials owing to the development of crystal engineering and supramolecular chemistry [1–4]. Most pharmaceutical cocrystals were constructed by active pharmaceutical ingredient (API) and cocrystal former (CCF) via intermolecular interactions such as hydrogen bonds, π⋯π stacking interactions, van der Waals interactions and halogen bonding [5–7]. Pharmaceutical cocrystals have attracted much attention as functional solid state materials mainly because of their ability of altering the physicochemical properties such as stability, solubility, melting point, bioavailability, and dissolution rate compared to the original APIs while retaining their pharmaceutical activities [8–12]. For most of the reported pharmaceutical cocrystals, API and CCF were connected via hydrogen bonds to form supramolecular synthons. According to the classification of Zaworotko, the synthons were subclassified to heterosynthon and homosynthon [13]. Among the heterosynthons, amide-pyridine-N⁎ Corresponding author. E-mail addresses: [email protected] (Q. Jiang), [email protected] (G. Zhu).
http://dx.doi.org/10.1016/j.inoche.2015.03.027 1387-7003/© 2015 Published by Elsevier B.V.
oxide has a high frequency of occurrence as CCF compared to other heterosynthons, such as carboxamide-pyridine-N-oxide heterosynthon and sulfonamide-pyridine-N-oxide [14,15]. In this paper, 4,4′-bipyridineN,N′-dioxide (BPNO) which is a strong acceptor can form hydrogen bonds with hydroxyl groups to construct supramolecular synthon was selected as CCF. Curcumin is a hydrophobic compound having the chemical name of (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione). It is derived from the rhizome of Curcuma longa, with a wide variety of medicinal benefits, such as anticancer, anti-inflammatory, anti-HIV, antimalarial, and antioxidant [16–18]. Commercially available curcumin crystals are monoclinic and the space group is P2/n. The molecule exists as tautomers of enolic form (enol) and β-diketonic form (di-keto) which are shown in Scheme 1. Besides, curcumin exists primarily in its enolic form in solution [19]. Nangia and co-workers have prepared two new crystalline polymorphs and an amorphous phase of the active ingredient curcumin [20]. After that, the same group reported two cocrystals of curcumin with resorcinol and pyrogallol via solid-state and liquid-assisted grinding strategy. These cocrystals exist primarily in
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Table 2 Hydrogen Bond Length and the Angles of JUC-C14, JUC-C15.
JUC-C14
JUC-C15
Scheme 1. Molecular structures of two forms of curcumin (enol and di-keto tautomers) and the co-crystal former of 4, 4′-bipyridine-N, N′-dioxide.
the enolic form with the O–H⋯O hydrogen bonds between the carbonyl group of curcumin and the phenolic OH groups of the cocrystal formers [21]. In this research, two new crystalline curcumin-based cocrystals were successfully synthesized using BPNO as CCF. One of them has a rarely observed di-keto form, which is probably achieved via the assistance of the solvent molecules. Cocrystallization of curcumin and 4, 4′-bipyridine-N, N′-dioxide was carried out by slow evaporation from a different solution that contains stoichiometric amounts of the API and CCF. First, equal quality of curcumin and BPNO was suspended in a mixed solvent of absolute ethanol and acetone and stirred at room temperature. After the suspension was heated at 60 °C for 72 h, the mixture was completely dissolved and allowed to be evaporated at room temperature for 24 h. Yellow block crystals of JUC-C14 were obtained. The details of refinement and crystallographic data of JUC-C14 are listed in Table 1, and the hydrogen bonding distances and angles are detailed in Table 2. The single-crystal X-ray diffraction confirmed that in JUC-C14 the curcumin and BPNO cocrystallized to form the cocrystals. JUC-C14 is resolved as a triclinic system and space group of P-1 with an asymmetric unit containing one curcumin molecule and one BPNO molecule. There were two types of hydrogen bonds in the structure: the intramolecular hydrogen bonds and the intermolecular hydrogen bonds. As shown in Fig. 1a, curcumin molecules form two intramolecular O–H⋯O hydrogen bonds: one is formed by connecting enolic OH with the nearby carbonyl group [O(3)–H(32)⋯O(4), 1.79 Å, 2.518(2) Å, 147°]. Single-crystal X-ray analysis revealed that curcumin existed in the enol form in JUC-C14,
