1. Lack of bioavailability Essential Metals in Biology Sea water (µM) Blood plasma (µM) Fe0.00122 Zn0.0117 Cu0.0048-24 Ni0.0080.04 Co0.000020.000025 Macro- and micronutrients Data adapted from Biological Inorganic Chemistry, Bertini, Gray, Stiefel, & Valentine, 2007 Problems to overcome: Too much of a good thing Wilson’s disease: Cu Accumulation in the eye This soup is too cold… This soup is too hot… www.ionicviper.org

2. Getting it “just right”: Transport and Storage: Iron This soup is just right… All of this trouble… begs the question, “why bother?” Iron scavengers- collecting iron from the environment Siderophores – Nature’s fabulous chelator Long- term storage (or short) Ferritin – the Fe storage protein Getting around Transferrin – the Fe transport protein www.ionicviper.org

3. Acid/Base Chemistry Activating Water to Make Potent Nucleophiles H+H+ H2OH2O HCO 3 - Figure generated from PDB file 1ZNC using Protein Workshop CO 2 www.ionicviper.org

4. Oxidation/Reduction Chemistry A Large Variety of Redox Potentials Potentials vs. NHE www.ionicviper.org

5. Structural Roles for Metals Ability to exceed octet Flexibility /Lability of structure Scaffolding for Protein folding What can metals get you that carbon can’t ? www.ionicviper.org