SYNTHESIS OF TETRAKIS-N,N,N-TRIMETHYLAMMONIUMMETHYL-C-3,4-DIMETHOXYPHENYLCALIX[4]RESORCINARENE IODIDE BASED VANILLIN AND ITS ANTIDOTE ACTIVITY FOR CHROMIUM(VI) INTOXICATION

https://doi.org/10.22146/ijc.21299

Suryadi Budi Utomo(1*), Jumina Jumina(2), Dwi Siswanta(3), Mustofa Mustofa(4)

(1) Chemical Education Study Program, PMIPA FKIP, Sebelas Maret University, Surakarta
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281
(4) Department of Pharmacology and Toxicology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta 55281
(*) Corresponding Author

Abstract


A research has been conducted to synthesize tetrakis-N,N,N-trimethylammoniummethyl-C-3,4-dimethoxyphenylcalix[4]resorcinarene iodide from vanillin and investigate its antidote capability for Cr(VI) intoxication. The synthesis was carried out in four steps i.e. (1) O-alkylation of 4-hydroxy-3-methoxybenzaldehyde, (2) HCl-catalyzed condensation of 3,4-dimethoxybenzaldehyde with resorcinol, (3) Mannich reaction of
C-3,4-dimethoxyphenylcalix[4]resorcinarene with formaldehyde and dimethylamine in the presence of HCl to yield tetrakis-N,N-dimethylaminomethyl-C-3,4-dimethoxyphenylcalix[4]resorcinarene, and (4) treatment the Mannich base with methyl iodide to produce the quaternary ammonium salt of tetrakis-N,N,N-trimethylammoniummethyl-C-3,4-dimethoxyphenylcalix[4]resorcinarene iodide. According to the analysis of 1H-NMR spectrometer, the targeted compounds tend to exist in the chair (C2h) conformation. The capability of resorcinarene for Cr(VI) antidote was examined by orally injection method on mice groups. Based on LD50 determination, the resorcinarene was classified as non toxic compound according to Loomis criteria. Therapeutic using quaternary ammonium-modified resorcinarene was able to reduce metal concentrations of Cr(VI) in liver, kidney, and serum in the magnitude of 78.30; 85.72, and 88.79%, respectively. The higher dose of drug administered the greater decrease in the level of heavy metal. Judging from the amount of milligrams of reduced chromium per gram of organ, kidney is the organ having highest decreasing metal concentrations.

Keywords


vanillin; tetrakis-N,N,N-trimethylammoniummethyl-C-3,4-dimethoxyphenyl-calix[4]resorcinarene iodide; LD50; antidote; Cr(VI)

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References

[1]   Utomo, S.B., Jumina, Siswanta, D., Mustofa, and Kumar, N., 2011, Indo. J. Chem., 11, 1, 1–8

[2]   Jumina, Sarjono, R.E., Paramita, B.W., Siswanta, D., Santosa, S.J., Anwar, C., Sastrohamidjojo, H., Ohto, K., and Oshima, T., 2007, J. Chin. Chem. Soc., 54, 5, 1167–1178.

[3]   Aoyoma, Y., Tanaka, Y., and Sugahara, S., 1989, J. Am. Chem. Soc., 111, 14, 5397–5404.

[4]   Boas, U., and Heegaard, P.M., 2004, Chem. Soc. Rev., 33, 1, 43–63.

[5]   Tunstand, L.M., Tucker, J.A., Dalcanale, E., Weiser, J., Bryant, J.A., Sherman, J.C., Helgeson, R.C., Knobler, C.B., and Cram, D.J., 1989, J. Org. Chem., 54, 6, 1305–1312.

[6]   Arora, V., Chawla, H.M., and Singh, S.P., 2007, Arkivoc, 2, 172–200.

[7]   Fox, O.D., Cookson, J., Wilkinson, E.J.S., Drew, M.G.B., MacLean, E.J., Teat, S.J., and Beer, P.D., 2006, J. Am. Chem. Soc., 128, 21, 6990–7002.

[8]   Utomo, S.B., Jumina, Siswanta, D., and Mustofa, 2012, Indo. J. Chem., 12, 1, 49–56.

