Step-by-Step Design of New Theranostic Nanoformulations: Multifunctional Nanovectors for Radio-Chemo-Hyperthermic Therapy under Physical Targeting

While investigating the possible synergistic effect of the conventional anticancer therapies, which, taken individually, are often ineffective against critical tumors, such as central nervous system (CNS) ones, the design of a theranostic nanovector able to carry and deliver chemotherapy drugs and magnetic hyperthermic agents to the target radiosensitizers (oxygen) was pursued. Alongside the original formulation of polymeric biodegradable oxygen-loaded nanostructures, their properties were fine-tuned to optimize their ability to conjugate therapeutic doses of drugs (doxorubicin) or antitumoral natural substances (curcumin). Oxygen-loaded nanostructures (diameter = 251 ± 13 nm, ζ potential = −29 ± 5 mV) were finally decorated with superparamagnetic iron oxide nanoparticles (SPIONs, diameter = 18 ± 3 nm, ζ potential = 14 ± 4 mV), producing stable, effective and non-agglomerating magnetic nanovectors (diameter = 279 ± 17 nm, ζ potential = −18 ± 7 mV), which could potentially target the tumoral tissues under magnetic driving and are monitorable either by US or MRI imaging.     

Structural Landscape of the Transition from an ssDNA Dumbbell Plus Its Complementary Hairpin to a dsDNA Microcircle Via a Kissing Loop Intermediate

The experimental construction of a double-stranded DNA microcircle of only 42 base pairs entailed a great deal of ingenuity and hard work. However, figuring out the three-dimensional structures of intermediates and the final product can be particularly baffling. Using a combination of model building and unrestrained molecular dynamics simulations in explicit solvent we have characterized the different DNA structures involved along the process. Our 3D models of the single-stranded DNA molecules provide atomic insight into the recognition event that must take place for the DNA bases in the cohesive tail of the hairpin to pair with their complementary bases in the single-stranded loops of the dumbbell. We propose that a kissing loop involving six base pairs makes up the core of the nascent dsDNA microcircle. We also suggest a feasible pathway for the hybridization of the remaining complementary bases and characterize the final covalently closed dsDNA microcircle as possessing two well-defined U-turns. Additional models of the pre-ligation complex of T4 DNA ligase with the DNA dumbbell and the post-ligation pre-release complex involving the same enzyme and the covalently closed DNA microcircle are shown to be compatible with enzyme recognition and gap ligation.     

Sequential Electrochemical Polymerization of Aniline and Their Derivatives Showing Electrochemical Activity at Neutral pH

Sequential electropolymerization of aniline followed by an aniline derivative bearing an ion moiety is presented. The studied derivatives contain sulfonic, carboxylate or amino groups. Its electrochemical behavior at acid and neutral pH is studied by cyclic voltammetry combined with quartz crystal microbalance or probe beam deflection in order to assess the mass transfer process involved in these new modified electrodes. All of them show a stable and quasi‐reversible electrochemical behavior at neutral pH that can be attributed to a self‐doping process. These new modified electrodes can be further modified due to the presence of functional groups.     

Unilateral NMR applied to the conservation of works of art

In conventional NMR, samples from works of art in sizes above those considered acceptable in the field of art conservation would have to be removed to place them into the bore of large superconducting magnets. The portable permanent-magnet-based systems, by contrast, can be used in situ to study works of art, in a noninvasive manner. One of these portable NMR systems, NMR-MOUSE®, measures the information contained in one pixel in an NMR image from a region of about 1 cm², which can be as thin as 2–3 µm. With such a high depth resolution, profiles through the structures of art objects can be measured to characterize the materials, the artists’ techniques, and the deterioration processes. A novel application of the technique to study a deterioration process and to follow up a conservation treatment is presented in which micrometer-thick oil stains on paper are differentiated and characterized. In this example, the spin–spin relaxation T ₂ of the stain is correlated to the iodine number and to the degree of cross-linking of the oil, parameters that are crucial in choosing an appropriate conservation treatment to remove them. It is also shown that the variation of T ₂ over the course of treatments with organic solvents can be used to monitor the progress of the conservation interventions. It is expected that unilateral NMR in combination with multivariate data analysis will fill a gap within the set of high-spatial-resolution techniques currently available for the noninvasive analysis of materials in works of art, where procedures to study the inorganic components are currently far more developed than those suitable for the study of the organic components.     

