Chemical space topologies

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. 

Chemical compounds can be characterized by a wide variety of molecular descriptors" such as physiochemical properties (e.g., their lipophilicity) and topological features (e.g., degree of branching) [5, 61. The term chemical space is commonly used in place of "multi-dimensional descriptor space" it is a region defined by a particular selection of molecular descriptors and the upper and lower values (limits) placed upon them [5,6]. In the context of small-molecule collections, chemical space is generally defined as the total descriptor space that encompasses all small carbon-based molecules that could, in principle, be created [5,6]. Each chemically unique small molecule will have a unique set of molecular properties and thus moleculardescriptorvalues,and will therefore reside at a discrete point in chemical space [5]. 

Krein MP, SukumarN (2011) Exploration ofthe topology of chemical spaces with network measures. J Phys Chem A 115 12905-12918... 

Ripphausen P, Nisius B, Wawer M, Bajorath J (2011) Rationalizing the role of SAR tolerance for ligand-based virtual sereening. J Chem Inf Model 51 837-842 Stumpfe D, Dimova D, Bajorath J (2014) Composition and topology of chemical spaces with network measures. J Chem InfModel 54 451-461... 

Thousands of numerical descriptors of molecular structure are known, and the number of possible property spaces is therefore unlimited. Recently, we showed that the chemical space of molecular quantum numbers (MQN), a set of 42 simple integer value descriptors counting atoms, bonds, polar groups and topological fea-... 

Chemical space. We used the Generated Database (GDB) as a proxy for cliemical space . I he GDB was obtained by exiiaustively enumerating all the possible topologies for molecules composed of only first-row elements (C, N, O and F), up to 11 nonliydrogen atoms, taking into account the stability, synthetic accessibility and dmg likeness of the resulting molecules. I he GDB contained 26,429,328 unique compounds widi no consideration of stereochemistiy. 

Frisch determines IPNs as topologically interpenetrating systems. According to Irzhak [25] the topological structure of a polymer is determined by the connectivity of the structural elements, and may be described as a graph independent of the real chemical and spatial structure and disposition of its elements in space. Topological knots are labile formations that reveal them-... 

The theory of atoms in molecules defines chemical properties such as bonds between atoms and atomic charges on the basis of the topology of the electron density p, characterized in terms of p itself, its gradient Vp, and the Laplacian of the electron density V p. The theory defines an atom as the region of space enclosed by a zero-/lMx surface the surface such that Vp n=0, indicating that there is no component of the gradient of the electron density perpendicular to the surface (n is a normal vector). The nucleus within the atom is a local maximum of the electron density. 

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