Crystal Structure, Cytotoxicity and Interaction with DNA of Zinc (II) Complexes with o-Vanillin Schiff Base Ligands

RESEARCH ARTICLE Crystal Structure, Cytotoxicity and Interaction with DNA of Zinc (II) Complexes with o-Vanillin Schiff Base Ligands Mei-Ju Niu1,2*, Zhen Li1,2, Guo-Liang Chang1,2, Xiang-Jin Kong1, Min Hong1, Qingfu Zhang1 1 School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, Shandong, 252059, China, 2 Shandong Provincial Key Laboratory of Chemical Energy Storage and Novel Cell Technology, Liaocheng University, Liaocheng, Shandong, 252059, China * Abstract OPEN ACCESS Citation: Niu M-J, Li Z, Chang G-L, Kong X-J, Hong M, Zhang Q-f (2015) Crystal Structure, Cytotoxicity and Interaction with DNA of Zinc (II) Complexes with o-Vanillin Schiff Base Ligands. PLoS ONE 10(6): e0130922. doi:10.1371/journal.pone.0130922 Editor: Paul Taylor, University of Edinburgh, UNITED KINGDOM Received: February 26, 2015 Accepted: May 27, 2015 Published: June 26, 2015 Copyright: © 2015 Niu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The authors acknowledge the financial support of the Natural Science Foundation of Shandong Province (No. ZR2013BM017). Competing Interests: The authors have declared that no competing interests exist. Two new zinc complexes, Zn(HL1)2 (1) and [Zn2(H2L2)(OAc)2]2 (2) [H2L1 = Schiff base derived from o-vanillin and (R)-(+)-2-amino-3-phenyl-1-propanol, H3L2 = Schiff base derived from o-vanillin and 2-amino-2-ethyl-1,3-propanediol], have been synthesized and characterized by single crystal X-ray diffraction, elemental analyses, TG analyses, solid fluorescence, IR, UV-Vis and circular dichroism spectra. The structural analysis shows that complex 1 has a right-handed double helical chain along the crystallographic b axis. A homochiral 3D supramolecular architecture has been further constructed by intermolecular C-H


π, O-H


O and C-H


O interactions. Complex 2 includes two crystallographically independent binuclear zinc molecules. The two binuclear zinc molecules are isostructural. The 2-D sheet supramolecular structure was formed by intermolecular hydrogen bonding interaction. The fluorescence of ligands and complexes in DMF at room temperature are studied. The interactions of two complexes with calf thymus DNA (CT-DNA) are investigated using UV-Vis, CD and fluorescence spectroscopy. The results show that complex 1 exhibits higher interaction with CT-DNA than complex 2. In addition, in vitro cytotoxicity of the complexes towards four kinds of cancerous cell lines (A549, HeLa, HL-60 and K562) were assayed by the MTT method. Investigations on the structures indicated that the chirality and nuclearity of zinc complexes play an important role on cytotoxic activity. Introduction Schiff bases are considered as privileged and the most widely used ligands, due to their metal complexes having variety of applications in catalysis, functional materials, antibacterial, anticancer, optical resolution [1–5] and organic synthesis [6]. Thus, the rational design and synthesis of new Schiff base metal complexes are very meaningful. In recent years, Schiff base zinc complexes, especially chiral Zn (II) complexes have attracted considerable research interest owing to their various coordination modes and special properties. Until now researchers have PLOS ONE | DOI:10.1371/journal.pone.0130922 June 26, 2015 1 / 14 Zinc (II) Complexes, Cytotoxicity and Interaction with DNA Fig 1. Syntheses of Schiff base ligands and complexes. doi:10.1371/journal.pone.0130922.g001 explored their potential applications in luminescent materials [7,8], SHG–active materials [9], fluorescent sensor [10,11]. For instance, Consiglio et al. [12] reported the synthesis and fluorescence properties of Zn (II)–Schiff–base complexes with 2–hydroxy–4–(undec–10–enyloxy) benzaldehyde and 1,2–diamine derivates. Roy et al. [13] reported two hexanuclear zinc (II) complexes with Schiff base ligands and explained their fluorescence properties. To this class of compounds, their anticancer activities are also hot topics [14,15]. It is important to understand the DNA binding of complexes containing zinc (II) ions and their possible relationship to cytotoxicity in tumor cell lines [16,17]. Among the most accessed methods for investigating drug– DNA interactions, the procedure using fluorescent changes of Ethidium bromide (abbr. EB)DNA system is attractive in nucleic acids chemistry owing to the high sensitivity and good accuracy [18]. Recently we have been focused on designing novel Schiff base polydentate ligands and investigating their self-assembly with metal centers, as well as their properties of corresponding complexes. We have reported several Schiff base nickel (II), cobalt (II)/(III) and copper (II) complexes, which exhibited significant effect for CT-DNA binding ability and cytotoxic activity [19–21]. To explore Schiff base zinc complexes as anticancer agents and stable blue fluorescent materials, two kinds of Schiff base zinc complexes were synthesized using ovanillin as Schiff base ligands (Fig 1). Their interactions with CT-DNA were also investigated by using UV-Vis, circular dichroism and fluorescence spectra. The in vitro cytotoxic effect of these complexes on cancerous cell lines, including human lung carcinoma cell line (A549), chronic myelogenous leukemia cells line (K-562), human promyelocytic leukemia cells (HL60) and human colon carcinoma cell lines (HCT-116), showed that chiral complex 1 exhibited substantial cytotoxic activity. In addition, complex 1 also exhibited significant effect for CT-DNA binding ability. The results indicated that the chirality and nuclearity have improtant influence on their anticancer activities and fluorescent emission. Experimental Section Materials and method All chemicals are commercially available and used without further purification. IR spectra were recorded on Nicolet-5700 FT-IR spectrophotometer with KBr pellets in the 4000–400 cm-1 region. UV-Vis spectra were performed on a UV-2550 ultraviolet spectrophotometer. 1H and 13 C NMR spectra were obtained on a Varian Mercury Plus 400 MHz NMR spectrometer. PLOS ONE | DOI:10.1371/journal.pone.0130922 June 26, 2015 2 / 14 Zinc (II) Complexes, Cytotoxicity and Interaction with DNA Elemental analyses for C, H and N were performed at a PE-2400-II apparatus. UV-vis absorption spectra were recorded on an HP-8453A diode array spectrophotometer. Fluorescence spectra were recorded on an LS55 spectrofluorometer. Circular dichroism (CD) spectra measurements were conducted on a Jasco J-810 spectropolarimeter. Thermal analyses were performed with a TGA SDTA 851e thermogravimetric analyzer. The Zn elemental contents for the complexes were measured by PE-Optima 2100 DV apparatus. Syntheses (...truncated)