Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi, 467-8603, Japan.
Inorg Chem. 2013 Apr 1;52(7):3653-62. doi: 10.1021/ic302101c. Epub 2013 Mar 12.
Antioxidant therapies have been considered for a wide variety of disorders associated with oxidative stress, and synthetic catalytic scavengers of reactive oxygen species would be clinically superior to stoichiometric ones. Among them, salen-manganese complexes (Mn(Salen)) seem promising, because they exhibit dual functions, i.e. superoxide dismutase- and catalase-mimetic activities. We have been developing enzyme-mimetic Mn(Salen) complexes bearing a functional group that enhances their catalytic activity. Here, we describe the design and synthesis of novel Mn(Salen) complexes with general acid-base catalytic functionality, inspired by the reaction mechanism of catalase. As expected, these Mn(Salen) complexes showed superior catalase-like activity and selectivity, while retaining moderate SOD-like activity. An unsubstituted pyridyl group worked well as a functionality to promote catalase-like activity. The introduced functionality did not alter the redox potential suggesting that the auxiliary-modified complex acted as an acid-base catalyst analogous to catalase. We believe that our approach provides a new design principle for sophisticated catalyst design. Further, the compounds described here appear to be good candidates for use in antioxidant therapy.
抗氧化疗法已被广泛应用于各种与氧化应激相关的疾病,而与化学计量比相比,合成的催化活性氧清除剂在临床上更具优势。其中,Salen-锰配合物(Mn(Salen))似乎很有前途,因为它们具有双重功能,即超氧化物歧化酶和过氧化氢酶模拟活性。我们一直在开发具有增强催化活性的功能基团的酶模拟 Mn(Salen)配合物。在这里,我们描述了受过氧化氢酶反应机制启发的具有一般酸碱催化功能的新型 Mn(Salen)配合物的设计和合成。正如预期的那样,这些 Mn(Salen)配合物表现出优异的过氧化氢酶样活性和选择性,同时保持中等的 SOD 样活性。未取代的吡啶基作为促进过氧化氢酶样活性的功能基团效果很好。引入的功能基团并未改变氧化还原电位,这表明辅助修饰的配合物充当类似于过氧化氢酶的酸碱催化剂。我们相信我们的方法为复杂催化剂设计提供了新的设计原则。此外,这里描述的化合物似乎是抗氧化治疗的良好候选物。