Curcumin-Fe(III) complex was prepared from Fe(NO3)3·9H2O precursor and curcumin by refluxing a slightly basic methanolic solution of their mixture with the objective of investigating its cytotoxicity. The enol form of curcumin ligand was established by FTIR, UV/Vis, 1H NMR, and 13C NMR spectroscopy. The as-prepared product was characterized by elemental analysis, FTIR, UV, and M？ssbauer spectroscopic techniques. An octahedral high-spin Fe(III) complex was obtained, δ, 0.37？mms？1; Q.S., 0.79？mms？1; no magnetic relaxation was observed at liquid N2 temperature, neither reduction of Fe(III). The tested cytotoxicity of the as-prepared complex on four cancer cell lines indicated inhibition of the curcumin activity upon complexing with iron. 1. Introduction The β diketone curcumin and curcuminoids (1,7-diaryl-1,6-heptadiene-3,5-diones) which are a group of naturally occurring 1,3-diketones have received considerable attention in the last few decades. This is due to the fact that they possess antitumor [1–3] and antioxidant effects [4] and have a good potential for metal ions complexation. It has been reported that metal complexation alters the various physiological properties especially the cytotoxic and antitumor activities of many naturally occurring compounds [5]. It is demonstrated that the coordination of metal ions, for example, Cu(II), Mn(II), Au(III), and so forth, with bioactive ligands can actually improve the pharmaceutical activity of drugs [6, 7]. The M？ssbauer metal isotopes, for example, Fe, Au, Ru, Ir, and so forth, form stable complexes with the curcumin ligand [8, 9]. Tonnesen and Greenhill [8] have reported the reduction of Fe(III) to Fe(II) in the presence of curcumin. However, there is no published M？ssbauer data on such complexes that could shed light on iron moiety and the correlation between the magnetic, symmetry, and oxidation states of metal ions in such chelates and their biological activity. In this paper we report the M？ssbauer data of Fe(curc)3 complex, compare it to the well-known Fe(acac)3 data, and identify and correlate oxidation state of the central iron metal ion, magnetic relaxation, and structural symmetry of the as-prepared complex to its antitumor cytotoxicity on four cancer cell lines. 2. Experimental 2.1. Chemicals and Materials All solvents (Sigma-Aldrich) were reagent grades and were used without further purifications. Curcumin (Sigma-Aldrich and Acros Organics) was extensively analyzed and the Sigma sample form was established. Fe(NO3)3·9H2O (BDH) laboratory reagent was used. 2.2. Analytical Instruments FTIR
References
[1]
R. H. Liu, “Potential synergy of phytochemicals in cancer prevention: mechanism of action,” Journal of Nutrition, vol. 134, no. 12, pp. 3479S–3485S, 2004.
[2]
B. K. Adams, E. M. Ferstl, M. C. Davis et al., “Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents,” Bioorganic and Medicinal Chemistry, vol. 12, no. 14, pp. 3871–3883, 2004.
[3]
E. R. Hahm, Y. S. Gho, S. Park, C. Park, K. W. Kim, and C. H. Yang, “Synthetic curcumin analogs inhibit activator protein-1 transcription and tumor-induced angiogenesis,” Biochemical and Biophysical Research Communications, vol. 321, no. 2, pp. 337–344, 2004.
[4]
S. V. Jovanovic, C. W. Boone, S. Steenken, M. Trinoga, and R. B. Kaskey, “How curcumin works preferentially with water soluble antioxidants,” Journal of the American Chemical Society, vol. 123, no. 13, pp. 3064–3068, 2001.
[5]
K. H. Thompson, K. B？hmerle, E. Polishchuk et al., “Complementary inhibition of synoviocyte, smooth muscle cell or mouse lymphoma cell proliferation by a vanadyl curcumin complex compared to curcumin alone,” Journal of Inorganic Biochemistry, vol. 98, no. 12, pp. 2063–2070, 2004.
[6]
S. Zhang, C. Tu, and X. Wang, “Novel C ytotoxic Copper(II) complexes of 8-aminoquinoline derivatives: crystal structure and different reactivity towards Glu tathioneInorg,” European Journal of Chemistry, vol. 98, pp. 4028–4035, 2004.
