Mechanistic Insights about the Ligand-Enabled Oxy-arylation/vinylation of Alkenes via Au(I)/Au(III) Catalysis

The mechanism of oxy-arylation/vinylation of alkenes catalyzed by the (MeDalphos)AuCl complex was comprehensively investigated by DFT. (P,N)Au(Ph)²⁺ and (P,N)Au(vinyl)²⁺ are key intermediates accounting for the activation of the alkenols and for their cyclization by outer-sphere nucleophilic attack of oxygen. The 5-exo and 6-endo paths have been computed and compared, reproducing the peculiar regioselectivity difference observed experimentally between 4-penten-1-ol, (E) and (Z)-4-hexen-1-ols. Examining the way the alkenol coordinates to gold (more η² or η¹) can offer, in some cases, a simple way to predict the favored path of cyclization.     

Hydrogen Peroxide-Responsive Triggers Based on Borinic Acids: Molecular Insights into the Control of Oxidative Rearrangement

Arylborinic acids represent new, efficient, and underexplored hydrogen peroxide-responsive triggers. In contrast to boronic acids, two concomitant oxidative rearrangements are involved in the complete oxidation of these species, which might represent a major limitation for an efficient effector (drug or fluorophore) release. Herein, a comprehensive study of H₂O₂-mediated unsymmetrical arylborinic acid oxidation to investigate the factors that could selectively guide their oxidative rearrangement is described. The o-CF₃ substituent was found to be an excellent directing group allowing a complete regioselectivity on borinic acid models. This result was successfully applied to synthesizing new borinic acid-based fluorogenic probes, which exclusively release the fluorescent moiety upon H₂O₂ treatment. These compounds maintained their superior kinetic properties compared to boronic acids, thus further enhancing the potential of arylborinic acids as valuable new H₂O₂-sensitive triggers.     

Marinobufagenin extraction from Rhinella marina toad glands: Alternative approaches for a systematized strategy

Marinobufagenin is a bufadienolide compound detected mainly in skin and parotoid gland secretions of Rhinella marina (L.) toad. Bufadienolides regulate the Na⁺/K⁺‐ATPase pump by inhibiting the cardiotonic steroid dependent‐site and act as cardiac inotropes with vasoconstrictive properties. Marinobufagenin and other bufadienolides, such as telocinobufagin and bufalin, are thought to be found endogenously in mammals in salt‐sensitive hypertensive states such as essential hypertension, congestive heart‐failure, and preeclampsia. The role of marinobufagenin as antimicrobial agent and its cytotoxic potential have also been recognized. The particular interest around marinobufagenin prompts us to consider the Rhinella marina toad venom as a possible source for molecules with pharmacological and/or diagnostic potential. In this article, two different approaches of extraction and purification of marinobufagenin from Rhinella marina (L.) venom are studied: (i) Preparative thin‐layer chromatography combined to mass spectrometry and/or ultraviolet detection and (ii) solid‐phase extraction coupled with fractionation on high‐performance liquid chromatography. Different chromatographic conditions are tested for each approach. The solid‐phase extraction combined with high‐performance liquid chromatography fractionation approach was preferred as it offered a greater yield, was less time‐consuming and allowed us to selectively isolate marinobufagenin. Both protocols aim to provide efficient and convenient methods for toad venom extraction, based on an easily automatable and systematized strategy.     

P450Jα: A New,Robust and α-Selective Fatty Acid Hydroxylase Displaying Unexpected 1-Alkene Formation

