Diastereoselective reductive N-alkylation of (R,R)-trans-1,2-diaminocyclohexane with prochiral ketones using the Ti(OiPr)4/NaBH4 system

A simple and convenient one-pot method for the reductive N-alkylation of (R,R)-trans-1,2-diaminocyclohexane by prochiral ketones using a Ti(OⁱPr)₄/NaBH₄ system to obtain the corresponding alkyl amine derivatives in 76–95% yields with good diastereoselectivity (dr = up to 23:1:1) is reported.     

Positive integer solutions of certain diophantine equations

In this study, the diophantine equations \(x^2 -32B_nxy-32y^2 =\pm 32^{r}\), \(x^4 -32B_nxy-32y^2 =\pm 32^{r}\) and \(x^2 -32B_nxy-32y^4 =\pm 32^{r}\) are considered and determined when these equations have positive integer solutions. Moreover, all positive integer solutions of these diophantine equations in terms of balancing and Lucas-balancing numbers are also found out.     

Recent advances in Garratt-Braverman cyclization: Mechanistic and synthetic explorations

Garratt-Braverman cyclization has emerged as one of the simplest synthetic tool to construct two consecutive CC bonds leading to the formation of various important structural scaffolds having significance in the field of therapeutics and material science. The strategic design of suitable precursor for this cycloaromatization reaction involves the deep understanding of reaction pathways involving diradicals and ions. On the other hand, the reaction offers an unprecedented mechanistic paradox for the chemists to solve. This report aims at outlining the recent mechanistic and synthetic developments with special emphasis on the research outcomes from our laboratory.     

Long-term exposure to CdTe quantum dots causes functional impairments in live cells

Several studies suggested that the cytotoxic effects of quantum dots (QDs) may be mediated by cadmium ions (Cd2+) released from the QDs cores. The objective of this work was to assess the intracellular Cd2+ concentration in human breast cancer MCF-7 cells treated with cadmium telluride (CdTe) and core/shell cadmium selenide/zinc sulfide (CdSe/ZnS) nanoparticles capped with mercaptopropionic acid (MPA), cysteamine (Cys), or N-acetylcysteine (NAC) conjugated to cysteamine. The Cd2+ concentration determined by a Cd2+-specific cellular assay was below the assay detection limit (<5 nM) in cells treated with CdSe/ZnS QDs, while in cells incubated with CdTe QDs, it ranged from approximately 30 to 150 nM, depending on the capping molecule. A cell viability assay revealed that CdSe/ZnS QDs were nontoxic, whereas the CdTe QDs were cytotoxic. However, for the various CdTe QD samples, there was no dose-dependent correlation between cell viability and intracellular [Cd2+], implying that their cytotoxicity cannot be attributed solely to the toxic effect of free Cd2+. Confocal laser scanning microscopy of CdTe QDs-treated cells imaged with organelle-specific dyes revealed significant lysosomal damage attributable to the presence of Cd2+ and of reactive oxygen species (ROS), which can be formed via Cd2+-specific cellular pathways and/or via CdTe-triggered photoxidative processes involving singlet oxygen or electron transfer from excited QDs to oxygen. In summary, CdTe QDs induce cell death via mechanisms involving both Cd2+ and ROS accompanied by lysosomal enlargement and intracellular redistribution.     

Hybrid Nanoreactors: Enabling an Off‐the‐Shelf Strategy for Concurrently Enhanced Chemo‐immunotherapy

Immunosuppressive tumors generally exhibit poor response to immune checkpoint blockade based cancer immunotherapy. Rationally designed hybrid nanoreactors are now presented that have integrated functions as Fenton catalysts and glutathione depletion agents for amplifying the immunogenic cell death and activating immune cells. A simple physical mixture of nanoreactors and chemodrugs in combination with immune checkpoint blockades show synergistically and concurrently enhanced chemo‐immunotherapy efficacy, inhibiting the growth of both treated primary immunosuppressive tumors and untreated distant tumors. The off‐the‐shelf strategy uses tumor antigens generated in situ and avoids cargo loading, and is thus a substantial advance in personalized nanomedicine for clinical translation.     

Development of a Validated Stability-Indicating High-Performance Thin-Layer Chromatographic Method for the Quantification of Levetiracetam

JPC – Journal of Planar Chromatography – Modern TLC - Levetiracetam (LT) is an FDA-approved orally active anticonvulsant drug. A high-performance thin-layer chromatographic (HPTLC)...     

One-pot Friedel-Crafts/Robinson-Gabriel synthesis of oxazoles using oxazolone templates

[reaction: see text] We report herein a one-pot synthesis of 2,4,5-trisubstituted oxazoles via a Friedel-Crafts/Robinson-Gabriel synthesis using a general oxazolone template. Treatment of the oxazolone template with a range of aromatic nucleophiles provided the highly substituted oxazoles in good yields.     

A Glycosylated Cationic Block Poly(β-peptide) Reverses Intrinsic Antibiotic Resistance in All ESKAPE Gram-Negative Bacteria

Carbapenem-resistant Gram-negative bacteria (GNB) are heading the list of pathogens for which antibiotics are the most critically needed. Many antibiotics are either unable to penetrate the outer-membrane or are excluded by efflux mechanisms. Here, we report a cationic block β-peptide (PAS8-b-PDM12) that reverses intrinsic antibiotic resistance in GNB by two distinct mechanisms of action. PAS8-b-PDM12 does not only compromise the integrity of the bacterial outer-membrane, it also deactivates efflux pump systems by dissipating the transmembrane electrochemical potential. As a result, PAS8-b-PDM12 sensitizes carbapenem- and colistin-resistant GNB to multiple antibiotics in vitro and in vivo. The β-peptide allows the perfect alternation of cationic versus hydrophobic side chains, representing a significant improvement over previous antimicrobial α-peptides sensitizing agents. Together, our results indicate that it is technically possible for a single adjuvant to reverse innate antibiotic resistance in all pathogenic GNB of the ESKAPE group, including those resistant to last resort antibiotics.