[7]
S. Dutta, A. Murugkar, N. Gandhe, and S. Padhye, “Enhanced antioxidant activities of metal conjugates of Curcumin derivatives,” Metal-Based Drugs, vol. 8, no. 4, pp. 183–188, 2001.
[8]
H. H. Tonnesen and J. V. Greenhill, “Studies on curcumin and curcuminoids. XXII: curcumin as a reducing agent and as a radical scavenger,” International Journal of Pharmaceutics, vol. 87, no. 1–3, pp. 79–87, 1992.
[9]
K. K. Sharma, S. Chandra, and D. K. Basu, “Synthesis and antiarthritic study of a new orally active diferuloyl methane (curcumin) gold complex,” Inorganica Chimica Acta, vol. 135, no. 1, pp. 47–48, 1987.
[10]
A. Hantzsch and C. H. Desch, Annalen, vol. 1, American Chemical Society, Washington, DC, USA, 1902.
[11]
J. Josepg, H. A. C. Mckay, and E. J. W. Verwey, “The infra-red spectra of metal acetylacetonates in the sodium chloride region,” Journal of Inorganic and Nuclear Chemistry, vol. 5, pp. 295–303, 1958.
[12]
M. I. Khalil and A. I. AL-Wassil, “The Nature of iron moiety, a mossbauer spctroscopic investigation,” Journal of the Serbian Chemical Society, vol. 3, pp. 19–25, 1999.
[13]
M. W. Hisham and F. J. Berry, “The influence of ball milling and subsequent calcination on the formation of LiFeO2,” Journal of Materials Science, vol. 37, no. 21, pp. 4621–4625, 2002.
[14]
E. Murad and R. M. Taylor, “The Mossbauer spectra of hydroxycarbonate green rusts,” Clay Minerals, vol. 19, no. 1, pp. 77–83, 1984.
[15]
C. W. Childs and J. H. Johnston, “Mossbauer spectra of proto-ferrihydrite at 77K and 295K,” Australian Journal of Soil Research, vol. 18, pp. 245–250, 1980.
[16]
H. H. Tonnesen and J. Karlsen, “Studies on curcumin and curcuminoids,” Zeitschrift für Lebensmittel-Untersuchung und -Forschung, vol. 180, pp. 402–404, 1985.
[17]
M. B. Pineda, M. T. R. Silva, M. R. Romo, E. G. Verqara, and A. R. Hennandez, “Spectroscopica,” Chemica Acta A, vol. 60, no. 5, pp. 1091–1097, 2004.
[18]
H. H. Tonnesen, J. Karlsenand, and G. B. Henegouwer, “Studies on curcumin and curcuminoids VIII. Photochemical stability of curcumin,” Zeitschrift für Lebensmittel-Untersuchung und -Forschung, vol. 183, no. 2, pp. 116–122, 1986.
[19]
L. R. C. Barclay, M. R. Vinqvist, K. Mukai et al., “On the antioxidant mechanism of curcumin: classical methods are needed to determine antioxidant mechanism and activity,” Organic Letters, vol. 2, no. 18, pp. 2841–2843, 2000.
[20]
S. V. Jovanovic, S. Steenken, C. W. Boone, and M. G. Simic, “H-atom transfer is a preferred antioxidant mechanism of curcumin,” Journal of the American Chemical Society, vol. 121, no. 41, pp. 9677–9681, 1999.
[21]
X. Sheng, X. M. Lu, Y. T. Chen et al., “Synthesis, DNA-binding, cleavage, and cytotoxic activity of new 1,7-dioxa-4,10-diazacyclododecane artificial receptors containing bisguanidinoethyl or diaminoethyl double side arms,” Chemistry, vol. 13, no. 34, pp. 9703–9712, 2007.
[22]
A. Valentini, F. Conforti, A. Crispini, et al., “Synthesis, oxidant properties, and antitumoral effects of a heteroleptic palladium(II) complex of curcumin on human prostate cancer cells,” Journal of Medicinal Chemistry, vol. 52, pp. 484–491, 2009.
[23]
G. Federici, S. Bernadini, and D. Pucci, “Effects of a heteroleptic palladium (II) comple x of curcumin on human prostate cancer ghedini,” Journal of Solid State Chemistry, vol. 160, pp. 230–236, 2002.
