Synthesis of New Enantiopure Aminoalcohol Fluorenes as Promising Antimalarial Compounds.

Herein, we report the design, synthesis, and characterisation of a new library of enantiopure aminoalcohol fluorenes, as well as their in vitro evaluation for biological properties, including activity against two strains of P. falciparum (3D7 and W2) and cytotoxicity on the HepG2 cell line. All tested compounds exhibited good to excellent antimalarial potency with IC values ranging from 0.

New 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazoline and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinoline Derivatives: Synthesis and Biological Evaluation as Novel Anticancer Agents by Targeting G-Quadruplex.

The syntheses of novel 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazolines and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinolines are reported here in six steps starting from various halogeno-quinazoline-2,4-(1,3)-diones or substituted anilines. The antiproliferative activities of the products were determined in vitro against a panel of breast (MCF-7 and MDA-MB-231), human adherent cervical (HeLa and SiHa), and ovarian (A2780) cell lines. Disubstituted 6- and 7-phenyl-bis(3-dimethylaminopropyl)aminomethylphenyl-quinazolines , , and displayed the most interesting antiproliferative activities against six human cancer cell lines.

Lattice Defects in Sub-Micrometer Spin-Crossover Crystals Studied by Electron Diffraction.

Spin-crossover particles of [Fe(Htrz)trz](BF) with sizes of some hundred nanometers are studied by electron microscopy. Despite their high radiation sensitivity, it was possible to analyze the particles by imaging and diffraction so that a detailed analysis of crystallographic defects in individual particles became possible. The presence of one or several tilt boundaries, where the tilt axis is the direction of the polymer chains, is detected in each particle.

Correction: Nguyen et al. Oligonucleotide Solid Nucleolipid Nanoparticles against Antibiotic Resistance of ESBL-Producing Bacteria. 2022, , 299.

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Development and preclinical evaluation of [F]FBVM as a new potent PET tracer for vesicular acetylcholine transporter.

Age-related neurodegenerative diseases have in common the occurrence of cognitive impairment, a highly incapacitating process that involves the cholinergic neurotransmission system. The vesicular acetylcholine transporter (VAChT) positron emission tomography (PET) tracer [F]fluoroethoxybenzovesamicol ((-)-[F]FEOBV) has recently demonstrated its high value to detect alterations of the cholinergic system in Alzheimer's disease, Parkinson's disease and dementia with Lewy body. We present here the development of the new vesamicol derivative tracer (-)-(R,R)-5-[F]fluorobenzovesamicol ((-)[F]FBVM) that we compared to (-)[F]FEOBV in the same experimental conditions.

Aminations and arylations by direct C-O activation for the design of 7,8-dihydro-6-5,8-ethanopyrido[3,2-]pyrimidines.

The design of some novel disubstituted 7,8-dihydro-6-5,8-ethanopyrido[3,2-]pyrimidine derivatives is reported. The series was developed from quinuclidinone, which afforded versatile platforms bearing one lactam function in position -2 that were then used to create C-N or C-C bonds for S Ar or palladium-catalyzed cross-coupling reactions by C-O activation. The reaction conditions were optimized under microwave irradiation, and a wide range of amines or boronic acids were used to determine the scope and limitations of each method.

Oligonucleotide Solid Nucleolipid Nanoparticles against Antibiotic Resistance of ESBL-Producing Bacteria.

Antibiotic resistance has become a major issue in the global healthcare system, notably in the case of Gram-negative bacteria. Recent advances in technology with oligonucleotides have an enormous potential for tackling this problem, providing their efficient intrabacterial delivery. The current work aimed to apply this strategy by using a novel nanoformulation consisting of DOTAU, a nucleolipid carrier, in an attempt to simultaneously deliver antibiotic and anti-resistance oligonucleotides.

Rational Direct Synthesis of RbMnFe Nanoparticles (RbMnFe = RbMn[Fe(CN)]·HO Prussian Blue Analogue).

In this paper, we report the chemical strategy followed to obtain, in a direct way, nanoparticles of the RbMn[Fe(CN)]·HO (RbMnFe) Prussian blue analogue with the aim of keeping the switching ability of this compound at the nanoscale. The switching properties come from a reversible electron transfer between the iron and manganese ions and depends on the rubidium content in the structure that has to be higher than 0.6.

Mapping the cooperativity pathways in spin crossover complexes.

