nanomaterials Article Interaction between Graphene-Based Materials and Small Ag, Cu, and CuO Clusters: A Molecular Dynamics Study Isabel Lado-Touriño * and Alicia Páez-Pavón   Citation: Lado-Touriño, I.; Páez-Pavón, A. Interaction between Graphene-Based Materials and Small Ag, Cu, and CuO Clusters: A Molecular Dynamics Study. Nanomaterials 2021, 11, 1378. https:// doi.org/10.3390/nano11061378 Academic Editors: Vladimir S. Bystrov, Hideya Kawasaki and Cinzia Sada Received: 20 April 2021 Accepted: 21 May 2021 Published: 23 May 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). School of Architecture, Engineering and Design, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain; ALICIA.PAEZ@universidadeuropea.es * Correspondence: misabel.lado@universidadeuropea.es; Tel.: +34-912-115-200 Abstract: The excessive use of antibiotics has contributed to the rise in antibiotic-resistant bacteria, and thus, new antibacterial compounds must be developed. Composite materials based on graphene and its derivatives doped with metallic and metallic oxide nanoparticles, particularly Ag, Cu, and Cu oxides, hold great promise. These materials are often modified with polyethylene glycol (PEG) to improve their pharmacokinetic behavior and their solubility in biological media. In this work, we performed molecular dynamics (MD) simulations to study the interaction between small Ag, Cu, and CuO clusters and several graphene-based materials. These materials include pristine graphene (PG) and pristine graphene nanoplatelets (PGN) as well as PEGylated graphene oxide (GO_PEG) and PEGylated graphene oxide nanoplatelets (GO-PEG_N). We calculated the adsorption energies, mean equilibrium distances between the nanoparticles and graphene surfaces, and mean square displacement (MSD) of the nanoclusters. The results show that PEGylation favors the adsorption of the clusters on the graphene surfaces, causing an increase in adsorption energies and a decrease in both distances and MSD values. The strengthening of the interaction could be crucial to obtain effective antibacterial compounds. Keywords: antibacterial activity; nanoclusters; molecular dynamics; graphene-based materials; polyethylene glycol 1. Introduction The excessive use of antibiotics has contributed to the rise in antibiotic-resistant bacte- ria, and new antibacterial compounds must be developed. Graphene is a 2D monolayer material with long edges and large accessible surfaces, which give it an excellent abil- ity to immobilize diverse molecules including nanoparticles or drugs. Hu et al. [1] first reported the antibacterial activity of graphene oxide (GO) and reduced graphene oxide (rGO) nanosheets against E. coli bacteria. Many subsequent studies showed that pristine graphene, GO, and rGO have all antibacterial activity [2–9]. As graphene-based materials tend to aggregate due to strong van der Waals interactions, thus reducing their effective surface and antibacterial activity, they are modified with metals, oxides, polymers, or a com- bination of these [10–16]. In particular, the use of Ag, Cu, and their oxides adsorbed on the graphene surface appears promising [17–25]. Moreover, graphene-based composites, pre- pared by incorporating both nanoparticles and polymers, exhibit synergistic antibacterial effects [16,26]. The polymers used include polyethylene glycol (PEG), which is a polymer that helps to obtain stable graphene-PEG materials dispersible in most biocompatible solvents [27,28]. For instance, PEG-GO remains highly dispersed in serum solutions [29] and shows good pharmacokinetic behavior [30] and biocompatibility [31,32]. Molecular dynamics (MD) simulations allow the study of materials from a molecular viewpoint, providing information on an atomic scale usually inaccessible to experimental techniques [33]. The interaction between graphene-based materials and different nanopar- ticles and polymers has been described in many research works by MD [34–42]. Several Nanomaterials 2021, 11, 1378. https://doi.org/10.3390/nano11061378 https://www.mdpi.com/journal/nanomaterials