Molecular and crystal structure of 1-methyl- 5-trifluoromethoxy-1H-indole-2,3-dione 3-[4-(4-methoxyphenyl)thiosemicarbazone]

Yıl 2021, Cilt: 51 Sayı: 1, 59 - 66, 30.04.2021

Özge Soylu Eter Zeliha Atioğlu Mehmet Akkurt Cem Cüneyt Ersanlı Nilgün Karalı

Öz

Background and Aims: The main purpose of this study is to determine the molecular structure and isomers of the new 1-methyl- 5-trifluoromethoxy-1H-indole-2,3-dione 3-[4-(4-methoxyphenyl)thiosemicarbazone] (5) and to prove the 3Z-conformer of the compound 5. Methods: The molecular structure of E- and Z-isomer mixture 5 was confirmed by analytical and spectral data (UV, IR, 1H NMR, HSQC-2D and MS). The Z-conformer of compound 5 was characterized by NMR spectroscopy and X-ray single crystal diffraction analysis method (SC-XRD). Results: The compound 5 was synthesized by condensation of 1-methyl-5-trifluoromethoxy-1H-indole-2,3-dione (2) with 4-(4-methoxyphenyl)thiosemicarbazide (4). The compound 5 was obtained in two separate forms, crystal and amorphous. It was proved by NMR data and X-ray diffraction findings that the crystal form is the Z-isomer and the amorphous form is a mixture of the E- and Z-isomers. The E- and Z-isomer ratios were determined by 1H NMR spectroscopy. The crystal structure and molecular interactions of the Z-conformer were determined by X-ray single crystal diffraction analysis. Conclusion: In the crystal, three intramolecular N—H···N, N—H···O and C—H···S hydrogen bonds provided isomer formation. Also, molecular packing was stabilized by intermolecular C—H···O hydrogen bonds, the π-π stacking interactions and weak CO···π (ring) contacts.

Anahtar Kelimeler

Synthesis, molecular structure, isomerism, crystal structure, hydrogen bond, π-π stacking interaction