Table 1 Crystal data and structure refinements. Compound
JUC-C14
JUC-C15
Chemical formula Formula weight Crystal system Space group a (Å) b (Å) c (Å) α (°) β (°) γ (°) V (Å3) Z ρcalc (g/cm3) μ (mm−1) N ref T (K) F (000) R int Goodness-of-fit on F2 Ra1, wRb2 [I N 2σ(I)] Ra1, wRb2 (all data)
C31H28N2O8 556.55 Triclinic P-1 9.8370 (9) 10.5287 (9) 14.3413 (13) 111.2870 (10) 95.819 (2) 101.2270 1333.2 (2) 2 1.386 0.101 6808 296 (2) 584.0 0.0182 1.083 0.0448, 0.1208 0.0587, 0.1299
C33H36N2O10 620.64 Orthorhombic Pccn 18.5630 (9) 9.5014 (5) 17.4834 (8) 90.00 90.00 90.00 3083.6 (3) 4 1.337 0.099 18188 296 (2) 1312.0 0.0216 1.081 0.0732, 0.2266 0.09344, 0.2488
D–H⋯A
d (H⋯A)
D (D⋯A)
θ/°
O(1)–H(1)⋯O(7) O(3)–H(32)⋯O(4) O(6)–H(33)⋯O(5) O(6)–H(33)⋯O(8) O(2)–H(2)⋯O(1) O(2)–H(2)⋯O(4) C(17)–H(17B)⋯O(3)
1.86 1.79 2.23 2.02 2.23 1.95 2.21
2.614 (2) 2.518 (2) 2.6729 (19) 2.653 (2) 2.6652 2.6306 2.9576
153 147 115 134 114 140 134
indicated by the intramolecular hydrogen bond which helps to stabilize the enol tautomer. The other hydrogen bond is formed between phenolic O–H group and the methoxy group via O(6)–H(33)⋯O(5) [2.23 Å, 2.6729(19) Å, 115°]. Besides the intramolecular hydrogen bonds, each curcumin molecule forms two intermolecular hydrogen bonds with two neighbouring BPNO molecules. The O atom of the BPNO pyridine ring interacts with the hydroxyl of the phenol ring of curcumin through O(1)–H(1)⋯O(7) and O(6)–H(33)⋯O(8) intermolecular hydrogen bonds, with O⋯O distances of 2.614(2) Å and 2.653(2) Å, respectively. Meanwhile, π⋯π interactions (3.485 Å) between the aromatic rings of two BPNO molecules in the adjacent chains result in the 1D double chain (Fig. 1b). Then, the 1D double chain repeats along the a axis and b axis to construct the long range ordered cocrystal structures as shown in Fig. 1c. When ethanol for the synthesis of JUC-C14 was replaced by equal molar of methanol, the product was red crystals, named JUC-C15. The crystal structure of JUC-C15 was solved in the orthorhombic space group Pccn with half curcumin molecule, half BPNO molecule and one methanol molecule in the asymmetric unit. There are strong intermolecular O–H⋯O supermolecular heterosynthons between curcumin molecules and BPNO molecules which are the same as JUC-C14 (Fig. 2a). However the difference between JUC-C14 and JUC-C15 is that the methanol molecules interact with the carbonyl group of the curcumin molecules with a hydrogen bond distance of 2.953(8) Å. The interaction between methanol and curcumin results in the di-keto structure of curcumin molecule in JUC-C15, which is extensively used to construct curcumin metal complexes [22], but rarely reported in all the other curcumin polymorphs [20,21]. Being different from JUC-C14, in JUCC15 a π⋯π interaction occurred between one pyridine ring of the BPNO and one phenyl ring of the curcumin. Similarly, the other pyridine ring of the same BPNO molecule interacts with a phenyl ring from another adjacent curcumin molecule (Fig. 2b), thus resulting in the formation of a 2D net structure as shown in Fig. 2c. The distance between two aromatic rings is 3.457 Å. The distances of the hydrogen bonds are summarized in Table 2. Methanol molecules interacting with the carbonyl on the other molecules were also reported by Michael J. Zaworotko and co-workers. They synthesized two cocrystals of quercetin:caffeine (QUECAF) and quercetin:caffeine:methanol (QUECAF·MeOH). The methanol molecule formed an O–H⋯O H-bonding with the carbonyl on the imide ring of a CAF molecule [5]. Then different cocrystals may be obtained through the methanol molecule