Crystal packing energy calculations are applied to the [Fe(PM-L)(NCS)] family of spin crossover (SCO) complexes (PM-L = 4-substituted derivatives of the -(2-pyridylmethylene)-4-aminobiphenyl ligand) with the aim of relating quantitatively the cooperativity of observed SCO transitions to intermolecular interactions in the crystal structures. This approach reveals a linear variation of the transition abruptness with the sum of the magnitudes of the interaction energy changes within the first molecular coordination sphere in the crystal structure. Abrupt transitions are associated with the presence of significant stabilising and destabilising changes in intermolecular interaction energies.

OctaDist: a tool for calculating distortion parameters in spin crossover and coordination complexes.

OctaDist is an interactive and visual program for determination of structural distortion in octahedral coordination complexes such as spin crossover complexes, single-ion magnets, perovskites or metal-organic frameworks. OctaDist computes the octahedral distortion parameters initially designed in the context of the spin-crossover phenomenon and denoted ζ, Σ, and Θ from standard structural files. The program also provides additional tools for molecular analyses and visualization.

Synthesis, Optimization, Antifungal Activity, Selectivity, and CYP51 Binding of New 2-Aryl-3-azolyl-1-indolyl-propan-2-ols.

A series of 2-aryl-3-azolyl-1-indolyl-propan-2-ols was designed as new analogs of fluconazole (FLC) by replacing one of its two triazole moieties by an indole scaffold. Two different chemical approaches were then developed. The first one, in seven steps, involved the synthesis of the key intermediate 1-(1-benzotriazol-1-yl)methyl-1-indole and the final opening of oxiranes by imidazole or 1-1,2,4-triazole.

Gold(I)-Catalyzed Intramolecular Hydroamination and Hydroalkoxylation of Alkynes: Access to Original Heterospirocycles.

We report here a simple and robust gold-catalyzed annulation reaction, giving - and -spirocycles in good to excellent yields. We have prepared a library of protected amines and tertiary alcohols that give, upon cyclization with alkynes, a representative set of heterospirocycles and illustrate reaction compatibility with diverse functional groups. A change in catalytic activity is possible by modifying the solvent, and two original tricyclic spirocycles were synthesized in a tandem reaction.

Multiscale Approach of Spin Crossover Materials: A Concept Mixing Russian Dolls and Domino Effects.

The spin crossover (SCO) phenomenon corresponds to a modification that originates at the atomic scale. However, the simple consideration of the transformations that occur following the SCO at this scale or in its close vicinity does not allow anyone to truly understand, anticipate and thus take advantage of what happens at the scale of the material, and even less at the device one. As the fruit of years of work and experience on this phenomenon, we formalize here the concept of the multiscale understanding of SCO.

Unprecedented Reverse Volume Expansion in Spin-Transition Crystals.

The current craze for research around the spin crossover phenomenon can be justified to some extent by the mechanical properties due to the decrease of volume associated with the transition of the metal ion from the HS state to the LS state. As demonstrated here, the molecular complex [Fe(PM-pBrA) (NCS) ] exhibits, on the contrary, an increase of the unit-cell volume from HS to LS. This counter-intuitive and unprecedented behavior that concerns both the thermal and the photoexcited spin conversions is revealed by a combination of single-crystal and powder X-ray diffraction complemented by magnetic measurements.

Synthesis of new piperazinyl-pyrrolo[1,2-]quinoxaline derivatives as inhibitors of multidrug transporters by a Buchwald-Hartwig cross-coupling reaction.

Two series of piperazinyl-pyrrolo[1,2-]quinoxaline derivatives were prepared a Buchwald-Hartwig cross-coupling reaction and then evaluated for their ability to inhibit the drug efflux activity of CaCdr1p and CaMdr1p transporters of overexpressed in a strain. In the initial screening of twenty-nine piperazinyl-pyrrolo[1,2-]quinoxaline derivatives, twenty-three compounds behaved as dual inhibitors of CaCdr1p and CaMdr1p. Only four compounds showed exclusive inhibition of CaCdr1p or CaMdr1p.

Pressure-Induced Spin-Crossover Features at Variable Temperature Revealed by In Situ Synchrotron Powder X-ray Diffraction.

An accurate high-pressure X-ray diffraction investigation, at various temperatures, on a powder of a spin-crossover (SCO) complex has allowed the rare deconvolution of the structural features of the high-spin and low-spin phases. As a result, the pressure dependence of the structural parameters of the high-spin and low-spin phases can be discussed independently in the pressure domain where both phases co-exist within the powder. Consequently, crucial unprecedented information is given, such as the variation of bulk moduli with temperature, similar here in amplitude for both spin phases, the temperature-dependence of the pressure-induced SCO abruptness, the temperature dependence of the pressure at which SCO occurs, and arguments for a possible piezo-hysteresis.

Solvatomorphism-Induced 45 K Hysteresis Width in a Spin-Crossover Mononuclear Compound.

