Copper(II) complexes of bis(amino amide) ligands: effect of changes in the amino acid residue

A family of ligands derived from bis(amino amides) containing aliphatic spacers has been prepared, and their protonation and stability constants for the formation of Cu(2+) complexes have been determined potentiometrically. Important differences are associated to both the length of the aliphatic spacer and the nature of the side chains derived from the amino acid. In general, ligands containing aliphatic side chains display higher basicities as well as stability constants with Cu(2+). In the same way, basicities and stability constants tend to increase when decreasing the steric hindrance caused by the corresponding side-chain. FT-IR, UV-vis and ESI-MS were used for analyzing the complex species detected in the speciation diagram. UV-vis studies showed the presence of different coordination environments for the copper(II) complexes. Complexes with different stoichiometries can be formed in some instances. This was clearly highlighted with the help of ESI-MS experiments.     

Theoretical study of neutral and protonated triple bonded molecules formed between C, N, Si, P, B and Al

A theoretical study of the possible protonation sites of simple molecules formed by C, N, Si, P, B and Al that present a triple bond between those atoms has been carried out. The calculations performed include MP2 and CCSD(T) methods with the aug-cc-pVTZ basis set. The nature of the protonated species has been analyzed with the Atoms In Molecules methodology. To Serafin, a free spirit and a good friend. Contribution to the Serafin Fraga Memorial Issue.     

Flexible ureasil hybrids with tailored optical properties through doping with metal nanoparticles

Hybrid organic-inorganic nanocomposites containing uniform distributions of metal nanoparticles have been prepared by mixing a preformed nanoparticle colloid with the precursors of a ureasil, prior to the sol-gel transition. These nanocomposites possess not only high optical quality and optical features dictated by the size and shape of the nanoparticle dopants but also a high degree of flexibility, which can largely enhance the range of applications in practical devices. The deposition of a uniform silica shell on the nanoparticle surface prior to the sol-gel transition was found to be required to maintain the colloidal stability during the process and, thus, to retain the optical properties in the final nanocomposite material. This method can be readily extended to other materials, such as semiconductor and magnetic nanoparticles.     

Lanthanide(III) Complexes of 2‐[4,7,10‐Tris(phosphonomethyl)‐1,4,7,10‐tetraazacyclododecan‐1‐yl]acetic Acid (H7DOA3P): Multinuclear‐NMR and Kinetic Studies

The protonation constants of 2‐[4,7,10‐tris(phosphonomethyl)‐1,4,7,10‐tetraazacyclododecan‐1‐yl]acetic acid (H₇DOA3P) and of the complexes [Ln(DOA3P)]^4? (Ln=Ce, Pr, Sm, Eu, and Yb) have been determined by multinuclear NMR spectroscopy in the range pD 2–13.8, without control of ionic strength. Seven out of eleven protonation steps were detected (pK =13.66, 12.11, 7.19, 6.15, 5.77, 2.99, and 1.99), and the values found compare well with the ones recently determined by potentiometry for H₇DOA3P, and for other related ligands. The overall basicity of H₇DOA3P is higher than that of H₄DOTA and trans‐H₆DO2A2P but lower than that of H₈DOTP. Based on multinuclear‐NMR spectroscopy, the protonation sequence for H₇DOA3P was also tentatively assigned. Three protonation constants (pK_MHL, pK_MH2L, and pK_MH3L) were determined for the lanthanide complexes, and the values found are relatively high, although lower than the protonation constants of the related ligand (pK , pK , and pK ), indicating that the coordinated phosphonate groups in these complexes are protonated. The acid‐assisted dissociation of [Ln(DOA3P)]^4? (Ln=Ce, Eu), in the region c_H+=0.05–3.00 mol dm^?3 and at different temperatures (25–60°), indicated that they have slightly the same kinetic inertness, being the [Eu(H₂O)₉]³⁺ aqua ion the final product for europium. The rates of complex formation for [Ln(DOA3P)]^4? (Ln=Ce, Eu) were studied by UV/VIS spectroscopy in the pH range 5.6–6.8. The reaction intermediate [Eu(DOA3P)]* as ‘out‐of‐cage’ complex contains four H₂O molecules, while the final product, [Eu(DOA3P)]^4?, does not contain any H₂O molecule, as proved by steady‐state/time‐resolved luminescence spectroscopy.     

Preparation of polymer-supported gold nanoparticles based on resins containing ionic liquid-like fragments: easy control of size and stability

Crosslinked polymers containing covalently attached functional sites with chemical structures related to those present in ILs and having macroscopic properties very similar to the ones of the corresponding bulk ILs can be advantageously applied to the preparation of gold nanoparticles (AuNPs). The size and morphology of the resulting metal nanoparticles (MNPs) can be easily modulated through a proper combination of the synthetic method used for the generation of the NPs and the structural elements of the polymer. Additionally, the resulting supported AuNPs are demonstrated to be stable for at least eight months with the vials open to the atmosphere. Several synthetic methodologies have been studied, as well as different structural parameters for the functional polymers. Those include the chemical nature (anions and cations) and loading of the ionic liquid-like fragments and the morphology of the polymeric matrix. The results obtained show the potential to prepare supported AuNPs with narrow size distributions and small diameters that can have potential interest for application in different fields.     

