Methods of Activating Molecules

In flash chemistry, extremely fast reactions are conducted in a highly controlled manner, and desired products are formed very quickly. Reaction times range from milliseconds to seconds. To accomplish such extremely fast reactions, we often need to activate molecules to make substrates with built-in high-energy content or prepare highly reactive reagents that react very quickly with substrates. There are several methods for activation, including thermal, photochemical, electrochemical, and chemical methods. In this chapter, we briefly survey these methods. 

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Therefore, the concept of flash chemistry may lead to a paradigm shift in laboratory chemical studies and industrial chemical production. It is hoped that various types of flash chemistry based on different methods of activating molecules and generating reactive reagents or intermediates, which may undergo a variety of reactions, will be developed and widely utilized in chemical research and in chemical plants to meet the demands of rapid and selective synthesis of various organic small molecules and polymers in the future. 

We now have six well-documented methods of activating molecules in chemical reactions, which can be grouped as follows the classical methods, including... 

A quantitative theory of rate processes has been developed on the assumption that the activated state has a characteristic enthalpy, entropy and free energy the concentration of activated molecules may thus be calculated using statistical mechanical methods. Whilst the theory gives a very plausible treatment of very many rate processes, it suffers from the difficulty of calculating the thermodynamic properties of the transition state. 

This method represents the most common and traditional application of computational tools to rational drug design. From a list of molecules of known activity, one can establish a 3D-pharmacophore hypothesis that is then transformed into a 3D-search query. This query is then used to search a 3D database for structures that fit the hypothesis within a certain tolerance. If the yield of active molecules is significant, then the query can be used to predict activities on novel compounds. In our situation, the enantiophore is built from the superposition of a list of sample molecules, which are all well separated on a given CSR Hence, the common features of this series of molecules can become a good enantiophore hypothesis for the enantiores-olution on this CSR... 

Various statistical treatments of reaction kinetics provide a physical picture for the underlying molecular basis for Arrhenius temperature dependence. One of the most common approaches is Eyring transition state theory, which postulates a thermal equilibrium between reactants and the transition state. Applying statistical mechanical methods to this equilibrium and to the inherent rate of activated molecules transiting the barrier leads to the Eyring equation (Eq. 10.3), where k is the Boltzmann constant, h is the Planck s constant, and AG is the relative free energy of the transition state [note Eq. (10.3) ignores a transmission factor, which is normally 1, in the preexponential term]. 

A method for visualizing recurrent topological substmctures in sets of active molecules./. Chem. Inf. Comput. Sci. 1998, 38, 915-924. 

Arrhenius explained the usual change of reaction rate with temperature by assuming that only those molecules react that have acquired a certain minimum energy. This view is now universally accepted. It is also agreed that the abnormally high energy of these activated molecules must be acquired either by collision with other molecules or by the absorption of radiation. There has, however, been some conflict of opinion as to which of these methods of activation is predominant and determines the rate of a reaction. 

Objective Find common feature configurations amongst a set of active molecules. Algorithm HipHop uses a pruned exhaustive search method. Starting with simple two-feature pharmacophores, the program tries to add one extra common feature at a time until no larger common pharmacophore configuration exists [10]. Combinations that cannot be completed to reach a minimum number of features are not further explored. 

In unimolecular reactions only one molecule is involved in the reaction. Since, however, the molecules prior to the reaction are stable, it is necessary to activate them in order to initiate the reaction. Based on the different methods of activation, we distinguish between the following two types of unimolecular reaction ... 

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