Supramolecular Assemblies of Three New Metronidazole Derivatives Constructed with Various Dihydroxy-benzoic Acids via Hydrogen Bonds

Abstract

Metronidazole(MTZ) is an important antibiotic, which has been widely applied to cure protozoal and bacterial diseases for human beings or animals. Herein, three novel drug supramolecular crystals constructed by MTZ with 2,5-dihydroxy-benzoic acid(2,5-DHBA)(1), 2,6-dihydroxy-benzoic acid(2,6-DHBA)(2) and 3,5-dihydroxy-benzoic acid(3,5-DHBA)(3), respectively, have been discovered. The hydrogen bonds of N—H⋯O(O—H⋯N), C—H⋯O and O—H⋯O play important roles in the 3D supramolecular framework formation for crystals 1–3. Interestingly, due to the vary locations of the substituent groups, the two-dimensional layers in crystals 1 or 2 are constructed via intermolecular hydrogen bonds between MTZ and 2,5-DHBA or 2,6-DHBA, while in crystal 3 water molecules play a significant role except the intermolecular hydrogen bonds between MTZ and 3,5 -DHBA. In addition, five synthons of I R² ₂(8), II R³ ₃(9) in crystal 1, III R² ₁(4), IV R² ₂(8) in crystal 2 and V R² ₂(7) in crystal 3 formed through various hydrogen bonds are founded in this work. Systematic studies of syntheses, crystal structures and thermal analysis are reported.

Keywords

Metronidazole / Supramolecular assembly / Hydrogen bond / Thermal stability

References

[1] Jafari M T, Rezaei B, Zaker B. Anal. Chem., 2009, 81(9): 3585.

[2] Reddy L. S., Babu N. J., Nangia A., Chem. Commun., 2006, (13), 1369

[3] Gospodinov I, Domasevitch K V, Unger C C, Thomas M, Klapötke T M, Stierstorfer J. Cryst. Growth Des., 2020, 20(2): 755.

[4] Aakeröy C B, Beatty A M, Helfrich B A, Nieuwenhuyzen M. Cryst. Growth Des., 2003, 3(2): 159.

[5] Li Y C, Liu Y, Yang Y, Yu F, Liu J, Song H, Liu J, Tang H, Ye B C, Sun Z P. ACS Appl. Mater. Interfaces., 2015, 7(28): 15474.

[6] Surov A O, Voronin A P, Manin A N, Manin N G, Kuzmina L G, Churakov A V, Perlovich G L. Mol. Pharmaceutics, 2014, 11(10): 3707.

[7] Basavoju S, Boström D, Velaga S P. Cryst. Growth Des., 200, 6(12): 2699.

[8] Luo C, Liang W D, Chen X, Wang J M, Deng Z W, Zhang H L. CrystEngComm, 2018, 20(22): 3025.

[9] Remenar J F, Morissette S L, Peterson M L, Moulton B, MacPhee J M, Guzman H R, Almarsson J. Am. Chem. Soc., 2003, 125(28): 8456.

[10] Bhattacharya B, Das S, Lal G, Soni S R, Ghosh A, Reddy C M, Ghosh S. J. Mol. Struct., 2020, 1199: 127028-10.

[11] Hickey M B, Peterson M L, Scoppettuolo L A, Morrisette S L, Vetter A, Guzmán H, Remenar J F, Zhang Z, Tawa M D, Haley S, Zaworotko M J, Almarsson Eur. J. Pharm. Biopharm., 2007, 67(1): 112.

[12] Bak A, Gore A, Yanez E, Stanton M, Tufekcic S, Syed R, Akrami A, Rose M, Surapaneni S, Bostick T, King A, Neervannan S, Ostovic D, Koparkar A. J. Pharm. Sci., 2008, 97(9): 3942.

[13] Weng J W, Wong S N, Xu X Y, Xuan B F, Wang C G, Chen R P, Sun C C, Lakerveld R, Kwok P C L, Chow S F. Cryst. Growth Des., 2019, 19(5): 2736.

[14] Desiraju G R. Angew. Chem. Int. Ed., 2007, 46(44): 8342.

[15] Mir N A, Dubey R, Desiraju G R. Acc. Chem. Res., 2019, 52(8): 2210.

[16] Mukherjee A. Cryst. Growth Des., 2015, 15(6): 3076.

