Synthesis of 1,4-Dihydropyridines by Regioselective Additions of Benzylic Zinc Bromides to Pyridinium Salts and Their Aromatizations to 4-Benzylpyridines

Benzylic zinc reagents add with high regioselectivity to 1-(phenoxycarbonyl) salts of methyl nicotinate to yield methyl-1-(phenoxylcarbonyl)-4-benzyl-1,4-dihydronicotinates. The dihydronicotinates on heating with sulfur in decalin afford methyl 4-benzylnicotinates.     

1H NMR and Calorimetric Studies of the Inclusion of Trimethylammonium Cations into Water Soluble Calixresorcinarenes

Abstract

The complexation of tetramethylammonium (TEMA), benzyltrimethylammonium (BTMA), p-nitrobenzyltrimethylammonium (BTMAN) and N, N, N-trimethylanilinium (TMA) by the tetrasulphonate derivative of the resorcinol cyclic tetramer (1), was studied in aqueous solution by ¹H NMR and calorimetry. Host 1 specifically recognizes the—N⁺ (CH₃)₃ group of TEMA, BTMA and BTMAN, whereas it binds TMA unselectively; TMA is included both via the charged group and the aromatic moiety. The binding constants of all four guests with 1, as determined by both ¹H NMR and calorimetric titrations, show that all inclusion processes are almost equally stabilised.

ΔHΔ and ΔSΔ values, determined by direct calorimetry, reveal specific interactions that are not expressed in the ΔGΔ terms and indicate that we are dealing with “non-classical hydrophobic effects”. The effects of the structural, conformational and electronic properties of the guests on the forces driving the inclusion processes are discussed.     

On Stein's extension operator preserving Sobolev–Morrey spaces

We prove that Stein's extension operator preserves Sobolev–Morrey spaces, that is spaces of functions with weak derivatives in Morrey spaces. The analysis concerns classical and generalized Morrey spaces on bounded and unbounded domains with Lipschitz boundaries in the n‐dimensional Euclidean space.     

Application of the thin-shell formulation to the numerical modeling of Stern layer in biomolecular electrostatics

In this article, the thin-shell formulation is applied to efficiently modeling the Stern layer within computational algorithms oriented toward the boundary element solution of the linearized Poisson-Boltzmann equation. The attention is focused on the calculation of the electrostatic potential in proximity to a biomolecule immersed in an electrolyte medium. Following the proposed approach, the Stern layer is made to collapse to a zero-thickness region (two-dimensional surface) with interface conditions linking the electrostatic potential over the molecular and the bulk ion accessible surfaces. Advantages lie in the limitation of divergent integral problems and in the halving of the unknown number, with a significant impact on computational time and memory requirements when modeling large biomolecules.     

Purely linear response of the quantum Hall current to space-adiabatic perturbations

Letters in Mathematical Physics - We provide an algorithm that factorizes one-dimensional quantum walks on an arbitrary but fixed cell structure into a protocol of two basic operations: a fixed...     

Identification of structural alerts for liver and kidney toxicity using repeated dose toxicity data

Background

The potential for a compound to cause hepatotoxicity and nephrotoxicity is a matter of extreme interest for human health risk assessment. To assess liver and kidney toxicity, repeated-dose toxicity (RDT) studies are conducted mainly on rodents. However, these tests are expensive, time-consuming and require large numbers of animals. For early toxicity screening, in silico models can be applied, reducing the costs, time and animals used. Among in silico approaches, structure–activity relationship (SAR) methods, based on the identification of chemical substructures (structural alerts, SAs) related to a particular activity (toxicity), are widely employed.

Results

We identified and evaluated some SAs related to liver and kidney toxicity, using RDT data on rats taken from the hazard evaluation support system (HESS) database. We considered only SAs that gave the best percentages of true positives (TP).

Conclusions

It was not possible to assign an unambiguous mode of action for all the SAs, but a mechanistic explanation is provided for some of them. Such achievements may help in the early identification of liver and renal toxicity of substances.

     

Morphology-rheology relationships in incompatible blends based on thermotropic liquid crystalline polymers

In this paper the effect of the inclusion of two different thermotropic liquid crystal polymers (TLCP) on the processing of a polyetherimide (ULTEM 1000) is studied.     

Sequence,Stoichiometry, and Dimensionality Control in Porphyrin/Bis‐calix[4]arene Self‐Assemblies in Aqueous Solution

The use of a water‐soluble octacationic bis‐calix[4]arene with divergent cavities (BC₄) as a templating agent for the assembly of a tetraanionic porphyrin (CuTPPS) has allowed the noncovalent synthesis of 2D or 3D multiporphyrin assemblies. Self‐assembly of CuTPPS and BC₄ molecules proceeded under hierarchical control in a stepwise fashion to yield discrete and isolable supramolecular nanostructures containing up to 33 molecular elements (i.e., the CuTPPS/BC₄ 17:16 assembly, obtained in less than three hours). The formation of these species could be conveniently monitored by means of UV/Vis spectroscopy by following the absorbance of the Soret band at 412 nm. In particular, the attainment of the pivotal CuTPPS/BC₄ 5:4 species with a cruciform structure, as the key fork‐point intermediate for the subsequent formation of the higher 2D and 3D assemblies, has been demonstrated by light‐scattering studies and by an unequivocal synthesis of mixed‐porphyrin/calixarene 5:4 species involving the use of two different types of metallated porphyrins, namely CuTPPS and MnTPPS. The remarkable stability of these assemblies permits a stepwise synthesis that makes it possible to choose the desired porphyrin sequence.     

Synthesis of hydroxy-substituted aza-analogues of antitumor anthrapyrazoles

Synthetic routes have been developed which lead to ring-hydroxylated aza-analogues of antitumor anthrapyrazoles, namely, 2,5-bis[(aminoalkyI)amino] substituted 10-hydroxymdazolo[3,4-fg]isoquinolin-6(2H)-ones 1 and 7-hydroxyindazolo[4,3-gh]isoquinolin-6(2H)-ones 2 . The regiospecific synthesis of 6,9-dihalo-4-hydroxybenz[g]isoquinolines 3 and 4 has been accomplished. Intermediate 3 was constructed in a multistep process involving Diels-Alder chemistry of benzoylacrylates whereas 4 was assembled using Ni(II) mediated coupling of methyl 3-chloro-5-methoxyisonicotinate ( 15b ) with the organic zinc reagent 18 derived from 2-fluoro-5-chlorobenzyl bromide ( 17 ). After protection of the hydroxy group with a p-methoxybenzyl moiety, the different nucleofugacities of the leaving groups present in 10 and 20 allowed sequential displacements by substituted hydrazines and amines, respectively, to lead to the desired p-methoxybenzyl protected analogues 12 and 22 . Deprotection led to the side arm modified compounds 1 and 2 . The displacements of 21a and 21b with N,N-dimethylethylenediamine also led to the tri[(aminoalkyl)amino]substituted analogues 23a and 23b , respectively, which arose from further S_NAr substitutions of the p-methoxybenzyloxy group.     

Weak curvatures of irregular curves in high-dimensional Euclidean spaces

Annals of Global Analysis and Geometry - We deal with a robust notion of weak normals for a wide class of irregular curves defined in Euclidean spaces of high dimension. Concerning polygonal...