Activation of small molecules

Solutions to the problem of continuous catalyst repair in artificial reaction chains are not apparent, but they lie buried in the chemistry of the coenzymes, which activate small carbon molecules. In the following, we briefly summarize the chemistry of some coenzymes. They are also mostly vitamins. This time we do not deal with electrons and protons, but with small, carbon-containing molecules such as carbon dioxide, formic acid, acetic acid, and a-amino acids. Some of these coenzymes interact very strongly with protein receptors, which also makes them useful in synkineses of reactive molecular complexes with peptides. 

Biotin is a hetero-bicycle with a urea and a thioether unit. It has three chiral centers. In synthesis one often starts with tartaric acid derivatives in order to produce the chiral sites at the ring junctions. me o-Dibromotartaric ester gives the desired cis configuration of a symmetrical bicycle, which becomes chiral upon introduction of the acid side chain. In one procedure the CHj groups of the thioether were activated by oxidation of the sulfur to the sulfoxide. Alkylation and removal of protecting groups gives the racemate. Separation of enantiomers occurs readily via the avidine molecular complex. 

CO2 must be activated in order to add to biotin. Nature uses ATP and presumably produces carboxyphosphate, the mixed anhydride of phosphoric and carbonic acids. In model reactions chloromethylformiate and 2-imidazolone were used. Saponification of die urethane gave the anion of iV-carboxy-2-imida-zolone, which decarboxylated again. Attempts to use the evolving carbon dioxide in the carboxylation of carbanions failed, even if it was bound to the imidazolone. 

More successful was the intramolecular attack of a carbanion bound to a neighboring thioenoether. The positive charge at the neighboring nitrogen atom obviously facilitates the rearrangement. 

Since both avidin and biotin are readily available, they are used for affinity chromatography. Any protein, amino acid, nucleotide, or nucleic acid that is covalently labeled with biotin can, for example, be adsorbed specifically on an avidin-sepharose column and subsequently be removed with a concentrated bi- 

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PubChem provides information on the biological activities 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. 

Spencer, A. Catalytic Activation of Small Molecules. In Wilkinson, G. Gillard, R. D. McCleverty, J. A., Eds., Comprehensive Coordination Chemistry, Vol. 8, Pergamon, Oxford, 1987, Chapter 61.2. 

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... 

WOMBAT [39] is a Cabinet database that provides information about biological activity of small molecules [40]. The dataset comes from publications in the Journal of Medicinal Chemistry and other periodicals. WOMBAT is updated twice a year. The data consist of series of compounds that were observed and compared for a specific activity, for example, Ki, IC50, D2 and EC50. The database also includes calculated LogP and Log S values, as well as other descriptors related to flexibility, size, and so on. 

Groves, J. T. Shalyaev, K. Lee, J. Oxometalloporphyrins in oxidative catalysis, The Porphyrin Handbook. Volume 4. Biochemistry and Binding Activation of Small Molecules Eds. Kadish, . M. Smith, . M. Guilard, R. Academic Press San Diego, 2000, pp. 17-40. 

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. 

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