adjusting the structure. The PXRD was executed to detect the phase purity of JUC-C14 and JUC-C15 at room temperature. The experimental patterns of each cocrystal exhibited good agreement with those simulated from the single-crystal structures, verifying that the cocrystal has been successfully formed (Fig. 3). Especially, the PXRD patterns of JUC-C14 and JUC-C15 reveal the isostructural nature of two cocrystals. The DSC curves of cocrystals are shown in Fig. 4, which are similar to QUECAF and QUECAF·MeOH [5]. It can be found that their melting points are both 211 °C, which are different from the active pharmaceutical ingredient and the co-crystal former. The changes of the melting point indicate that the cocrystals have been successfully prepared. In summary, two curcumin based cocrystals with BPNO as the co-crystal former were successfully synthesized through crystal engineering. Both cocrystals possess intermolecular O–H⋯O hydrogen
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H. Su et al. / Inorganic Chemistry Communications 55 (2015) 92–95
Fig. 1. (a) O–H⋯O hydrogen bond between curcumin and BPNO molecules in JUC-C14; (b) the packing diagram of JUC-C14 shows pairs of two BPNO molecules through the π⋯π stacking interactions; (c) the view of the 1D chain along the a axis and b axis in JUC-C14.
bonds but only the cocrystal JUC-C14 contains the intramolecular O–H⋯O hydrogen bonds with the enol tautomer in the structure. Single-crystal X-ray diffraction indicated that JUC-C14 exhibits 1D chain structure, while JUC-C15 is a 2D net structure linked via hydrogen bonds and π⋯π packing interactions. In addition, the curcumin molecules in JUC-C15 exist as the di-keto form which is rarely reported. We comment that the interactions between methanol and curcumin help the stabilization of the substable di-keto structure over the enol tautomer. The experimental PXRD patterns of the two cocrystals are consistent with the simulated ones, indicating the phase purity of both
cocrystals. Besides, JUC-C14 and JUC-C15 would be a potential candidate for the pharmaceutical studies and dissolution studies in the future.
Acknowledgments We are grateful to the financial support from the National Basic Research Program of China (973 Program, grant no. 2012CB821700, grant no. 2014CB931804) and the Major International (Regional) Joint Research Project of NSFC (grant no. 21120102034).
Fig. 2. (a) O–H⋯O hydrogen bond between curcumin and BPNO molecules in JUC-C15; (b) the packing diagram of JUC-C15 exhibits BPNO molecule and curcumin molecule through the π⋯π stacking interaction; (c) the structure of 2D net in JUC-C15.
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Fig. 3. Comparison PXRDs of JUC-C14 (a) and JUC-C15 (b) (black, simulated; red as-synthesized material). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 4. DSC curves of JUC-C14 (a) and JUC-C15 (b) (black, active pharmaceutical ingredient; blue, co-crystal former and red, cocrystals). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Appendix A. Supplementary material Experimental details, the FT-IR spectra for JUC-C14 and JUC-C15 and the TGA plot of JUC-C14 and JUC-C15. CCDC reference numbers 1041366 and 1042367, respectively. Supplementary data associated with this article can be found, in the online version, at http://dx.doi. org/10.1016/j.inoche.2015.03.027. References [1] P. Vishweshwar, J.A. Mcmahon, J.A. Bis, M.J. Zaworotko, J. Pharm. Sci. 95 (2006) 449. [2] . Almarsson, M.J. Zaworotko, Chem. Commun. 2004 (1889). [3] B. Rodriguez-Spong, C.P. Price, A. Jayasankar, A.J. Matzter, N. Rodríguez-Hornedo, Adv. Drug Deliv. Rev. 56 (2004) 241. [4] H.G. Brittain, Cryst. Growth Des. 12 (2012) 1046. [5] P. Metrangolo, H. Neukirch, T. Pilati, G. Resnati, Acc. Chem. Res. 38 (2005) 386. [6] H.L. Nguyen, P.N. Horton, M.B. Hursthouse, A.C. Legon, D.W. Bruce, J. Am. Chem. Soc. 126 (2004) 16. [7] G.W. Coates, A.R. Dunn, L.M. Henling, D.A. Dougherty, R.H. Grubbs, Angew. Chem. Int. Ed. Engl. 36 (1997) 248.