Spin-transition compounds are coordination complexes that can present two stable or metastable high-spin and low-spin states at a given temperature (thermal hysteresis). The width of the thermal hysteresis (difference between the maximum and minimum temperature between which the compound exhibits bi-stability) depends on the interactions between the coordination complexes within the compound, and which may be modulated by the absence or presence of solvent within the structure. The new compound [Fe(3-bpp) ][Au(CN) ] (1, 3-bpp=2,6-di-(1H-pyrazol-3-yl)pyridine) was synthesized and its properties were compared with those of the solvated compound [Fe(3-bpp) ][Au(CN) ] ⋅2 H O (1.

Variation of M···H-C Interactions in Square-Planar Complexes of Nickel(II), Palladium(II), and Platinum(II) Probed by Luminescence Spectroscopy and X-ray Diffraction at Variable Pressure.

Luminescence spectra of isoelectronic square-planar d complexes with 3d, 4d, and 5d metal centers show d-d luminescence with an energetic order different from that of the spectrochemical series, indicating that additional structural effects, such as different ligand-metal-ligand angles, are important factors. Variable-pressure luminescence spectra of square-planar nickel(II), palladium(II), and platinum(II) complexes with dimethyldithiocarbamate ({CH}DTC) ligands and their deuterated analogues show unexpected variations of the shifts of their maxima. High-resolution crystal structures and crystal structures at variable pressure for [Pt{(CH)DTC}] indicate that intermolecular M···H-C interactions are at the origin of these different shifts.

Extreme downsizing in the surfactant-free synthesis of spin-crossover nanoparticles in a microfluidic flow-focusing junction.

A new surfactant-free, flow-focusing droplet microfluidic approach was developed as an important alternative to existing synthesis techniques for the preparation of spin crossover nanoparticles. It enables great control of the mixing of the reactants, and produces crystals of [Fe(pyrazine)(Pt(CN)4)] with an unexpected 20-fold downsizing compared to classical bulk synthesis.

Single helically folded aromatic oligoamides that mimic the charge surface of double-stranded B-DNA.

Numerous essential biomolecular processes require the recognition of DNA surface features by proteins. Molecules mimicking these features could potentially act as decoys and interfere with pharmacologically or therapeutically relevant protein-DNA interactions. Although naturally occurring DNA-mimicking proteins have been described, synthetic tunable molecules that mimic the charge surface of double-stranded DNA are not known.

An unprecedented trinuclear Fe triazole-based complex exhibiting a concerted and complete sharp spin transition above room temperature.

We report a triazole-based trinuclear complex as the first example that displays a complete one-step first-order [HS-HS-HS] ↔ [LS-LS-LS] spin transition at 318 K. The strong ferro-elastic interactions, between the three metal centers, have been identified as the source of the concerted spin transition in this trinuclear complex.

Preformulation studies of ceftriaxone for pediatric non-parenteral administration as an alternative to existing injectable formulations.

Ceftriaxone, a third generation cephalosporin, has a wide antibacterial spectrum that has good CNS penetration, which makes it potentially suitable for initial treatment of severe neonatal pediatric infections providing suitable formulation. We evaluated its physicochemical and technical characteristics to assess its potential for development as a non-parenteral dosage form. As ceftriaxone is marked only for injectable use, these data are not available.

Synthesis and Antiproliferative Effect of Ethyl 4-[4-(4-Substituted Piperidin-1-yl)]benzylpyrrolo[1,2-a]quinoxalinecarboxylate Derivatives on Human Leukemia Cells.

Acute leukemia is a hematological malignancy with high incidence and recurrence rates and is characterized by an accumulation of blasts in bone marrow due to proliferation of immature lymphoid or myeloid cells associated with a blockade of differentiation. The heterogeneity of leukemia led us to look for new specific molecules for leukemia subtypes or for therapy-resistant cases. Among heterocyclic derivatives that attracted attention due to their wide range of biological activities, we focused our interest on the pyrrolo[1,2-a]quinoxaline heterocyclic framework that has been previously identified as an interesting scaffold for antiproliferative activities against various human cancer cell lines.

Controlled Dimroth Rearrangement in the Suzuki-Miyaura Cross Coupling of Triazolopyridopyrimidines.

Polynitrogen heterocycles are often subject to Dimroth rearrangement which consists of ring opening, bond rotation, and ring closure. In this note, we report a synthesis of two new families of triazolopyridopyrimidines. Successful functionalization via a Suzuki-Miyaura coupling was performed with total control of triazole (Dimroth) isomerization based on the judicious choice of reaction conditions.