Organotin Complexes Derived From Arenebenzeneseleninic Acid: Synthesis, Structural Characterization, In Vitro Antitumor Activity

Since the 1950 s, the studies of extensive applications in industry and agriculture such as PVC stabilizers, asymmetric synthesis, pharmaceutical chemistry and the other areas grow prosperous. The synthesis of organotin compounds having biological activity is the frontier field of organotin chemistry.Besides, organoselenium compound has drawn great attention due to their special structure, excellent performance and extensive applications recently,and organoselenium compound with high biological activity not only can be more effectively for the body to absorb, but have less toxic than inorganoselenium compound. Organoselenium medicaments which have remakeable effect on the antivirus and anticancer make significant contributions to overcome diseases for humankind. Therefore, intensive study of organotin compounds derived from areneseleninic acids has practical application potential. On the other hand, the structure and coordination model of benzeneseleninic acids are similar to carboxylic acids, organotin compounds can also exhibit complicated and interesting structures. In view of the above reasons, we selected and synthesized some benzeneseleninic acids,further synthesized a series of organotin complexes derived from areneseleninic acids, and made research of their structure and properties in detail. The research of the paper is as follows:1. 4-fluorobenzeneseleninic acid and 4-bromobenzeneseleninic acid were synthesized and investigated via reactions of diorganotin and triorganotin. Finally, we succeeded to get six organotin compounds, these complexes were characterized by means of IR, NMR, elemental analysis. Five complexes were also characterized by X-ray crystallographic diffraction analysis. The analysis revealed that:(1) when 4-fluorobenzeneseleninic acid or 4-bromobenzeneseleninic acid reacts with R3 Sn Cl(R = Me, Ph) at 1:1 molar ratio, they adopt infinite 1D polymeric chain structure. 4-fluorobenzeneseleninic acid and 4-bromobenzeneseleninic acid is bridging ligands, the basal plane is defined by three carbon atoms from the methyl group linked to the Sn atom and the axial position of the trigonal bipyramid is derived from two oxygen atoms of ligands, so the central tin atom displays pentacoordinated distorted trigonal bipyramid geometry.(2) when 4-fluorobenzeneseleninic acid reacts with Me2 Sn Cl2 in a molar ratio of 2:1, we gained one helical chain polymers structures containing Sn2O4Se2 eight-membered ring. Four O atoms from two 4-fluorobenzene seleninato ligands bond with the tin atom of dimethyltin dichloride, and the central tin atom defines a six-coordinated distorted octahedron geometry. When 4-fluorobenzeneseleninic acid reacts with Ph2 Sn Cl2 in a molar ratio of 2:1, obtained tetranuclear cage structure, the central tin atom defines a hexacoordinated distorted octahedron.2. 2-(trifluoromethyl) benzeneseleninic acid and 3-(trifluoromethyl) benzeneseleninic acid were synthesized and investigated via reactions of diorganotin and triorganotin. Finally, we succeeded to get six new organotin compounds, these complexes were characterized by the means of IR, NMR, elemental analysis. Six complexes were also characterized by X-ray crystallographic diffraction analysis. Results indicate that(1) when 2-(trifluoromethyl) benzeneseleninic acid reacts with trimethyltin(IV) chloride, the novel complex adopt a sixteen member ring structure; when reacts with other trialkyltin chloride, they adopt infinite 1D polymeric chain. 2-(trifluoromethyl) benzeneseleninic acid as bridging ligands, the basal plane is defined by three carbon atoms from the methyl group linked to the Sn atom and the axial position of the trigonal bipyramid is derived from two oxygen atoms of two ligands. The central atom displays penta-coordinate distorted trigonal bipyramid geometry.(2) when 2-(trifluoromethyl) benzeneseleninic acid and 3-(trifluoromethyl) benzeneseleninic acid reacts with R2 Sn Cl2(R=Me, Bu), we acquired one 1D helical chain polymers structures containing Sn2O4Se2 eight-membered ring. Four O atoms from two 4-fluorobenzene seleninato ligands bond with the tin atom of dimethyltin dichloride, and tin atom displays a penta-coordinate distorted octahedron geometry.3. Based on the structure of these organotin(IV) compounds, their antitumor activity against KG-1, A-549, Hep G2, and HO-8910 cells were tested by means of MTT testing. The interaction between organotin complexes derived from areneseleninic acids with bovine serum albumin(BSA) has also been studied. The obtained test indicate that these complexes have obvious inhibitory effect on cancer cells, in general, triorganotin(IV) compounds display better biological activity than their diorganotin complexes, triphenyltin derivatives have a better antitumor activity than trimethyltin derivatives, and dibuthyltin derivatives have a better antitumor activity than dimethyltin derivatives. In addition, through preliminary screening, found that complex 2 significantly inhibit the growth of A549 cells. The effect of complex 2 on A549 cells has also made a comprehensive tests, such as flow cytometry quantitative calculation of the proportion of apoptosis, Annexin V- PE / 7-AAD double staining to detect cell apoptosis, using fluorescent staining to detect the change of ROS and the MMP in A549 cell. The fluorescene spectrometry revealed the fact that the intrinsic fluorescene of BSA was quenched by some complexes.