Tropolone-Conjugated DNA: A Fluorescent Thymidine Analogue Exhibits Solvatochromism, Enzymatic Incorporation into DNA and HeLa Cell Internalization.

Tropolone is a non-benzenoid aromatic scaffold with unique photophysical and metal-chelating properties. Recently, it has been conjugated with DNA, and the photophysical properties of this conjugate have been explored. Tropolonyl-deoxyuridine (tr-dU) is a synthetic fluorescent DNA nucleoside analogue that exhibits pH-dependent emissions. However, its solvent-dependent fluorescence properties are unexplored owing to its poor solubility in most organic solvents. It would be interesting to incorporate it into DNA primer enzymatically. This report describes the solvent-dependent fluorescence properties of the silyl-derivative, and enzymatic incorporation of its triphosphate analogue. For practical use, its cell-internalization and cytotoxicity are also explored. tr-dU nucleoside was found to be a potential analogue to design DNA probes and can be explored for various therapeutic applications in the future.

Cu-Catalyzed Synthesis of Alkylaminotroponyl Sulfones as Pseudomonas Aeruginosa Quorum Sensing Inhibitors Targeting lasI/R QS Circuitry.

The scarcity of novel bioactive molecules against multidrug-resistant (MDR) bacterial strains like Pseudomonas aeruginosa is alarming. This bacterial virulence is regulated via Quorum sensing (QS), a cell-cell communication process. Disabling QS circuits (las, pqs, rhl) with small molecules has been proposed as a potential strategy to prevent bacterial pathogenicity. This strategy focuses on interruption of bacterial virulence, rather than killing them to tackle the drug resistance problem. Herein, we describe the synthesis of rationally designed Alklyamionotroponyl Sulfone (ATS) derivatives by Cu-catalyzed C(sp2 )-H functionalization at tropone ring and the screening of their anti-QS activity against P. aeruginosa. Importantly, two sulfones (∼20 µM) remarkably exhibit the down regulation of the lasI/R QS genes. These molecules also inhibit swarming motility, biofilm formation and pyocyanin production, which reduce P. aeruginosa virulence in cells. Hence, ATS derivatives could be considered as potential therapeutic candidates for the treatment of P. aeruginosa infections.

Instability of Amide Bond with Trifluoroacetic Acid (20%): Synthesis, Conformational Analysis, and Mechanistic Insights into Cleavable Amide Bond Comprising ß-Troponylhydrazino Acid.

The instability of an amide bond with dilute trifluoroacetic acid (TFA) is a rare chemical event. The native amide bonds are stable even in the neat TFA, which is one of the reagents that releases the peptides from the solid support in the solid-supported peptide synthesis method. In the repertoire of unnatural peptidomics, α-/ß-hydrazino acids and their peptides are explored for the synthesis of N-amino peptide derivatives, and their amide bonds are stable in TFA (∼100%) as natural amide bonds. This report describes the synthesis of a ß-hydrazino acid analogue as ß-troponylhydrazino acid, containing a nonbenzenoid natural troponyl scaffold. The structural and conformational studies of their hybrid di-/tripeptides with the natural amino acid show that the 2-aminotroponyl residue is involved in hydrogen bonding. Surprisingly, the amide bond of ß-troponylhydrazino peptides is cleavable with TFA (∼20%) through the formation of a new heterocyclic molecule N-troponylpyrazolidinone or troponylpyrazolidinone. Tropolone and related compounds are excellent biocompatible chromophores. Hence, ß-troponylhydrazino acid could be employed for tuning the peptide structure and considered a promising chromophoric acid-sensitive protecting group of a free amine of amino acids/peptides. It could be applied for the estimation of the free amine group functionality by a UV-vis spectrophotometer.