Synthesis, crystal structures, DNA interaction and anticancer activity of organobismuth(V) complexes
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.
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 1–3
The crystals of the complexes belong to triclinic system. Space group of complexes 1 and 3 is 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 , P3(1) and . 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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