Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N, 36050, Guanajuato, México.
Consejo Superior de Investigaciones Científicas (IFF-CSIC), Instituto de Física Fundamental, Serrano 123, 28006, Madrid, Spain.
J Comput Chem. 2018 Jan 15;39(2):71-80. doi: 10.1002/jcc.24920. Epub 2017 Aug 21.
Cisplatin (CP) has been widely used as an anticancer drug for more than 30 years despite severe side effects due to its low bioavailability and poor specificity. For this reason, it is paramount to study and design novel nanomaterials to be used as vectors capable to effectively deliver the drug to the biological target. The CP square-planar geometry, together with its low water solubility, suggests that it could be possibly easily adsorbed on 2D graphene nanostructures through the interaction with the related highly conjugated π-electron system. In this work, pyrene has been first selected as the minimum approximation to the graphene plane, which allows to properly study the noncovalent interactions determining the CP adsorption. In particular, electronic structure calculations at the MP2C and DFT-SAPT levels of theory have allowed to obtain benchmark interaction energies for some limiting configurations of the CP-pyrene complex, as well as to assess the role of the different contributions to the total interaction: it has been found that the parallel configurations of the aggregate are mainly stabilized around the minimum region by dispersion, in a similar way as for complexes bonded through π-π interactions. Then, the benchmark interaction energies have been used to test corresponding estimations obtained within the less expensive DFT to validate an optimal exchange-correlation functional which includes corrections to take properly into account for the dispersion contribution. Reliable DFT interaction energies have been therefore obtained for CP adsorbed on graphene prototypes of increasing size, ranging from coronene, ovalene, and up to C H . Finally, DFT geometry optimizations and frequency calculations have also allowed a reliable estimation of the adsorption enthalpy of CP on graphene, which is found particularly favorable (about -20 kcal/mol at 298 K and 1 bar) being twice that estimated for the corresponding benzene adsorption. © 2017 Wiley Periodicals, Inc.
顺铂（CP）作为一种抗癌药物已经使用了 30 多年，尽管其生物利用度低且特异性差，导致严重的副作用。因此，研究和设计新型纳米材料作为载体，有效地将药物递送到生物靶标，这一点至关重要。CP 的平面四方几何形状及其低水溶性表明，它可以通过与相关的高度共轭π电子系统的相互作用，很容易被吸附到二维石墨烯纳米结构上。在这项工作中，首先选择了芘作为与石墨烯平面的最小近似，这使得可以正确研究决定 CP 吸附的非共价相互作用。特别是，在 MP2C 和 DFT-SAPT 理论水平的电子结构计算允许获得 CP-芘配合物的一些极限构型的基准相互作用能，以及评估不同贡献对总相互作用的作用：发现，聚集物的平行构型主要通过色散在最小区域周围稳定，类似于通过π-π相互作用键合的复合物。然后，将基准相互作用能用于测试在更便宜的 DFT 中获得的对应估计值，以验证包含对色散贡献进行适当考虑的修正的最佳交换相关泛函。因此，对于从 coronene、ovalene 到 CH 的越来越大的石墨烯原型上吸附的 CP，已经获得了可靠的 DFT 相互作用能。最后，DFT 几何优化和频率计算也允许可靠地估计 CP 在石墨烯上的吸附焓，其结果特别有利（在 298 K 和 1 巴下约为-20 kcal/mol），是相应苯吸附的两倍。
