Conformational studies of Gram-negative bacterial quorum sensing 3-oxo N-acyl homoserine lactone molecules. Issue 16 (15th August 2017)

• Record Type: Journal Article
• Authors: Crowe, Darren; Nicholson, Alan; Fleming, Adrienne; Carey, Ed; Sánchez-Sanz, Goar; Kelleher, Fintan
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 16(2017)
• Page Start: 4285
• Page End: 4296
• Publication Date: 2017-08-15
• Subjects: Homoserine lactones -- β-Keto amide -- DFT calculations -- Keto-enol tautomers -- Quorum sensing; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.06.006
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: H-bond stabilised lowest energy conformation of keto tautomer of OHLs. Measurement of Kt for OHLs in CDCl3 by 1 H NMR spectroscopy. DFT calculations of OHL keto/enol tautomers in gas phase and solvent models. DFT calculations of OHL analogue keto/enol tautomers in gas phase & solvent models. Demonstration of flexibility of OHL conformations in gas phase and solvent models. Abstract: In their 1 H NMR spectra in CDCl3 3-oxo- N -acyl homoserine lactones (OHLs) show significant downfield chemical shifts of the amide NH proton when compared to the parent N -acyl homoserine lactones (AHLs). NMR spectroscopic and DFT calculation studies have shown that this is most likely due to the presence of a stabilising intramolecular H-bond from the NH to the 3-oxo group. The 1 H NMR spectra also show evidence for the enol tautomers and that the amount of enol present for a range of OHLs is 4.1–4.5% in CDCl3 and 6.5–7.2% in CD3 CN. In contrast, DFT calculations show that the lowest energy enol tautomer and the keto tautomer are of equal energy in the gas phase, but that the keto tautomer is more stable in chloroform, acetonitrile and water solution. The calculations also show that there is no evidence for any n → π ∗ or C5H-bonding interactions being present in either the lowest energy keto or enol tautomer of the OHLs in solution or the gas phase, which is in contrast to the reported solid-state structure.