[9]   Utomo, S.B., Jumina, and Wahyuningsih, T.D., 2009, Indo. J. Chem., 9, 3, 437–444.

[10] Moore, S.S., Tarnowski, T.L., Newcomb, M., and Cram, D.J., 1977, J. Am. Chem. Soc., 99, 19, 6398–6405.

[11] Zhao, J., Bolte, M., Dordea, C., Gruner, B., and Bohmer, V., 2009, Synthesis, 23, 4063–4067.

[12] Kalenius, E., Kekäläinen, T., Neitola, R., Beyeh, K., Rissanen, K., and Vainiotalo, P., 2008, Chem. Eur. J., 14, 17, 5220–5228.

[13] Henge-Napoli, M.H., Archimbaud, M., Ansoborlo, E., Metivier, H., and Gourmelon, P., 1995, Int. J. Radiat. Biol., 68, 4, 389–393.

[14] Shinkai, S., Mori, S., Koreishi, H., Tsubaki, T., and Manabe, O., 1986, J. Am. Chem. Soc., 108, 9, 2409–2416.

[15] Yang, W., and Villiers, M.M., 2005, AAPS J., 7, 1, 241–248.

[16] Widianarko, B., Verweij, R.A., van Gestel, C.A., and van Straalen, N.M., 2000, Ecotoxicol. Environ. Saf., 46, 1, 95–100.

[17] Hartono and Santosa, E.B., 2005, Enviro, 6, 2, 58–63.

[18] Abidin, Z., and Sunardi, 2009, Indo. J. Chem., 9, 3, 425–431.

[19] William, P.L. and James, R.C., 2000, Principles of Toxicology, 2nd ed., John Wiley and Sons, New York.

[20] Hansen, M.B., Johansen, J.D., and Menné, T., 2003, Contact Dermatitis, 49, 4, 206–212.

[21] Vasant, C., Rajaram, R., and Ramasami, T., 2003, Free Radical Biol. Med., 35, 9, 1082–1100.

[22] Silva, R.C., Júnior, J.C.R., Varaschin, M.S., de Sousa, R.V., Oliveira, L.C.A., Daniel, J.L.P., de Lima, R.F., and Moreiva, A.O., 2010, Anim. Prod. Sci., 50, 4, 293–299.

[23] Wedeen, R.P., and Qian, L.F., 1991, Environ. Health Perspect., 92, 71–74.

[24] Dartsch, P.C., Hildenbrand, S., Kimmel, R., and Schmahl, F.W., 1998, Int. Arch. Occup. Environ. Health, 71, S40–S45.

[25] Kirpnick-Sobol, Z., Reliene, R, and Schiestl, R.H., 2006, Cancer Res., 66, 7, 3480–3484.

[26] Jumina, Rastuti, U., and Matsjeh, S., 2003, Indo. J. Chem., 3, 1, 14–18

[27] Sangster, J., 1997, Octanol-Water Partition Coefficients: Fundamentals and Physical Chemistry, Vol. 2 of Wiley Series in Solution Chemistry, John Wiley & Sons, New York.

[28] Jacob, A.J., Guertin, J., and Avakian, C., 2005, Chromium (VI) Handbook, CRC Press, New York

[29] Suginome, M., Uehlin, L., and Murakami, M., 2004, J. Am. Chem. Soc., 126, 41, 13196–13197.

[30] Matsuo, J.I., Tanaki, Y., and Ishibashi, H., 2006, Org. Lett., 8, 4371–4374.

[31] Song, J., Shih, H.-W., and Deng, L., 2007, Org. Lett., 9, 603–606.

[32] Högberg, A.G.S., 1980, J. Am. Chem. Soc., 102, 19, 6046–6050.

[33] Erdtman, H., Högberg, S., Abrahamsson, S., and Nilsson, B., 1968, Tetrahedron Lett., 9, 14, 1679–1682.

[34] Gutsche, C.D., 1989, Calixarenes. Monograph in Supramolecular Chemistry, Royal Society of Chemistry, Cambridge.

[35] Loomis, T.A., and Hayes, A.W., 1996, Loomis’s Essentials of Toxicology, 4th ed., Academic press, California.



DOI: https://doi.org/10.22146/ijc.21299

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