University of Belgrade - Faculty of Physical Chemistry, Studentski trg 12-16, 11 158 Belgrade, Serbia.
Phys Chem Chem Phys. 2021 Jan 6;23(1):574-584. doi: 10.1039/d0cp05798c.
The planarity and the appropriate size of the porphyrin ring make porphyrin derivatives ideal ligands for stacking to guanine quartets and they could thus be used as anti-cancer drugs. In this contribution we analyzed complexes of a guanine quartet with a porphyrin molecule, magnesium porphyrin and calcium porphyrin. As magnesium and calcium ions are located in the center and above the porphyrin ring, respectively, the two metalloporphyrins are expected to have different impacts on the target. The optimized structures of the three systems revealed geometrical changes in the guanine quartet upon complexation: while stacking of porphyrin and magnesium porphyrin does not induce significant changes, calcium porphyrin considerably distorts the quartet's structure, which has significant implications for the binding properties among guanine molecules. Ab initio molecular dynamics simulations revealed that the systems perform small fluctuations around the equilibrium structures. The largest atom displacements are performed by the calcium ion. The interacting quantum atoms methodology enabled analysis of the binding properties in the studied complexes. Interestingly, although the proximity of the calcium ion is responsible for the quartet's pronounced deformation and weakening of guanine-guanine binding, it also enables stronger binding of the metal ion to the quartet, resulting in a more stable complex. These results imply that metalloporphyrin-like ligands with out-of-plane central ions might represent promising drug candidates in anti-tumor treatment.
卟啉衍生物的平面性和合适的尺寸使其成为与鸟嘌呤四重体堆积的理想配体，因此可以用作抗癌药物。在本研究中，我们分析了鸟嘌呤四重体与卟啉分子（镁卟啉和钙卟啉）的配合物。由于镁和钙离子分别位于卟啉环的中心和上方，因此预计这两种金属卟啉对靶标具有不同的影响。三个系统的优化结构表明，在配合物形成后，鸟嘌呤四重体的几何形状发生了变化：卟啉和镁卟啉的堆积不会引起明显的变化，而钙卟啉则会显著扭曲四重体的结构，这对鸟嘌呤分子之间的结合性质具有重要意义。从头算分子动力学模拟表明，这些系统在平衡结构周围会发生小的波动。最大的原子位移是由钙离子引起的。量子原子相互作用方法能够分析研究复合物中的结合性质。有趣的是，尽管钙离子的接近导致四重体明显变形和鸟嘌呤-鸟嘌呤结合减弱，但它也使金属离子与四重体更强地结合，从而形成更稳定的配合物。这些结果表明，具有离域中心离子的金属卟啉类似配体可能成为抗肿瘤治疗中有前途的药物候选物。
