Lanthanide-Based Probes for Imaging Detection of Enzyme Activities by NIR Luminescence,T1- and ParaCEST MRI

Applying a single molecular probe to monitor enzymatic activities in multiple, complementary imaging modalities is highly desirable to ascertain detection and to avoid the complexity associated with the use of agents of different chemical entities. We demonstrate here the versatility of lanthanide (Ln³⁺) complexes with respect to their optical and magnetic properties and their potential for enzymatic detection in NIR luminescence, CEST and T1 MR imaging, controlled by the nature of the Ln³⁺ ion, while using a unique chelator. Based on X-ray structural, photophysical, and solution NMR investigations of a family of Ln³⁺ DO3A-pyridine model complexes, we could rationalize the luminescence (Eu³⁺, Yb³⁺), CEST (Yb³⁺) and relaxation (Gd³⁺) properties and their variations between carbamate and amine derivatives. This allowed the design of $$ probes which undergo enzyme-mediated changes detectable in NIR luminescence, CEST and T1-weighted MRI, respectively governed by variations in their absorption energy, in their exchanging proton pool and in their size, thus relaxation efficacy. We demonstrate that these properties can be exploited for the visualization of β-galactosidase activity in phantom samples by different imaging modalities: NIR optical imaging, CEST and T1-weighted MRI.     

A new theoretical approach for the determination of molecular orientation persistence length of adsorbed nanofilms by FTIR reflectance spectroscopy

FTIR-Reflectance experiments have proved to be a powerful tool for the determination of molecular orientation in thin films adsorbed onto highly reflecting metals. We propose an original method for determination of the persistence length of molecular orientation in the film. This approach is based on the fact that molecular orientation persists only over a given distance from the geometrical interface. This distance is called the “persistence length of molecular orientation”. We then suppose that the nanofilm adsorbed is stratified and consists of an oriented layer (in the near-interface region) plus an isotropic one. Correlation between infrared reflection absorption band intensities and simulated band intensities allows experimentators to determine accurate molecular orientation and persistence length of orientation of a considered functional group. This is accomplished by using various IR reflection angles and p-polarization state of the incident IR wave. Film thickness and complex refractive index spectra, n(v) − i · k(v), are only needed to deduce calculated specular reflectance intensities.     

Poly[sodium(I)‐μ6‐hydrogen benzene‐1,4‐dicarboxylato]

Alkali metal salts of terephthalic acid are common reagents in the preparation of metal–ligand coordination complexes containing terephthalate anions. In the title compound, sodium hydrogen terephthalate, [Na(C₈H₅O₄)]_n, the cations occupy crystallographic inversion centres, and each bridging anion coordinates to six octahedral cations and vice versa. As seen in the known potassium derivative [Kaduk (2000). Acta Cryst. B 56 , 474–485; Miyakubo, Takeda & Nakamura (1994). Bull. Chem. Soc. Jpn, 67 , 2301–2303], sodium hydrogen terephthalate contains short O—H⋯O hydrogen bonds between anions [O⋯O = 2.4734 (17) Å]. The structure is centrosymmetric and exhibits disorder of the H‐atom position in the hydrogen bond and of the non‐bridging ring C atoms in the terephthalate ion.     

{[Ca5(C8H4O4)5(H2O)9]·8H2O}n: the first crystallographically characterized non‐transition metal salt of isophthalic acid

The reaction of CaCO₃ with isophthalic acid in water yields nona­aqua­penta‐μ‐isophthalato‐pentacalcium octahydrate, {[Ca₅(C₈H₄O₄)₅(H₂O)₉]·8H₂O}_n, a complex polymeric one‐dimensional column structure bearing metal–carboxyl­ate bonds and Ca‐bound terminal and bridging water mol­ecules, in addition to hydrogen‐bonded water mol­ecules of crystallization. The asymmetric unit comprises half of the formula unit, with one Ca²⁺ ion located on a twofold axis, and contains 16 unique strong O—H⋯O hydrogen bonds, some of which link the columns together.     

