Schiff bases are molecules that carry a characteristic imine bond that are derived from carbonyl compounds and are widely studied due to the versatility of their steric and electronic properties. Schiff bases are significant because of their biologically active properties that can improve and develop agrochemicals, anti‐inflammatories, antivirals, and even radiopharmaceuticals for cancer targeting. This study is focused on synthesizing a family of novel metal Schiff base complexes that have potential to act as antimicrobials over a wide range of pathogenic species.In a previous study, a family of metal Schiff base complexes with an NN'NN coordination sphere was synthesized. This study found that antimicrobial activity using Schiff base complexes with chromium, iron, or manganese as their center showed greater inhibition of Aspergillus sp. growth than a variety of known antimicrobial drugs (Kumar et al., 2012). In an attempt to expand the antimicrobial potential of these compounds, we changed the structure of these Schiff base ligands to utilize an NN'OS coordination sphere with the same set of metal centers. We hypothesized that the chemical activity of the sulfur atom would provide an improved range of antimicrobial function.Our synthesis of NN'OS coordination sphere‐based antimicrobials began with the compound cyclopentanone. Cyclopentanone was condensed with carbon disulfide, recrystallized, protonated, and methylated with dimethyl sulfate. The resultant methylated product was aminated with two different diamines to form a set of novel primary amines. These primary amines were reacted with salicylaldehydes with different substitutions to form a family of Schiff base ligands. The last step in the synthesis process was to add a transition metal to the Schiff base ligands (chromium, iron, or manganese) through a reflux reaction. After synthesis, each metal Schiff base complex was characterized through 1H and 13C nuclear magnetic resonance, infrared, and gas chromatography‐mass spectroscopy.With synthesis complete, current work focuses on the examination of these compounds as effective antimicrobials. The compounds are being tested for these properties against Aspergillus furmigatus as a representative of a broad range of Aspergillus species. Characterized Schiff base complexes are being compared for their level of antimicrobial activity against that shown by Miconazole, an established antimicrobial used to treat an array of fungal infections. The results of these tests may establish Schiff base ligands with NN'OS coordination spheres as a novel effective means of treating an array of dangerous microbial infections.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.