Unveiling the adsorption and electronic interactions of drugs on 2D graphsene: insights from DFT and machine learning approaches

Abstract

Efficient identification of promising drug candidates for nanomaterial-based delivery systems is essential for advancing next-generation therapeutics. In this work, we present a synergistic framework combining density functional theory (DFT) and machine learning (ML) to explore the adsorption behavior and electronic interactions of drugs on a novel 2D graphene allotrope, termed graphsene (GrS). Graphsene, characterized by its porous ring topology and large surface area, offers an excellent platform for efficient adsorption and strong electronic coupling with drug molecules. A dataset comprising 67 pairs of different drugs adsorbed on various 2D substrates was employed to train the ML model, which was subsequently applied to predict suitable drug candidates for GrS based on molecular size and adsorption energy criteria (a database link is provided in a later section). The ML model exhibited robust predictive accuracy, achieving a mean absolute error of 0.075 eV upon DFT validation, though its sensitivity to initialization highlighted the need for larger and more diverse datasets. DFT-based analyses, including adsorption energetics, projected density of states (PDOS), and Bader charge calculations, revealed pronounced charge transfer and electronic coupling between the drug molecules and the GrS surface, elucidating the fundamental nature of drug–substrate interactions. This study reveals that the integrated DFT-ML strategy offers a rapid, cost-efficient approach for screening and understanding drug–nanomaterial interactions, paving the way for data-driven design of advanced nanomaterial-enabled drug delivery systems.