Synthesis of New Cyclomarin Derivatives and Their Biological Evaluation towards Mycobacterium Tuberculosis and Plasmodium Falciparum

Cyclomarins are highly potent antimycobacterial and antiplasmodial cyclopeptides isolated from a marine bacterium (Streptomyces sp.). Previous studies have identified the target proteins and elucidated a novel mode of action, however there are currently only a few studies examining the structure–activity relationship (SAR) for both pathogens. Herein, we report the synthesis and biological evaluation of 17 novel desoxycyclomarin-inspired analogues. Optimization via side chain modifications of the non-canonical amino acids led to potent lead structures for each pathogen.     

g-C3N4 quantum dots-modified mesoporous TiO2–SiO2 for enhanced photocatalysis

Research on Chemical Intermediates - The utilization of TiO2-based photocatalysts for an efficient removal of dye pollutants is limited due to their low surface area, high recombination rate of the...     

Modular Medical Imaging Agents Based on Azide–Alkyne Huisgen Cycloadditions: Synthesis and Pre-Clinical Evaluation of 18F-Labeled PSMA-Tracers for Prostate Cancer Imaging

Since the seminal contribution of Rolf Huisgen to develop the [3+2] cycloaddition of 1,3-dipolar compounds, its azide–alkyne variant has established itself as the key step in numerous organic syntheses and bioorthogonal processes in materials science and chemical biology. In the present study, the copper(I)-catalyzed azide–alkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate-specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and in vitro studies, all the way to pre-clinical in vivo evaluation of fluorine-18- labeled PSMA-targeting ‘F-PSMA-MIC’ radiotracers (t_1/2=109.7 min). Pre-clinical data indicate that the modular PSMA-scaffold has similar binding affinity and imaging properties to the clinically used [⁶⁸Ga]PSMA-11. Furthermore, we demonstrated that targeting the arene-binding in PSMA, facilitated through the [3+2]cycloaddition, can improve binding affinity, which was rationalized by molecular modeling. The here presented PSMA-binding scaffold potentially facilitates easy coupling to other medical imaging moieties, enabling future developments of new modular imaging agents.     

Electropolymerized biotinylated poly (pyrrole–viologen) film as platform for the development of reagentless impedimetric immunosensors

We describe herein the synthesis and electrochemical polymerization of a viologen monomer functionalized by a biotin group and the use of its redox properties for the impedimetric sensing of protein binding. The electrochemical oxidation of the pyrrole group at 0.85 V in CH₃CN led to a biotinylated polypyrrole film allowing the successive anchoring of an avidin layer and a biotinylated cholera toxin layer. EIS performed at ?0.45 V/SCE without redox probe in solution showed the specific immobilization of the anti-cholera toxin antibody.     

Hygrothermal aging of Nafion

The membrane durability is a critical issue for the development of Proton Exchange Membrane Fuel Cells (PEMFC). Since PEMFC in situ tests were not conclusive to determine Nafion^® membrane degradation mechanism, ex situ aging tests were performed on Nafion^® 112 in practical fuel cell usage conditions. The polymer chemical structure evolution was investigated by infrared spectroscopy (IR) and Nuclear Magnetic Resonance (NMR) while its hydrophilicity, directly linked to its protonic conductivity, is established through sorption isotherms by Dynamical Vapour Sorption (DVS). Durability studies over a period of 400 days revealed membrane degradation through a modification of sulfonic acid end-groups. Formation of sulfonic anhydride (from the condensation of sulfonic acids) was strongly demonstrated by IR spectroscopy and, indirectly, by NMR. The substitution of ionic end-groups by less hydrophilic anhydrides leads to a significant decrease of water uptake and thus of its hydrophilicity. Surprisingly, kinetic study reveals that the hygrometric level accelerates this condensation reaction.     

Fluctuations in the number of points on smooth plane curves over finite fields

In this note, we study the fluctuations in the number of points on smooth projective plane curves over a finite field Fq as q is fixed and the genus varies. More precisely, we show that these fluctuations are predicted by a natural probabilistic model, in which the points of the projective plane impose independent conditions on the curve. The main tool we use is a geometric sieving process introduced by Poonen (2004) [8].     

Flyscan opportunities in medicine: the case of quantum rattle based on gold quantum dots

The new rapid scan method, Flyscan mode, implemented on the DiffAbs beamline at Synchrotron SOLEIL, allows fast micro‐X‐ray fluorescence data acquisition. It paves the way for applications in the biomedical field where a large amount of data is needed to generate meaningful information for the clinician. This study presents a complete set of data acquired after injection of gold‐cluster‐enriched mesoporous silica nanospheres, used as potential theranostic vectors, into rats. While classical X‐ray fluorescence investigations (using step‐by‐step acquisitions) are based on a limited number of samples (approximately one per day at the DiffAbs beamline), the Flyscan mode has enabled gathering information on the interaction of nanometer‐scale vectors in different organs such as liver, spleen and kidney at the micrometer scale, for five rats, in only a single five‐day synchrotron shift. Moreover, numerous X‐ray absorption near‐edge structure spectra, which are beam‐time‐consuming taking into account the low concentration of these theranostic vectors, were collected.     

Mediating Gel Formation from Structurally Controlled Poly(Electrolytes) Through Multiple “Head‐to‐Body” Electrostatic Interactions

Tuning the chain‐end functionality of a short‐chain cationic homopolymer, owing to the nature of the initiator used in the atom transfer radical polymerization (ATRP) polymerization step, can be used to mediate the formation of a gel of this poly(electrolyte) in water. While a neutral end group gives a solution of low viscosity, a highly homogeneous gel is obtained with a phosphonate anionic moiety, as characterized by rheometry and diffusion nuclear magnetic resonance (NMR). This novel type of supramolecular control over poly(electrolytic) gel formation could find potential use in a variety of applications in the field of electro‐active materials.

     

New advances in the synthesis of tripyridinophane macrocycles suitable to enhance the luminescence of Ln(III) ions in aqueous solution

A series of four new 18-membered hexaaza macrocyclic ligands bearing three endocyclic pyridine units and acetate or methylenephosphonate pendant arms has been prepared. The new synthetic procedure is based on the use of amine and diamine precursors incorporating masked carboxylate or phosphonate functions and on an efficient sodium template effect which controls the crucial macrocyclization step (yields of macrocyclization reactions: 62–88%). This procedure appears as a suitable alternative compared to the classical Richman-Atkins methodology generally used for the preparation of this class of macrocycles. As demonstrated with the Eu^III and Tb^III complexes derived from two ligands, these tripyridinophane chelators form luminescent and stable mononuclear Ln^III complexes in aqueous solution at physiological pH. In such a medium, Tb^III complexes exhibit a brightness of 1700 (λ_exc?=?279?nm) and 3000 (λ_exc?=?268?nm)?M^?1?cm^?1.