Zinc oxide nanosheet as a promising route for carrier 5-fluorouracil anticancer drug in the presence metal impurities: Insights from DFT calculations

Highlights

• Electronic properties of the 5-FU/pristine and metal-doped ZnONS are studied.

• Adsorption energy is stronger with shorter distance between 5-FU and metal-doped ZnONS.

• The electronic properties of the ZnONS are affected and altered with metal impurities.

• The complex structures became more stable and lower reactive with metal impurities.

• We can utilize various metal-doped ZnONS as a membrane to deliver 5-FU drug molecule.

Abstract

Zinc oxide nanosheet (ZnONS) is a favorable road to deliver numerous drug molecules in the human body. The electronic properties of the 5-FU/pristine ZnONS and 5-FU/metal-doped ZnONS are studied by using DFT method, which implemented in the quantum espresso package. Metal impurities are utilized to recognize the suitability and optimization of the adsorption 5-FU on the ZnONS superficial. For metal-doped ZnONS and 5-FU/metal-doped ZnONS, we observed that the shape of the electronic band structure is changed. So, the electronic band gap and Fermi level are reduced and shifted up, respectively compared to the pristine ZnONS, but they still have semiconductor behaviors. Moreover, all complex structures become more stable and lower reactive due to the total energy increased. Results disclosed a weaker interaction between the pristine ZnONS and 5-FU, but there is a stronger interaction between the 5-FU and metal-doped ZnONS. We detected very exciting results. The adsorption process is depended on the type of the impurities and the distance between the 5-FU molecule and metal-doped ZnONS. So, it became stronger when we made the distance between this molecule and metal-doped ZnONS is smaller. Additionally, all structures have a lower and higher electron affinity and chemical hardness, respectively. That means these structures needed a higher energy to donating/accepting an electron to be cation/anion. Besides, there is a great interaction between the pristine ZnONS and 5-FU molecule in the present (Cu, Au, and Ag) impurities between them, but other metal impurities made a weak interaction between them. Then, we can utilize the new substrate (metal-doped ZnONS structures) as a carrier to the 5-FU drug molecule.

