Fragment methods

K, V N Viswanadhan and J J Wendoloski 1998. Prediction of Hydrophobic (Lipophilic) lerties of Small Organic Molecules Using Fragmental Methods An Analysis of ALOGP and GP Methods. Journal of Physical Chemistry 102 3762-3772. 

Fragmental methods (Table 14.1) cut molecules down into fragments and apply correction factors in order to compensate for intramolecular interactions. Frag-... 

The actual 2/ system [34] lists 13 correction rules and 169 fragment values, including 14 new heterocyclic fragments as well as doubly and triply halogenated methyls. A typical calculation is depicted in Fig. 14.1 for quinidine. The 2/system is the only fragment method allowing manual log P calculation. Computerized... 

Fig. 14.1 LogP calculation for quinidine with the fragmental method according to Rekker and Mannhold. Calculation starts with the gross formula C20H24N2O2 definition of...

XLOGP [67, 68] is a further atom-additive method, as expressed by its almost exclusive use of atomic contributions. However, in contrast to pure atom-based methods correction rules are defined, to account for intramolecular interactions, which is typical for fragmental methods. 

Japertas, P., Didziapetris, R., Petrauskas, A. A. Fragmental methods in the design of new compounds. Applications of the advanced algorithm builder. Quant. Struct.-Act. Relat. 2002, 27, 23-37. 

Ghose, A. K., Viswanadhan, V. N., Wendoloski,).). Prediction of hydrophobic (lipophilic) properties of small organic molecules using fragmental methods an analysis of... 

Considering the success of fragment methods, which apply additive models for log P predichon, one can assume that addihve approaches may also sahsfactory work for MLP. Indeed, similar to the Generalized Born model, one can consider fragments of molecules as centers of some potenhal functions and use an empirically defined distance function ) to calculate the MLP value by ... 

Schtiurmann, G., Ebert, R. U Ktihne, R. Prediction of physicochemical properties of organic compounds from 2D molecular structure - fragment methods vs. LEER models. Chimia 2006, 60, 691-698. 

Abraham, D. J., Leo, A. J. Extension of the fragment method to calculate amino acid zwitterion and side chain partition coefficients. Proteins 1987, 2,130-152. 

HPLC-screening method calculated-PCKOC fragment method, Muller Kordel 1996) 3.40-5.33 3.80-5.40 (range, calculated from sequential desorption of 11 urban soils lit. range, Krauss... 

HPLC-screening method calculated-PCKOC fragment method, Muller Kordel 1996)... 

Fig. 7. Estimates of the logarithm of partition coefficient in octanol water (log P) of 4-PIOL analog substituents obtained by use of Crippen s fragmentation method. Correlation between affinity tpAT,) and lipophilicity (log P) of the substituents of the 4-PIOL analogs. The two gray lines connect the high-affinity compounds (open squares) and the low-affinity compounds (open triangles), respectively, and the black line shows the correlation between the remaining compounds (black circles).

The first part of this book is dedicated to a discussion of mass spectrometry (MS) instrumentation. We start with a list of basic definitions and explanations (Chapter 1). Chapter 2 is devoted to the mass spectrometer and its building blocks. In this chapter we describe in relative detail the most common ion sources, mass analyzers, and detectors. Some of the techniques are not extensively used today, but they are often cited in the MS literature, and are important contributions to the history of MS instrumentation. In Chapter 3 we describe both different fragmentation methods and several typical tandem MS analyzer configurations. Chapter 4 is somewhat of an outsider. Separation methods is certainly too vast a topic to do full justice in less than twenty pages. However, some separation methods are used in such close alliance with MS that the two techniques are always referred to as one combined analytical tool, for example, GC-MS and LC-MS. In effect, it is almost impossible to study the MS literature without coming across at least one separation method. Our main goal with Chapter 4 is, therefore, to facilitate an introduction to the MS literature for the reader by providing a short summary of the basic principles of some of the most common separation methods that have been used in conjunction with mass spectrometry. 

Relatively few kinetic data are available for the carbon-carbon bond forming reactions of alkene radical cations. Nevertheless, rate constants for the cyclization illustrated in Scheme 9, with generation of the alkene radical cation by the fragmentation method, have been measured. These cyclization rate constants are significantly faster than those of the corresponding neutral radicals [89]. 

Although cycloaddition reactions have yet to be observed for alkene radical cations generated by the fragmentation method, there is a very substantial literature covering this aspect of alkene radical cation chemistry when obtained by one-electron oxidation of alkenes [2-16,18-26,28-31]. Rate constants have been measured for cycloadditions of alkene and diene radical cations, generated oxidatively, in both the intra- and intermolecular modes and some examples are given in Table 4 [91,92]. 

Pleiss, M.A. and Grunewald, G.L. An extension of the f-fragment method for the calculation of hydrophobic constants (Log F) of conformationally defined systems, / Merf Chem., 26(12) 1760-1764,1983. 

Atomic and fragmental methods suffer from the problem that not all contributions may be parameterized. This leads to the observation that for a typical pharmaceutical file about 25 % of the compounds cannot be computed. Recent efforts have tried to improve the missing value problem [53]. 

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