Kaynakça

• Akkurt, M., Karaca, S., Cihan, G., Çapan, G., & Büyükgüngör, O. (2009). N′-[(2Z)-3-Allyl-4-oxo-1,3-thiazolidin- 2-ylidene]- 5-fluoro-3-phenyl- 1H-indole-2-carbohydrazide. Acta Crystallographica Section E, 65, o1009-o1010. https://doi.org/10.1107/S1600536809012677
• • Akkurt, M., Öztürk, S., Erçağ, A., Özgür, M. Ü., & Heinemann, F.W. (2003). (3E)-3-[(4-Butylphenyl) imino]- 1,3-dihydro- 2H-indol-2- one. Acta Crystallographica Section E, 59, o780-o782. https://doi. org/10.1107/S160053680300953X
• • Ali, A. Q., Teoh, S. G., Salhin, A., Eltayeb, N. E., Ahamed, M. B. K., & Majid, A. A. (2014). Synthesis of isatin thiosemicarbazones derivatives: in vitro anti-cancer, DNA binding and cleavage activities. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 125, 440-448. https://doi.org/10.1016/j.saa.2014.01.086
• • Atioğlu, Z., Sevinçli, Z. Ş., Karalı, N., Akkurt, M., & Ersanlı, C. C. (2017a). 2-(5-Fluoro-1-methyl-2-oxoindolin-3-ylidene)-N-[4- (methylsulfanyl)phenyl]hydrazine-1-carbothioamide. IUCrData, 2, x170671. https://doi.org/10.1107/S2414314617009002
• • Atioğlu, Z., Sevinçli, Z. Ş., Karalı, N., Akkurt, M., & Ersanlı, C. C. (2017b). (2Z)-2-(5-Fluoro-1-methyl-2-oxoindolin-3-ylidene)-N-(3- fluorophenyl)hydrazine-1-carbothioamide. IUCrData, 2, x170900. https://doi.org/10.1107/S2414314617009002
• • Bain, G. A., West, D. X., Krejci, J., Valdés-Martinez, J., Hernández- Ortega, S., & Toscano, R. A. (1997). Synthetic and spectroscopic investigations of N(4)-substituted isatin thiosemicarbazones and their copper (II) complexes. Polyhedron, 16(5), 855-862. https:// doi.org/10.1016/S0277-5387(96)00323-3
• • Bal, T. R., Anand, B., Yogeeswari, P., & Sriram, D. (2005). Synthesis and evaluation of anti-HIV activity of isatin beta-thiosemicarbazone derivatives. Bioorganic & Medicinal Chemistry Letters, 15(20), 4451-4455. https://doi.org/10.1016/j.bmcl.2005.07.046
• • Bernstein, J., Davis, R. E., Shimoni, L., & Chang, N. L. (1995). Patterns in hydrogen bonding: functionality and graph set analysis in crystals. Angewandte Chemie International Edition in English, 34, 1555-1573. http://doi.org./10.1002/anie.199515551
• • DeSilva, N. W. S. V. N., & Albu, T. V. (2007). A theoretical investigation on the isomerism and the NMR properties of thiosemicarbazones. Central European Journal of Chemistry, 5(2), 396-419. https://doi.org/10.2478/s11532-007-0012-1
• • Farrugia, L. J. (2012). WinGX and ORTEP for Windows: an update. Journal of Applied Crystallography, 45, 849-854. https://doi. org/10.1107/S0021889812029111
• • Güzel, Ö., Karalı, N., & Salman, A. (2008). Synthesis and antituberculosis activity of 5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone derivatives. Bioorganic & Medicinal Chemistry, 16(19), 8976-8987. https://doi.org/10.1016/j.bmc.2008.08.050
• • Hall, M.D., Brimacombe, K.R., Varonka, M.S., Pluchino, K.M., Monda, J.K., Li, J. … Gottesman, M.M. (2011). Synthesis and structureactivity evaluation of isatin-β-thiosemicarbazones with improved selective activity towards multidrug-resistant cells expressing Pglycoprotein. Journal of Medicinal Chemistry, 54(16), 5878-5889. http://doi.org/10.1021/jm2006047
• • Hall, M.D., Salam, N.K., Hellawell, J.L., Fales, H.M., Kensler, C.B., Ludwig, J.A. … Gottesman, M.M. (2009). Synthesis, activity, and pharmacophore development for isatin-β-thiosemicarbazones with selective activity toward multidrug-resistant cells. Journal of Medicinal Chemistry, 52(10), 3191-3204. http://doi.org/10.1021/ jm800861c
• • Haribabu, J., Subhashree, G., Saranya, S., Gomathi, K., Karvembu, R., & Gayathri, D. (2016). Isatin based thiosemicarbazone derivatives as potential bioactive agents: Anti-oxidant and molecular docking studies. Journal of Molecular Structure, 1110, 185-195. https://doi.org/10.1016/j.molstruc.2016.01.044
• • Howard, J.A.K., Hoy, V.J., O’Hagan, D., & Smith, G.T. (1996). How good is fluorine as a hydrogen bond acceptor?. Tetrahedron, 52(38), 12613-12622. https://doi.org/10.1016/0040-4020(96)00749-1
