Computer-aided design of host molecules for recognition of organic guests

This paper presents an overview of a computational approach to design molecular host architectures. After positioning donor groups about a targeted guest molecule, the donor groups are connected with hydrocarbon linkages taken from an extensive database of molecular fragments. Initial ranking of the host structures is based on how well bond vectors on the donor groups match bond vectors on the linkages. The top candidates are then subjected to further evaluation with molecular mechanics identifying host architectures that are both complementary and preorganized for binding the guest. The efficacy of this computer-aided design methodology is illustrated with a search for hydrogen bonding receptors that are structurally organized for complexation with oxygen mustard. (C) 2013 Elsevier B.V. All rights reserved.