Elsevier

Inorganica Chimica Acta

Volume 437, 1 October 2015, Pages 41-46
Inorganica Chimica Acta

Synthesis, crystal structures, DNA interaction and anticancer activity of organobismuth(V) complexes

https://doi.org/10.1016/j.ica.2015.07.008Get rights and content

Highlights

  • Three organobismuth(V) complexes were synthesized and their structures were characterized.

  • The interaction of the complex Ph3Bi(OOCC6H3F2)2 with calf-thymus DNA was investigated.

  • Anticancer activity of three complexes were also investigated.

Abstract

We have synthesized three novel organobismuth(V) complexes Ph3Bi(OOCC6H3F2)2 1, Ph3Bi(OOCC6H4CF3)2 2 and Ph3Bi(OOCC4H3S)2 3, and their structures were characterized by IR spectroscopy, elemental analysis, 1H NMR and single crystal X-ray diffraction. X-ray crystallography showed that all of the bismuth atoms adopt distorted trigonal–bipyramidal geometries. The complex molecules lead to one-dimensional chain structure and two-dimensional network structure through C–H…X (X = O, F, C) interactions. The interaction of the complex 1 with calf-thymus DNA (CT-DNA) was investigated by UV absorption spectroscopy, fluorescence emission spectroscopy and viscosity. All results revealed that the complex 1 binds to DNA via a intercalative mode. Furthermore the proliferation inhibitory activities of the three complexes on MDA-MB-231 breast cancer cells were investigated. The results indicated that all of the three complexes have superior inhibition of cellular proliferation.

Graphical abstract

In the complex Ph3Bi(OOCC4H3S)2, the complex molecules lead to a one-dimensional chain structure through C–H…C interactions and two-dimensional structure is obtained through C–H…O interactions.

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Introduction

Bismuth is a unique element in terms of its low level of toxicity and noncarcinogenic nature, despite its heavy metal status. Bismuth compounds have been widely used in the clinic for centuries because of their high effectiveness and low toxicity in the treatment of a variety of microbial infections, including syphilis, diarrhea, gastritis and colitis [1], [2], [3], [4]. Apart from antimicrobial activity, bismuth compounds exhibit anticancer and antiviral activities, 212Bi and 213Bi compounds have also been used as targeted radio-therapeutic agents for cancer treatment [5], [6], [7], [8], [9], [10], [11], [12]. Furthermore, bismuth ion with a larger ionic radius (1.16 Å) has one inert electron pair (6s2) and forms the complexes with higher coordination numbers which makes their structural characterization interesting and meaningful.

Traditionally, inorganic bismuth compounds have found widespread uses in medicine and veterinary practice. Various types of bismuth salts have been introduced as fungicides. They are also used as medicines for the treatment of gastrointestinal disorders due to their astringent, bacteristatic, and disinfectant actions [13], [14], [15]. However, bismuth salts exhibit only modest antibacterial activity [16]. Since the 1990s, the physiological aspect of bismuth chemistry has received considerable attention, and much effort has been devoted to the synthesis of different types of bismuth compounds in order to improve their antibacterial activities [17], [18], [19], [20]. Organobismuth compounds have at least one direct carbon to Bi bond and represent an important class of organometallic compounds. The chemistry of organobismuth compounds is continuing to develop and many classes have been reported including bismuth(III) containing heterocylces (bismacycles and heterobismacycles) and triphenylbismuth(V) bis(carboxylate) complexes for instance [21], [22], [23]. But only a small amount of literatures reported organobismuth(V) complexes and their anticancer activities. One reason may be that the crystals suitable for X-ray diffraction study of these compounds have been difficult to obtain. The other reason that Bi(V) is generally not stable in biological solutions [24]. It is envisaged that they are likely to exhibit interesting properties structurally and biologically. Particularly, information on the mechanism of these compounds is sparse and valuable. Therefore, it seems important for us to obtain their bismuth(V) complexes as a strategy of preparation of new drug candidates in which the metal and ligand could act synergistically.

Bi is known to have a high affinity for oxygen, nitrogen and sulfur ligands [25]. Benzoic acid and 2-thiophenecarboxylic acid have high application value in medicine [26], so it caused our great interest in organobismuth(V) complexes. In this paper, three organobismuth(V) complexes have been synthesized by the reaction of Ph3BiCl2 with Na(O2CR) and characterized. The interactions of the complex 1 with calf-thymus DNA (CT-DNA) were also investigated by UV absorption spectroscopy, fluorescence emission spectroscopy and viscosity. In addition, we also studied the anticancer activities on MDA-MB-231 breast cancer cells of the three complexes.

Section snippets

Measurement and reagents

All solvents were pretreated to get rid of the water before using. 3,5-Difluorobenzoic acid, 4-(trifluoromethyl)benzoic acid and triphenylbismuth dichloride were purchased from TCI. 2-Thiophenecarboxylic acid was obtained from Aladdin. Calf thymus DNA (CT-DNA, biochemical reagent) was purchased from Sigma–Aldrich and used without further purification. A solution of CT-DNA in Tris–HCl buffer (5 × 10−3 mol L−1 Tris–HCl; 5 × 10−2 mol L−1 NaCl, pH = 7.2) gave an absorbance ratio, A260/A280, between 1.8 and

Crystal structures of compounds 13

The crystals of the complexes belong to triclinic system. Space group of complexes 1 and 3 is P1¯ and space group of complex 2 is P3(1). The bismuth atoms in these compounds adopt distorted trigonal–bipyramidal geometries. Each Bi atom is coordinated by five atoms: namely, two O atoms from COO–, three C atoms from benzene rings. Three benzene rings linked to Bi atom are not in the same plane as two of them is located in the horizontal plane, while another is located in the vertical plane. The

Conclusion

In summary, we synthesized three organobismuth(V) complexes, and analyzed their structures by the single crystal X-ray diffraction. All of the three complexes crystallizes in the triclinic crystal system, space group P1¯, P3(1) and P1¯. We studied the binding mode and binding strength between the complex 1 and CT-DNA by UV spectroscopy, fluorescence spectroscopy and viscosity. The results show that the complex 1 bound to CT-DNA via a intercalative mode. Further we studied anticancer activity of

Acknowledgment

This research was supported by the National Natural Science Foundation of China to C.F. Bi (No. 21371161).

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