[8] A.J. Smith, P. Kavuru, L. Wojtas, M.J. Zaworotko, R.D. Shytle, Mol. Pharm. 8 (2011) 1867. [9] D.R. Weyna, M.L. Cheney, N. Shan, M. Hanna, M.J. Zaworotko, V. Sava, S. Song, J.R. Sanchez-Ramos, Mol. Pharm. 9 (2012) 3716. [10] Y. Yan, J.M. Chen, N. Geng, T.B. Lu, Cryst. Growth Des. 12 (2012) 2226. [11] T.T. Zhang, Y. Yang, X.J. Zhao, J.T. Jia, H.M. Su, H.M. He, J.K. Gu, G.S. Zhu, CrystEngComm 16 (2014) 7667. [12] T.T. Zhang, H.T. Wang, J.T. Jia, X.Q. Cui, Q. Li, G.S. Zhu, Inorg. Chem. Commun. 39 (2014) 144. [13] R.D.B. Walsh, M.W. Bradner, S.G. Fleischman, L.A. Morales, B. Moulton, N. RodriguezHornedo, M.J. Zaworotko, Chem. Commun. (2003) 186. [14] N.R. Goud, N.J. Babu, A. Nangia, Cryst. Growth Des. 11 (2011) 1930. [15] L.S. Reddy, N.J. Babu, A. Nangia, Chem. Commun. (2006) 1369. [16] M. Salem, S. Rohani, E.R. Gillies, RSC Adv. 4 (2014) 10815. [17] R.A. Sharma, A.J. Gescher, W.P. Steward, Eur. J. Cancer 41 (2005) 1955. [18] R.K. Maheshwari, A.K. Singh, J. Gaddipati, R.C. Srimal, Life Sci. 78 (2006) 2081. [19] A. Goel, A.B. Kunnumakkara, B.B. Aggarwal, Biochem. Pharmacol. 75 (2008) 787. [20] P. Sanphui, N.R. Goud, U.B.R. Khandavilli, S. Bhanoth, A. Nangia, Chem. Commun. 47 (2011) 5013. [21] P. Sanphui, N.R. Goud, U.B.R. Khandavilli, S. Bhanoth, A. Nangia, Cryst. Growth Des. 11 (2011) 4135. [22] M.I. Khalil, A.M. AL-Zahem, M.M. Qunaibit, Med. Chem. Res. 23 (2014) 1683.
Contents lists available at ScienceDirect
Inorganic Chemistry Communications journal homepage: www.elsevier.com/locate/inoche
Feature article
Syntheses and characterizations of two curcumin-based cocrystals Hongmin Su a, Hongming He b, Yuyang Tian b, Nian Zhao b, Fuxing Sun b, Xiaoming Zhang b, Qing Jiang a,⁎, Guangshan Zhu b,⁎ a b
Key Laboratory of Automobile Materials, Ministry of Education and School of Materials Science and Engineering, Jilin University, Changchun 130022, China State Key Laboratory of Inorganic Synthesis & Preparative Chemistry, Jilin University, Changchun 130012, China
a r t i c l e
i n f o
Article history: Received 15 January 2015 Received in revised form 11 March 2015 Accepted 14 March 2015 Available online 16 March 2015 Keywords: Curcumin Pharmaceutical cocrystal Single crystal X-ray diffraction Powder X-ray diffraction Differential scanning calorimetry
a b s t r a c t Two pharmaceutical cocrystals, named Jilin University China–Cocrystal-14 (JUC-C14) and Jilin University China– Cocrystal-15 (JUC-C15), which were composed of curcumin and 4, 4′-bipyridine-N, N′-dioxide, were successfully prepared by crystal engineering strategy. The crystal structures of the two cocrystals were solved and refined by single crystal X-ray diffraction. It is indicated that the crystal structures are assembled via intermolecular interactions including hydrogen bonds and π⋯π stacking. Additionally, in the structure of JUC-C15 curcumin existed in a di-keto form which is rare in other reported curcumin polymorphs. Power X-ray diffraction, Fouriertransform infrared spectra, thermogravimetric analyses and differential scanning calorimetry were executed as well to confirm the formation of the cocrystals. © 2015 Published by Elsevier B.V.