Novel combination of non-aqueous capillary electrophoresis and multivariate curve resolution-alternating least squares to determine phenolic acids in virgin olive oil

This paper presents the development of a non-aqueous capillary electrophoresis method coupled to UV detection combined with multivariate curve resolution-alternating least-squares (MCR-ALS) to carry out the resolution and quantitation of a mixture of six phenolic acids in virgin olive oil samples. p-Coumaric, caffeic, ferulic, 3,4-dihydroxyphenylacetic, vanillic and 4-hydroxyphenilacetic acids have been the analytes under study. All of them present different absorption spectra and overlapped time profiles with the olive oil matrix interferences and between them. The modeling strategy involves the building of a single MCR-ALS model composed of matrices augmented in the temporal mode, namely spectra remain invariant while time profiles may change from sample to sample. So MCR-ALS was used to cope with the coeluting interferences, on accounting the second order advantage inherent to this algorithm which, in addition, is able to handle data sets deviating from trilinearity, like the data herein analyzed. The method was firstly applied to resolve standard mixtures of the analytes randomly prepared in 1-propanol and, secondly, in real virgin olive oil samples, getting recovery values near to 100% in all cases. The importance and novelty of this methodology relies on the combination of non-aqueous capillary electrophoresis second-order data and MCR-ALS algorithm which allows performing the resolution of these compounds simplifying the previous sample pretreatment stages.     

Chemical Proteomics and Phenotypic Profiling Identifies the Aryl Hydrocarbon Receptor as a Molecular Target of the Utrophin Modulator Ezutromid

Duchenne muscular dystrophy (DMD) is a fatal muscle‐wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first‐in‐class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent K_D of 50 nm  and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies.     

Molecular dynamics assessment of doxorubicin–carbon nanotubes molecular interactions for the design of drug delivery systems

Carbon nanotubes (CNTs) constitute an interesting material for nanomedicine applications because of their unique properties, especially their ability to penetrate membranes, to transport drugs specifically and to be easily functionalized. In this work, the energies of the intermolecular interactions of single-walled CNTs and the anticancer drug doxorubicin (DOX) were determined using the AMBER 12 molecular dynamics MM/PBSA and MM/GBSA methods with the aim of better understanding how the structural parameters of the nanotube can improve the interactions with the drug and to determine which structural parameters are more important for increasing the stability of the complexes formed between the CNTs and DOX. The armchair, zigzag, and chiral nanotubes were finite hydrogen-terminated open tubes, and the DOX was encapsulated inside the tube or adsorbed on the nanotube surface. Pentagon/heptagon bumpy defects and polyethylene glycol (PEG) nanotube functionalization were also studied. The best interaction occurred when the drug was located inside the cavity of the nanotube. Armchair and zigzag nanotubes doped with nitrogen, favored interaction with the drug, whereas chiral nanotubes exhibited better drug interactions when having bumpy defects. The π-π stacking and N-H…π electrostatic interactions were important components of the attractive drug-nanotube forces, enabling significant flattening of the nanotube to favor a dual strong interaction with the encapsulated drug, with DOX–CNT equilibrium distances of 3.1–3.9 Å. These results can contribute to the modeling of new drug-nanotube delivery systems.

     

Hydrogen physisorption energies for bumpy,saturated, nitrogen-doped single-walled carbon nanotubes

Finite saturated regular carbon nanotubes (CNTs) are predicted to exhibit higher capacity as hydrogen storage media compared to unsaturated regular CNTs. In the present study, molecular hydrogen physisorption energies (MHPEs) for finite saturated and unsaturated bumpy defected CNTs were calculated by density functional theory (DFT-D3) methods at the B3LYP/6-31G(d) theory level, with rigorous inclusion of van der Waals interactions. The calculated MHPEs for both regular and bumpy defected armchair, chiral and zigzag CNTs with similar diameters and lengths, with and without nitrogen doping, were compared in terms of Eph/H₂, defined as the MHPE per hydrogen molecule adsorbed inside the nanotube. For all studied systems, Eph/H₂ increased with the number of physisorbed hydrogen molecules. Nitrogen doping of regular and bumpy CNTs resulted in an increase in the Eph/H₂ values, with the exception of bumpy chiral nanotubes. The results of this study demonstrate that bumpy defects are important nanotube structural features whose effects depend on nanotube chirality. For instance, bumpy defects were beneficial for undoped and doped zigzag nanotubes, resulting in a decrease in Eph/H₂ values for regular structures from 0.5 and 0.74 to 0.26 and 0.42 eV, respectively. By contrast, for doped armchair regular structures with an Eph/H₂ value of 0.38 eV, bumpy defects increased Eph/H₂ to 0.45 eV. These Eph/H₂ values for bumpy doped armchair and the zigzag nanotubes are all within the range of 0.1–0.5 eV/H₂ reported as ideal for reversible hydrogen storage under environmental conditions.