The chemistry of the S-nitrosoglutathione/glutathione system

S-Nitrosothiols have generated considerable interest due to their ability to act as nitric oxide (NO) donors and due to their possible involvement in bioregulatory systems—e.g., NO transfer reactions. Elucidation of the reaction pathways involved in the modification of the thiol group by S-nitrosothiols is important for understanding the role of S-nitroso compounds in vivo. The modification of glutathione (GSH) in the presence of S-nitrosoglutathione (GSNO) was examined as a model reaction. Incubation of GSNO (1 mM) with GSH at various concentrations (1–10 mM) in phosphate buffer (pH 7.4) yielded oxidized glutathione, nitrite, nitrous oxide, and ammonia as end products. The product yields were dependent on the concentrations of GSH and oxygen. Transient signals corresponding to GSH conjugates, which increased by one mass unit when the reaction was carried out with 15N-labeled GSNO, were identified by electrospray ionization mass spectrometry. When morpholine was present in the reaction system, N-nitrosomorpholine was formed. Increasing concentrations of either phosphate or GSH led to lower yields of N-nitrosomorpholine. The inhibitory effect of phosphate may be due to reaction with the nitrosating agent, nitrous anhydride (N2O3), formed by oxidation of NO. This supports the release of NO during the reaction of GSNO with GSH. The products noted above account quantitatively for virtually all of the GSNO nitrogen consumed during the reaction, and it is now possible to construct a complete set of pathways for the complex transformations arising from GSNO + GSH.

Manipulation of the phenolic chemistry of willows by gall-inducing sawflies

The ability to induce galls on plants has evolved independently in many insect orders, but the adaptive significance and evolutionary consequences of gall induction are still largely unknown. We studied these questions by analyzing the concentrations of various plant defense compounds in willow leaves and sawfly galls. We found that the galls are probably nutritionally beneficial for the sawfly larvae, because the concentrations of most defensive phenolics are substantially lower in gall interiors than in leaves. More importantly, changes in chemistry occur in a similar coordinated pattern in all studied willow species, which suggests that the insects control the phenolic biosynthesis in their hosts. The resulting convergence of the chemical properties of the galls both within and between host species indicates that the role of plant chemistry in the evolution of host shifts may be fundamentally less significant in gallers than in other phytophagous insects.

Dendrimer-supported combinatorial chemistry.

A new methodology for the construction of combinatorial libraries is described. The approach, termed dendrimer-supported combinatorial chemistry (DCC), centers on the use of dendrimers as soluble supports. Salient features of DCC include solution phase chemistry, homogeneous purification, routine characterization of intermediates, and high support loadings. To demonstrate the feasibility of DCC, single compounds and a small combinatorial library were prepared via the Fischer indole synthesis. Excellent product yields and purities were obtained, and dendrimer-protected intermediates could be routinely analyzed by 1H and 13C NMR and by mass spectrometry. The results indicate that DCC is a general and efficient strategy for the generation of combinatorial libraries.

Sample size determination in combinatorial chemistry.

Combinatorial chemistry is gaining wide appeal as a technique for generating molecular diversity. Among the many combinatorial protocols, the split/recombine method is quite popular and particularly efficient at generating large libraries of compounds. In this process, polymer beads are equally divided into a series of pools and each pool is treated with a unique fragment; then the beads are recombined, mixed to uniformity, and redivided equally into a new series of pools for the subsequent couplings. The deviation from the ideal equimolar distribution of the final products is assessed by a special overall relative error, which is shown to be related to the Pearson statistic. Although the split/recombine sampling scheme is quite different from those used in analysis of categorical data, the Pearson statistic is shown to still follow a chi2 distribution. This result allows us to derive the required number of beads such that, with 99% confidence, the overall relative error is controlled to be less than a pregiven tolerable limit L1. In this paper, we also discuss another criterion, which determines the required number of beads so that, with 99% confidence, all individual relative errors are controlled to be less than a pregiven tolerable limit L2 (0 < L2 < 1).

The physics and chemistry of heavy fermions.

The heavy fermions are a subset of the f-electron intermetallic compounds straddling the magnetic/nonmagnetic boundary. Their low-temperature properties are characterized by an electronic energy scale of order 1-10 K. Among the low-temperature ground states observed in heavy fermion compounds are exotic superconductors and magnets, as well as unusual semiconductors. We review here the current experimental and theoretical understanding of these systems.