skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: De novo structure-based design of bisurea hosts for tetrahedral oxyanion guests

Abstract

This paper presents a computational approach to the deliberate design of improved host architectures. De novo molecule building software, HostDesigner, is interfaced with molecular mechanics software, GMMX, providing a tool for generating and screening millions of potential structures. The efficacy of this computer-aided design methodology is illustrated with a search for bis-urea podands that are structurally organized for complexation with tetrahedral oxyanions.

Authors:
;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
878261
Report Number(s):
PNNL-SA-46785
Journal ID: ISSN 0002-7863; JACSAT; 16305; 830403000; TRN: US200611%%70
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of the American Chemical Society; Journal Volume: 128; Journal Issue: 6
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; COMPUTER-AIDED DESIGN; DESIGN; CHEMISTRY; De novo; dis-urea podands; tetrahedral oxyanions; Environmental Molecular Sciences Laboratory

Citation Formats

Bryantsev, Vyacheslav, and Hay, Benjamin P. De novo structure-based design of bisurea hosts for tetrahedral oxyanion guests. United States: N. p., 2006. Web. doi:10.1021/ja056699w.
Bryantsev, Vyacheslav, & Hay, Benjamin P. De novo structure-based design of bisurea hosts for tetrahedral oxyanion guests. United States. doi:10.1021/ja056699w.
Bryantsev, Vyacheslav, and Hay, Benjamin P. Wed . "De novo structure-based design of bisurea hosts for tetrahedral oxyanion guests". United States. doi:10.1021/ja056699w.
@article{osti_878261,
title = {De novo structure-based design of bisurea hosts for tetrahedral oxyanion guests},
author = {Bryantsev, Vyacheslav and Hay, Benjamin P.},
abstractNote = {This paper presents a computational approach to the deliberate design of improved host architectures. De novo molecule building software, HostDesigner, is interfaced with molecular mechanics software, GMMX, providing a tool for generating and screening millions of potential structures. The efficacy of this computer-aided design methodology is illustrated with a search for bis-urea podands that are structurally organized for complexation with tetrahedral oxyanions.},
doi = {10.1021/ja056699w},
journal = {Journal of the American Chemical Society},
number = 6,
volume = 128,
place = {United States},
year = {Wed Feb 15 00:00:00 EST 2006},
month = {Wed Feb 15 00:00:00 EST 2006}
}
  • This paper presents a computational approach to the deliberate design of improved host architectures. The approach, which involves the use of computer-aided design software, is illustrated by application to cation hosts containing multiple aliphatic ether oxygen binding sites. De novo molecule building software, HostDesigner, is interfaced with molecular mechanics software, GMMX, providing a tool for generating and screening millions of potential bidentate building block structures. Enhanced cation binding affinity can be achieved when highly organized building blocks are used to construct macrocyclic hosts.
  • This tutorial review presents an account of how de novo structure-based design methods have been used to facilitate the discovery of novel anion receptors formed by combination of hydrogen bond donor groups. Topics include the development of criteria needed for the design, how the input structures for each design were obtained, and subsequent use of molecular modeling to more accurately rank the initial list of candidates produced by the builder. The effectiveness of the design approach is illustrated in several cases where host molecules identified on the computer were subsequently synthesized and shown to function as efficient anion hosts.
  • The origins, definitions, tools, and guiding principles of host-guest chemistry are developed. Perching, nesting, and capsular complexes are exemplified through molecular model and crystal structure comparisons. The degree of preorganization of a host for binding is a central determinant of its binding power. Complementarity of binding site placement in host and guest is a central determinant of structural recognition in complexation. Examples are given of chiral recognition in complexation, of partial transacylase mimics, of caviplexes, and of a synthetic molecular cell. 54 references, 6 figures.