Computational screening of metal-substituted HKUST-1 materials for the delivery of 5-fluorouracil

• Published in: Computational and theoretical chemistry Vol. 1239; p. 114791
• Main Authors: Lu, Jin-Xia, Pang, Chun-Xiu, Wang, Wen-Lu, Shi, Ling-Fei, Zhang, Jia-Chen, Jiang, Zhi-Qing, Chen, Jing-Hua, Sun, Wei-Ming
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2024
• Subjects: Density functional theory; Drug delivery; Fluorouracil; HKUST-1; Metal organic frameworks; Density functional theory; Drug delivery; Metal organic frameworks; HKUST-1; Fluorouracil
• ISSN: 2210-271X
• DOI: 10.1016/j.comptc.2024.114791

A detailed computational study on the adsorption of 5-fluorouracil onto a series of transition metal-substituted HKUST-1 materials has been performed to deeply understand the interaction between MOF materials and antitumor drugs, and screen the best drug carrier. [Display omitted] •The first row transition metal-substituted HKUST-1 (M−HKUST−1) was screened for the 5-Fu delivery.•Sc-HKUST-1 is proved to be the best carrier for 5-Fu among the studied M−HKUST−1 materials.•Bonding analyses by various approaches revealed that 5-Fu is adsorbed to M−HKUST−1 via forming strong polar covalent bonds.•Ionization potential of metal centre of MOF may be a reliable descriptor for screening drug carriers.•The calculated UV–Vis and IR spectra are conducive to the experimental characterization of the proposed drug delivery system. Metal organic frameworks (MOFs) have been widely adopted as drug carriers in experiments, but there is still no systemic theoretical insights on the interaction between MOFs and drugs. Hence, a detailed computational study on the adsorption of 5-fluorouracil (5-Fu) onto the first row transition metal-substituted HKUST-1 (denoted as M−HKUST−1; M=Sc ∼ Zn) materials has been performed. By substituting transition metal atoms for Cu, the adsorption energy (−18.34 kcal/mol) of 5-Fu onto HKUST-1 can be increased to −29.51 kcal/mol for 5-Fu@Sc-HKUST-1 or reduced to −14.02 kcal/mol for 5-Fu@Zn-HKUST-1, providing an effective way to modulate the interaction bewteen drug and carriers. Bonding analyses proved that 5-Fu is chemically adsorbed to M−HKUST−1 via forming strong polar covalent M−O bonds. Most of these proposed MOFs show good performance for delivering this drug, in particular M−HKUST−1 (M=Sc, V, Cu, and Cr). This DFT study provides a novel strategy to screen different MOFs for delivering various drugs, and intrigue intense experimentalists’ interests to verify our conclusions by synthesizing various M−HKUST−1 for the 5-Fu delivery.