Telomerase Inhibitors from Cyanobacteria: Isolation and Synthesis of Sulfoquinovosyl Diacylglycerols from Microcystis aeruguinosa PCC 7806

By using the Telospot assay, 27 different extracts of cyanobacteria were evaluated for telomerase inhibition. All extracts showed varying, but significant activity. We selected Microcystis aeruguinosa PCC 7806 to identify the active compound and a bioassay guided fractionation led us to isolate mixtures of sulfoquinovosyl diacylglycerols (SQDGs), which were identified by 2D NMR and MS/MS experiments. Pure SQDG derivatives were then synthesized. The IC₅₀ values of pure synthetic sulfoquinovosyl dipalmitoylglycerol and the monopalmitoylated derivative against telomerase were determined to be 17 and 40 μM , respectively. A structure–activity relationship study allowed the identification of compounds with modified lipophilic acyl groups that display improved activity.     

In Situ Water Quantification in Natural Deep Eutectic Solvents Using Portable Raman Spectroscopy

Raman spectroscopy is a label-free, non-destructive, non-invasive analytical tool that provides insight into the molecular composition of samples with minimum or no sample preparation. The increased availability of commercial portable Raman devices presents a potentially easy and convenient analytical solution for day-to-day analysis in laboratories and production lines. However, their performance for highly specific and sensitive analysis applications has not been extensively evaluated. This study performs a direct comparison of such a commercially available, portable Raman system, with a research grade Raman microscope system for the analysis of water content of Natural Deep Eutectic Solvents (NADES). NADES are renewable, biodegradable and easily tunable “green” solvents, outcompeting existing organic solvents for applications in extraction from biomass, biocatalysis, and nanoparticle synthesis. Water content in NADES is, however, a critical parameter, affecting their properties, optimal use and extraction efficiency. In the present study, portable Raman spectroscopy coupled with Partial Least Squares Regression (PLSR) is investigated for rapid determination of water content in NADES samples in situ, i.e., directly in glassware. Three NADES systems, namely Betaine Glycerol (BG), Choline Chloride Glycerol (CCG) and Glucose Glycerol (GG), containing a range of water concentrations between 0% (w/w) and 28.5% (w/w), were studied. The results are directly compared with previously published studies of the same systems, using a research grade Raman microscope. PLSR results demonstrate the reliability of the analysis, surrendering R² values above 0.99. Root Mean Square Errors Prediction (RMSEP) of 0.6805%, 0.9859% and 1.2907% w/w were found for respectively unknown CCG, BG and GG samples using the portable device compared to 0.4715%, 0.3437% and 0.7409% w/w previously obtained by analysis in quartz cuvettes with a Raman confocal microscope. Despite the relatively higher values of RMSEP observed, the comparison of the percentage of relative errors in the predicted concentration highlights that, overall, the portable device delivers accuracy below 5%. Ultimately, it has been demonstrated that portable Raman spectroscopy enables accurate quantification of water in NADES directly through glass vials without the requirement for sample withdrawal. Such compact instruments provide solvent and consumable free analysis for rapid analysis directly in laboratories and for non-expert users. Portable Raman is a promising approach for high throughput monitoring of water content in NADES that can support the development of new analytical protocols in the field of green chemistry in research and development laboratories but also in the industry as a routine quality control tool.     

Supramolecular control of the template-induced selective photodimerization of 4-methyl-7-O-hexylcoumarin

A symmetric ditopic molecular receptor (3), containing two identical hydrogen-bonding recognition subunits, was designed and synthesized. These subunits are capable of binding substrates with complementary donor and acceptor sites to form a supramolecular complex through hydrogen bonding. Receptor 3 was designed to accept two guest molecules, which are held in close proximity within the supramolecular species. The substrate molecule, 4-methyl-7-O-hexylcoumarin (1 c), forms a 2:1 complex with a binding constant of 150 m(-1) for the second substrate, passing first through a 1:1 complex with an affinity constant of 510 m(-1). The orientation of two molecules of 1 c when bound to the template leads to the selective formation of the trans-syn [2+2] photoproduct 2 cB upon irradiation. Other photoproducts typically produced in the absence of the template are suppressed.     

