HOMOGENIZATION,SYMMETRY, AND PERIODIZATION IN DIFFUSIVE RANDOM MEDIA

We present a systematic study of homogenization of diffusion in random media with emphasis on tile-based random microstructures.We give detailed examples of several such media starting from their physi...     

De novo chiral amino alcohols in catalyzing asymmetric additions to aryl aldehydes

[reaction: see text] A de novo structural class of chiral amino alcohol catalysts has been identified through a synergistic effort combining novel architectures from [4 + 3] cycloadditions and quantum mechanical interaction field predictions that closely match subsequent experimental measurements.     

Synthesis and acid functionalization of cerium oxide nanoparticles

Colloidal cerium oxide has been obtained by controlled oxidation of soluble Ce(III) salts in hydrothermal conditions. The homogeneous nucleation of CeO₂ through thermolysis of this oxidizing solution allows the formation of well dispersed colloidal particles. Under optimal conditions, well crystallized particles with an average size of 8 nm are obtained. The surface is terminated by acetate groups which can be substituted by grafting phosphonic acids or phosphoric acids. Particularly, the grafting of 2-carboxyethylphosphonic acid or phosphonoacetic acid increases the acidic character of the surface as observed by impedance spectroscopy.     

Chromatographic Enantioresolution of Six Purine Derivatives Endowed with Anti-Human Breast Cancer Activity

Three (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purine derivatives (1–3) and three (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine derivatives (4–6) showed relevant activity against human breast cancer cell line MCF-7, when assayed as racemates. The relevant structural analogy among these compounds stimulated us to evaluate and compare their chromatographic behaviour with five polysaccharide-based chiral stationary phases (CSPs). For a column screening purpose, four cellulose-based (Chiralcel OD-H, Chiralpak IB, Lux Cellulose-2, and Sepapak-4; CSPs 1–4, respectively) and an amylose-based (Lux Amylose-2; CSP 5) CSPs were initially assayed by employing the same “standard” eluent mixture. With CSP 2, the performance from “non standard” eluent systems was also evaluated. The different type and position of the substituents onto the carbamate moiety, the coated or immobilized nature of the modified polymer chain, and the different type of winding as well as the eluent composition were found to deeply affect the enantiorecognition mechanism. While the different winding of the polymer and the derived different morphology of the binding cleft in the 2,5-disubstituted chloromethyl phenyl carbamate amylose-based CSP 5 was found to be unsuited to get profitable enantio-discriminations of all the analyzed compounds, CSP 3 and CSP 4 produced the highest α and R _S values in the enantioselective analysis of four out of six racemates (that is 1–3 and 6). In CSP 2, the conformational change of the polysaccharide chain upon immobilization produced a profound influence on the chromatographic behaviour of compounds 1–6. A relevant improvement of the enantioresolution quality of CSP 2 was obtained when used in combination with “non standard” solvents as constituents of the mobile phase mixture.     

Parameters for Irreversible Inactivation of Monoamine Oxidase

The irreversible inhibitors of monoamine oxidases (MAO) slow neurotransmitter metabolism in depression and neurodegenerative diseases. After oxidation by MAO, hydrazines, cyclopropylamines and propargylamines form a covalent adduct with the flavin cofactor. To assist the design of new compounds to combat neurodegeneration, we have updated the kinetic parameters defining the interaction of these established drugs with human MAO-A and MAO-B and analyzed the required features. The K_i values for binding to MAO-A and molecular models show that selectivity is determined by the initial reversible binding. Common to all the irreversible inhibitor classes, the non-covalent 3D-chemical interactions depend on a H-bond donor and hydrophobic-aromatic features within 5.7 angstroms apart and an ionizable amine. Increasing hydrophobic interactions with the aromatic cage through aryl halogenation is important for stabilizing ligands in the binding site for transformation. Good and poor inactivators were investigated using visible spectroscopy and molecular dynamics. The initial binding, close and correctly oriented to the FAD, is important for the oxidation, specifically at the carbon adjacent to the propargyl group. The molecular dynamics study also provides evidence that retention of the allenyl imine product oriented towards FADH⁻ influences the formation of the covalent adduct essential for effective inactivation of MAO.     

