Department of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Kurpińskiego 5, 85-096 Bydgoszcz, Poland.
Int J Mol Sci. 2023 Jan 12;24(2):1548. doi: 10.3390/ijms24021548.
Pt (II) derivatives show anti-cancer activity by interacting with nucleobases of DNA, thus causing some spontaneous and non-spontaneous reactions. As a result, mono- and diaqua products are formed which further undergo complexation with guanine or adenine. Consequently, many processes are triggered, which lead to the death of the cancer cell. The theoretical and experimental studies confirm that such types of interactions can also occur with other chemical compounds. The vitamins from B group have a similar structure to the nucleobases of DNA and have aromatic rings with single-pair orbitals. Theoretical and experimental studies were performed to describe the interactions of B vitamins with Pt (II) derivatives such as cisplatin, oxaliplatin and carboplatin. The obtained results were compared with the values for guanine. Two levels of simulations were implemented at the theoretical level, namely, B3LYP/6-31G(d,p) with LANL2DZ bases set for platinum atoms and MN15/def2-TZVP. The polarizable continuum model (IEF-PCM preparation) and water as a solvent were used. UV-Vis spectroscopy was used to describe the drug-nucleobase and drug-B vitamin interactions. Values of the free energy (ΔG) show spontaneous reactions with mono- and diaqua derivatives of cisplatin and oxaliplatin; however, interactions with diaqua derivatives are more preferable. The strength of these interactions was also compared. Carboplatin products have the weakest interaction with the studied structures. The presence of non-covalent interactions was demonstrated in the tested complexes. A good agreement between theory and experiment was also demonstrated.
Pt(II)衍生物通过与 DNA 的碱基相互作用显示出抗癌活性,从而导致一些自发和非自发反应。结果形成了单水和双水产物,它们进一步与鸟嘌呤或腺嘌呤络合。因此,触发了许多导致癌细胞死亡的过程。理论和实验研究证实,这种类型的相互作用也可能与其他化合物发生。B 族维生素与 DNA 的碱基具有相似的结构,并且具有具有单电子对轨道的芳环。进行了理论和实验研究来描述 B 族维生素与顺铂、奥沙利铂和卡铂等 Pt(II)衍生物的相互作用。将获得的结果与鸟嘌呤的值进行了比较。在理论水平上实施了两个模拟水平,即 B3LYP/6-31G(d,p),带有 LANL2DZ 基组的铂原子和 MN15/def2-TZVP。使用极化连续体模型(IEF-PCM 准备)和水作为溶剂。使用紫外-可见光谱描述药物-碱基和药物-B 族维生素相互作用。自由能(ΔG)的值表明顺铂和奥沙利铂的单水和双水衍生物发生了自发反应,但是与双水衍生物的相互作用更可取。还比较了这些相互作用的强度。卡铂产物与研究结构的相互作用最弱。在测试的配合物中证明了存在非共价相互作用。理论和实验之间也表现出良好的一致性。