Chemical biologically relevant

Thus, the hazard identification, in addition to an identification of the inherent toxicological properties (type of effects), also involves an evaluation of the nature of the observed effects, i.e. (1) whether an observed effect constitutes an adverse effect and thus results in an impairment of body function(s), and (2) whether an effect is a direct toxic effect exerted by the chemical (biologically relevant) or is due to normal unspecific reactions toward changes in the environment (homeostasis). Examples of effects, which generally are not considered as being adverse, include ... 

Electronic structure methods are aimed at solving the Schrodinger equation for a single or a few molecules, infinitely removed from all other molecules. Physically this corresponds to the situation occurring in the gas phase under low pressure (vacuum). Experimentally, however, the majority of chemical reactions are carried out in solution. Biologically relevant processes also occur in solution, aqueous systems with rather specific pH and ionic conditions. Most reactions are both qualitatively and quantitatively different under gas and solution phase conditions, especially those involving ions or polar species. Molecular properties are also sensitive to the environment. 

The challenge in the synthesis of chemical libraries is the vast number of different, potentially drug-like small molecules which is estimated to be as high as 1060. As all of these molecules can never be synthesized and tested, it is essential to define criteria for the composition of libraries spanning the biologically relevant areas of the chemical space most efficiently. An important criterion of a compound library is its chemical diversity, a term describing the similarity or dissimilarity of all library components. Thus, chemical diversity expresses how well a library represents all theoretical possibilities within the chemical property space. A library with low... 

Several dozens of aldolases have been identified so far in nature [23,24], and many of these enzymes are commercially available at a scale sufficient for preparative applications. Enzyme catalysis is more attractive for the synthesis and modification of biologically relevant classes of organic compounds that are typically complex, multifunctional, and water soluble. Typical examples are those structurally related to amino acids [5-10] or carbohydrates [25-28], which are difficult to prepare and to handle by conventional methods of chemical synthesis and mandate the laborious manipulation of protective groups. 

This book is about fundamental aspects of the science of biogeochemistry. As such, and while it is relevant to the major issues of global change, it is not issue oriented. Not does this book attempt to review all of the research on these topics. It does, however, emphasize fundamental aspects of the physical, chemical, biological, and Earth sciences that are of lasting importance for integrative studies of the Earth. 

Quinone methides have been shown to be important intermediates in chemical synthesis,1 2 in lignin biosynthesis,3 and in the activity of antitumor and antibiotic agents.4 They react with many biologically relevant nucleophiles including alcohols,1 thiols,5-7 nucleic acids,8-10 proteins,6 11 and phosphodiesters.12 The reaction of nucleophiles with ortho- and /iara-quinone methides is pH dependent and can occur via either acid-catalyzed or uncatalyzed pathways.13-17 The electron transfer chemistry that is typical of the related quinones does not appear to play a role in the nucleophilic reactivity of QMs.18... 

Considering that the chemical transformations attempted hitherto involved only one or two atoms, the series of articles from the group of Peter Kollman appeared to represent a quantum leap forward. It was soon recognized, however, that these calculations were evidently too short and probably not converged. They demonstrated, nonetheless, that modeling biologically relevant systems was a realistic goal for the computational chemist. 

The term biology-oriented synthesis (BIOS) [45] has been used to describe the design of compound libraries based on biologically relevant chemical space [46]. The areas in protein structures that participate in productive protein-ligand interactions have been, for the most part, already defined by natural products and drugs. Thus libraries inspired by natural products and other bioactive molecules are expected to have a higher probability of biologically activity than randomly synthesized molecules [47,48]. 

As intracellular reduction mechanisms are important for Pt(II) and Pt(IV) drugs alike, the chemical reduction of cis,trans-[Pt(en)I2(OH)2] (3) by GSH was further explored under biologically relevant conditions (24), which led to the unexpected detection of a long-lived chelate-ring-opened Pt(II) complex capable of forming DNA-Pt adducts. 

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