Click to learn, learn to click: undergraduate synthetic organic chemistry experiments

The optimization of an undergraduate experiment for Organic Chemistry students is described to explore the concept of click chemistry. The preparation of a terminal fluorescent alkyne and an organic azide is reported consisting of simple steps. These are employed in the Cu(I)-catalized azide-alkyne cycloaddition to obtain a novel molecule containing a triazole ring whose characterization allows the students to practice a variety of techniques: NMR (1H, 13C, COSY and HSQC), melting point, thin layer chromatography, IR, fluorescence spectroscopy and mass spectrometry to confirm the structure of their obtained product. An alternative methodology in a one-pot reaction is also explored and a full laboratory manual provided.FQM-208. GlycoChemBio: Glycochemistry and Bioconjugatio

Intracellular delivery of a catalytic organometallic complex

A homogeneous carbene-based palladium catalyst was conjugated to a cell-penetrating peptide, allowing intracellular delivery of catalytically active Pd complexes that demonstrated bioorthogonal activation of a profluorophore within prostate cancer cells

Red-Shifted Environmental Fluorophores and Their Use for the Detection of Gram-Negative Bacteria

Two novel, water-soluble, merocyanine fluorophores were readily prepared by microwave-assisted synthesis. Full optical characterization was performed in a series of protic and aprotic solvents, and the dyes displayed fluorescence in the red region with up to a 20-fold decrease in brightness in water, demonstrating a strong environmental sensitivity hereby termed as solvato-fluorogenicity (to distinguish from solvatochromism). Shorter fluorescent lifetimes were also measured in water, which confirmed this character. These dyes were conjugated to a modified polymyxin scaffold that allowed fluorescence “switch-on” upon binding to Gram-negative bacterial membranes, and selective fluorescence detection of bacteria in a wash-free protocol

Fibroblast Activation Protein specific optical imaging in Non-Small Cell Lung Cancer

Fibroblast activation protein (FAP) is a cell surface propyl-specific serine protease involved in the regulation of extracellular matrix. Whilst expressed at low levels in healthy tissue, upregulation of FAP on fibroblasts can be found in several solid organ malignancies, including non-small cell lung cancer, and chronic inflammatory conditions such as pulmonary fibrosis and rheumatoid arthritis. Their full role remains unclear, but FAP expressing cancer associated fibroblasts (CAFs) have been found to relate to a poor prognosis with worse survival rates in breast, colorectal, pancreatic, and non-small cell lung cancer (NSCLC). Optical imaging using a FAP specific chemical probe, when combined with clinically compatible imaging systems, can provide a readout of FAP activity which could allow disease monitoring, prognostication and potentially stratify therapy. However, to derive a specific signal for FAP any sequence must retain specificity over closely related endopeptidases, such as prolyl endopeptidase (PREP), and be resistant to degradation in areas of active inflammation. We describe the iterative development of a FAP optical reporter sequence which retains FAP specificity, confers resistance to degradation in the presence of activated neutrophil proteases and demonstrates clinical tractability ex vivo in NSCLC samples with an imaging platform