Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA.
Inorg Chem. 2011 Dec 5;50(23):12099-107. doi: 10.1021/ic201645b. Epub 2011 Nov 3.
We previously showed that Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6) binds to dsDNA only upon irradiation with visible light and that photolysis results in a 34-fold enhancement of its cytotoxicity toward Hs-27 human skin fibroblasts, making it potentially useful for photodynamic therapy (PDT). With the goal of gaining further insight on the photoinduced binding of DNA to the complex, we investigated by NMR spectroscopy the mechanism by which 2,2'-bipyridine (bpy), a model for biologically relevant bidentate nitrogen donor ligands, binds to Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6) upon irradiation in D(2)O. The photochemical results are compared to the reactivity in the dark in D(2)O and CD(3)CN. The photolysis of Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6) with equimolar bpy solutions in D(2)O with visible light affords Rh(2)(O(2)CCH(3))(2)(eq/eq-bpy)(CH(3)CN)(2)(D(2)O(ax))(2) (eq/eq) with the reaction reaching completion in ~8 h. Only vestiges of eq/eq are observed at the same time in the dark, however, and the reaction is ~20 times slower. Conversely, the dark reaction of Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6) with an equimolar amount of bpy in CD(3)CN affords Rh(2)(O(2)CCH(3))(2)(η(1)-bpy(ax))(CH(3)CN)(5) (η(1)-bpy(ax)), which remains present even after 5 days of reaction. The photolysis results in D(2)O are consistent with the exchange of one equiv CH(3)CNeq for solvent, and the resulting species quickly reacting with bpy to generate eq/eq; the initial eq ligand dissociation is assisted by absorption of a photon, thus greatly enhancing the reaction rate. The photolytic reaction of Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6):bpy in a 1:2 ratio in D(2)O affords the eq/eq and (eq/eq)(2) adducts. The observed differences in the reactivity in D(2)O vs CD(3)CN are explained by the relative ease of substitution of eq D(2)O vs CD(3)CN by the incoming bpy molecule. These results clearly highlight the importance of dissociation of an eq CH(3)CN molecule from the dirhodium core to attain high reactivity and underscore the importance of light for the reactivity of these compounds, which is essential for PDT agents.
我们之前已经证明，Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6) 只有在可见光照射下才能与 dsDNA 结合，光解会使其对 Hs-27 人皮肤成纤维细胞的细胞毒性增强 34 倍，使其有可能用于光动力疗法（PDT）。为了进一步了解该复合物与 DNA 的光诱导结合机制，我们通过 NMR 光谱研究了 2,2'-联吡啶（bpy）与 Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6) 在光照下结合的机制，bpy 是一种具有生物相关双齿氮供体配体的模型。将光化学结果与黑暗条件下在 D(2)O 和 CD(3)CN 中的反应性进行了比较。在 D(2)O 中，用等摩尔 bpy 溶液对 Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6) 进行光解，光照下得到 Rh(2)(O(2)CCH(3))(2)(eq/eq-bpy)(CH(3)CN)(2)(D(2)O(ax))(2)（eq/eq），反应在~8 小时内完成。然而，在黑暗中同时仅观察到 eq/eq 的痕迹，反应速度慢 20 倍。相反，Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6) 在 CD(3)CN 中与等摩尔 bpy 的黑暗反应生成 Rh(2)(O(2)CCH(3))(2)(η(1)-bpy(ax))(CH(3)CN)(5)（η(1)-bpy(ax)），即使在反应 5 天后仍存在。D(2)O 中的光解结果与一个 CH(3)CNeq 取代溶剂的取代反应一致，生成的物质与 bpy 快速反应生成 eq/eq；初始 eq 配体的解离由吸收光子辅助，从而大大提高了反应速率。Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6):bpy 在 D(2)O 中的 1:2 光解反应得到 eq/eq 和 (eq/eq)(2) 加合物。D(2)O 与 CD(3)CN 中反应性的差异可以用 eq D(2)O 相对于 CD(3)CN 的取代相对容易程度来解释，因为 bpy 分子进入。这些结果清楚地强调了从双核铑核心中解离一个 eq CH(3)CN 分子以获得高反应性的重要性，并强调了光对这些化合物反应性的重要性，这对于 PDT 剂至关重要。
