Theoretical investigation of the complexation, structural, and electronic properties of complexes between oseltamivir drug and cucurbit[n = 6–9]urils

Wandee Rakrai,Chatthai Kaewtong,Banchob Wanno,Chanukorn Tabtimsai

doi:10.1007/s11224-022-01888-1

Wandee Rakrai, Chatthai Kaewtong + Show 2 more

Open Access

https://doi.org/10.1007/s11224-022-01888-1

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Abstract

The structural geometries of cucurbit[n]uril CB[n] with n = 6–9 and their complexes with oseltamivir (OST) drug were obtained using the density functional theory computations. The stationary points of the most stable complexes were confirmed using vibrational frequency calculation. The complexation energies and electronic properties of CB[n]/OST complexes were investigated. The calculated results indicate that the intermolecular interactions in all the studied complexes occur via a large number of dipole–dipole interactions, especially hydrogen bonds between oxygen atoms of CB[n] and hydrogen atoms of amine of oseltamivir drug. The negative complexation energies of CB[n]/OST complexes in both gas and water phases indicate that the host–guest complexes are exothermic process and the complexes are more stable than its bare CB[n]. In addition, the CB[7]/OST complex is more stable than that of all studied CB[n]/OST complexes. The frequency calculation results of the most stable complexes for each of CBs indicate that complexations occur via a spontaneous process. The NBO analysis of complexes shows the transferring of partial charge from CB[n]s to oseltamivir which correspond to their MEP contours. The HOMO and the LUMO orbitals are localized on the oseltamivir in CB[n]/OST complexes. After drug complexation, the electronic properties also display that the energy gaps of CB[n] are significantly changed. All of the complexation properties point out that CB[n]s can act as a host for appropriately oseltamivir guest, even in aqueous solution.

Highlights

In the field of supramolecular chemistry, the design of drug delivery system through the host–guest formation is interested [1]
The negative complexation energies of CB[n]/OST complexes in both gas and water phases indicate that the host–guest complexes are exothermic process and the complexes are more stable than its bare CB[n]
The frequency calculation results of the most stable complexes for each of CBs indicate that complexations are occurred via a spontaneous process

Summary

Introduction

In the field of supramolecular chemistry, the design of drug delivery system through the host–guest formation is interested [1]. One efficiency method is the drug encapsulation with macrocyclic host. Macrocyclic host for drug encapsulation has been widely interested such as cyclodextrins [6,7,8] calixarenes [9,10], crown ethers [11] and cucurbit[n]urils [12,13,14,15]. CB[n] compounds are widely interest for drug delivery applications through host–guest formation because the CB[n] and their derivatives are non–toxic [20]. We present a theoretical study on the possibility of the complexations between oseltamivir and cucurbit[n]uril (CB[n], n = 6, 7, 8 and 9) and investigate their energetical and geometrical properties using the density functional theory (DFT) calculations. The charge transfer, energies of the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), and molecular electrostatic potential (MEP) for the species and complexes have been computed

Computational Details

Results And Discussion

Conclusions