The Fe(III) and Ga(III) coordination chemistry of 3-(1-hydroxymethylidene) and 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione: Novel tetramic acid degradation products of homoserine lactone bacterial quorum sensing molecules

Bacteria use small diffusible molecules to exchange information in a process called quorum sensing (QS). An important class of quorum sensing molecules used by Gram-negative bacteria is the family of N-acylhomoserine lactones (HSL). It was recently discovered that a degradation product of the QS molecule 3-oxo-C12-homoserine lactone, the tetramic acid 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione, is a potent antibacterial agent, thus implying roles for QS outside of simply communication. Because these tetramic acids also appear to bind iron with appreciable affinity it was suggested that metal binding might contribute to their biological activity. Here, using a variety of spectroscopic tools, we describe the coordination chemistry of both the methylidene and decylidene tetramic acid derivatives with Fe(III) and Ga(III) and discuss the potential biological significance of such metal binding.

Tetramic acids are degradation products of 3-oxo-N-acylhomoserine lactone bacterial quorum sensing molecules. They bind iron with significant affinity to produce Fe(TA)3 complexes but the biological significance of this ability remains unresolved.Figure optionsDownload as PowerPoint slideHighlights
► Tetramic acids are formed as degradation products of some HSL quorum sensors.
► Tetramic acids bind iron to produce complexes at low pH and high ligand concentrations.
► The properties of the tetramic acids and their iron complexes depend on chain length.
► Tetramic acids do not facilitate iron uptake in P. aeruginosa.
► The biological significance of the iron binding ability of these molecules is unclear.