The Amyloid Fibril-Forming β-Sheet Regions of Amyloid β and α-Synuclein Preferentially Interact with the Molecular Chaperone 14-3-3ζ

14-3-3 proteins are abundant, intramolecular proteins that play a pivotal role in cellular signal transduction by interacting with phosphorylated ligands. In addition, they are molecular chaperones that prevent protein unfolding and aggregation under cellular stress conditions in a similar manner to the unrelated small heat-shock proteins. In vivo, amyloid β (Aβ) and α-synuclein (α-syn) form amyloid fibrils in Alzheimer’s and Parkinson’s diseases, respectively, a process that is intimately linked to the diseases’ progression. The 14-3-3ζ isoform potently inhibited in vitro fibril formation of the 40-amino acid form of Aβ (Aβ₄₀) but had little effect on α-syn aggregation. Solution-phase NMR spectroscopy of ¹⁵N-labeled Aβ₄₀ and A53T α-syn determined that unlabeled 14-3-3ζ interacted preferentially with hydrophobic regions of Aβ₄₀ (L11-H21 and G29-V40) and α-syn (V3-K10 and V40-K60). In both proteins, these regions adopt β-strands within the core of the amyloid fibrils prepared in vitro as well as those isolated from the inclusions of diseased individuals. The interaction with 14-3-3ζ is transient and occurs at the early stages of the fibrillar aggregation pathway to maintain the native, monomeric, and unfolded structure of Aβ₄₀ and α-syn. The N-terminal regions of α-syn interacting with 14-3-3ζ correspond with those that interact with other molecular chaperones as monitored by in-cell NMR spectroscopy.     

A Fused Hexacyclic Ring System: Diastereoselective Polycyclization of 2,4‐Dienals through an Interrupted iso‐Nazarov Reaction

We report an unprecedented domino polycyclization from readily available 2,4‐dienals and cyclic α,β‐unsaturated imines that is initiated by an iso‐Nazarov reaction. This Brønsted acid promoted reaction enables the concomitant formation of four bonds, three cycles, and four contiguous stereogenic centers to yield elaborated structures in a single operation. A range of fused hexacyclic molecules is obtained in a highly diastereoselective manner.     

Modular Access to Eight‐Membered N‐Heterocycles by Directed Carbonylative C−C Bond Activation of Aminocyclopropanes

Aminocyclopropanes equipped with pendant nucleophiles undergo carbonylative heterocyclization triggered by C?C bond activation to generate eight‐membered N‐heterocycles. In these processes, intramolecular “capture” of a rhodacyclopentanone intermediate by an aryl or N‐based nucleophile is followed by C?C or C?N bond‐forming “collapse” to the targets. These studies demonstrate how the combination of cyclopropane strain release and the templating effect of catalytically generated metallacycles can be harnessed to enable otherwise challenging medium ring closures.     

A one-pot electrophilic cyanation–functionalization strategy for the synthesis of disubstituted malononitriles

Malononitriles are valuable synthetic intermediates for many applications, including the synthesis of herbicides and other biologically active molecules, and the synthesis of chiral ligands for asymmetric catalysis. This article describes the development of a procedure for the conversion of primary nitriles to malononitriles using dimethylmalononitrile, a commercial, non-toxic, carbon-bound source of electrophilic cyanide. This procedure avoids the use of toxic cyanide or malononitrile as a starting material. This protocol is further applied to the dicyanation of benzyl Grignard reagents, generated from benzyl bromides, yielding fully functionalized malononitriles from a nitrile-free precursor.     

Chemical Composition,Antioxidant and Anti-Inflammatory Activities of Clary Sage and Coriander Essential Oils Produced on Polluted and Amended Soils-Phytomanagement Approach

The potential of essential oils (EO), distilled from two aromatic plants—clary sage (Salvia sclarea L.) and coriander (Coriandrum sativum L.)—in view of applications as natural therapeutic agents was evaluated in vitro. These two were cultivated on a trace element (TE)-polluted soil, as part of a phytomanagement approach, with the addition of a mycorrhizal inoculant, evaluated for its contribution regarding plant establishment, growth, and biomass production. The evaluation of EO as an antioxidant and anti-inflammatory, with considerations regarding the potential influence of the TE-pollution and of the mycorrhizal inoculation on the EO chemical compositions, were the key focuses. Besides, to overcome EO bioavailability and target accession issues, the encapsulation of EO in β-cyclodextrin (β-CD) was also assessed. Firstly, clary sage EO was characterized by high proportions of linalyl acetate (51–63%) and linalool (10–17%), coriander seeds EO by a high proportion of linalool (75–83%) and lesser relative amounts of γ-terpinene (6–9%) and α-pinene (3–5%) and coriander aerial parts EO by 2-decenal (38–51%) and linalool (22–39%). EO chemical compositions were unaffected by both soil pollution and mycorrhizal inoculation. Of the three tested EO, the one from aerial parts of coriander displayed the most significant biological effects, especially regarding anti-inflammatory potential. Furthermore, all tested EO exerted promising antioxidant effects (IC₅₀ values ranging from 9 to 38 g L⁻¹). However, EO encapsulation in β-CD did not show a significant improvement of EO biological properties in these experimental conditions. These findings suggest that marginal lands polluted by TE could be used for the production of EO displaying faithful chemical compositions and valuable biological activities, with a non-food perspective.