Reactions Sites, Detection

An extension of SOCRATES to handle chemical reactions, called CONTRAST, has also been developed at Sandwich, again with some collaboration from Peter Willett at Sheffield. In SOCRATES the precursors of our company compounds are stored in the compound registry file, and so application of a reaction site detection algorithm to the starting material and product generates a set of modified connection tables and fragment screens, and a set ofreaction bit-screens. The substructure search graphical structure input menu was modified to enable the chemist to identify the atoms involved in the reaction, but otherwise is essentially the same interface as in SOCRATES. 

The application of surface-enhanced Raman spectroscopy (SERS) for monitoring redox and other processes at metal-solution interfaces is illustrated by means of some recent results obtained in our laboratory. The detection of adsorbed species present at outer- as well as inner-sphere reaction sites is noted. The influence of surface interaction effects on the SER spectra of adsorbed redox couples is discussed with a view towards utilizing the frequency-potential dependence of oxidation-state sensitive vibrational modes as a criterion of reactant-surface electronic coupling effects. Illustrative data are presented for Ru(NH3)63+/2+ adsorbed electrostatically to chloride-coated silver, and Fe(CN)63 /" bound to gold electrodes the latter couple appears to be valence delocalized under some conditions. The use of coupled SERS-rotating disk voltammetry measurements to examine the kinetics and mechanisms of irreversible and multistep electrochemical reactions is also discussed. Examples given are the outer- and inner-sphere one-electron reductions of Co(III) and Cr(III) complexes at silver, and the oxidation of carbon monoxide and iodide at gold electrodes. 

Since the line-broadening effects of the magnetic susceptibility variations are directly proportional to the NMR frequency, lower frequency nuclei (like 13C) may produce narrower linewidths. In fact, this technique has been mostly used for this nucleus [37-43]. In some cases, the poor sensitivity associated with 13C detection was compensated by incorporating 13C labels near the reaction site of interest. This approach was called fast 13C NMR [44 48] and allowed to obtain data in a few minutes for each sample. 

In order to understand the manner in which the interfacial region influences the observed kinetics, especially in terms of the theoretical models discussed below, it is clearly important to gain detailed information on the spatial location of the reaction site as well as a knowledge of the mechanistic pathway. Information on the latter for multistep processes can often be obtained by the use of electrochemical perturbation techniques in order to detect reaction intermediates, especially adsorbed species [13]. Various in-situ spectroscopic techniques, especially those that can detect interfacial species such as infrared and Raman spectroscopies, are beginning to be used for this purpose and will undoubtedly contribute greatly to the elucidation of electrochemical reaction mechanisms in the future. 

For the majority of electrode reactions, however, for which the precursor states are insufficiently stable to allow analytical detection, resort must be made to less direct methods of determining the reaction site, such as the following. 

Glass surfaces were used in the same manner as were TaO surfaces. These surfaces were observed for antigen/antibody reaction sites either by vapor pattern technique or by staining. Water vapor pattern allows detection of wettable reaction sites, as reported 22). 

Enzyme-substrate complexes have been studied by kinetic analysis, chemical modification, inhibition of enzymes by specific compounds that interact with active sites, detection of characteristic spectral absorption bands during reaction of enzymes with substrates, and X-ray crystallographic analysis of enzymes combined with compounds which are in similar structure to the natural substrates. The interaction between enzymes and substrates has been analyzed by the concepts of lock-and-key" and "induced fit". The former presumes that the substrate surface must fit the enzyme surface like a key in a lock, while the latter refined theory assumes that binding of the substrate induces ( informational changes in the enzyme to provide a better fit. 

In 1985, mono-segmented flow analysis was proposed [64] as a means of achieving extended sample incubation times without excessive sample dispersion. The sample was inserted between two air bubbles into an unsegmented carrier stream therefore the innovation combined the favourable characteristics of both segmented and unsegmented flow systems. Further development revealed other potential applications, especially with regard to relatively slow chemical reactions, flow titrations, sample introduction to atomic absorption spectrometers, liquid-liquid extraction and multi-site detection (Chapters 7 and 8). This innovation was also referred to as segmental flow injection analysis [65]. 

Lynch MF, Willett P. The automatic detection of chemical reaction sites. J Chem Inf Comput Sci 1978 18 154-159. 

The 14C label provides a sensitive analytical method for determining the extent of reaction and detecting subtle differences in the response of coal, and the sites of methylation can be established from the solid-state 13C NMR spectra of the 13C-enriched coal derivatives. To further characterize the types of reactive sites, the methylated coals were subjected to base hydrolysis with n-Bu4NOH in aqueous THF (12). The number of base-labile methyl groups was taken as a measure of the maximum number of methyl esters formed during the alkylation. The results from this study are presented in Table I. 

Equation (2) for the coupling reaction shows that product C formation is equal to activated monomer (F) destruction. Following the disappearance of monomer leads to information about the progress of the coupling. If the amount of activated monomer is much greater than the amount of reaction sites on the solid support, then the detection and quantification of the monomer disappearance may be difficult or inaccurate. 

---