Aromatic-Carbonyl Interactions as an Emerging Type of Non-Covalent Interactions.

Aromatic-carbonyl (Ar···C═O) interactions, attractive interactions between the arene plane and the carbon atom of carbonyl, are in the infancy as one type of new supramolecular bonding forces. Here the study and functionalization of aromatic-carbonyl interactions in solution is reported. A combination of aromatic-carbonyl interactions and dynamic covalent chemistry provided a versatile avenue. The stabilizing role and mechanism of arene-aldehyde/imine interactions are elucidated through crystal structures, NMR studies, and computational evidence. The movement of imine exchange equilibria further allowed the quantification of the interplay between arene-aldehyde/imine interactions and dynamic imine chemistry, with solvent effects offering another handle and matching the electrostatic feature of the interactions. Moreover, arene-aldehyde/imine interactions enabled the reversal of kinetic and thermodynamic selectivity and sorting of dynamic covalent libraries. To show the functional utility diverse modulation of fluorescence signals is realized with arene-aldehyde/imine interactions. The results should find applications in many aspects, including molecular recognition, assemblies, catalysis, and intelligent materials

Aromatic‐Carbonyl Interactions as an Emerging Type of Non‐Covalent Interactions

Abstract Aromatic‐carbonyl (Ar···C═O) interactions, attractive interactions between the arene plane and the carbon atom of carbonyl, are in the infancy as one type of new supramolecular bonding forces. Here the study and functionalization of aromatic‐carbonyl interactions in solution is reported. A combination of aromatic‐carbonyl interactions and dynamic covalent chemistry provided a versatile avenue. The stabilizing role and mechanism of arene‐aldehyde/imine interactions are elucidated through crystal structures, NMR studies, and computational evidence. The movement of imine exchange equilibria further allowed the quantification of the interplay between arene‐aldehyde/imine interactions and dynamic imine chemistry, with solvent effects offering another handle and matching the electrostatic feature of the interactions. Moreover, arene‐aldehyde/imine interactions enabled the reversal of kinetic and thermodynamic selectivity and sorting of dynamic covalent libraries. To show the functional utility diverse modulation of fluorescence signals is realized with arene‐aldehyde/imine interactions. The results should find applications in many aspects, including molecular recognition, assemblies, catalysis, and intelligent materials

A novel fragment based strategy for membrane active antimicrobials against MRSA

10.1016/j.bbamem.2015.01.001Biochimica et Biophysica Acta - Biomembranes184841023-103

Amino acid modified xanthone derivatives: Novel, highly promising membrane-active antimicrobials for multidrug-resistant gram-positive bacterial infections

10.1021/jm501285xJournal of Medicinal Chemistry582739-75

Symmetrically Substituted Xanthone Amphiphiles Combat Gram-Positive Bacterial Resistance with Enhanced Membrane Selectivity

This is the first report of the design of a new series of symmetric xanthone derivatives that mimic antimicrobial peptides using a total synthesis approach. This novel design is advantageous because of its low cost, synthetic simplicity and versatility, and easy tuning of amphiphilicity by controlling the incorporated cationic and hydrophobic moieties. Two water-soluble optimized compounds, <b>6</b> and <b>18</b>, showed potent activities against Gram-positive bacteria, including MRSA and VRE (MICs = 0.78–6.25 μg/mL) with a rapid bactericidal effect, low toxicity, and no emergence of drug resistance. Both compounds demonstrated enhanced membrane selectivity that was higher than those of most membrane-active antimicrobials in clinical trials or previous reports. The compounds appear to kill bacteria by disrupting their membranes. Significantly, <b>6</b> was effective in vivo using a mouse model of corneal infection. These results provide compelling evidence that these compounds have therapeutic potential as novel antimicrobials for multidrug-resistant Gram-positive infections

Rapid bactericidal action of alpha-mangostin against MRSA as an outcome of membrane targeting

10.1016/j.bbamem.2012.09.004Biochimica et Biophysica Acta - Biomembranes18282834-844BBBM