Contents Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 Appendix A. Supplementary material . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
During the past decade, cocrystallization has rapidly developed as an emerging approach to design and prepare pharmaceutical materials owing to the development of crystal engineering and supramolecular chemistry [1–4]. Most pharmaceutical cocrystals were constructed by active pharmaceutical ingredient (API) and cocrystal former (CCF) via intermolecular interactions such as hydrogen bonds, π⋯π stacking interactions, van der Waals interactions and halogen bonding [5–7]. Pharmaceutical cocrystals have attracted much attention as functional solid state materials mainly because of their ability of altering the physicochemical properties such as stability, solubility, melting point, bioavailability, and dissolution rate compared to the original APIs while retaining their pharmaceutical activities [8–12]. For most of the reported pharmaceutical cocrystals, API and CCF were connected via hydrogen bonds to form supramolecular synthons. According to the classification of Zaworotko, the synthons were subclassified to heterosynthon and homosynthon [13]. Among the heterosynthons, amide-pyridine-N⁎ Corresponding author. E-mail addresses: [email protected] (Q. Jiang), [email protected] (G. Zhu).
http://dx.doi.org/10.1016/j.inoche.2015.03.027 1387-7003/© 2015 Published by Elsevier B.V.
oxide has a high frequency of occurrence as CCF compared to other heterosynthons, such as carboxamide-pyridine-N-oxide heterosynthon and sulfonamide-pyridine-N-oxide [14,15]. In this paper, 4,4′-bipyridineN,N′-dioxide (BPNO) which is a strong acceptor can form hydrogen bonds with hydroxyl groups to construct supramolecular synthon was selected as CCF. Curcumin is a hydrophobic compound having the chemical name of (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione). It is derived from the rhizome of Curcuma longa, with a wide variety of medicinal benefits, such as anticancer, anti-inflammatory, anti-HIV, antimalarial, and antioxidant [16–18]. Commercially available curcumin crystals are monoclinic and the space group is P2/n. The molecule exists as tautomers of enolic form (enol) and β-diketonic form (di-keto) which are shown in Scheme 1. Besides, curcumin exists primarily in its enolic form in solution [19]. Nangia and co-workers have prepared two new crystalline polymorphs and an amorphous phase of the active ingredient curcumin [20]. After that, the same group reported two cocrystals of curcumin with resorcinol and pyrogallol via solid-state and liquid-assisted grinding strategy. These cocrystals exist primarily in
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Table 2 Hydrogen Bond Length and the Angles of JUC-C14, JUC-C15.
JUC-C14
JUC-C15
Scheme 1. Molecular structures of two forms of curcumin (enol and di-keto tautomers) and the co-crystal former of 4, 4′-bipyridine-N, N′-dioxide.
