Atom-centered fragments

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]. 

Atom-Centered Fragments (ACE) consist of a single central atom surrounded by one or several shells of atoms separated from the central one by the same topological distance. This type of structural fragments was introduced in the early 1950s by Tatevskii, " and then by Benson to predict some physicochemical properties of organic compounds in the framework of additive schemes. 

Edge adjacency indices 107 18 Atom-centered fragments 120... 

The software program SMILOGP for the calculation of log P is based on the Broto-Moreau-Vandycke hydrophobic constants and the SMILES notation for the recognition of molecule atom-centered fragments [Convard, Dubost et al., 1994]. 

A smaller set of atom-centered fragments was later proposed to avoid ambiguity sometimes occurring in atom-type assignment. It is comprehensive for the common elements in organic molecules, and also includes metals and noble gases [Wildman and Crippen, 1999]. 

Other atom-centered fragments were proposed on the basis of different sets of rules and mainly used in —> group contrifowtion methods for estimation of molecular properties such as lipophilicity and —> molar refractivity [Ghose and Crippen, 1986 Viswanadhan, Ghose et al, 1989 Mekenyan, Bonchev et al, 1987 Meylan, Howard et al, 1992 Lohninger, 1994 Baumann and Glerc, 1997 Wildman and Crippen, 1999]. 

The use of atom-centered fragments and related descriptors greatly increases the specific chemical information concerning different functional groups, but carmot discriminate between different arrangements of functional groups within a molecule. 

Chemical structures can be described by binary molecular descriptors (used as the Y-matrix in multivariate data analysis). In the case of yes/no-classifications a single binary y-variable can be used to indicate whether a particular structural property is present or not. The type of molecular descriptors (small or large fragments, atom-centered fragments, functional groups or classes of compounds) is essential to obtain a close relationship between structures and spectra. 

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 interpretive library search is limited either to the retrieval of predefined substructures (either a set identified by the chemist or a set of atom-centered fragments present in the compounds of the library) or to any multi-atom substructure contained in compounds of the library. In the case of predefined substructures, chemical shift ranges for all or some of its carbon atoms must be established. 

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. 

CASE = computer-assisted structure elucidation CHEM-ICS = combined handling of elucidation methods for interpretable chemical structures COCOA = constrained combination of atom-centered fragments CONGEN = constrained structure generator. 

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