Acetyl nitrate nitrations in [bmpy][N(Tf)2] and [bmpy][OTf], and the recycling of ionic liquids

In this work we have examined the nitration by acetyl nitrate of a range of activated and deactivated aromatic substrates in two ionic liquids and compared the results to the same reaction in dichloromethane. Both ionic liquids are stable to the reaction conditions, and in both ionic liquids the yields of reaction are higher after unit time than the same reactions in dichloromethane, although the regioselectivity is little affected by solvent choice. This result gives further support to the suggestion that in the ionic liquid, acetyl nitrate dissociates to give the nitronium ion, and that this is the effective nitrating agent here. However, it is shown that [bmpy][N(Tf)(2)] is a better solvent for aromatic nitration than [bmpy][OTf]. This is due to the ease of formation of nitronium ion in the former ionic liquid, and is consistent with the fact that [bmpy][N(Tf)(2)] is a weaker hydrogen bond acceptor solvent than [bmpy][OTf]. Finally, a method by which [bmpy][N(Tf)(2)] may be recovered and reused for aromatic nitration has been demonstrated.     

Synthesis and biological evaluation of novel imidazole-containing macrocycles

A new family of compounds made of a 5-aryl-1H-imidazole motif included in a macrocycle has been designed and synthesized. The synthesis of the imidazole core makes use of our previously developed method for the regioselective preparation of 1,2,5-trisubstituted imidazoles while the construction of the macrocycle is based on a three steps sequence: S_NAr, Suzuki coupling, and RCM reaction. Biological evaluation of synthesized imidazole-containing macrocycles revealed that they display actual binding activity toward A₃ adenosine (h) receptor, dopamine D₁ (h) receptor, chloride channel (GABA-gated), and choline transporter (h) CHT1.     

Efficient access to 2-aryl-3-substituted benzo[b]thiophenes

[reaction: see text] Benzo[b]thiophene derivatives are important in part because of their use as selective estrogen receptor modulators. They are usually synthesized by intramolecular cyclization. Here, we propose a method for the synthesis of 2-arylbenzo[b]thiophenes with heteroatoms at the 3-positions directly from the benzo[b]thiophene core by using an aromatic nucleophilic substitution reaction and Heck-type coupling. This methodology provides 2-aryl-3-amino or phenoxybenzo[b]thiophenes in about 35% overall yield in 5 steps.     

Hierarchical Self‐Assembly of Supramolecular Muscle‐Like Fibers

An acid–base switchable [c2]daisy chain rotaxane terminated with two 2,6‐diacetylamino pyridine units has been self‐assembled with a bis(uracil) linker. The complementary hydrogen‐bond recognition patterns, together with lateral van der Waals aggregations, result in the hierarchical formation of unidimensional supramolecular polymers associated in bundles of muscle‐like fibers. Microscopic and scattering techniques reveal that the mesoscopic structure of these bundles depends on the extended or contracted states that the rotaxanes show within individual polymer chains. The observed local dynamics span over several length scales because of a combination of supramolecular and mechanical bonds. This work illustrates the possibility to modify the hierarchical mesoscopic structuring of large polymeric systems by the integrated actuation of individual molecular machines.     

An Integrated Chemical Cytometry Method: Shining a Light on Akt Activity in Single Cells

Tools to evaluate oncogenic kinase activity in small clinical samples have the power to guide precision medicine in oncology. Existing platforms have demonstrated impressive insights into the activity of protein kinases, but these technologies are unsuitable for the study of kinase behavior in large numbers of primary human cells. To address these limitations, we developed an integrated analysis system that utilizes a light‐programmable, cell‐permeable reporter deliverable simultaneously to many cells. The reporter's ability to act as a substrate for Akt, a key oncogenic kinase, was masked by a 2‐4,5‐dimethoxy 2‐nitrobenzyl (DMNB) moiety. Upon exposure to ultraviolet light and release of the masking moiety, the substrate sequence enabled programmable reaction times within the cell cytoplasm. When coupled to automated single‐cell capillary electrophoresis, statistically significant numbers of primary human cells were readily evaluated for Akt activity.