Synthesis and characterisation of estrogenic carriers for cytotoxic Pt(II) fragments: biological activity of the resulting complexes

This paper describes the synthesis and the spectroscopic characterisation of cis-dichloro[N-(4-(17alpha-ethynylestradiolyl)-benzyl)-ethylenediamine]platinum(II) and cis-diamino[2-(4-(17alpha-ethynylestradiolyl)-benzoylamino)-malonato]platinum(II). These complexes were synthesised in good yield according to multi-step procedures based on the classical and non-classical Sonogashira coupling reaction, respectively. These compounds retain an acceptable degree of relative binding affinity (RBA) for the alpha form of estrogen receptor. Combined treatment of breast cancer cell lines, namely hormone-sensitive MCF-7 and hormone-insensitive MDA-MB-231 cell lines, indicates that these compounds maintain agonistic activity so that the potential advantage in vehiculation of the cytotoxic moiety by means of the receptor system is counteracted by the proliferative effect of the estrogenic component of the entire molecule, especially at low concentrations.     

A further test of the linearity of temporal summation in forward masking

An experiment tested the hypothesis that the masking effects of two nonoverlapping forward maskers are summed linearly over time. First, the levels of individual noise maskers required to mask a brief 4-kHz signal presented at 10-, 20-, 30-, or 40-dB sensation level (SL) were found. The hypothesis predicts that a combination of the first masker presented at the level required to mask the 10-dB SL signal and the second masker presented at the level required to mask the 20-dB SL signal, should produce the same amount of masking as the converse situation (i.e., the first masker presented at the level required to mask the 20-dB SL signal and the second masker presented at the level required to mask the 10-dB SL signal), and similarly for the 30- and 40-dB SL signals. The results were consistent with the predictions.     

Carboxy-terminated oligo(ethylene glycol)-alkane phosphate: synthesis and self-assembly on titanium oxide surfaces

The surface immobilization of oligo- and poly(ethylene glycol) on solids is a widely used approach to prevent the nonspecific adsorption of proteins, bacteria, and cells. A novel tri(ethylene glycol) derivative, phosphoric acid-mono(22-carboxy-12,15,18,21-tetraoxadocosyl) ester, was synthesized with the aim to produce self-assembled monolayers (SAMs) on metal/metal oxide surfaces. This compound contains two reactive, terminal moieties: the phosphoric acid group as anchor to the surface, and the carboxylic group as linker for further attachment of molecules such as peptides and proteins to be present at the surface. The adsorption on titanium-dioxide-coated substrates was studied quantitatively and the resulting SAMs were characterized by angle-dependent X-ray photoelectron spectroscopy (XPS) and spectroscopic ellipsometry. XPS data showed that the monomolecular layer is attached with the phosphate group to the substrate, but not fully ordered. The dry adlayer thickness was determined to be 13.4 A, which is less than expected for a densely packed monolayer. Surface concentration calculated from ellipsometry data resulted in a grafting density of 2.03 molecules/nm2.     

An Accurate Approach for Computational pKa Determination of Phenolic Compounds

Computational chemistry is a valuable tool, as it allows for in silico prediction of key parameters of novel compounds, such as pKa. In the framework of computational pKa determination, the literature offers several approaches based on different level of theories, functionals and continuum solvation models. However, correction factors are often used to provide reliable models that adequately predict pKa. In this work, an accurate protocol based on a direct approach is proposed for computing phenols pKa. Importantly, this methodology does not require the use of correction factors or mathematical fitting, making it highly practical, easy to use and fast. Above all, DFT calculations performed in the presence two explicit water molecules using CAM-B3LYP functional with 6-311G+dp basis set and a solvation model based on density (SMD) led to accurate pKa values. In particular, calculations performed on a series of 13 differently substituted phenols provided reliable results, with a mean absolute error of 0.3. Furthermore, the model achieves accurate results with -CN and -NO₂ substituents, which are usually excluded from computational pKa studies, enabling easy and reliable pKa determination in a wide range of phenols.     

