Naphthalimide-Based AIEgens for Sensing Protein Disulfide Isomerase through Thiol-Disulfide Redox Exchange.

Aggregation-induced emission (AIE)-based fluorescent organic nanoparticles (FONPs) with distinctive characteristics are emerging as superior sensors due to their facile fabrication, high signal-to-noise ratio, and good biocompatibility. The present article delineates the detection and analysis of the redox behavior of the protein disulfide isomerase (PDI) enzyme by exploitation of the AIE of novel naphthalimide (NI) derivatives having thiol (-SH) and disulfide (-S-S-) moieties. Self-aggregated spherical-shaped organic nanoparticles were prepared by synthesized NI-based amphiphiles (NISH, NISS, NINSS, and TNINSH) through J-type aggregation in DMSO-water (fw = 99 vol %). Naphthyl residue containing NI-derived amphiphiles (NINSS and TNINSH) exhibited AIE (blue and yellow) at 470 and 550 nm, respectively, in DMSO-water (fw = 99 vol %). NINSS and TNINSH FONPs were suitably utilized in sensing PDI through their redox nature of thiol-disulfide exchange. Fluorescence quenching of NINSS FONPs was observed due to reduction of disulfide to thiol by PDI, whereas emission intensity was progressively red-shifted and enhanced ("Dual-AIE") for TNINSH (containing ER-targeting N-tosylethylenediamine), owing to oxidation of thiol to disulfide by PDI. NINSS and TNINSH FONPs were found to be highly efficient in sensing PDI through the AIE-based "fluorescence off/on" mechanism having limits of detection of ∼12.6-17.7 and ∼11.7-16.5 ng/mL, respectively. In vitro cell imaging for NIH3T3 (noncancer) and B16F10 (melanoma) cells with NINSS and TNINSH FONPs displayed excellent diagnosis of eukaryotic cells upon interaction with indigenous PDI. Notably, detection of cancer cells was more sensitive over the noncancerous cells by these FONPs due to overexpression of PDI within cancer cells.

Peptide Amphiphilic Supramolecular Nanogels: Competent Host for Notably Efficient Lipase-Catalyzed Hydrolysis of Water-Insoluble Substrates.

The present work depicts the development of stable nanogels in an aqueous medium that were exploited for efficient surface-active lipase-catalyzed hydrolysis of water-insoluble substrates. Surfactant-coated gel nanoparticles (neutral NG1, anionic NG2, and cationic NG3) were prepared from peptide amphiphilic hydrogelator (G1, G2, and G3, respectively) at different hydrophilic and lipophilic balance (HLB). Chromobacterium viscosum (CV) lipase activity towards hydrolysis of water-insoluble substrates (p-nitrophyenyl-n-alkanoates (C4-C10)) in the presence of nanogels got remarkably improved by ~1.7-8.0 fold in comparison to that in aqueous buffer and other self-aggregates. An increase in hydrophobicity of the substrate led to a notable improvement in lipase activity in the hydrophilic domain (HLB>8.0) of nanogels. The micro-heterogeneous interface of small-sized (10-65 nm) nanogel was found to be an appropriate scaffold for immobilizing surface-active lipase to exhibit superior catalytic efficiency. Concurrently, the flexible conformation of lipase immobilized in nanogels was reflected in its secondary structure having the highest α-helix content from the circular dichroism spectra.

Newly synthesized 3-sulfenylindole derivatives from 4-hydroxydithiocoumarin using an oxidative cross dehydrogenative coupling reaction (OCDCR): potential lead molecules for antiproliferative activity.

An expedient and efficient synthetic method was developed for the oxidative cross dehydrogenative coupling reaction between 4-hydroxydithiocoumarin and indole at the C-3 position regio-selectively using a combination of 10 mol% molecular iodine and TBHP in the presence of 10 mol% CuBr2 as an additive at room temperature. Mild reaction conditions, good yields and a broad substrate scope are some of the salient features of the present protocol. Additionally, the synthesized 3-sulfenylindoles derived from 4-hydroxydithiocoumarin were converted into biologically active sulfone derivatives. Interestingly, some of the compounds exhibit anti-cell proliferative activity on breast cancer (MCF-7) cells due to reactive oxygen species (ROS) mediated cell damage.