Alkylation of Porous Silicon by Direct Reaction with Alkenes and Alkynes

The hydrogen-terminated surface of porous silicon (PS) is sufficiently reactive for the uncatalyzed hydrosilation of alkenes and alkynes. These modifications produce dramatic changes to both the physical and chemical properties of the PS.     

Vinyl Halide-Modified Unsaturated Cyclitols are Mechanism-Based Glycosidase Inhibitors

Suitably configured allyl ethers of unsaturated cyclitols act as substrates of β-glycosidases, reacting via allylic cation transition states. Incorporation of halogens at the vinylic position of these carbasugars, along with an activated leaving group, generates potent inactivators of β-glycosidases. Enzymatic turnover of these halogenated cyclitols (F, Cl, Br) displayed a counter-intuitive trend wherein the most electronegative substituents yielded the most labile pseudo-glycosidic linkages. Structures of complexes with the Sulfolobus β-glucosidase revealed similar enzyme-ligand interactions to those seen in complexes with a 2-fluorosugar inhibitor, the lone exception being displacement of tyrosine 322 from the active site by the halogen. Mutation of Y322 to Y322F largely abolished glycosidase activity, consistent with lost interactions at O5, but minimally affected (7-fold) rates of carbasugar hydrolysis, yielding a more selective enzyme for unsaturated cyclitol ether hydrolysis.     

New Delhi metallo-β-lactamase: structural insights into β-lactam recognition and inhibition

The β-lactam antibiotics have long been a cornerstone for the treatment of bacterial disease. Recently, a readily transferable antibiotic resistance factor called the New Delhi metallo-β-lactamase-1 (NDM-1) has been found to confer enteric bacteria resistance to nearly all β-lactams, including the heralded carbapenems, posing a serious threat to human health. The crystal structure of NDM-1 bound to meropenem shows for the first time the molecular details of how carbapenem antibiotics are recognized by dizinc-containing metallo-β-lactamases. Additionally, product complex structures of hydrolyzed benzylpenicillin-, methicillin-, and oxacillin-bound NDM-1 have been solved to 1.8, 1.2, and 1.2 ?, respectively, and represent the highest-resolution structural data for any metallo-β-lactamase reported to date. Finally, we present the crystal structure of NDM-1 bound to the potent competitive inhibitor l-captopril, which reveals a unique binding mechanism. An analysis of the NDM-1 active site in these structures reveals key features important for the informed design of novel inhibitors of NDM-1 and other metallo-β-lactamases.     

A Method of Determining Production Load and Size of Inventories when Demand is Variable

One of the more complex problems in a manufacturing organization is that of determining production load and inventories needed to satisfy variable demand. It will be shown that sometimes a relationship between the average demand (μ) and the standard deviation (σ) expressed as σ = kμ² can be used in a multi-product system to determine inventory levels and capacity required for a production-warehouse system. Models for several production-warehouse systems will be developed. An application of the method to a linen control system will be described.     

Study of the Nature of the Surface of Mixed Titanosilicas by Flash Photolysis of Adsorbed Pyrenemethanol

We have used nanosecond laser flash photolyis in diffuse reflectance mode to study processes of photoinduced charge transfer between an adsorbed acene (pyrenemethanol) and the surface of titanosilicas containing 1% TiO₂, and we have determined the role of titanium in the processes of adsorption and formation of radical cations. We have shown that the nature of the reactivity of mixed TiO₂/SiO₂ materials is determined by synthesis method (sol–gel or impregnation).     

The application of diffuse reflectance laser photolysis to study photochemistry at interfaces and in dyed fabrics

Recently we have extended to heterogeneous, opaque and often highly scattering systems, the application of flash photolysis by using diffuse reflected light instead of transmitted light as the analysing source on timescales extending from several seconds to picoseconds. Laser-induced transient spectra and decay kinetics have been observed from a wide variety of samples including fractions of monolayers of organic molecules adsorbed on catalytic metal oxide surfaces, within inorganic and organic microcrystals, from dyed fabrics and from paper pulp. The potential of the technique to study photochemical reactions at interfaces is demonstrated with particular reference to ion-electron recombination on porous silica surfaces and to photochemical and photophysical processes occurring in dyed fabrics.