Study of Ruthenium(II) Complexes with Anticancer Drugs as Ligands. Design of Metal-Based Phototherapeutic Agents

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• 作者：Renzo Cini ; Gabriella Tamasi ; Sandra Defazio ; Maddalena Corsini ; Piero Zanello ; Luigi Messori ; Giordana Marcon ; Francesca Piccioli ; and Pierluigi Orioli
• 刊名：Inorganic Chemistry
• 出版年：2003
• 出版时间：December 1, 2003
• 年：2003
• 卷：42
• 期：24
• 页码：8038 - 8052
• 全文大小：287K
• 年卷期：v.42,no.24(December 1, 2003)
• ISSN：1520-510X

文摘

The reaction of trans-[RuCl₂(PPh₃)₃] (Ph = C₆H₅) with 2-thio-1,3-pyrimidine (HTPYM) and 6-thiopurines (TPs) producedmainly crystalline solids that consist of cis,cis,trans-[Ru(PPh₃)₂(N,S-TPYM)₂] (1) and cis,cis,trans-[Ru(PPh₃)₂(N⁷,S-TPs)₂]X₂ (X = Cl^-, CF₃SO₃^-). In the case of TPs, other coordination isomers have never been isolated andreported. Instead, the mother liquor obtained after filtration of 1 produced red single crystals of trans,cis,cis-[Ru(PPh₃)₂(N,S-TPYM)₂]·2H₃O⁺·2Cl^- (2·2H₃O⁺·2Cl^-). Selected ruthenium(II)-thiobase complexes were studied fortheir structural, reactivity, spectroscopic, redox, and cytotoxic properties. Single crystals of 1 contain thiopyrimidinatoanions chelated to the metal center via N and S. The Ru-N bonds are significantly elongated for 1 [2.122(2) and2.167(2) Å] with respect to 2 [2.063(3) Å] because of the trans influence from PPh₃. The coordination pseudo-octahedron for 2 is significantly elongated at the apical sites (PPh₃ ligands). Solutions of cis,cis,trans isomers in airare stable for weeks, whereas those of 2 turn green within 24 h, in agreement with the respective redox potentials.cis,cis,trans- and trans,cis,cis-[Ru(PH₃)₂(N,S-TPYM)₂], as optimized through the DFT methods at the Becke3LYPlevel are in good agreement with experimental geometrical parameters (1 and 2), with cis,cis,trans being morestable than trans,cis,cis by 3.88 kcal. The trend is confirmed by molecular modeling based on semiempirical (ZINDO/1) and molecular mechanics (MM) methods. Cytotoxic activity measurements for cis,cis,trans-[Ru(PPh₃)(N-THZ)(N⁷,S -H₂TP)₂]Cl₂ (4) (THZ = thiazole, H₂TP = 6-thiopurine) and cis,cis,trans-[Ru(PPh₃)₂(N⁷,S-HTPR)2]Cl₂ (5)(HTPR = 6-thiopurine riboside) against ovarian cancer cells A2780/S gave IC₅₀ values of 17 ± 1 and 29 ± 9 M,respectively. Furthermore, the spectral analysis of HTPYM, TPs, and their Ru(II) complexes in solution shows thatintense absorptions occur in the UVA/vis region of light, whereas standard nucleobases absorb in the UVB region.