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Medicinal Inorganic Chemistry: Ligand Design Objectives and Principles

  1. Katherine H. Thompson

Published Online: 15 DEC 2011

DOI: 10.1002/9781119951438.eibc0365

Encyclopedia of Inorganic and Bioinorganic Chemistry

Encyclopedia of Inorganic and Bioinorganic Chemistry

How to Cite

Thompson, K. H. 2011. Medicinal Inorganic Chemistry: Ligand Design Objectives and Principles. Encyclopedia of Inorganic and Bioinorganic Chemistry. .

Author Information

  1. University of British Columbia, Vancouver, BC, Canada

Publication History

  1. Published Online: 15 DEC 2011

Abstract

Metal-based pharmaceutical agents are composed of one or more metal ions and at least one ligand. Additional molecular substituents may include targeting moieties, linking groups, antioxidants, or pendant carbohydrates, or some combination of these. There are two main applications of metal-based pharmaceutical agents: diagnostic and therapeutic. Ligand requirements for the two streams of development differ in some important ways, but are still based on the same basic principles for molecular design, including consideration of thermodynamic and hydrolytic stability, pharmacokinetics, molecular weight and charge, lipophilicity and hydrophilicity, aqueous solubility, functional groups, and ligand nontoxicity (sometimes achieved by using naturally occurring binding groups). Examples of the principles that are discussed in this article include Gd(III)-based magnetic resonance imaging (MRI) contrast agents, Cu(II)-clotrimazole, proposed as an antiparasitic agent, 67 Ga-citrate for tumor imaging, and 99 mTc(I)-sestamibi for cardiac imaging.

Keywords:

  • ligand;
  • chelation;
  • metallodiagnostic;
  • metallotherapeutic;
  • lanthanide;
  • gallium citrate;
  • membrane permeability;
  • oxidation state;
  • lipophilicity;
  • multifunctionality;
  • synergy