the enolic form with the O–H⋯O hydrogen bonds between the carbonyl group of curcumin and the phenolic OH groups of the cocrystal formers [21]. In this research, two new crystalline curcumin-based cocrystals were successfully synthesized using BPNO as CCF. One of them has a rarely observed di-keto form, which is probably achieved via the assistance of the solvent molecules. Cocrystallization of curcumin and 4, 4′-bipyridine-N, N′-dioxide was carried out by slow evaporation from a different solution that contains stoichiometric amounts of the API and CCF. First, equal quality of curcumin and BPNO was suspended in a mixed solvent of absolute ethanol and acetone and stirred at room temperature. After the suspension was heated at 60 °C for 72 h, the mixture was completely dissolved and allowed to be evaporated at room temperature for 24 h. Yellow block crystals of JUC-C14 were obtained. The details of refinement and crystallographic data of JUC-C14 are listed in Table 1, and the hydrogen bonding distances and angles are detailed in Table 2. The single-crystal X-ray diffraction confirmed that in JUC-C14 the curcumin and BPNO cocrystallized to form the cocrystals. JUC-C14 is resolved as a triclinic system and space group of P-1 with an asymmetric unit containing one curcumin molecule and one BPNO molecule. There were two types of hydrogen bonds in the structure: the intramolecular hydrogen bonds and the intermolecular hydrogen bonds. As shown in Fig. 1a, curcumin molecules form two intramolecular O–H⋯O hydrogen bonds: one is formed by connecting enolic OH with the nearby carbonyl group [O(3)–H(32)⋯O(4), 1.79 Å, 2.518(2) Å, 147°]. Single-crystal X-ray analysis revealed that curcumin existed in the enol form in JUC-C14,
Table 1 Crystal data and structure refinements. Compound
JUC-C14
JUC-C15
Chemical formula Formula weight Crystal system Space group a (Å) b (Å) c (Å) α (°) β (°) γ (°) V (Å3) Z ρcalc (g/cm3) μ (mm−1) N ref T (K) F (000) R int Goodness-of-fit on F2 Ra1, wRb2 [I N 2σ(I)] Ra1, wRb2 (all data)
C31H28N2O8 556.55 Triclinic P-1 9.8370 (9) 10.5287 (9) 14.3413 (13) 111.2870 (10) 95.819 (2) 101.2270 1333.2 (2) 2 1.386 0.101 6808 296 (2) 584.0 0.0182 1.083 0.0448, 0.1208 0.0587, 0.1299
C33H36N2O10 620.64 Orthorhombic Pccn 18.5630 (9) 9.5014 (5) 17.4834 (8) 90.00 90.00 90.00 3083.6 (3) 4 1.337 0.099 18188 296 (2) 1312.0 0.0216 1.081 0.0732, 0.2266 0.09344, 0.2488
D–H⋯A
d (H⋯A)
D (D⋯A)
θ/°
O(1)–H(1)⋯O(7) O(3)–H(32)⋯O(4) O(6)–H(33)⋯O(5) O(6)–H(33)⋯O(8) O(2)–H(2)⋯O(1) O(2)–H(2)⋯O(4) C(17)–H(17B)⋯O(3)
1.86 1.79 2.23 2.02 2.23 1.95 2.21
2.614 (2) 2.518 (2) 2.6729 (19) 2.653 (2) 2.6652 2.6306 2.9576
153 147 115 134 114 140 134
indicated by the intramolecular hydrogen bond which helps to stabilize the enol tautomer. The other hydrogen bond is formed between phenolic O–H group and the methoxy group via O(6)–H(33)⋯O(5) [2.23 Å, 2.6729(19) Å, 115°]. Besides the intramolecular hydrogen bonds, each curcumin molecule forms two intermolecular hydrogen bonds with two neighbouring BPNO molecules. The O atom of the BPNO pyridine ring interacts with the hydroxyl of the phenol ring of curcumin through O(1)–H(1)⋯O(7) and O(6)–H(33)⋯O(8) intermolecular hydrogen bonds, with O⋯O distances of 2.614(2) Å and 2.653(2) Å, respectively. Meanwhile, π⋯π interactions (3.485 Å) between the aromatic rings of two BPNO molecules in the adjacent chains result in the 1D double chain (Fig. 1b). Then, the 1D double chain repeats along the a axis and b axis to construct the long range ordered cocrystal structures as shown in Fig. 1c. When ethanol for the synthesis of JUC-C14 was replaced by equal molar of methanol, the product was red crystals, named JUC-C15. The crystal structure of JUC-C15 was solved in the orthorhombic space group Pccn with half curcumin molecule, half BPNO molecule and one methanol molecule in the asymmetric unit. There are strong intermolecular O–H⋯O supermolecular heterosynthons between curcumin molecules and