Oxyfunctionalization of fatty acids (FAs) is a key step in the design of novel synthetic pathways for biobased/biodegradable polymers, surfactants and fuels. Here, we show the isolation and characterization of a robust FA α-hydroxylase (P450_Jα) which catalyses the selective conversion of a broad range of FAs (C6:0-C16:0) and oleic acid (C18:1) with H₂O₂ as oxidant. Under optimized reaction conditions P450_Jα yields α-hydroxy acids all with >95 % regioselectivity, high specific activity (up to 15.2 U mg⁻¹) and efficient coupling of oxidant to product (up to 85 %). Lauric acid (C12:0) turned out to be an excellent substrate with respect to productivity (TON=394 min⁻¹). On preparative scale, conversion of C12:0 reached 83 % (0.9 g L⁻¹) when supplementing H₂O₂ in fed-batch mode. Under similar conditions P450_Jα allowed further the first biocatalytic α-hydroxylation of oleic acid (88 % conversion on 100 mL scale) at high selectivity and in good yields (1.1 g L⁻¹; 79 % isolated yield). Unexpectedly, P450_Jα displayed also 1-alkene formation from shorter chain FAs (≤C10:0) showing that oxidative decarboxylation is more widely distributed across this enzyme family than reported previously.     

A novel approach toward the synthesis of strigolactones through intramolecular [2+2] cycloaddition of ketenes and ketene-iminiums to olefins. Application to the asymmetric synthesis of GR-24

An intramolecular [2+2] cycloaddition of ketenes and ketene-iminium was developed for the preparation of GR-24, a synthetic analogue of the family of strigolactone plant hormones. Excellent levels of regioselectivity and of chiral induction were obtained using a bulky chiral amine for the formation of the cyclobutanone and a subsequent regioselective Baeyer-Villiger afforded the tricyclic lactone core of (+)-GR-24.     

Multiscale surface self-assembly of an amyloid-like peptide

We present the 2D self-assembly properties of an amyloid-like peptide (LSFDNSGAITIG-NH2) (i.e., LSFD) over a whole range of spatial scales. This peptide is known to adopt an amyloid-like behavior in water where it aggregates into fibrils. Monolayers of this 12 amino acid peptide were built by direct spreading and compression of an organic unstructured LSFD solution at the air/water interface. Investigation by infrared spectroscopy of the peptide secondary structure reveals beta-sheet formation at the water surface. As evidenced by Brewster angle microscopy, compression of the peptidic film results in the formation of large condensed domains. We used atomic force microscopy to show that these domains are made of rather monodisperse, elongated domains of monomolecular thickness, which are about 1 microm long and hundred of nanometers wide. These nanodomains can be compacted up to the formation of a homogeneous monolayer on the micrometer scale. These bidimensional structures appear as a surface-induced counterpart of the bulk amyloid fibrils that do not form at the air/water interface. These self-assembled peptide nanostructures are also very promising for building organized nanomaterials.     

Accuracy evaluation of an optical lattice clock with bosonic atoms

We report what we believe to be the first accuracy evaluation of an optical lattice clock based on the S01-->P03 transition of an alkaline earth boson, namely, Sr88 atoms. This transition has been enabled by using a static coupling magnetic field. The clock frequency is determined to be 429228066418009(32)Hz. The isotopic shift between Sr87 and Sr88 is 62188135Hz with fractional uncertainty 5x10(-7). We discuss the necessary conditions to reach a clock accuracy of 10(-17) or less by using this scheme.     

Target analysis of primary photoprocesses involved in the oxyblepharismin-binding protein

Target analysis is performed on previously published transient absorption spectra of the 200-kDa oxyblepharismin-binding protein (OBIP) thought to trigger the photophobic response of the ciliate Blepharisma japonicum. The OBIP sample is considered as heterogeneous and made of two distinct classes of chromophore-protein complexes. A so-called nonreactive class is seen to be comparable to free oxyblepharismin in organic solution. Another, reactive, class is shown to undergo a fast picosecond photocycle involving the formation in 4 ps of an intermediate state noted Y1. The spectrum associated to Y1 bears striking similarities with that of the oxyblepharismin radical cation. This element favors the hypothesis that an excited-state intermolecular electron-transfer could be the primary step of the sensory transduction chain of B. japonicum. Proton release is also considered as a possible secondary step. These possibilities support the idea that reactive OBIP functions like an electron or proton pump. We alternatively propose a new hypothesis stating that the fast photocycle of reactive OBIP actually does not generate any photoproduct or protein change of conformation but is involved in another biological function. It would act as a kind of solar screen, providing additional protection to the light-adapted form of B. japonicum in case of excessive illumination.