Electrochemical and molecular modelling studies to assess the photoreactive properties of Efavirenz
Authors:   , Mthiyane Thethiwe Promise 
Published: April 2023

Efavirenz (EFV) is commonly used as an antiretroviral drug to treat HIV/AIDS and is known to undergo photoreactions that could be exploited for photodegradation applications. In addition, there is limited information on the photoreactivity of EFV. This work focuses on two case studies to assess the photocatalytic properties of EFV supported by experimental and molecular modelling (commonly referred to as computational chemistry). The first case study deals with the design of an innovative electrochemical sensor for the detection of EFV, using titanium dioxide nanoparticles (TiO2-NPs) doped on glassy carbon electrode (GCE) with nafion as an anchor agent (GCE/TiO2-NPs-nafion). TiO2-NPs were synthesized using Eucalyptus globulus leaf extract and characterized using Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-vis), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and energy-dispersive spectroscopy (EDS). The electrochemical and sensing properties of the developed sensor for EFV were assessed using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), differential pulse voltammetry (DPV) and chronoamperometry. The oxidation peak current response for EFV on the GCE/TiO2-NPs-nafion electrode was greater compared to the bare and modified GCE/TiO2-NPs electrodes. A linear dynamic range of 4.5 to 18.7 µM with a 0.01 µM limit of detection was recorded on the electrode using DPV. The electrochemical sensor demonstrated good selectivity as well as practicability for the detection of EFV drugs with excellent recoveries ranging from 92.0-103.9%. The density functional theory (DFT)-based quantum chemical modelling was used to establish the chemical reactivity for EFV, suggesting the benzoxazine ring as the active site. Monte Carlo (MC) simulations revealed a strong electrostatic interaction on the GCE/TiO2-NPs-nafion-EFV (substrate-adsorbate) system. The results showed good agreement between the MC computed adsorption energies and the experimental CV results for EFV. The stronger adsorption energy of nafion onto the GCE/TiO2-NPs substrate contributed to the catalytic role in the signal amplification sensing of EFV. The second case study deals with the assessment of the photocatalytic degradation of EFV in combination with green synthesized TiO2-NPs. The photocatalytic activity of TiO2-NPs was examined by the degradation of EFV in an aqueous medium and a maximum degradation efficiency of 91.77% was observed at a reaction time of 5 h. In addition, the electronic spectra of the EFV complex bound to single TiO2-NPs in a gas- and solution-phase were investigated using time-dependent density functional theory (TD-DFT) calculations. The calculated spectra obtained in this work were benchmarked against the gas-phase photodecomposition of the EFV- TiO2-NPs complex using UV-vis spectrophotometry. Overall, the results show that the biosynthesized TiO2-NPs have the potential for sensing pharmaceutical applications and their degradation. The results provide an effective way to explore the design of new 2D materials for the sensing of EFV, which is highly significant in the field of medicinal and materials chemistry.