Molecular mechanism for the encapsulation of the doxorubicin in the cucurbit[n]urils cavity and the effects of diameter, protonation on loading and releasing of the anticancer drug:Mixed quantum mechanical/ molecular dynamics simulations.,Computer Methods and Programs in Biomedicine

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Molecular mechanism for the encapsulation of the doxorubicin in the cucurbit[n]urils cavity and the effects of diameter, protonation on loading and releasing of the anticancer drug:Mixed quantum mechanical/ molecular dynamics simulations.
Computer Methods and Programs in Biomedicine ( IF 4.9 ) Pub Date : 2020-06-03 , DOI: 10.1016/j.cmpb.2020.105563
Zohre Hasanzade ₁ , Heidar Raissi ₁

Affiliation

Background and objectives

Doxorubicin is a common apoptotic chemotherapeutic which has shown an obvious inhibitory effect in cancer chemotherapy. Here, cucurbit[n]urils (n = 7,10) have been proposed as a doxorubicin carrier, and the effects of diameter, protonation on loading and releasing of the anticancer drug doxorubicin has been studied.

Methods

The Density Functional Theory (DFT) calculation and Molecular Dynamics (MD) simulation are performed to study the adsorption process of the (guest) Doxorubicin molecule in the neutral and protonated states within the (host) cucurbit[n]urils (n = 7,10).

Results

DFT results show that the adsorption process in water is thermodynamically favorable. It is found that the binding energies for protonated drug encapsulation in cucurbit[n]urils are weaker than those of the neutral drug, implying the protonation of doxorubicin can promote the drug release from the adsorption situation. The electron density values and their Laplacian are evaluated to identify the nature of the intermolecular interactions through the topological parameters using the Bader's theory of atoms in molecules. Furthermore, the natural bond orbital analysis shows that the electrons aretransferred from cucurbit[n]urils to drug in all complexes. MD simulation results indicate that value of drug diffusion coefficient is small, therefore, we expect DOX to be slowly released from the CB cavity.

Conclusions

Based on obtained results, cucurbit[n]urils may be a prominent nano-carrier to loading and release drug on to target cells.

中文翻译：

将阿霉素包封在葫芦腔中的分子机理以及直径，质子化对抗癌药负载和释放的影响：混合量子力学/分子动力学模拟。

背景和目标

阿霉素是一种常见的凋亡化疗药，在癌症化疗中已显示出明显的抑制作用。在这里，已提出葫芦[n] urils（n = 7,10）作为阿霉素载体，并且已经研究了直径，质子化对抗癌药物阿霉素的负载和释放的影响。

方法

进行密度泛函理论（DFT）计算和分子动力学（MD）模拟，以研究（客体）葫芦[n] urils（n = 7）中（来宾）阿霉素分子在中性和质子化状态下的吸附过程。 10）。

结果

DFT结果表明，在水中的吸附过程在热力学上是有利的。发现葫芦巴中质子化药物封装的结合能比中性药物弱，这表明阿霉素的质子化可以促进药物从吸附状态的释放。使用巴德分子中的原子理论，通过拓扑参数评估电子密度值及其拉普拉斯算子，以识别分子间相互作用的性质。此外，自然键轨道分析表明，在所有配合物中，电子都从葫芦素转移到药物中。MD模拟结果表明，药物扩散系数的值较小，因此，我们希望DOX从CB腔中缓慢释放。