Fast chromatographic determination of the bile salt critical micellar concentration

In a line of research focused on the design, synthesis and development of new bile acid-based compounds, the physico-chemical profile of the molecules must be thoroughly explored and analyzed. In this scenario, a fast and reliable information on the critical micellar concentration (CMC) of specific compounds through a profitable chromatographic parameter can be of aid to rationally direct the synthesis of new molecular entities, mainly during the early stages of the drug-discovery process. The derived ‘chromatographic hydrophobicity index’ (CHI), usually employed for a fast access to the log P/log D value of physico-chemically diverse compounds and obtained via RP-gradient elution, was for the first time engaged in the bile acid field. Accordingly, 14 unconjugated bile acids harboured with a different number, position and orientation of hydroxy groups, as well as other substituents onto the steroidal backbone and side chain, were selected to build up a calibration curve. Such a collection of compounds was rationally assembled in order to manage an almost continuous range of CMC values (spanning the spectrophotometrically obtained CMCs between 5 and 25 mM). A high degree of correlation between CMC and CHI values was obtained (R ² and cross-validated R _xv² of the pCMC vs CHI plot equal to 0.975 and 0.966, respectively). A selected new subset of five confidential research bile acids with experimental CMCs in the range 6–19 mM was finally recruited to validate the proposed method. The high statistical quality of the established mathematical model turned out into a very appreciable predictive power.     

Synthesis and chromatographic enantioresolution of anti-HIV quinolone derivatives

The successful enantioseparation of five 6-desfluoroquinolones with three polysaccharide-based stationary phases (namely, the cellulose-based Chiralpak IB and the two amylose-based Chiralpak AD-H and Lux Amylose-2) is herein described. The investigated species differ for the nature of substituents and/or the position of the stereogenic centre on the quinolone scaffold.The effect on the enantioseparation performance exerted by the different morphology of the cellulose-based and amylose-based polymers, was systematically evaluated for all compounds. In this frame, the impact of alternative alcoholic (ethanol, 2-ethoxyethanol, methanol, 2-propanol) and acidic (acetic, methanesulfonic and trifluoroacetic acid) modifiers as well as of a “non-standard” solvent (chloroform), was investigated in normal phase conditions along with the stereo-electronic peculiarities of the selected polymers. While 7-[4-(1,3-benzothiazol-2-yl)-2-methyl-1-piperazinyl]-1-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (1) was enantioresolved with conventional normal-phase conditions by means of the largely employed amylose-based Chiralpak AD-H column, the recruitment of a bulky alcohol (2-ethoxyethanol) succeeded in the enantioresolution of 6-amino-1-methyl-7-[2-methyl-4-(2-pyridinyl)-1-piperazinyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (2) and 6-amino-1-[1-(hydroxymethyl)propyl]-4-oxo-7-(4-pyridin-2-ylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (3) with the same column. The use of the amylose-based Lux Amylose-2 column, carrying both an electro-withdrawing (chlorine) and an electro-donating (methyl) group on the carbamate residue, allowed to get 6-amino-1-methyl-4-oxo-7-[3-(2-pyridinyl)-1-pyrrolidinyl]-1,4-dihydro-3-quinolinecarboxylic acid hydrochloride (4) enanantioresolved, and 6-amino-1-methyl-4-oxo-7-(3-pyridin-2-ylpiperidin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (5) enantioseparated.     

Phase diagram of epidemic spreading — unimodal vs. bimodal probability distributions

Disease spreading on complex networks is studied in SIR model. Simulations on empirical complex networks reveal two specific regimes of disease spreading: local containment and epidemic outbreak. The variables measuring the extent of disease spreading are in general characterized by a bimodal probability distribution. Phase diagrams of disease spreading for empirical complex networks are introduced. A theoretical model of disease spreading on m-ary tree is investigated both analytically and in simulations. It is shown that the model reproduces qualitative features of phase diagrams of disease spreading observed in empirical complex networks. The role of tree-like structure of complex networks in disease spreading is discussed.     

Symmetries of Equivelar 4-Toroids

We derive some general results on the symmetries of equivelar toroids and provide detailed analysis of the subgroup lattice structure of the dihedral group D ₄ and of the octahedral group to complete classification by symmetry type of those in ranks 3 and 4.     

Temporary Silicon‐Tethered Ring‐Closing Metathesis: Recent Advances in Methodology Development and Natural Product Synthesis

Temporary silicon‐tethered ring‐closing metathesis represents an important cross‐coupling strategy for the formation of medium‐sized silacycles. These intermediates are valuable synthons in organic synthesis due to their propensity to undergo a facile refunctionalization through protodesilylation, oxidation, silane‐group transfer or transmetallation. A particularly attractive utility of this methodology is an application in the synthesis of biologically important natural products. The purpose of this review article is to highlight the recent progress in methodology development and its strategic application toward the target‐directed synthesis.