Fluctuation-dissipation theorem and the dynamical renormalization group

The relation between a recently introduced dynamical real-space renormalization group and the fluctuation-dissipation theorem is discussed. An apparent incompatibility is pointed out and resolved.     

Expeditious synthesis of water-soluble, monolayer-protected gold nanoparticles of controlled size and monolayer composition

A protocol is reported for the preparation of water-soluble, thiol-protected Au nanoparticles (Au-MPC) where dioctylamine is used as a stabilizing agent when the gold cluster is formed using the two-phase Brust and Schiffrin procedure. The amount of amine controls the size of the nanoparticles in the 1.9-8.9 nm diameter range. The final stabilization of the gold clusters by addition of functionalized thiols is performed under very mild conditions compatible with most biomolecules. The procedure is suitable for a wide variety of functional groups present in the thiol and allows one to use thiol mixtures with a precise control of their composition in the monolayer. As a proof of principle, examples of nanoparticles protected with thiols comprising functional groups ranging from polyethers, saccharides, polyamines and ammonium ions are reported.     

Enhancement of gemcitabine affinity for biomembranes by conjugation with squalene: differential scanning calorimetry and Langmuir-Blodgett studies using biomembrane models

Molecular interactions between gemcitabine, alone or conjugated with squalene to form the gem-squalene prodrug, with dimyristoylphosphatidylcholine have been investigated by differential scanning calorimetry and Langmuir film balance techniques to gain information about the interaction of gemcitabine and its prodrug with mammalian cell membranes and to evaluate the potential of liposomes as a delivery system for gemcitabine prodrugs. Phospholipids assembled as multilamellar vesicles or monolayers (at the air water interface) have been used as biomembrane models. Different interactions of gemcitabine, its prodrug, and squalene with the lipid were detected by dispersing the compounds in the MLV and were compared with kinetic experiments carried out to consider the ability of the examined compounds to dissolve in an aqueous medium, to migrate through it, and to be captured by multilamellar vesicles. Their ability to be released from drug-loaded liposomes and be taken up by empty vesicles mimicking biomembranes was also considered. Analysis of the differential scanning calorimetry curves reveals that gemcitabine has very little interaction with multilamellar vesicles whereas the gem-squalene prodrug strongly interacts with multilamellar vesicles. The kinetic experiments suggest that an aqueous medium does not permit the prodrug uptake by the biomembrane models, whereas it is allowed when gem-squalene is gradually released by the liposomes. The molecular area/surface pressure isotherms of the gemcitabine/lipid, gem-squalene/lipid, and pure compound monolayers, in agreement with the calorimetric results, indicate that gem-squalene interacts with the phospholipid monolayer with the squalene moiety in contact with the phospholipid chains and gemcitabine protruding in the aqueous medium.     

Enantioselective Copper‐Catalyzed Quinoline Alkynylation

A highly enantioselective copper‐catalyzed alkynylation of quinolinium salts is reported. The reaction employs StackPhos, a newly developed imidazole‐based chiral biaryl P,N ligand, and copper bromide to effect a three‐component reaction between a quinoline, a terminal alkyne, and ethyl chloroformate. Under the reaction conditions, the desired products are delivered in high yields with ee values of up to 98 %. The transformation tolerates a wide range of functional groups with respect to both the alkyne and the quinoline starting materials and the products are easily transformed into useful synthons. Efficient, enantioselective syntheses of the tetrahydroquinoline alkaloids (+)‐galipinine, (+)‐angustureine, and (?)‐cuspareine are reported.     

Synthesis,in silico and in vitro Evaluation of Novel Oxazolopyrimidines as Promising Anticancer Agents

New potential bioactive oxazolopyrimidines have been synthesized using two main approaches: the pyrimidine ring annulation on a functionalized oxazole and the benzoyl bromide trimerization followed by rearrangement and formation of the oxazolo[5,4-d]pyrimidine scaffold. The docking analyzes have shown that 7-piperazine substituted oxazolo[4,5-d]pyrimidines 8a – 8c could be potential VEGFR2 inhibitors with high free energy of ligand–protein complex formation (ΔG: −10.1, −9.6, −9.8 kcal/mol, respectively). In vitro antitumor assays confirmed theoretical predictions that oxazolo[4,5-d]pyrimidines 8a – 8c containing positively charged piperazine moiety should demonstrate significantly higher cytotoxic effects. 4-[5-(4-Chlorophenyl)-2-phenyl[1,3]oxazolo[4,5-d]pyrimidin-7-yl]piperazin-1-ium trifluoroacetate ( 8c ) exhibited a slightly higher antiproliferative effect (IC₅₀=0.21 μm ) than doxorubicin (IC₅₀=0.36 μm ) on MDA-MB-231 cell line and has relatively good results on OVCAR-3 (IC₅₀=1.7 μm ) and HCT-116 (IC₅₀=0.24 μm ) cells.