Topology-based electronic descriptor

Moreover, atom-type -state indices were proposed as molecular descriptors encoding topological and electronic information related to particular atom types in the molecule [Hall and Kier, 1995a Hall et al., 1995b]. They are calculated by summing the -state values of all atoms of the same atom type in the molecule. Each atom type is first defined by atom identity, based on the atomic number Z, and valence state, itself identified by the valence state indicator (VST) defined as ... 

MODEL Molecular Descriptor Lab (MODEL) (http //jing.cz3.nus.edu.sg/ cgi-bin/model/model.cgi) is a free Web-based server for computing a comprehensive set of 3778 molecular descriptors, which can be divided into 6 classes constitutional descriptors, electronic descriptors, physical chemistry properties, topological indexes, geometrical molecular descriptors, and quantum chemistry descriptors [73], Compounds can be provided to the server in various molecular formats such as PDB, MDL, MOL2, and COR, and the computed molecular descriptors are displayed in a few seconds or less. Cross-links to the relevant sections of the reference manual page are also provided for some of the descriptors and descriptor classes. 

TDB-electronic descriptors autocorrelation descriptors (0 3D-topological distance based descriptors)... 

Atom-type designations in atom-pairs have constitutional, topological, and electronic character - atoms of the same type share atomic identity, the same number of non-hydrogen bonding partners, and the same number of bonding n electrons (Fig. 13.1-4(b)). Because of this representation, molecules tend to have many, fewer than the theoretical maximum possible, atom-pairs (1/2 [n (n—l)]2 for a molecule with n atoms), both by virtue of having multiple atoms of the same type, and because the order of the two atoms appearance within an atom-pair is not important (Fig. 13.1-4(c)). A very significant aspect of the definition of atom-types is that Carhart et al. provided both a distance metric and a normalized similarity score for molecules based on the atom-pair definition (Fig. 13.1-4(d)). Formally, such a provision is a requirement for any metric descriptor space intended to afford a basis for comparison of molecular... 

Log P and MR are considered thermodynamic descriptors, pR a combined thermodynamic and electronic index, and a an electronic property index, E is designed to account for steric effects. Corrections for non-additivity, based upon the chemical bonding topology, have been suggested and used. These include proximity, bond type, ring, and group shape correction features. (8-10)... 

ADMET Predictor Constitutional, functional group counts, topological, E-state, Moriguchi descriptors, Meylan flags, molecular patterns, electronic properties, 3D descriptors, hydrogen bonding, acid-base ionization, empirical estimates of quantum descriptors 297... 

Helguera-Morales et al. [83] used a topological sub-structural molecular design (TOPS-MODE) approach to predict the carcinogenicity of 48 nitro-aromatic compounds in female rodents. Topological descriptors are derived mainly from knowledge of the connectivity between atoms within a molecule, and are based to some extent on information on atom types and their electronic environment. The model was able to describe 79.1% of the experimental data. It was found that the carcinogenic activity of the compounds analyzed increases in the presence of a primary... 

Although various computational approaches for the prediction of intestinal drug permeability and solubility have been reported [219], recent computer-based absorption models utilize a large number of topological, electronic, and geometric descriptors in an effort to take both aqueous drug solubility and permeability into account. Thus, descriptors of partitioned total surface areas [168], Abraham molecular descriptors [220,221], and a variety of structural descriptors in combination with neural networks [222] have been shown to be determinants of oral drug absorption. 

Bauknecht et al. [48] and Sadowski et al. [49] have also developed molecular descriptors that are based on the physicochemical properties of the atoms in a molecule. They calculate several different electronic properties for each atom in a molecule and then use autocorrelation to generate a fixed-length vector that is independent of the size of the molecule. Autocorrelation was first applied to the topology of a molecular structure by Moreau and Broto [50] using the following function ... 

These descriptors can vary in complexity from simple atom counts to electronic properties derived from high-level ab initio calculations. Available molecular descriptors fall into three broad categories (1) Two-dimensional, encoding the topology of a molecule. (2) Three-dimensional, based on the 3D structure of a molecule. (3) Physicochemical (and electronic) representing whole molecule properties. 

Yalkowsky and Banerjee have pubhshed an extensive review of methods for estimating aqueous water solubility of organic compounds. Many methods have been developed based on measured properties such as partition coefficients, chromatographic parameters, and activity coefficients. " Purely in silico methods are based on LFER, and a variety of geometric, electronic, and topological molecular descriptors. ... 

Quantitative structure-activity relationship (QSAR) dates back to the nineteenth century and is a computer-based tool that attempts to correlate variations in structural or molecular properties of compounds with their biological activities. These physicochemical descriptors, which include parameters to account for hydrophobicity, topology, electronic properties, and steric effects, are determined empirically or, more recently, by computational methods. The premise is that the structure of a chemical determines the physiochemical properties and reactivities that underlie its biological and toxicological properties. Being able to predict potential adverse effects not only aids in the designed development of new chemicals but also reduces the need for animal testing. It may ultimately or potentially lead to better... 

These works established the existence of a novel variety of electron pair in DRAs. Extensions of traditional electron pair concepts are clearly needed for these anions. The electron localization function (ELF) 19 is an interesting and robust descriptor of chemical bonding, which has been successfully applied to a wide variety of molecular systems.20-24 This function, which is based on a topological analysis of a quantum function related to Pauli repulsion, describes the degree of localization (or delocalization) of electron pairs within the molecular space. 

Another set of topological descriptors is the electrotopological state indices (E-state indices) developed by Kier and Hall [26, 27]. These descriptors are based on the topological state of a particular atom with corrections for electronic interactions due to other atoms in the structure. This methodology originally devised for nonhydrogen atoms only has been extended to also include E-state indices for hydrogen atoms [28] and to also include atom-type E-state indices, for... 

The two considered atoms need not be directly connected and the separation can be the topological distance between them [Carhart, Smith et al., 1985] these descriptors are usually called topological atom pairs being based on the topological representation of the molecules. Atom type is defined by the element itself, the number of heavy-atom cormections and number of 7t electron pairs on each atom. 

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