• • Huang, H., Chen, Q., Ku, X., Meng, L., Lin, L., Wang, X. … Liu, H. (2010). A Series of α-Heterocyclic Carboxaldehyde Thiosemicarbazones Inhibit Topoisomerase IIα Catalytic Activity. Journal of Medicinal Chemistry, 53(8), 3048-3064. http://doi.org/10.1021/ jm9014394
• • Jakusová, K., Gáplovský, M., Donovalová, J., Cigáň, M., Stankovičová, H. … Anton, G. (2013). Effect of reactants’ concentration on the ratio and yield of E, Z isomers of isatin-3-(4-phenyl)semicarbazone and N-methylisatin-3-(4-phenyl)semicarbazone. Chemical Papers, 67(1), 117-126. https://doi.org/10.2478/s11696-012-0248-x
• • Karalı, N. (2002). Synthesis and primary cytotoxicity evaluation of new 5-nitroindole-2,3-dione derivatives. European Journal of Medicinal Chemistry, 37(11), 909-918. https://doi.org/10.1016/S0223- 5234(02)01416-2
• • Karalı, N., Gürsoy, A., Kandemirli, F., Shvetsc, N., Kaynak, F.B., Özbey, S. … Dimoglo, A. (2007). Synthesis and structure-antituberculosis activity relationship of 1H-indole-2,3-dione derivatives. Bioorganic & Medicinal Chemistry, 15(17), 5888-5904. https://doi. org/10.1016/j.bmc.2007.05.063
• • Karalı, N., Soylu, Ö., Gül, A., Orer, H., Erman, B., Hasanusta, B., Ersoy, B., 5-Fluoro/(trifluoromethoxy)-2-indolinone derivatives. 11.02.2020 PCT/TR 2020/050401
• • Kaynak, F.B., Özbey, S., & Karalı, N. (2013). Three Novel Compounds Of 5-Trifluoromethoxy-1H-Indole-2,3-Dione 3-Thiosemicarbazone: Synthesis, Crystal Structures And Molecular Interactions. Journal of Molecular Structure, 1049, 157-164. https://doi. org/10.1016/j.molstruc.2013.06.039
• • Ma, J., Bao, G., Wang, L., Li, W., Xu, B., Du, B. … Gong, P. (2015). Design, synthesis, biological evaluation and preliminary mechanism study of novel benzothiazole derivatives bearing indolebased moiety as potent antitumor agents. European Journal of Medicinal Chemistry, 96, 173-186. http://doi.org/10.1016/j.ejmech. 2015.04.018
• • Matesic, L., Locke, J., Bremner, J.B., Pyne, S.G., Skropeta, D., Ranson, M., & Vine, K.L. (2008). N-phenethyl and N-naphthylmethyl isatins and analogues as in vitro cytotoxic agents. Bioorganic & Medicinal Chemistry, 16(6), 3118-3124. https://doi.org/10.1016/j. bmc.2007.12.026
• • Matheus, M.E., DeAlmeida Violante, F., Garden, S.J., Pinto, A.C., & Fernandes, P.D. (2007). Isatins inhibit cyclooxygenase-2 and inducible nitric oxide synthase in a mouse macrophage cell line. European Journal of Pharmacology, 556(1-3), 200-206. https://doi. org/10.1016/j.ejphar.2006.10.057
• • Muralisankar, M., Sujith, S., Bhuvanesh, N.S.P., & Sreekanth, A. (2016). Synthesis and crystal structure of new monometallic and bimetallic copper (II) complexes with N-substituted isatin thiosemicarbazone ligands: Effects of the complexes on DNA/proteinbinding property, DNA cleavage study and in vitro anticancer activity. Polyhedron, 118, 103-117. https://doi.org/10.1016/j. poly.2016.06.017
• • O’Sullivan, D.G., & Sadler, P.W. (1956). The structure of isatin and substituted isatins. Journal of the Chemical Society (Resumed), 0(0), 2202-2207. https://doi.org/10.1039/JR9560002202
• • Pandeya, S.N., & Sriram, D. (1998). Synthesis and screening for antibacterial activity of Schiff’s and Mannich bases of isatin and its derivatives. Acta Pharmaceutica Turcica, 40(1), 33-38.
• • Pandeya, S.N., Sriram, D., Yogeeswari, P., & Ananthan, S. (2001). Antituberculous activity of norfloxacin mannich bases with isatin derivatives. Chemotherapy, 47(4), 266-269. https://doi. org/10.1159/000048533
• • Pape, V.F.S., Tóth, S., Füredi, A., Szebényi, K., Lovrics, A., Szabó, P. … Szakács, G. (2016). Design, synthesis and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance. European Journal of Medicinal Chemistry, 117, 335-354. https://doi.org/10.1016/j.ejmech.2016.03.078
• • Pervez, H., Saira, N., Iqbal, M.S., Yaqub, M., & Khan, K.M. (2011). Synthesis and toxicity evaluation of some new N4-aryl substituted 5-trifluoromethoxyisatin-3-thiosemicarbazones. Molecules, 16(8), 6408-6421. http://doi.org/10.3390/molecules16086408
• • Pervez, H., Manzoor, N., Yaqub, M., Khan, A., Khan, K.M., Nasim, F.H., & Choudhary, M.I. (2010). Synthesis and urease inhibitory properties of some new N4-substituted 5-nitroisatin-3-thiosemicarbazones. Letters in Drug Design & Discovery, 7(2), 102-108. https://doi. org/10.2174/157018010790225840
