Blas J Ramón, López-Bes Jose Maria, Márquez Manuel, Sessler Jonathan L, Luque F Javier, Orozco Modesto
Molecular Modeling and Bioinformatics Unit, Institut de Recerca Biomèdica, Parc Científic de Barcelona, Josep Samitier 1-5, Barcelona 08028, Spain.
Chemistry. 2007;13(4):1108-16. doi: 10.1002/chem.200600757.
Molecular dynamics simulations show that calix[4]pyrrole (CP) and octafluorocalix[4]pyrrole (8F-CP) are extremely flexible molecules. CP mainly adopts the 1,3-alternate conformation in all the solvents, although the percentage of alternative conformations increases in polar solvents, especially those with good hydrogen-bonding acceptor properties. However, in the case of 8F-CP, the cone conformation is the most populated in some solvents. Transitions between conformers are common and fast, and both CP and 8F-CP can adopt the cone conformation needed for optimum interaction with anions more easily than would be predicted on the basis of previous gas-phase calculations. Furthermore, the present studies show that when a fluoride anion is specifically placed initially in close proximity to CP and 8F-CP in their respective 1,3-alternate conformations, an extremely fast change to the cone conformation is observed in both cases. The results suggest that preorganization does not represent a major impediment to anion-binding for either CP or 8F-CP, and that ion-induced conformational changes can follow different mechanisms depending on the solvent and the chemical substituents present on the calix[4]pyrrole beta-pyrrolic positions.
分子动力学模拟表明，杯[4]吡咯（CP）和八氟杯[4]吡咯（8F-CP）是极具柔性的分子。CP在所有溶剂中主要采取1,3-交替构象，尽管在极性溶剂中，尤其是那些具有良好氢键受体性质的溶剂中，交替构象的比例会增加。然而，对于8F-CP，在某些溶剂中锥式构象占比最大。构象之间的转变常见且迅速，并且与基于先前气相计算所预测的情况相比，CP和8F-CP都能更轻松地采取与阴离子实现最佳相互作用所需的锥式构象。此外，目前的研究表明，当氟离子最初被特意放置在分别处于1,3-交替构象的CP和8F-CP附近时，在这两种情况下都观察到了向锥式构象的极快速转变。结果表明，预组织对于CP或8F-CP与阴离子结合而言并非主要障碍，并且离子诱导的构象变化可能会根据溶剂以及杯[4]吡咯β-吡咯位置上存在的化学取代基而遵循不同的机制。