[17] Friščić T, Jones W. Faraday Discuss., 2007, 136: 167.

[18] Horstman E M, Bertke J A, Kim E H, Gonzalez L C, Zhang G G Z, Gong Y, Kenis P J A. CrystEngComm, 2015, 17(28): 5299.

[19] Almarsson Ö., Zaworotko M. J., Chem. Commun., 2004, (17), 1889

[20] Rodríguez-Hornedo N. Mol. Pharmaceutics, 2007, 4(3): 299.

[21] MacGillivray L R. CrystEngComm, 2004, 6(16): 77.

[22] Lehn J M. Science, 2002, 295(5564): 2400.

[23] Metrangolo P, Neukirch H, Pilati T, Resnati G. Acc. Chem. Res., 2005, 38(5): 386.

[24] Nishio M. CrystEngComm, 2004, 6(27): 130.

[25] Bishop R. CrystEngComm, 2015, 17(39): 7448.

[26] Shan N, Zaworotko M J. Drug Discov. Today, 2008, 13(9/10): 440.

[27] Zhang X, Li L B, Wang J X, Wen H M, Krishna R, Wu H, Zhou W, Chen Z N, Li B, Qian G D, Chen B L. J. Am. Chem. Soc., 2020, 142(1): 633.

[28] Wang B, Lv X L, Lv J, Ma L, Lin R B, Cui H, Zhang J, Zhang Z J, Xiang S C, Chen B L. Chem. Commun., 2020, 56(1): 66.

[29] Higashi T., Iohara D., Motoyama K., Arima H., Chem. Pharm. Bull., 66(3), 207

[30] Bhogala B R, Basavoju S, Nangia A. Cryst. Growth Des., 2005, 5(5): 1683.

[31] Bhogala B R, Basavoju S, Nangia A. CrystEngComm, 2005, 7(90): 551.

[32] Bis J A, Zaworotko M J. Cryst. Growth Des., 2005, 5(3): 1169.

[33] Wang L, Zhao L, Xue R Y, Lu X F, Wen Y H, Yang Y. Sci. China Chem., 2012, 55(12): 2515.

[34] Wang L, Zhao L, Hu Y J, Wang W Q, Chen R X, Yang Y. CrystEngComm, 2013, 15(15): 2835.

[35] Wang L, Hu Y J, Wang W Q, Liu F Q, Huang K K. CrystEngComm, 2014, 16(20): 4142.

[36] Wang L, Hu Y J, Xu W Y, Pang Y Y, Liu F Q, Yang Y. RSC Adv., 2014, 4(100): 56816.

[37] Wang X P, Zhang K, Geng Y L, Sun Y X, Chen F S, Wang L. J. Mol. Struct., 2018, 1165: 106.

[38] Dingsdag S A, Hunter N. J. Antimicrob. Chemoth., 2018, 73(2): 265.

[39] Sang Y L, Duan Y T, Qiu H Y, Wang P F, Makawana J A, Wang Z C, Zhu H L, He Z X. RSC Adv., 2014, 4(32): 16694.

[40] Xiao C, Ma K, Cai G F, Zhang X Y, Vessally E. J. Mol. Graph. Model., 2020, 96: 107539 7

[41] Boxi S S, Paria S. RSC Adv., 2014, 4(71): 37752.

[42] Barskiy D A, Shchepin R V, Coffey A M, Theis T, Warren W S, Goodson B M, Chekmenev E Y. J. Am. Chem. Soc., 201, 138(26): 8080.

[43] Grecu T, Prohens R, McCabe J F, Carrington E J, Wright J S, Brammer L, Hunter C A. CrystEngComm, 2017, 19(26): 3592.

[44] Duggirala N K, Perry M L, Almarsson, Zaworotko M J. Chem. Commun., 201, 52(4): 640.

[45] Rigaku CrystalClear, Version 1.3.5, 1999, The Woodlands, TX: Rigaku Corp.

[46] Sheldrick G M. Acta Crystallogr. A, 2008, 64(1): 112.

[47] Dolomanov O V, Bourhis L J, Gildea R J, Howard J A K, Puschmann H. J. Appl. Cryst., 2009, 42(2): 339.

[48] Yang B. Acta Crystallogr. E, 2008, 64(7): 1338.

[49] Sarmah K K, Boro K, Arhangelskis M, Thakuria R. CrystEngComm, 2017, 19(5): 826.