BPNO molecules which are the same as JUC-C14 (Fig. 2a). However the difference between JUC-C14 and JUC-C15 is that the methanol molecules interact with the carbonyl group of the curcumin molecules with a hydrogen bond distance of 2.953(8) Å. The interaction between methanol and curcumin results in the di-keto structure of curcumin molecule in JUC-C15, which is extensively used to construct curcumin metal complexes [22], but rarely reported in all the other curcumin polymorphs [20,21]. Being different from JUC-C14, in JUCC15 a π⋯π interaction occurred between one pyridine ring of the BPNO and one phenyl ring of the curcumin. Similarly, the other pyridine ring of the same BPNO molecule interacts with a phenyl ring from another adjacent curcumin molecule (Fig. 2b), thus resulting in the formation of a 2D net structure as shown in Fig. 2c. The distance between two aromatic rings is 3.457 Å. The distances of the hydrogen bonds are summarized in Table 2. Methanol molecules interacting with the carbonyl on the other molecules were also reported by Michael J. Zaworotko and co-workers. They synthesized two cocrystals of quercetin:caffeine (QUECAF) and quercetin:caffeine:methanol (QUECAF·MeOH). The methanol molecule formed an O–H⋯O H-bonding with the carbonyl on the imide ring of a CAF molecule [5]. Then different cocrystals may be obtained through the methanol molecule adjusting the structure. The PXRD was executed to detect the phase purity of JUC-C14 and JUC-C15 at room temperature. The experimental patterns of each cocrystal exhibited good agreement with those simulated from the single-crystal structures, verifying that the cocrystal has been successfully formed (Fig. 3). Especially, the PXRD patterns of JUC-C14 and JUC-C15 reveal the isostructural nature of two cocrystals. The DSC curves of cocrystals are shown in Fig. 4, which are similar to QUECAF and QUECAF·MeOH [5]. It can be found that their melting points are both 211 °C, which are different from the active pharmaceutical ingredient and the co-crystal former. The changes of the melting point indicate that the cocrystals have been successfully prepared. In summary, two curcumin based cocrystals with BPNO as the co-crystal former were successfully synthesized through crystal engineering. Both cocrystals possess intermolecular O–H⋯O hydrogen
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Fig. 1. (a) O–H⋯O hydrogen bond between curcumin and BPNO molecules in JUC-C14; (b) the packing diagram of JUC-C14 shows pairs of two BPNO molecules through the π⋯π stacking interactions; (c) the view of the 1D chain along the a axis and b axis in JUC-C14.
bonds but only the cocrystal JUC-C14 contains the intramolecular O–H⋯O hydrogen bonds with the enol tautomer in the structure. Single-crystal X-ray diffraction indicated that JUC-C14 exhibits 1D chain structure, while JUC-C15 is a 2D net structure linked via hydrogen bonds and π⋯π packing interactions. In addition, the curcumin molecules in JUC-C15 exist as the di-keto form which is rarely reported. We comment that the interactions between methanol and curcumin help the stabilization of the substable di-keto structure over the enol tautomer. The experimental PXRD patterns of the two cocrystals are consistent with the simulated ones, indicating the phase purity of both
cocrystals. Besides, JUC-C14 and JUC-C15 would be a potential candidate for the pharmaceutical studies and dissolution studies in the future.
Acknowledgments We are grateful to the financial support from the National Basic Research Program of China (973 Program, grant no. 2012CB821700, grant no. 2014CB931804) and the Major International (Regional) Joint Research Project of NSFC (grant no. 21120102034).
Fig. 2. (a) O–H⋯O hydrogen bond between curcumin and BPNO molecules in JUC-C15; (b) the packing diagram of JUC-C15 exhibits BPNO molecule and curcumin molecule through the π⋯π stacking interaction; (c) the structure of 2D net in JUC-C15.
