Bond-centered fragments

A tremendous number of various fragments are used in structure-property studies atoms, bonds, topological torsions , chains, cycles, atom- and bond-centered fragments, maximum common substructures, line notation (WLN and SMILES) fragments, atom pairs and topological multiplets, substituents and molecular frameworks, basic subgraphs, etc. Their detailed description is given below. 

However, one of the most successfiil approaches to systematically encoding substructures for NMR spectrum prediction was introduced quite some time ago by Bremser [9]. He used the so-called HOSE (Hierarchical Organization of Spherical Environments) code to describe structures. As mentioned above, the chemical shift value of a carbon atom is basically influenced by the chemical environment of the atom. The HOSE code describes the environment of an atom in several virtual spheres - see Figure 10.2-1. It uses spherical layers (or levels) around the atom to define the chemical environment. The first layer is defined by all the atoms that are one bond away from the central atom, the second layer includes the atoms within the two-bond distance, and so on. This idea can be described as an atom center fragment (ACF) concept, which has been addressed by several other authors in different approaches [19-21]. 

A wide range of thermochemical properties can be measured, including not only proton affinity or gas-phase basicity, but also electron affinity, ionization energy, gas-phase acidity and cation affinity Entropy changes upon attachment of an ion to a molecule are also accessible and provide information on both the nature of the bonding and fragmentation mechanisms in cluster ions, especially in biological compounds. Thermochemical determinations by the kinetic method also provide very useful structural information e.g., two-electron three-center bond has been observed in the gas phase by means of the kinetic method. " In the last years, the kinetic method has been also applied to characterize chiral ions in the gas phase. 

An ene reaction is a concerted intramolecular rearrangement in which a hydrogen atom transfer to a Ti-bond center is accompanied simultaneously by a 7i-bond development, a Ji-bond migration, and a decomposition of the reactant into two unsaturated molecular fragments. The general skeletal transformation is illustrated below... 

Finally, there are examples of a so-called seven center fragmentation (equation 6) which can lead to four fragments depending on the bonding situation. 

ACF = atom-centered fragment AI = artificial intelligence BAM = bond adjacency matrix CHEMICS = combined handling elucidation method for interpretable chemical structures COSY = correlated spectroscopy FBMX = free-bond connection matrix HMBC = heteronuclear multiple bond correlation spectroscopy HMQC = heteronuclear multiple quantum coherence correlation spectroscopy SESAMI = systematic elucidation of structure applying machine intelligence. 

The CISOC-SES system is also structure-reduction based and shares some similarities with the approach described above for COCOA. The procedure also uses a bond adjacency matrix - the free-bond connection matrix - to represent the bonding possibilities between non-hydrogen atoms. However, in contrast to COCOA, individual half-bonds of element groups are not specified in the matrix, only the number of equivalent free bonds, i.e., all possible hybridizations of an element group consistent with the number of free bonds are allowed. The program also utilizes a single-layered, spherical atom-centered fragment in structure reduction and can accept user-entered constraints. 

An enhancement of the simple substructure approach is the Fragment Reduced to an Environment that is Limited (FREL) method introduced by Dubois et al. [7] With the FREL method several centers of the molecule are described, including their chemical environment. By taking the elements H, C, N, O, and halogens into account and combining all bond types (single, double, triple, aromatic), the authors found descriptors for 43 different FREL centers that can be used to characterize a molecule. 

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