Chemical structure, representation fragments

Data attached to arbitrary atoms (and bonds) can be used to (a) annotate a particular set of atoms, e.g., as part of a pharmacophore or as reactive sites (b) annotate fragments, e.g., with stoichiometric multipliers of a salt or solvate, as major or minor, or as active or inert (c) describe an unknown portion of a structure by attaching descriptive data to a nvdl or atom (d) explain more fully the nature of a particular site (atom), e.g., stereochemical purity, isotopic purity (see Figure 10). In short, the use of SGroup data permits a user-extensible chemical structure representation. The user can define new data fields and attach values to atoms. These values are fully a part of the connection table and are searchable both with exact match and with substructure searching. 

Over and beyond the representations of chemical structures presented so far, there are others for specific applications. Some of the representations discussed in this section, e.g., fragment coding or hash coding, can also be seen as structure descriptors, but this is a more philosophical question. Structure descriptors are introduced in Chapter 8. 

Four main approaches have been suggested for the representation of chemical structures in machine-readable form fragment codes, systematic nomenclature, linear notations, and connection tables. 

The importance of methods to predict log P from chemical structure was described in Chapter 14, which is focused on fragment- and atom-based approaches. In this chapter property-based approaches are reviewed, which comprise two main categories (i) methods that use three-dimensional (3D) structure representation and (ii) methods that are based on topological descriptors. 

With the variety of chemical substance representations, i.e., fragment codes, systematic nomenclature, linear notations, and connection tables, a diversity of approaches and techniques are used for substructure searching. Whereas unique, unambiguous representations are essential for some registration processes, it is important to note that this often cannot be used to advantage in substructure searching. With connection tables, there is no assurance that the atoms cited in the substructure will be cited in the same order as the corresponding atoms in the structure. With nomenclature or notation representation systems, a substructural unit may be described by different terms or... 

Another approach is to label the selected chemical fragments of easily recognizable features (for example -OH or -C( = 0)- group, aromatic ring, structural skeletons, etc.) with consecutive numbers, letters, or special characters. The full structure representation is than either a list of all present or a list of all different structural features. If different fragments are labeled as fi, then structure S can be written as a set of m fragments ... 

Each fragment has different characteristic physicochemical properties. For example, representative properties of primary amines are hydrophilicity, the ability to form cations, and the ability to form hydrogen bonds. It is often difficult to know which property is the most important one. Nevertheless, representation by the 2D chemical structure is a good way to generate ideas for further chemical modification. 

The problem of poor retrieval precision, and the development of search systems based on unambiguous (complete) representations of the structure has led to the general demise of fragment codes as a primary representation of chemical structures, at least for specific compounds. However, hidden from the user they remain an important component of structure search systems, and a few user-visible fragment-code systems continue to be used in the handling of Markush structures from chenaical patents these are discussed in more detail in Markush Structure Searching in Patents. 

Fragment-based fingerprint representations are also used in the calculation of numerical similarity measures between chemical structures. Various ratios involving the numbers... 

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