THE ACTIVATION OF SMALL MOLECULES

The metal-oxo molecular models outlined above have a quite remarkable potential for studying the metal activity in a quite unusual environment. Some of the possibilities could be (1) the generation and the chemistry of M—C, M=C, M=C functionalities (2) the interaction with alkenes, alkynes, hydrocarbons, and hydrogen (3) the activation of small molecules like N26 and CO (4) the support of metal-metal bonded functionalities and (5) the generation of highly reactive low-valent metals. 

In eukaryotes, translation initiation is rate-limiting with much regulation exerted at the ribosome recruitment and ternary complex (elF2 GTP Met-tRNAjMet) formation steps. Although small molecule inhibitors have been extremely useful for chemically dissecting translation, there is a dearth of compounds available to study the initiation phase in vitro and in vivo. In this chapter, we describe reverse and forward chemical genetic screens developed to identify new inhibitors of translation. The ability to manipulate cell extracts biochemically, and to compare the activity of small molecules on translation of mRNA templates that differ in their factor requirements for ribosome recruitment, facilitates identification of the relevant target. 

This section addresses a wide variety of systems that all, in a direct or indirect way, involve the activation of small molecules. The treated systems are of biological, environmental, or industrial interest and form the basis of homogeneously catalyzed processes. 

I trust that you will all agree that the topics covered in this issue are very stimulating and that the contributions report the most recent advances in inorganic and bioinorganic chemistry that especially deals with the activation of small molecules and molecular recognition. The next volume of this series will be a thematic issue on Metal Ion Controlled Reactivity . 

Perhaps the most viable short-term use for dendritic macromolecules lies in their use as novel catalytic systems since it offers the possibility to combine the activity of small molecule catalysts with the isolation benefits of crosslinked polymeric systems. These potential advantages are intimately connected with the ability to control the number and nature of the surface functional groups. Unlike linear or crosslinked polymers where catalytic sites may be buried within the random coil structure, all the catalytic sites can be precisely located at the chain ends, or periphery, of the dendrimer. This maximizes the activity of each individual catalytic site and leads to activities approaching small molecule systems. However the well defined and monodisperse size of dendrimers permits their easy separation by ultrafiltration and leads to the recovery of catalyst-free products. The first examples of such dendrimer catalysts have recently been reported... 

A number of topics have not been tendered the attention due them enzyme processes, catalytic effects of metal ions in oxidation-reduction reactions, and the activation of small molecules such as H2, 02, and H202 by metal ions. This can be justified only by preoccupation with less well explored groups of reactions, which, it is to be hoped, will receive increased attention in future years. 

The tris-carbene ligand family with fac geometry points its three wingtip groups downwards around the metal shielding it effectively from the approach of any but small substrates. Its main application is therefore the activation of small molecules, including the activation of dioxygen and proton coupled electron transfer (PCET), a reaction normally performed by certain enzymes [70,71],... 

The prototypical photochemical system for CO2 reduction contains a photosensitizer (or photocatalyst) to capture the photon energy, an electron relay catalyst (that might be the same species as the photosensitizer) to couple the photon energy to the chemical reduction, an oxidizable species to complete the redox cycle and CO2 as the substrate. Figure 1 shows a cartoon of the photochemical CO2 reduction system. An effective photocatalyst must absorb a significant part of the solar spectrum, have a long-lived excited state and promote the activation of small molecules. Both organic dyes and transition metal complexes have been used as photocatalysts for CO2 reduction. In this chapter, CO2 reduction systems mediated by cobalt and nickel macrocycles and rhenium complexes will be discussed. 

In addition to studying the more general problem of the activation of small molecules by transition metal compounds, a number of researchers have made a detailed study of the nitrosyl ligand using molecular... 

Cyclometallation reactions form only a part of the broad class of C-H bond metallations or C-H activation. Such reactions facilitate the synthesis of organic compounds, including pharmaceuticals, the activation of small molecules, and industrial processes. Better control of ligand electronic effects and ligand sphere geometry will enhance the development and versatility of this class of metallation reactions. 

J.R. thanks the Fannie and John Hertz Foundation for a pre-doctoral fellowship. The work on PCET and the activation of small molecules by PCET has been supported by grants from the NIH (GM47274) and the DOE DE-FG02-05ER15745. 

The periphery of the cluster rings shows a rather high electron density with implications for the activation of small molecules coordinated to the surface sites. 

The unique reactivity of the above system with H2 appears to arise from the unquenched Lewis basicity and acidity of the respective donor P and the acceptor B centers. This inference prompted questions about the nature and reactivity of other phosphine-borane systems and, more broadly, of Lewis acid/base combinations. Is it necessary to have a link between the donor and acceptor sites Could similar H2 activation arise from combinations of donors and acceptors in which steric encumbrance frustrates Lewis acid-base adduct formation If indeed such frustrated Lewis pairs could be uncovered, could one exploit them for the activation of small molecules and applications in catalysis ... 

Oxidative addition is the initial step of many important organometallic reactions. This can be the basis of the preparation of new products or can be the first step in the activation of small molecules such as H2 or N2. For example, the oxidative addition of HCl can be performed in aqueous environment and produces hydrides (Figure 8). 

In view of the potential appHcation of metal porphyrazine complexes as catalysts for various oxidation reactions (45), much attention has been focused on the mechanistic investigations involving the activation of small molecules such as O2, NO, CO, and CO2 by these macrocychc systems. Since the electronic and structural properties of the porphyrazine l%and differ significantly from that of porphyrin rings, the relevant question is if changes in the macrocycle Hgand wiU be reflected in the mechanism of nitric... 

Vigato, P.A., S. Tamburrini, and D.E. Eenton (1990). The activation of small molecules by dinuclear complexes of copper and other metals. Coord. Chem. Rev. 106, 25-170. 

The homogenous hydrogenation of alkenes is one of the most studied reactions the results of these studies have been very important for the understanding of the activation of small molecules by metal complexes. 

---