Virtual screening in the design of ionic liquids as environmentally safe bactericides

Abstract

Due to the excessive use of antibiotics in human and livestock treatments, growing antibiotic resistance has been observed. The high velocity of bacterial mutation impedes the healing process, especially for hospital patients with weak immune protection, often resulting in death. The World Health Organization (WHO) stressed the gravity of this issue and in 2017 published the first global priority pathogen list, which includes 20 bacteria, including Staphylococcus aureus. In the face of growing resistance to available antibiotics, new types of substances are under consideration as biocides, and moreover, increasing attention is given to ionic liquids (ILs). To this end, we performed computational high-throughput screening of 60 270 ionic liquids for agents active towards S. aureus. Moreover, in addition to the target properties, we analyzed the biodegradation process of prospective ILs to preliminarily estimate the environmental safety of the final biocide product. According to the U.S. Environmental Protection Agency (U.S. EPA) and the Organization for Economic Co-operation and Development (OECD) recommendations, we applied virtual screening via a classification QSAR model and a multimedia mass-balance model as a supporting tool in the design of safer ionic liquids. As a result, we explored the biocidal activity and prescreened the environmental safety of a large dataset of ionic liquids in a much shorter period of time and with less workload than required by the experimental research that could otherwise be performed. Finally, we listed 73 ILs with biocidal potential towards S. aureus that do not potentially exhibit environmentally adverse features.