Meggers Eric
Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104, USA.
Curr Opin Chem Biol. 2007 Jun;11(3):287-92. doi: 10.1016/j.cbpa.2007.05.013. Epub 2007 Jun 4.
Altering biological processes with small synthetic molecules is a general approach for the design of drugs and molecular probes. Medicinal chemistry and chemical biology are focused predominately on the design of organic molecules, whereas inorganic compounds find applications mainly for their reactivity (e.g. cisplatin as a DNA-reactive therapeutic) or imaging properties (e.g. gadolinium complexes as MRI diagnostics). In such inorganic pharmaceuticals or probes, coordination chemistry in the biological environment or at the target site lies at the heart of their modes of action. However, past and very recent results suggest that it is also worth exploring a different aspect of metal complexes: their ability to form structures with unique and defined shapes for the design of 'organic-like' small-molecule probes and drugs. In such metal-organic compounds, the metal has the main purpose to organize the organic ligands in three-dimensional space. It is likely that such an approach will complement the molecular diversity of organic chemistry in the quest for the discovery of compounds with superior biological activities.
利用小分子合成物改变生物过程是药物和分子探针设计的常用方法。药物化学和化学生物学主要专注于有机分子的设计，而无机化合物主要因其反应活性（如顺铂作为一种能与DNA发生反应的治疗药物）或成像特性（如钆配合物作为磁共振成像诊断剂）而得到应用。在这类无机药物或探针中，生物环境或靶点部位的配位化学是其作用方式的核心。然而，过去以及最近的研究结果表明，探索金属配合物的另一个方面也是值得的：它们形成具有独特且明确形状的结构的能力，以用于设计“类有机”小分子探针和药物。在这类金属有机化合物中，金属的主要作用是在三维空间中组织有机配体。在寻找具有卓越生物活性的化合物的过程中，这种方法很可能会补充有机化学的分子多样性。