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Fig. 3. Comparison PXRDs of JUC-C14 (a) and JUC-C15 (b) (black, simulated; red as-synthesized material). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 4. DSC curves of JUC-C14 (a) and JUC-C15 (b) (black, active pharmaceutical ingredient; blue, co-crystal former and red, cocrystals). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Appendix A. Supplementary material Experimental details, the FT-IR spectra for JUC-C14 and JUC-C15 and the TGA plot of JUC-C14 and JUC-C15. CCDC reference numbers 1041366 and 1042367, respectively. Supplementary data associated with this article can be found, in the online version, at http://dx.doi. org/10.1016/j.inoche.2015.03.027. References [1] P. Vishweshwar, J.A. Mcmahon, J.A. Bis, M.J. Zaworotko, J. Pharm. Sci. 95 (2006) 449. [2] . Almarsson, M.J. Zaworotko, Chem. Commun. 2004 (1889). [3] B. Rodriguez-Spong, C.P. Price, A. Jayasankar, A.J. Matzter, N. Rodríguez-Hornedo, Adv. Drug Deliv. Rev. 56 (2004) 241. [4] H.G. Brittain, Cryst. Growth Des. 12 (2012) 1046. [5] P. Metrangolo, H. Neukirch, T. Pilati, G. Resnati, Acc. Chem. Res. 38 (2005) 386. [6] H.L. Nguyen, P.N. Horton, M.B. Hursthouse, A.C. Legon, D.W. Bruce, J. Am. Chem. Soc. 126 (2004) 16. [7] G.W. Coates, A.R. Dunn, L.M. Henling, D.A. Dougherty, R.H. Grubbs, Angew. Chem. Int. Ed. Engl. 36 (1997) 248.
[8] A.J. Smith, P. Kavuru, L. Wojtas, M.J. Zaworotko, R.D. Shytle, Mol. Pharm. 8 (2011) 1867. [9] D.R. Weyna, M.L. Cheney, N. Shan, M. Hanna, M.J. Zaworotko, V. Sava, S. Song, J.R. Sanchez-Ramos, Mol. Pharm. 9 (2012) 3716. [10] Y. Yan, J.M. Chen, N. Geng, T.B. Lu, Cryst. Growth Des. 12 (2012) 2226. [11] T.T. Zhang, Y. Yang, X.J. Zhao, J.T. Jia, H.M. Su, H.M. He, J.K. Gu, G.S. Zhu, CrystEngComm 16 (2014) 7667. [12] T.T. Zhang, H.T. Wang, J.T. Jia, X.Q. Cui, Q. Li, G.S. Zhu, Inorg. Chem. Commun. 39 (2014) 144. [13] R.D.B. Walsh, M.W. Bradner, S.G. Fleischman, L.A. Morales, B. Moulton, N. RodriguezHornedo, M.J. Zaworotko, Chem. Commun. (2003) 186. [14] N.R. Goud, N.J. Babu, A. Nangia, Cryst. Growth Des. 11 (2011) 1930. [15] L.S. Reddy, N.J. Babu, A. Nangia, Chem. Commun. (2006) 1369. [16] M. Salem, S. Rohani, E.R. Gillies, RSC Adv. 4 (2014) 10815. [17] R.A. Sharma, A.J. Gescher, W.P. Steward, Eur. J. Cancer 41 (2005) 1955. [18] R.K. Maheshwari, A.K. Singh, J. Gaddipati, R.C. Srimal, Life Sci. 78 (2006) 2081. [19] A. Goel, A.B. Kunnumakkara, B.B. Aggarwal, Biochem. Pharmacol. 75 (2008) 787. [20] P. Sanphui, N.R. Goud, U.B.R. Khandavilli, S. Bhanoth, A. Nangia, Chem. Commun. 47 (2011) 5013. [21] P. Sanphui, N.R. Goud, U.B.R. Khandavilli, S. Bhanoth, A. Nangia, Cryst. Growth Des. 11 (2011) 4135. [22] M.I. Khalil, A.M. AL-Zahem, M.M. Qunaibit, Med. Chem. Res. 23 (2014) 1683.