Method transfer investigation process

The final part is devoted to a survey of molecular properties of special interest to the medicinal chemist. The Theory of Atoms in Molecules by R. F.W. Bader et al., presented in Chapter 7, enables the quantitative use of chemical concepts, for example those of the functional group in organic chemistry or molecular similarity in medicinal chemistry, for prediction and understanding of chemical processes. This contribution also discusses possible applications of the theory to QSAR. Another important property that can be derived by use of QC calculations is the molecular electrostatic potential. J.S. Murray and P. Politzer describe the use of this property for description of noncovalent interactions between ligand and receptor, and the design of new compounds with specific features (Chapter 8). In Chapter 9, H.D. and M. Holtje describe the use of QC methods to parameterize force-field parameters, and applications to a pharmacophore search of enzyme inhibitors. The authors also show the use of QC methods for investigation of charge-transfer complexes. 

A microscopic theory for describing ultrafast radiationless transitions in particular for, photo-induced ultrafast radiationless transitions is presented. For this purpose, one example system that well represents the ultrafast radiationless transaction problem is considered. More specifically, bacterial photosynthetic reaction centers (RCs) are investigated for their ultrafast electronic-excitation energy transfer (EET) processes and ultrafast electron transfer (ET) processes. Several applications of the density matrix method are presented for emphasizing that the density matrix method can not only treat the dynamics due to the radiationless transitions but also deal with the population and coherence dynamics. Several rate constants of the radiationless transitions and the analytic estimation methods of those rate... 

In order to improve the sensitivity of the collinear method new efficient detection schemes based on particle counting have been introduced. The first scheme, particularly qtplicable to alkaline-earth ions, is utilizing the state selectivity of the charge-transfer neutralization process and atonoAon counting [56]. The technique has been used in systematic investigations of jpCa [57-60] and 3 Sr [61-65]. 

Reactive states of aromatic molecules in solution may be observed directly by the pulse radiolysis method. Extensive investigations of both aromatic molecule ions (particularly the radical anions) and electronically excited states have provided new information about not only the radiation chemical processes but also the general kinetic behavior of these reactive intermediates. Absolute rate constants have been determined for many elementary processes such as energy transfer and electron and proton transfer reactions. 

Individual protocols and reports can be written for each test to facilitate transfer of specific mefhods. This approach allows a discrepancy fo be investigated while not holding up unaffected method transfer activities. To facilitate internal and regulatory inspections, the method transfer protocols and reports should be compiled for easy review at the receiving site. The raw data should be readily accessible. Transfer of any relevant documentation such as methods, specifications, validation reports, reference standard information should be completed. From this point on, the change control process should assure that methods and specifications remain the same at the qualified fesfing sifes except perhaps for document format. 

Among the tentative mechanisms discussed by Walling, two involved hydrogen transfers in the rate-determining part of the process, and should therefore be detectable by the kinetic isotope-effect method. Such investigations were started shortly after the publication of the book mentioned. Mil3mtinskaya et al. (1957) determined the deuterium content of biphenyl and the tarry b3 roducts formed in the reactions... 

Meanwhile, the anode and cathode reactions of Eqs. 8.1a and 8.1b are multi-component reaction systems. As mentioned regarding the ISA method, the anode and cathode reactions are mass-transfer control processes. Then the mass-transfer of each species would provide overpotential due to the species. To investigate the overpotential attributed to each species, the reaction gas addition method was attempted. This is very similar to the ISA except that a reactant gas is added to an electrode instead of an inert gas [41]. Figure 8.13 shows the voltage behaviors due to the addition of a reactant gas. Here, the subscript A denotes a reactant gas species. 

We have used this combined flow method to investigate the electron transfer behaviour of the complex ions of silver (II)-porphyri and cytochrome(II)c with the very fast oxidizing agents Os(dipy) and I Cl. These reactions are of interest because complexes containing a porphyrin ring system represent a class of compounds which participate in important life processes, for example, in photosynthesis, in mitochondrial respiration and as oxygen carriers in the transport system of blood. 

---