• • Pervez, H., Chohan, Z.H., Ramzan, M., Nasim, F.H., & Khan, K.M. (2009). Synthesis and biological evaluation of some new N4 -substituted isatin-3-thiosemicarbazones. Journal of Enzyme Inhibition and Medicinal Chemistry, 24(2), 437-446. http://doi. org/10.1080/14756360802188420
• • Pervez, H., Iqbal, M.S., Tahir, M.Y., Nasim, F.H., Choudhary, M.I., & Khan, K.M. (2008). In vitro cytotoxic, antibacterial, antifungal and urease inhibitory activities of some N 4-substituted isatin-3-thiosemicarbazones. Journal of Enzyme Inhibition and Medicinal Chemistry, 23(6), 848-854. http://doi.org/10.1080/14756360701746179
• • Priyanka, K.B., Manasa, C., & Sammaiah, G. (2014). Synthesis and evaluation of new isatin derivatives for cytotoxic activity. World Journal of Pharmaceutical Sciences, 3, 2393-2242.
• • Ronen, D., Sherman, L., Bar-Nun, S., & Teitz, Y. (1987). N-methylisatin- beta-4',4'-diethylthiosemicarbazone, an inhibitor of Moloney leukemia virus protein production: characterization and in vitro translation of viral Mrna. Antimicrobial Agents and Chemotherapy, 31(11), 1798-1802. http://doi.org/10.1128/AAC.31.11.1798
• • Sabet, R., Mohammadpour, M., Sadeghi, A., & Fassihi, A. (2010). QSAR study of isatin analogues as in vitro anti-cancer agents. European Journal of Medicinal Chemistry, 45(3), 1113-1118. https:// doi.org/10.1016/j.ejmech.2009.12.010
• • Sadler, P. (1965). Antiviral chemotherapy with isatin- β-thiosemicarbazone and its derivatives. Annals of the New York Academy of Sciences, 130(1), 71-79. https://doi. org/10.1111/j.1749-6632.1965.tb12541.x
• • Sadler, P. (1961). Hydrogen bonding in some thiosemicarbazones and thioamides. Journal of the Chemical Society (Resumed), 0(0), 957-960. https://doi.org/10.1039/JR9610000957
• • Sakai, T., Miki, Y., Nakatani, M., Ema, T., Uneyama, K., & Utaka, M. (1998). Lipase-catalyzed kinetic resolution of 2-acyloxy- 2-(pentafluorophenyl)acetonitrile. Tetrahedron Letters, 39(29), 5233-5236. https://doi.org/10.1016/S0040-4039(98)01029-6
• • Sheldrick, G.M. (2015). Crystal structure refinement with SHELXL. Acta Crystallographica Section C, 71, 3-8. https://doi.org/10.1107/ S2053229614024218
• • Sheldrick, G.M. (2008). A short history of SHELX. Acta Crystallographica Section A, 64, 112-122. https://doi.org/10.1107/ S0108767307043930
• • Spek, A.L. (2009). Structure validation in chemical crystallography. Acta Crystallographica Section D, 65, 148-155. https://doi. org/10.1107/S090744490804362X
• • Swathi, K., & Sarangapani, M. (2014). Synthesis and anti-inflammatory activity of a novel series of isatin hydrazone & isatin thiosemicarbazone derivatives. World Journal of Pharmacy and Pharmaceutical Sciences, 3(2), 2070-2078. • Tisler, M. (1956). Syntheses in the 4- substituted thiosemicarbazide series. Croatica Chemica Acta, 28, 147-154.
• • Vine, K.L., Matesic, L., Locke, J.M., Ranson, M., & Skropeta, D. (2009). Cytotoxic and anticancer activities of isatin and its derivatives: a comprehensive review from 2000-2008. Anti- Cancer Agents in Medicinal Chemistry, 9(4), 397-414. https://doi. org/10.2174/1871520610909040397
• • Vine, K.L., Locke, J.M., Ranson, M., Pyne, S.G., & Bremner, J.B. (2007a). An investigation into the cytotoxicity and mode of action of some novel N-alkyl-substituted isatins. Journal of Medicinal Chemistry, 50(21), 5109-5117. http://doi.org/10.1021/jm0704189
• • Vine, K.L., Locke, J.M., Ranson, M., Pyne, S.G., & Bremner, J.B. (2007b). In vitro cytotoxicity evaluation of some substituted isatin derivatives. Bioorganic & Medicinal Chemistry, 15(2), 931-938. https://doi.org/10.1016/j.bmc.2006.10.035
• • Zhang, X-M., Guo, H., Li, Z-S., Song, F-H., Wang, W-M., Dai, H-Q. … Wang, J-G. (2015). Synthesis and evaluation of isatin-β- thiosemicarbazones as novel agents against antibiotic-resistant Gram-positive bacterial species. European Journal of Medicinal Chemistry, 101, 419-430. https://doi.org/10.1016/j.ejmech. 2015.06.047