Development of Structure Information from Molecular Topology for Modeling Chemical and Biological Properties: A Tribute to the Creativity of Lemont Burwell Kier on his 80th Birthday

Lowell      H. Hall

doi:10.2174/157340912800492393

Abstract

This review is a salute to Monty Kier’s creativity. Emphasis is placed on creative aspects in the development of the representation of molecular topological structure information and the resultant formalisms: molecular connectivity and electrotopological state (E-State). Less attention is given to detailed analysis of individual papers and the generally well known books and book chapters. This discussion reveals creative paths that led to the concept of the atomic descriptors, simple connectivity delta, encoding local topology, and valence delta value which encodes valence electron information. The fundamental developments that led to the creation of molecular connectivity chi indices are described along with extensions to different chi and delta chi formalisms. Continued thinking about structure in the topological sense led to the development of the only valence state electronegativity formalism based entirely on structure, Kier-Hall electronegativity (KHE). That creation further inspired the development of the electronegativity/topology-based atomic intrinsic state along with perturbation terms that together give electrotopological state indices (E-State). Further creation led to atom and bond type E-State descriptors. All these developments are briefly illustrated with examples in QSAR, chemical similarity, and database searching.

Keywords: Electrotopological state, molecular connectivity, molecular similarity, molecular topology, QSAR, structure information representation (SIR), valence state electronegativity, Kier-Hall electronegativity, acetylcholine antagonists, atom descriptors