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Complex Formation Between Ferric(III), Chromium(III), and Cupric(II) Metal Ions and (O,N) and (O,O) Donor Ligands with Biological Relevance in Aqueous Solution

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Abstract

The complexation equilibria of L-norleucine and gallic acid were studied in aqueous solutions at 25.00 °C and ionic strength 0.15 mol⋅dm−3 (NaNO3), by means of potentiometry and spectrophotometry. The ferric (FeIII), chromium (CrIII), and cupric (CuII) complexing abilities of L-norleucine and gallic acid, along with their overall stability constants, were obtained with the HYPERQUAD 2008 program from the potentiometric data. The concentration distributions of the various complex species in solution were evaluated and discussed. UV–visible spectroscopic measurements were carried out to give qualitative information about the composition of the complexes formed in these solutions. The cytotoxic activities of the binary and ternary metal complexes of L-norleucine and gallic acid were tested and evaluated against HEp-2 (human laryngeal carcinoma), Daoy (human medulloblastoma), MCF-7 (human breast adenocarcinoma), and WiDr (human colon adenocarcinoma) tumor cell lines. Also, their antioxidant activities were examined by free radical scavenging assay.

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Acknowledgements

Financial Support was provided by National Taiwan University of Science and Technology Research Fund (contract No. 99-0541064-001-0001).

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Author notes

  1. Ahmed E. Fazary

    Present address: Chemistry Department, Faculty of Science, King Khalid University, Abha, 9044, Kingdom of Saudi Arabia

Authors and Affiliations

  1. Department of Chemical Engineering, National Taiwan University of Science and Technology, 43 Keelung Road, Section 4, Taipei, 106-07, Taiwan

    Ahmed E. Fazary, Erzalina Hernowo, Artik Elisa Angkawijaya, Mohamed Taha & Yi-Hsu Ju

  2. School of Pharmacy, College of Medicine, National Taiwan University, Jen-Ai Rd. Sec. 1, Taipei, 100, Taiwan

    Tse-Chuan Chou & Chih Hung Lin

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Appendices

Supplementary Data

Potentiometric titration experimental data points for all systems associated with this article, listed in 3 tables as a supplementary file and can be found in the online version.

Appendix: Cytotoxic Activities and Antioxidant Activities of L-norleucine, Gallic Acid and Their Metal Complexes

2.1 A.1 Cytotoxic Activities

Some of the nonprotein amino acid and phenolic chelates studied were found to behave as rather efficient anti-proliferative and cytotoxic agents, with their effect on healthy cells being reversible upon drug removal. From the results now obtained (Table 5), it is possible to conclude that for the complexes studied under physiological conditions, the nature of the amine ligand(s) (e.g., the number of N atoms), the characteristics of the leaving groups on the copper, chromium, and iron ions, the number and coordination mode of the metal ion(s), and their chemical environment determine their antitumor activity, most probably through induction of DNA structural rearrangements. Thus, the design of new, more effective anticancer drugs should be governed by these crucial factors, since slight changes in the metal coordination are sufficient to significantly change the in vitro anti-proliferative and/or cytotoxic properties of these compounds. Among the complex species tested against the four human cancer cell lines, i.e., HEp-2 (human laryngeal carcinoma), Daoy (human medulloblastoma), MCF-7 (human breast adenocarcinoma), and WiDr (human colon adenocarcinoma), the chromium complexes of Nle and GA showed weak cytotoxic activities. It was observed that, the copper complexes of Nle and GA exhibited strong cytotoxic activities against the four cancer cell lines, while iron complex species showed a moderate cytotoxic activity (Table 5).

Table 5 Cytotoxic activities of L-norleucine, gallic acid and their metal complexes against human tumor cells
Full size table

2.2 A.2 Antioxidant Activities

It is known that copper, chromium, and iron metal ions are essential trace metals for many living organisms [40]. These metal ions play a crucial role in various enzymes that catalyze oxidation/reduction reactions correlated with the antioxidant system of these organisms [41]. It has been reported that certain copper, chromium, iron complexes catalyze radical formation while others seem to have antioxidant efficacy [42]. However, these different behaviors depend upon the chemical environment and nature of the chelating agent. In the present work, the copper and iron complexes of GA showed a very strong antioxidant activity, while chromium complexes of GA exhibited moderate antioxidant activities (Table 6). Also, the iron, and copper complexes of Nle exhibited a moderate antioxidant activity, while the chromium complexes of Nle exhibited weak antioxidant activities. It worth noting that the iron and copper ternary complexes of Nle and GA showed a very strong antioxidant activity, while chromium ternary complexes of Nle and GA showed good antioxidant activity (Table 6).

Table 6 DPPH radical scavenging assay of L-norleucine, gallic acid and their metal complexes
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Fazary, A.E., Hernowo, E., Angkawijaya, A.E. et al. Complex Formation Between Ferric(III), Chromium(III), and Cupric(II) Metal Ions and (O,N) and (O,O) Donor Ligands with Biological Relevance in Aqueous Solution. J Solution Chem 40, 1965–1986 (2011). https://doi.org/10.1007/s10953-011-9768-1

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