Enhancement of four-wave mixing and line narrowing by use of quantum coherence in an optically dense double-? solid

We have demonstrated enhanced nondegenerate four-wave mixing by use of a resonant probe in a double- ? system consisting of an optically dense spectral hole-burning solid. The observed probe diffraction efficiency is ~16% in amplitude at 6 K, which is higher than for an off-resonant probe in a ? -type scheme. We have also observed two-photon coherence line narrowing, which has potential application to high-resolution spectroscopy.     

Frequency-selective time-domain optical data storage by electromagnetically induced transparency in a rare-earth-doped solid

We report the experimental observation of optical data storage by frequency-selective stimulated spin echoes based on electromagnetically induced transparency in an inhomogeneously broadened rare-earth-doped solid. We find that the spin dephasing time T(2) is almost constant in the range 2-6 K, whereas the optical T(2) shortens rapidly above 4 K. This experiment demonstrates the potential of spin echoes excited by electromagnetically induced transparency for higher-capacity optical data storage at higher temperature.     

Strategy in inhibition of cathepsin B, a target in tumor invasion and metastasis

Cathepsin B, a cysteine protease, is an important target in fighting cancer. This enzyme has been implicated in enhancing tumor invasiveness and metastasis, therefore inhibitors for cathepsin B are highly sought as potential anticancer and antimetastatic agents. A structure-based design effort was pursued in arriving at a template for inhibition of cathepsin B. Focused compound libraries were synthesized based on this template, which were screened for cathepsin B inhibitory properties. Compound 2, 1-(2(R)-[1(S)-acetoxy-2-[2(S)-(2,4-difluoro-benzoylamino)-3-phenyl-propionylaminooxy]-2-oxo-ethyl]-pentanoyl)-pyrrolidine-2(S)-carboxylic acid benzyl ester, is the prototype of this novel class of cysteine protease inhibitor that emerged from the search. The molecule modifies the active site of cathepsin B covalently, irreversibly, and efficiently, a process for which the kinetic parameters were evaluated. A set of three judiciously altered variants of compound 2 was also synthesized to explore the details of the proposed mechanism of action by this inhibitor. Compound 2 and its analogues may prove useful tools in reversing the deleterious effect of cathepsin B in fighting cancer.     

Ab initio QM/MM study of class A beta-lactamase acylation: dual participation of Glu166 and Lys73 in a concerted base promotion of Ser70

Beta-lactamase acquisition is the most prevalent basis for Gram-negative bacteria resistance to the beta-lactam antibiotics. The mechanism used by the most common class A Gram-negative beta-lactamases is serine acylation followed by hydrolytic deacylation, destroying the beta-lactam. The ab initio quantum mechanical/molecular mechanical (QM/MM) calculations, augmented by extensive molecular dynamics simulations reported herein, describe the serine acylation mechanism for the class A TEM-1 beta-lactamase with penicillanic acid as substrate. Potential energy surfaces (based on approximately 350 MP2/6-31+G calculations) reveal the proton movements that govern Ser70 tetrahedral formation and then collapse to the acyl-enzyme. A remarkable duality of mechanism for tetrahedral formation is implicated. Following substrate binding, the pathway initiates by a low energy barrier (5 kcal mol(-1)) and an energetically favorable transfer of a proton from Lys73 to Glu166, through the catalytic water molecule and Ser70. This gives unprotonated Lys73 and protonated Glu166. Tetrahedral formation ensues in a concerted general base process, with Lys73 promoting Ser70 addition to the beta-lactam carbonyl. Moreover, the three-dimensional potential energy surface also shows that the previously proposed pathway, involving Glu166 as the general base promoting Ser70 through a conserved water molecule, exists in competition with the Lys73 process. The existence of two routes to the tetrahedral species is fully consistent with experimental data for mutant variants of the TEM beta-lactamase.     

The complex of a designer antibiotic with a model aminoacyl site of the 30S ribosomal subunit revealed by X-ray crystallography

The ribosome is an important target for aminoglycoside antibiotics; however, the clinical effectiveness of aminoglycosides has diminished due to bacterial resistance mechanisms. Here we report the X-ray structure of a novel synthetic aminoglycoside bound to the A site of the ribosome, its target for manifestation of activity. The structure validates the in silico design paradigms for the antibiotic and reveals the molecular interactions made by this novel antibiotic in prokaryotes.     

Preparation of Zinc (II) and cadmium (II) complexes of the tetradentate Schiff base ligand 2-((E)-(2-(2-(pyridine-2-yl)- ethylthio)ethylimino)methyl)-4-bromophenol (PytBrsalH)

We describe the synthesis and characterization of two new zinc (II) and cadmium (II) complexes of the tetradentate dissymmetric Schiff base ligand 2-((E)-(2-(2-(pyridine-2-yl)ethylthio)ethylimino)methyl)-4-bromophenol (PytBrsalH), prepared from 1-(2-pyridyl)-3-thia-5-aminopentane (pyta) and 5-bromosalicylaldehyde. The complexes were synthesized by treating an ethanolic solution of the ligand with equimolar amounts of appropriate metal salts in 1 M methanolic solution of NaOH or alternatively, by a more direct route in which the two reactants are added to a solution of the ligand immediately after formation of the latter and prior to any isolation. The complexes were characterized by elemental analysis, FTIR, (1)H-NMR, electronic spectra and molar conductivity. According to obtained data, the probable coordination geometries of zinc and cadmium in these complexes with mixed N, S and O donor atoms are tetrahedral- and octahedral-like,respectively. Both complexes were found to be 1:1 electrolyte systems in acetonitrile.     

Design and synthesis of a structurally constrained aminoglycoside

The synthesis of a constrained tricyclic aminoglycoside derivative is described. This constrained compound fixes the spatial orientation of two critical rings for the minimal motif for binding to biological macromolecules such as RNA and proteins. Methanolysis of neomycin B under acidic conditions produced the bicyclic neamine. Transient protection by the Cu2+ ion and regioselective introduction of protective groups led to intermediate 7, which was used for a key annulation reaction that introduced the tricyclic nucleus into the structural framework. A final hydrogenolysis step to remove the protective groups produced the desired target molecule. The efficient eight-step synthesis was accomplished in 8% overall yield.