Conformational studies of Gram-negative bacterial quorum sensing acyl homoserine lactone (AHL) molecules: The importance of the n → π* interaction

Abiotic Hydrolysis Kinetics of N‐Acyl‐L‐homoserine Lactones: Natural Silencing of Bacterial Quorum Sensing Signals

“…Though not presented within the context of hydrolysis rates, NBO analysis has also been performed on various biologically relevant AHLs (e.g., BHL and OOHL),, finding that 3‐oxo‐ and 3‐hydroxy‐AHL species have weaker n→pi* stabilizing energies than their saturated counterparts. This is perhaps rationalized because these groups can withdraw or obstruct electrons from flowing towards the n→pi* interaction site.…”

Solvent and Substituent Effects on the Phosphine + CO2 Reaction

“…The general solvent effects consider the solvent as bulk and are studied empirically using solvent scales (Kamlet et al [4], Reichardt [5], Abraham [6], Catalán [7]), as well as theoretically using the polarizable continuum model, PCM (Tomasi et al [8]), the conductor-like screening model, COSMO (Orozco and Luque [9]), and Density Functional Solvation Model, DGSOL (Zhu et al [10]). Note that several authors have studied solvent effects on weak interactions using the PCM approximation [11][12][13][14][15][16].…”

Conformational and docking studies of acyl homoserine lactones as a robust method to investigate bioactive conformations

“…These two conformations (the lowest energy conformation and the conformation 6106) are very close in energy (only 1 kcal/mol different) though dissimilar in terms of torsion angles values. No n→π* interaction, known to be observed preferentially for non-bound AHLs [8,10] was observed here logically, as only "bound-like" conformations are selected during the protocol. A rigid docking was then applied to the conformation 6106 within the binding site of CviR (Figure 3).…”

“…The molecular structure of AHL can be divided in three blocks: block 1, the lactone moiety; block 2, the 3-oxo amide functional group; and block 3, the alkyl chain. [6] In terms of conformation of homoserine lactones, [7][8][9][10] conformational analysis studies have shown that they can adopt different conformations depending on the occurrence or not of a n→π* interaction between p-type lone pair (n) of the N-acyl oxygen of the amide with the π* orbital of the lactone carbonyl functional group. Notably the study by Raines and co-workers using DFT calculations showed particularly the importance of this n→π* interaction for free AHLs whereas for bound conformations this interaction do not exist.…”

“…[8] The importance of the solvents effects was further highlighted by the study by Kelleher and co-workers who showed, also using DFT calculations, that n→π* interactions become stronger with the polarity of the solvent. [9,10] All functional groups found in AHLs and their close analogues are known to influence their molecular recognition by their cognate receptors, through hydrogen bonds and hydrophobic interactions. As example, the XRD data for the complex between OOHL and TraR (pdb code 1L3L) [11] shows that the lactone is involved in a hydrogen bond with Trp57, the amide with Asp70 (NH) and Tyr53 (C=O), and the 3-oxo functional group with a water molecule (Fig.…”