Consistency of the intensional level of the Minimalist Foundation with Church’s thesis and axiom of choice

Consistency with the formal Church’s thesis, for short CT, and the axiom of choice, for short AC, was one of the requirements asked to be satisfied by the intensional level of a two-level foundation for constructive mathematics as proposed by Maietti and Sambin (in Crosilla, Schuster (eds) From sets and types to topology and analysis: practicable foundations for constructive mathematics, Oxford University Press, Oxford, 2005). Here we show that this is the case for the intensional level of the two-level Minimalist Foundation, for short MF, completed in 2009 by the second author. The intensional level of MF consists of an intensional type theory à la Martin-Löf, called mTT. The consistency of mTT with CT and AC is obtained by showing the consistency with the formal Church’s thesis of a fragment of intensional Martin-Löf’s type theory, called \(\mathbf{MLtt}_1\), where mTT can be easily interpreted. Then to show the consistency of \(\mathbf{MLtt}_1\) with CT we interpret it within Feferman’s predicative theory of non-iterative fixpoints \(\widehat{ID_1}\) by extending the well known Kleene’s realizability semantics of intuitionistic arithmetics so that CT is trivially validated. More in detail the fragment \(\mathbf{MLtt}_1\) we interpret consists of first order intensional Martin-Löf’s type theory with one universe and with explicit substitution rules in place of usual equality rules preserving type constructors (hence without the so called \(\xi \)-rule which is not valid in our realizability semantics). A key difficulty encountered in our interpretation was to use the right interpretation of lambda abstraction in the applicative structure of natural numbers in order to model all the equality rules of \(\mathbf{MLtt}_1\) correctly. In particular the universe of \(\mathbf{MLtt}_1\) is modelled by means of \(\widehat{ID_1}\)-fixpoints following a technique due first to Aczel and used by Feferman and Beeson.     

Hierarchical differential evolution for minimal cut sets identification: Application to nuclear safety systems

In this paper, we present a Hierarchical Differential Evolution (HDE) algorithm for minimal cut set (mcs) identification of coherent and non-coherent Fault Trees (FTs). In realistic application of large-size systems, problems may be encountered in handling a large number of gates and events. In this work, to avoid any approximation, mcs identification is originally transformed into a hierarchical optimization problem, stated as the search for the minimum combination of cut sets that can guarantee the best coverage of all the minterms that make the system fail: during the first step of the iterative search, a multiple-population, parallel search policy is used to expedite the convergence of the second step of the exploration algorithm. The proposed hierarchical method is applied to the Reactor Protection System (RPS) of a Pressurized Water Reactor (PWR) and to the the Airlock System (AS) of a CANadian Deuterium Uranium (CANDU) reactor. Results are evaluated with respect to the accuracy and computational demand of the solution found.     

Thiol‐ene and thiol‐yne‐based synthesis of glycodendrimers as nanomolar inhibitors of wheat germ agglutinin

Alkene and alkyne functional polyester‐based dendrimers of generation 1 to 4 have been prepared and reacted under free‐radical conditions with 2‐acetamido‐2‐deoxy‐1‐thio‐β‐D ‐glucose (GlcNAc‐SH). As the alkene‐dendrimers underwent the addition of one thiyl radical per ene group whereas each yne group of alkyne‐dendrimers was saturated by two thiyl radicals, a collection of glycodendrimers with glycan density ranging from six to ninety‐six GlcNAc per dendrimer was obtained. The recognition properties of the prepared glycodendrimers toward the wheat germ agglutinin (WGA) were evaluated by enzyme‐linked lectin assay (ELLA). The eight glycodendrimers were excellent ligands showing IC₅₀ values in the nanomolar range and relative potencies per sugar unit up to 2.27 e⁶ when compared to monosaccharidic GlcNAc used as monovalent reference. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2422–2433     

Straightforward Synthesis of (R,S)-β-Methyleneaspartic Acid, an Inhibitor of Glutamate-Aspartate Transaminase

A Baylis-Hillman adduct of methyl acrylate and ethyl glyoxalate was converted into the trichloroacetimidate that in the presence of DABCO rearranged to the corresponding trichloroacetamide. Eventually, hydrolysis under acidic conditions, led to the hydrochloride of racemic β-methyleneaspartic acid.