Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA.
Org Biomol Chem. 2011 Oct 26;9(22):7727-33. doi: 10.1039/c1ob05996c. Epub 2011 Oct 6.
The diffusion coefficients of a series of closely matched pairs of macrocyclic and linear molecules have been compared using NMR spectroscopy. The macrocyclic series was designed both to overlap with and extend beyond the molecular weight range typically employed for drug-like molecules. The linear molecules each represent a carbogenic fission of their macrocyclic counterparts, designed to minimize differences in functionality and physicochemical properties. Each series of molecules was prepared using copper catalyzed azide-alkyne cycloaddition (CuAAC) reactions conducted in a flow using a copper tube. The macrocyclic series exhibited consistently higher diffusion across the entire molecular weight range studied. The fold difference in diffusion coefficients between the macrocyclic and linear analogues appeared to be independent of either solvent viscosity or dielectric environment.
使用 NMR 光谱比较了一系列紧密匹配的大环和线性分子的扩散系数。大环系列的设计既与通常用于类似药物分子的分子量范围重叠，又超出了该范围。线性分子各自代表其大环对应物的碳架断裂，旨在最小化功能和物理化学性质的差异。使用铜催化的叠氮化物-炔烃环加成（CuAAC）反应在铜管中进行流动反应，分别制备了两个系列的分子。在所研究的整个分子量范围内，大环系列的扩散系数始终较高。大环和线性类似物之间扩散系数的折叠差异似乎与溶剂粘度或介电环境无关。
