Topology / topological / topographical

These pharmacophore techniques are different in format from the traditional pharmacophore definitions. They can not be easily visualized and mapped to the molecular structures rather, they are encoded as keys or topological/topographical descriptors. Nonetheless, they capture the same idea as the classic pharmacophore concept. Furthermore, this formalism is quite useful in building quantitative predictive models that can be used to classify and predict biological activities. 

The upper diagram is an attempt to show the topological relationship between the reactants and products on an energy-contour diagram. The pathways of minimum energy, which would correspond on a topographic map to trails through mountain passes, are shown by dashed arrows. 

Fig. 3. (A) Far-field confocal micrograph (35 pm x 35 pm) of a mica-supported DPPC monolayer showing LE-LC phase coexistence, deposited at a surface pressure of 9mN/m. (B) Atomic force micrograph of the film depicted in (A). Bright features denote topographically higher substructure of the film. (C) Near-held fluorescence image of the him shown in (A). (D) Near-held topology image collected simultaneously with the image depicted in (C). Reproduced with permission from Ref. [18]. Copyright 1998 Biophysical Society.

For illustration, we shall consider here one of the nonlinear variable selection methods that adopts a k-Nearest Neighbor (kNN) principle to QSAR [kNN-QSAR (49)]. Formally, this method implements the active analog principle that lies in the foundation of the modern medicinal chemistry. The kNN-QSAR method employs multiple topological (2D) or topographical (3D) descriptors of chemical structures and predicts biological activity of any compound as the average activity of k most similar molecules. This method can be used to analyze the structure-activity relationships (SAR) of a large number of compounds where a nonlinear SAR may predominate. 

Chemical Space. A loosely defined concept that all the known or possible chemical structures define some multidimensional syace in which the structures are points. Structures that are topologically or topographically similar to each other (i.e., look similar), cluster in chemical space, and by the principle of chemical similarity, should show similar physicochemical and biological properties. This is the basis for diversity analysis of chemical libraries. The challenge is to select or discover properties of the structures that define the chemical space and can be used. 

Comparison of the reduction process with that of the acyclic analogue [Cu(l)2]" allowed to discriminate topographical and topological contributions to the overall electrochemical behavior of Cu.5+. For Cu-S" " (as for [Cu(l)2] ), two reversible one-electron transfers are observed at very negative potentials (-1.650 and -1.860 V versus SCE for Cu-S ). This behavior is distinctly different from that of other complexes containing unsubstituted chelates, like bpy and phen (Figure 3). For instance, the following reductive dissociation takes place at -0.262 V [23] ... 

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