Novel Chirality Descriptors Derived from Molecular Topology

Abstract

Several series of novel chirality descriptors of chemical organic molecules have been introduced. The descriptors have been developed on the basis of conventional topological descriptors of molecular graphs. They include modified molecular connectivity indices, Zagreb group indices, extended connectivity, overall connectivity, and topological charge indices. These modified descriptors make use of an additional term called chirality correction, which is added to the vertex degrees of asymmetric atoms in a molecular graph. Chirality descriptors can be real or complex numbers. Advantages and drawbacks of different series of chirality descriptors are discussed. These descriptors circumvent the inability of conventional topological indices to distinguish chiral or enantiomeric isomers, which so far has been the major drawback of 2D descriptors as compared to true 3D descriptors (e.g., shape, molecular fields) of molecular structure. These novel chirality descriptors have been implemented in a quantitative structure-activity releationship (QSAR) study of a set of ecdysteroids with a high content of chiral and enantiomeric compounds using the k nearest neighbor QSAR method (kNN) recently developed in this laboratory. We show that the results of this study compare favorably with those obtained with the comparative molecular field analysis (CoMFA) applied to the same dataset. The novel chirality descriptors of molecular structure should find their applications in QSAR studies and related investigations of molecular sdatasets.

Combinatorial QSAR of Ambergris Fragrance Compounds

“…Low prediction accuracy of all models built with CMTD descriptors can be explained by the fact that they require exhaustive calculations with different chirality correction values and different subclasses of descriptors, as it was described in our previous papers. 27 …”

“…Therefore, there is a challenge in the pharmaceutical, biochemical, and theoretical chemistry to develop predictive QSAR models for stereoisomers. [27][28][29] Herein, we report on the development of robust QSAR models of 98 ambergris-type compounds of different structural types with known stereochemistry (Table 1). In the majority of previously reported studies the QSAR models are typically generated with a single modeling technique, frequently lacking external validation.…”

“…27 CoMMA descriptors were used in combination with MOE descriptors. MolconnZ descriptors were used in combination with chirality descriptors.…”

Chemical Structure Indices in In Silico Molecular Design

“…They have been investigated in a QSAR study of some 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors [92]. Golbraikh et al have introduced several new chirality descriptors starting from the modified Zagreb group index, connectivity indices and topological charge indices with the use of an additional term called chirality correction to vertex degrees of asymmetric atoms in a molecular graph [93]. They extended this approach to compute topological indices to distinguish between Z and E isomers [94].…”

AN IMPROVED TOPOLOGICAL DESCRIPTOR EDm AND ITS APPLICATION

“…More and more attention has been given to develop new topological descriptors adapted to cis/trans isomers [35][36][37][38][39] . Chenzhong Cao and Hua Yuan presented the modified vertex degree-distance index (MVDI) and modified edge degree-distance index (MEDI), and used them together with the odd-even index (OEI) and the number of carbon atoms (N) to characterize the molecular structural information for the cis-and transisomers of alkenes 35 .…”