o-Nitrobenzyloxycarbonyl and a number of related groups have been tested for the photolabile protection of nucleoside 5'-hydroxyls. The rates of photodeprotection were found to vary by approximately 17-fold in a series of 5'-O-protected thymidine derivatives irradiated at 365 nm under identical conditions. The homologous 2-(o-nitrophenyl)ethoxycarbonyl group and its derivatives were found to be removed approximately 2-fold faster than the corresponding o-nitrobenzyloxycarbonyl group, possibly due to an increased rate of o~-hydrogen abstraction by the photo-excited nitro group. Photolysis rates were affected by substitutions on both the phenyl ring and m-carbon, with the strongest rate enhancements caused by the presence of a methyl or second o-nitrophenyl group in the tx-position. Among the ring-substituted derivatives studied, o-nitro and o-iodo had the strongest enhancement effects on photodeprotection, while an o-fluoro group reduced the rate of photodeprotection. In general, substitutions at other positions on the phenyl ring had less effect on photolysis rates. © 1997 Elsevier Science Ltd.The use of photolabile protecting groups in nucleic acid 1-8, carbohydrate 9, and peptide 10-12 chemistry has been well established. More recently, photolabile protection of the 5'-hydroxyl of 2'-deoxyribonucleoside 3'-phosphoramidites has been employed in the solid-phase synthesis of DNA probe arrays. 13-16 Useful photolabile protecting groups must be stable to mild chemical treatments, but photolytically cleaved in high yield by irradiation at wavelengths which do not damage the protected molecule.The o-nitrobenzyl group or groups containing this photosensitive moiety have been used for photolabile protection of hydroxyl, carboxyl, amino, thiol, and carbonyl functions. 17 The removal of photolabile groups from a protected hydroxyl oxygen by irradiation at wavelengths >320 nm involves abstraction of a hydrogen from the m-methylene carbon by the excited nitro group followed by rearrangement to o-nitrosobenzaldehyde and the deprotected alcohol. In the case of the 2-nitrobenzyloxycarbonyl group, carbon dioxide is also released (Fig. 1). The quantum yield of photodeprotection may be strongly influenced by substitution on the phenyl ring or methylene carbon of the o-nitrobenzyl group. Reichmanis et al. 18 reported a 5-fold increase in quantum yield for photocleavage of the o-nitrobenzyl esters of trimethylacetic acid when the parent ester is substituted with an s-methyl group. 4247

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Radioactive waste / Solvent extraction / Crown ether / Calixarene / Cesium / Macrocycle SummaryIn terms of extractive strength and selectivity over sodium, calix[4]arene-bis-(2,3-naphtho-crown-6) exhibits superior properties in comparison with simple crown ethers for separating cesium from an alkaline Solution simulating a Hanford tank supematant waste. The calixarene was studied at O.Ol M in four diluents. In two cases a cesium distribution coefficient near unity was obtained. Successive water washes sufficed to Strip the loaded solvents. In addition, selectivity ratios for cesium over sodium exceeded 10" for all of the diluents. By contrast, bis-(tert-butylbenzo)-21-crown-7 gave distribution coefficients an average of 200 times lower under identical conditions; its selectivity ratio for cesium over sodium was at best 200 in one of the four diluents tried. Although Cs/Na selectivity in the case of the calixarene is so high as to make Na^ ion extraction inconsequential, Cs/K selectivity lay in the lower ränge 122-935. Owing to the relatively high concentration of K^ ion in the waste, strong competition due to K^ ion extraction resulting in high loading of the calixarene was observed to limit the effectiveness of cesium extraction and Stripping. For both the calixarene and crown ether, extraction strength correlates with the empirical solvent polarity Parameters DP* and E-r.

Glatiramer acetate (GA) has been available under the brand name Copaxone® for nearly two decades. Recently, the US Food and Drug Administration (FDA) approved the first generic GA, Glatopa™, as fully substitutable for all indications for which Copaxone 20mg is approved; Glatopa also represents the first FDA-approved "AP-rated," substitutable generic for treating patients with MS. Glatiramer acetate is a complex mixture of polypeptides and, consequently, its characterization presented challenges not generally encountered in drug development. Despite its complexity, and without requiring any clinical data, approval was accomplished through an Abbreviated New Drug Application in which equivalence to Copaxone was evaluated across four criteria: starting materials and basic chemistry; structural signatures for polymerization, depolymerization, and purification; physicochemical properties; and biological and immunological properties. This article describes the rigorous overall scientific approach used to successfully establish equivalence between Glatopa and Copaxone, and presents key representative data from several of the comprehensive sets of physicochemical (structural) and biological (functional) assays that were conducted.

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