The quality of combinatorial libraries determines the success of biological screening in drug discovery programs. In this paper, we evaluate and compare various methods for measuring identity, purity, and quantity (yield) of combinatorial libraries. Determination of quantitative purity reveals the true library quality and often indicates potential quality problems before full-scale library production. The relative purity can be determined for every member in a large library in a high-throughput mode, but must be cautiously interpreted. In particular, many impurities are not observable by relative purity measurements using detectors such as UV(214), UV(254), and evaporative light-scattering detection. These "invisible" impurities may constitute a significant portion of the sample weight. We found that TFA, plastic extracts, inorganic compounds, and resin washout are among these impurities. With compelling evidence, we reach a conclusion that purification is the only way to remove "invisible" impurities and improve the quantitative purity of any compound even though some compounds may have a high relative purity before purification.

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A l u m i n o s i l i c a t e a z i d e c a n c r i n i t e , Na 8 [AlSiO 4 ] 6 (N 3 ) 2.4 (H 2 O) 4.6 , has been prepared for the first time from zeolite-A, followed by hydrothermal processing at low temperature. After crystallization, the sample was characterized by appropriate physicochemical techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), infrared spectroscopy (IR), thermal gravimetric analysis (TGA), and Brunauer− Emmett−Teller (BET) surface area. In the present study, attention was focused on investigating the removal performance of heavy metal ions (Cd 2+ , Pb 2+ , and Ni 2+ ) in aqueous solution on pure aluminosilicate azide cancrinite. The kinetics of the process and sorption capacity of the adsorbent was determined in relation to the effect of various factors affecting on the adsorption process. The parameters in this study included contact time, metal ion concentration, temperature, and adsorbent dosage. The removal mechanism of metal ions followed adsorption and ion exchange process. Adsorption data has been interpreted in terms of Langmuir and Freundlich equations. The selectivity of the studied metal ions was determined as Pb 2+ > Cd 2+ > Ni 2+ . Thermodynamic parameters, i.e., equilibrium constant (K c ), free energy (ΔG°), entropy (ΔS°), and enthalpy (ΔH°) for adsorption, were computed from the experimental data.

Convenient and reliable large-scale procedures for the protection of various amino acids with N-(9-fluorenylmethoxycarbonyl)oxysuccinimide (FMOC-OSu) are described. Commercially available 4-aminomethylbenzoic acid and trans-4-(aminomethyl)cyclohexanecarboxylic acid were converted into their corresponding FMOC-derivatives in excellent yields without the need for an extractive workup. In addition, FMOC-cis-β-amino acids were also prepared, employing a [2 + 2]-cycloaddition strategy between a cyclic olefin and N-chlorosulfonyl isocyanate (CSI).The resulting N-chlorosulfonyl β-lactams were reduced to the parent β-lactams with sodium sulfite and then converted to the cis-β-amino acid hydrochlorides by exposure to aqueous hydrochloric acid. The resulting cis-β-amino acids were converted to their FMOC-derivatives under conditions similar to those developed for the commercially available amino acids. Differences in the conditions employed between these β-amino acids and the commercial derivatives were observed, primarily in the nature of the base required for the reaction. A possible rationale for the differences in behavior is described. These FMOC-amino acid derivatives are valuable intermediates for the solid-phase synthesis of combinatorial libraries.

The 14-hydroxy group is known to increase the antagonist potency of mu-selective opioid ligands. To investigate the role of this group at the delta opioid receptor, the 14-desoxy analogues (7 and 9) of the delta-selective ligands, naltrindole (1, NTI) and spiroindanyloxymorphone (2, SIOM), have been synthesized and tested. The in vitro pharmacologic activities of 7 and 9 suggest that the 14-hydroxy group plays an important role in determining the delta selectivity and potency of NTI and SIOM.