Conventional and Microwave‐Assisted Synthesis of Benzimidazole Derivatives and Their In Vitro Inhibition of Human Cyclooxygenase

A large series of 1,2‐diaryl‐benzimidazole and 2‐aryl‐1H‐benzimidazole derivatives were synthesized with slight differences using both microwave irradiation and conventional heating methods. Usually higher yields and time reactions reduction were obtained with the former method. All compounds were assayed for their in vitro ability to inhibit human cyclooxygenases, and most of them showed an encouraging inhibitory activity and isoform selectivity in the micromolar range.     

Cyclotomy and endomotives

We compare two different models of noncommutative geometry of the cyclotomic tower, both based on an arithmetic algebra of functions of roots of unity and an action by endomorphisms, the first based on the Bost-Connes (BC) quantum statistical mechanical system and the second on the Habiro ring, where the Habiro functions have, in addition to evaluations at roots of unity, also full Taylor expansions. Both have compatible endomorphisms actions of the multiplicative semigroup of positive integers. As a higher dimensional generalization, we consider a crossed product ring obtained using Manin’s multivariable generalizations of the Habiro functions and an action by endomorphisms of the semigroup of integer matrices with positive determinant. We then construct a corresponding class of multivariable BC endomotives, which are obtained geometrically from self maps of higher dimensional algebraic tori, and we discuss some of their quantum statistical mechanical properties. These multivariable BC endomotives are universal for (torsion free) Λ-rings, compatibly with the Frobenius action. Finally, we discuss briefly how Habiro’s universal Witten-Reshetikhin-Turaev invariant of integral homology 3-spheres may relate invariants of 3-manifolds to gadgets over and semigroup actions on homology 3-spheres to endomotives. The text was submitted by the author in English.     

Interactions between the ganglioside GM1 and hexadecylphosphocholine (miltefosine) in monolayers at the air/water interface

The ganglioside, GM1, was studied as Langmuir monolayers at the air/water interface with surface pressure-area measurements in addition to Brewster angle microscopy. A characteristic plateau transition, observed on aqueous subphases of pH 2 and 6, 20 degrees C, at the surface pressure of ca. 20 mN/m, was attributed to the reorientation of GM1 polar group upon film compression. This transition was found to disappear at alkaline subphases (pH 10) due to the hydration of fully ionized polar group, hindering its reorientation. The interactions between GM1 and hexadecylphosphocholine (miltefosine) were investigated in mixed monolayers and analyzed with the mean molecular areas, excess areas of mixing and the excess free energy of mixing versus film composition plots. The monolayers stability, quantified by the collapse pressure values, as well as the strength of interaction was found to diminish in the following order: pH 6>pH 2>pH 10. The strongest interaction occurs for mixed films of miltefosine molar fraction, XM=0.7-0.8, especially at low pressure region, and are explained as being due to the surface complex formation of 3:1 or 4:1 (miltefosine:ganglioside) stoichiometry (XM=0.75 or 0.8, respectively).     

Synthesis and biological evaluation of guanidine-type iminosugars

The preparation of carbohydrate mimics in which the endocyclic oxygen has been replaced by a guanidine-type nitrogen atom is reported. The synthetic strategy involves the furanose --> piperidine rearrangement of 5-deoxy-5-guanidino-L-idose precursors. The reaction proceeds through elimination of water to give 3-oxopiperidines, which were isolated as the corresponding hydrates. Biological evaluation of the new glycomimetics evidenced a strong influence of the nature of the substituents at the nitrogen atoms on the glycosidase inhibitory properties.     

Electrochemical synthesis of manganese(II)-Schiff base complexes and their behaviour towards H2O,H2O2 and SO2

Manganese(II) complexes with ONNO tetradentate Schiff bases have been prepared by electrochemical synthesis and characterised by analytical and spectroscopic techniques, magnetism and by studying their redox reversibility character by cyclic and normal pulse voltammetry. The ability of these systems to catalyse the decomposition of water, to yield dioxygen, and their catalase-like activity was checked. Reaction of the complexes with sulfur dioxide was studied in the solid state and in toluene slurries at room temperature. The adducts formed underwent thermogravimetric desorption analyses that highlights the SO₂-irreversible linkage present in all complexes.     

Ferromagnetism in dinuclear copper(II)-phenolate complexes with exogenous O-donor bridges: a comparative study

The copper(II) complex Cu2L(OAc)(H2O)3.5, 1 x 3.5H2O was obtained and its reactivity in a basic medium investigated. Complex 1 x 3.5H2O shows different reaction patterns in air and in an inert atmosphere. Accordingly, interaction of 1 x 3.5H2O with Me4NOH x 5H2O in methanol-acetonitrile in air yields the hydroxide complex Cu2L(OH)(H2O)1.125, 2 x 1.125H2O while Cu2L(OMe)(MeOH)0.5(H2O), 3 x 0.5MeOH x H2O is isolated under an argon atmosphere. The products 1-3 were fully characterised and single crystals of {[Cu2L(OAc)] x MeCN x 3.5H2O}2, 1 x MeCN x 3.5H2O, {[Cu2L(OH)] x MeCN x 1.125H2O}2, 2 x MeCN x 1.125H2O and [Cu2L(OMe)] x 0.5MeOH x H2O, 3 x 0.5MeOH x H2O solved. The single X-ray study shows that 1-3 are dinuclear complexes with an endogenous phenol oxygen and an exogenous O-bridge. Magnetic characterisation of the three dinuclear complexes was performed, showing an apparent anomalous intramolecular ferromagnetic coupling between the metal atoms in all cases.     

Ring-Opening Metathesis Polymerization Kinetics of Cyclooctene with Second Generation Grubbs’ Catalyst

A kinetic study of the ring-opening metathesis polymerization (ROMP) of cis-cyclooctene using the ruthenium initiator benzylidene [1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene]-dichloro-(tricyclohexylphosphine) (second generation Grubbs’ catalyst) was carried out by ¹H-NMR. The dependence on the reaction rate with the temperature and the influence of the addition of a chain transfer agent were evaluated. Some kinetic constants are also reported for this system.     

Scalable Syntheses of Both Enantiomers of DNJNAc and DGJNAc from Glucuronolactone: The Effect of N‐Alkylation on Hexosaminidase Inhibition

The efficient scalable syntheses of 2‐acetamido‐1,2‐dideoxy‐D ‐galacto‐nojirimycin (DGJNAc) and 2‐acetamido‐1,2‐dideoxy‐D ‐gluco‐nojirimycin (DNJNAc) from D ‐glucuronolactone, as well as of their enantiomers from L ‐glucuronolactone, are reported. The evaluation of both enantiomers of DNJNAc and DGJNAc, along with their N‐alkyl derivatives, as glycosidase inhibitors showed that DGJNAc and its N‐alkyl derivatives were all inhibitors of α‐GalNAcase but that none of the epimeric DNJNAc derivatives inhibited this enzyme. In contrast, both DGJNAc and DNJNAc, as well as their alkyl derivatives, were potent inhibitors of β‐GlcNAcases and β‐GalNAcases. Neither of the L ‐enantiomers showed any significant inhibition of any of the enzymes tested. Correlation of the in vitro inhibition with the cellular data, by using a free oligosaccharide analysis of the lysosomal enzyme inhibition, revealed the following structure–property relationship: hydrophobic side‐chains preferentially promoted the intracellular access of iminosugars to those inhibitors with more‐hydrophilic side‐chain characteristics.