Copper(I) thiophenolate in copper N-heterocyclic carbene preparation

Copper(I) thiophenolate was considered as a copper source for the synthesis of Cu(I)-N-heterocyclic carbenes (Cu(I)-NHCs). It displayed a dual mode of reactivity allowing the synthesis of both thiophenolato-Cu(I)-NHCs via the free carbene in a one-pot procedure starting from imidazolium chlorides and chloro-Cu(I)-NHCs by a salt metathesis reaction starting from chloro-Ag(I)-NHCs.     

HPLC‐DAD method for the simultaneous determination of zofenopril and hydrochlorothiazide in oral pharmaceutical formulations

An HPLC method with DAD detection was developed and validated for the simultaneous determination of zofenopril and hydrochlorothiazide in tablets. The separation was carried out through a gradient elution using an Agilent LiChrospher C18 column (250×4.0 mm id, 5 μm) and a mobile phase consisting of (A) water–TFA (99.9:0.1 v/v) and (B) acetonitrile–TFA (99.1:0.1 v/v) delivered at a flow‐rate of 1.0 mL/min. 8‐Chlorotheophylline was used as internal standard. Calibration curves were found to be linear for the two drugs over the concentration ranges of 5.0–40 and 1.0–20 μg/mL for zofenopril and hydrochlorothiazide, respectively. Linearity, precision, accuracy, specificity and robustness were determined in order to validate the proposed method, which was further applied to the analysis of commercial tablets. The proposed method is simple and rapid, and gives accurate and precise results.     

Homonuclear Decoupling in 1H NMR of Solids by Remote Correlation

The typical linewidths of ¹H NMR spectra of powdered organic solids at 111 kHz magic-angle spinning (MAS) are of the order of a few hundred Hz. While this is remarkable in comparison to the tens of kHz observed in spectra of static samples, it is still the key limit to the use of ¹H in solid-state NMR, especially for complex systems. Here, we demonstrate a novel strategy to further improve the spectral resolution. We show that the anti-z-COSY experiment can be used to reduce the residual line broadening of ¹H NMR spectra of powdered organic solids. Results obtained with the anti-z-COSY sequence at 100 kHz MAS on thymol, β-AspAla, and strychnine show an improvement in resolution of up to a factor of two compared to conventional spectra acquired at the same spinning rate.     

A Supramolecular Stabilizer of the 14‐3‐3ζ/ERα Protein‐Protein Interaction with a Synergistic Mode of Action

We report on a stabilizer of the interaction between 14‐3‐3ζ and the Estrogen Receptor alpha (ERα). ERα is a driver in the majority of breast cancers and 14‐3‐3 proteins are negative regulators of this nuclear receptor, making the stabilization of this protein‐protein interaction (PPI) an interesting strategy. The stabilizer ( 1 ) consists of three symmetric peptidic arms containing an arginine mimetic, previously described as the GCP motif. 1 stabilizes the 14‐3‐3ζ/ERα interaction synergistically with the natural product Fusicoccin‐A and was thus hypothesized to bind to a different site. This is supported by computational analysis of 1 binding to the binary complex of 14‐3‐3 and an ERα‐derived phosphopeptide. Furthermore, 1 shows selectivity towards 14‐3‐3ζ/ERα interaction over other 14‐3‐3 client‐derived phosphomotifs. These data provide a solid support of a new binding mode for a supramolecular 14‐3‐3ζ/ERα PPI stabilizer.