Rachel Persky

Stereocontrolled Synthesis of Erythro N-Protected α-Amino Epoxides and Peptidyl Epoxides.

Abstract N-protected α-amino epoxides of erythro configuration, derived from α-amino acids, were synthesized in a stereoselective manner. The erythro (2S,3S) configu- ration was achieved by the synthetic sequence: amino acid → haloketone → halohydrin → epoxide. A mechanistic explanation for the observed stereoselectivity is presented. This stereoselective synthetic approach was applied to the synthesis of a variety of short peptidyl epoxides, bearing a predefined absolute configuration of the chiral epoxide moiety.

DESIGN OF A NEW SELECTIVE CYSTEINE PROTEASE INACTIVATOR AND ITS MECHANISTIC IMPLICATIONS

Abstract Cbz-Phe-epoxide was designed as a selective inactivator of cysteine proteases. It exhibits a time- and concentration-dependent inactivation of cysteine proteases, while showing no activity towards serine proteases. The inhibition is irreversible, correlated with loss of the free active-site thiol, and its rate is at least 10 4 faster than the rate of a model reaction in solution. These results support the proposed active-site directed, protonation-dependent, mechanism-based mode of inactivation of cysteine proteases by the new inhibitor.

Tethered non-ionic micelles: a matrix for enhanced solubilization of lipophilic compounds

A specific mechanism for tethering micelles composed of non-ionic detergents is presented. The mechanism does not require any precipitant, high ionic strength or temperature alterations. Rather, it relies on complexes between hydrophobic chelators embedded within the micelle and appropriate metal cations in the aqueous phase, serving as mediators. The approach was applied to: (i) four non-ionic detergents (tetraethylene glycol monooctyl ether (C8E4), n-dodecyl-β-D-maltoside (DDM), octyl β-D-1-thioglucopyranoside (OTG), and n-octyl-β-D-glucopyranoside (OG)), (ii) two hydrophobic chelators (bathophenanthroline and N-(1,10-phenanthrolin-5-yl)decanamide, Phen-C10) and (iii) five transition metals (Fe2+, Ni2+, Zn2+, Cd2+, and Mn2+). The mandatory requirement for a hydrophobic chelator and transition metals, capable of binding two (or more) chelators simultaneously, was demonstrated. The potential generality of the mechanism presented derives from the observation that different combinations of [detergent : chelator : metal] are able to induce specific micellar clustering. The greater solubilization capacity of tethered-micelles in comparison with untethered micelles was demonstrated when the water insoluble aromatic molecule fluorenone (8 mM = 1.44 mg mL−1) and two highly lipophilic antibiotics: chloramphenicol (5 mM = 1.62 mg mL−1) and tetracycline (1.5 mM = 0.66 mg mL−1) were solubilized – only when the micelles were tethered.

Thermal Behavior Study of Tri-Sodium Styrylbisphosphonate Using TGA/TGA-MS and 31P NMR

GRAPHICAL ABSTRACT Abstract Extensive thermal behavior study of tri-sodium styrylbisphosphonate (StBP), a new vinylic monomer developed in our laboratory, is described. StBP was scanned for TGA, DSC, and TGA-MS using the standard procedures at a temperature range of 0 to 600°C under nitrogen atmosphere. In addition, post-burn samples from different cycles were quenched in various temperatures and analyzed by 31P NMR spectroscopy. The novelty of this research lies the identification of the intermediate products of the thermal decomposition during the thermogravimetric analysis. The combination of TGA/DSC/TGA-MS and 31P NMR spectroscopy results elucidate the decomposition process and intermediate products of StBP.