Introduction

Scientists have prepared and development new nanoparticles and various nanomaterials with different impurities and methods in diverse applications. Liu et al. studied the effective synthesis of the Ag-ZnO nanoparticles for the sunlight produced photocatalytic dissolution. They proved the efficiency of two steps polymer-network gel procedures in the installation of Ag-ZnO nanocatalyst with excellent photocatalytic properties. They discovered that Ag-ZnO nanoparticles displayed a wonderful high photocatalytic effectiveness compared to pristine ZnO nanoparticle [1]. Ashraf et al. studied the graphene/Ag₂ doped TiO₂ nanocomposite, which got from traditional centrifuging and desiccation, and freezing desiccation approaches at 500 °C. They discovered that the TiO₂/Ag nanoparticles distributed by graphene nanosheet in the freezing dried nanocomposite was best than the traditional dried model. In addition, the freezing dried nanocomposite had a higher photocatalytic effectiveness than another nanocomposite [2]. Liao et al. studied the boost and properties development of carbon/copper complexes by using nickel impurities. They discovered that nickel impurities made the modulated carbon matrix is intensive. Then, this modification of the carbon matrix, the porosity of the carbon/copper structure expressively decreased. Moreover, the interfacial bonding method altered from natural mechanical overlap to solid solution bonding. Then, the inter-face state is knowingly developed [3]. Su et al. utilized zirconium metal-organic framework nanocomposite entrenched with bioactive silver nanoclusters (Ag NCs) to carry antitumor drug by using AS1411 aptamer (Apt), which known by UiO-66@AgNCs@Apt. They advanced a multi-functional targeted drug delivery system by using one tube covering procedure based on UiO-66@AgNCs@Apt@DOX. So, the AS1411 aptamer and DOX utilized as directing ligand and therapeutic factor, collected with Ag NCs as fluorescent sensors. They detected that the UiO-66@AgNCs@Apt@DOX delivered into the core of cancer cells. Then, releasing the laden drug due to the lower pH level of cancer cells. Cell possibility analyze proved that the UiO-66@AgNCs@Apt nanocomposites have a lower cytotoxicity to human breast cancer cell in an inclusive concentricity range of 5–50 μg × mL⁻¹. Also, it improved cytotoxicity of UiO-6@AgNCs@Apt@DOX, which reached by the collective therapeutic influences of DOX and AS1411 [4]. In addition, nanomaterials, such as graphene nanosheet (GNS), graphene oxide nanosheet (GONS), and zinc oxide nanosheet (ZnONS) also used in the numerous fields of biomedicine and environment. These nanomaterials can be utilized as biosensors for initial analysis and therapy of tumors [5]. Surudžić et al. presented that the polyvinyl alcohol/graphene nanosheet (PVA/GNS) nanocomposites was a good filter for biomedical soft tissue plants and injury ribbon [6]. Jiao et al. detected that the polymer prepared via joining carboxymethyl cellulose (CMC) to GONS could be utilized as drug carriers [7]. Nowadays, zinc oxide nanomaterial is very useful for using as a drug delivery due to it has unique physical properties and prepared in a wide variety of morphologies. Therefore, it exhibits in various forms, such as nanosheet, nanotube, nanowire, nanorod and nanoribbon [8], [9], [10]. One of these forms is zinc oxide nanosheet (ZnONS), which is very significant and gorgeous in an assortment of applications because it has a chemical active exposed surface, high explicit surface area, and restricted thickness. ZnONS is a semiconductor compound and it has a direct electronic band gap at the Γ point with 1.7 eV electronic band gap of the pure ZnONS [11]. In addition, the valence electrons of ZnONS are allocated as; (Zn: 3d¹⁰4s², which has twelve electrons, and O: 2s²2p⁴, which has six electrons). Whereas the conduction band of pure ZnONS contains from 4 s and 2p of Zn and O orbitals, respectively [12]. In addition, ZnONS, (2-D) honeycomb structure is a multifunctional material because it possesses unique physical and chemical properties. Then, ZnONS can be used in different applications such as optoelectronics, sensors and drug delivery [13]. There are various studies of ZnONS theoretical and experimental. Chen et al. observed that ZnONS has a weak interaction between layers. The covalent bond is controlled on the interlayer interaction of the ZnONS [14]. Due to ZnONS has nontoxic nature, which can be used to recompense the metal ion toxicity. Therefore, it can be useful for using for biomedical applications. Experimentally, Pasquet et al. is used ZnO as a new antimicrobial [15]. So, it is widely used in objective figuration to address sundry skin conditions, such as burns, scars, and irritations [16]. Mohammed and Falah are utilized ZnONS as a carrier to the (5-Fu, 6-Mp, GB, and CY) anticancer drugs in the vertical and horizontal directions with various concentrations of the Ga impurities. They found out that different concentrations of the Ga impurities were changed the behavior of ZnONS from semiconducting to semimetal. Also, the total energy was increased for Ga-doped ZnONS structures and made these structures more stable and lower reactive. In additional, the electronic properties of the complex structures (anticancer drug/Ga-doped ZnONS) were dependent on the kind and direction of the adsorption of the anticancer drugs on the Ga-doped ZnONS [10].

Moreover, the 5-FU anticancer drug is a heterocyclic aromatic organic compound. 5-FU has a similar structure to the pyrimidine molecules of DNA and RNA, which is mostly used as a solid cancer treating, such as esophagus, stomach, intestines, carcinoma [17], [18], [19]. Therefore, 5-FU is exciting in pharmacology because it intervenes with nucleoside metabolism by the competitive prevent of thymidylate synthetase, the enzyme catalyzes the methylation of deoxyuridylic acid to thymidylic acid. Therefore, it prevents DNA replication and reform and its depletion encourages cytotoxicity and cell death [20], [21].

At this juncture, we investigated the adsorption of the 5-FU anticancer drug on the pristine ZnONS with and without various metals impurities (Cu, Ag, Au, Ni, Pt, and Pd) by using density functional theory (DFT) method. The main objective of this study is how can utilize the new substrates (pristine ZnONS and metal-doped ZnONS) as a carrier to the 5-FU anticancer drug by computing various electronic properties, such as electronic band structure, electronic band gap, total energy, and adsorption energy.