Solving 21st Century Problems in Biological Inorganic Chemistry Using Synthetic Models.

Abstract

N uses d-block elements to perform many functions. The ability of proteins to create environments that tune the redox and acid−base properties of these metal ions, control the pathways and timing by which substrates enter and products exit the active sites, and accelerate reaction rates far beyond what is attainable in the laboratory continues to amaze and confound chemists who try to emulate these achievements with synthetic models. Here are presented 26 Accounts that display a diverse array of studies of synthetic models that explore the ability of metal centers to activate small molecules like hydrogen and oxygen, of metal chemistry to report on biological signaling events such as those performed by nitric oxide, and of novel small molecule and protein based ligands designed to reveal the versatility of a metal ion to perform chemical tasks. Investigation of synthetic models is advantageous for determining the chemistry of metal ions in coordination environments that bear a close resemblance to those in a biological system in structure, spectroscopic features, and especially function. Ligand design involving the first or second coordination sphere, or both enables systematic variations to elucidate key factors that create special properties of the metal center at an active site. Ultimately, the goal is to generate systems able to effect biomimetic molecular transformations, learning in the process some of the tricks invented by nature to achieve what has otherwise seemed impossible. Bioinorganic principles are also employed for purposes beyond catalysis. These may include the development of sensors for metals or small molecules, tools to report on biological signaling agents, and drug development. Models are essential in the scientific method. In bioinorganic model chemistry, the goal is to represent the biological environment of the metal with a synthetic mimic of what biopolymers have created. As a synthetic chemist, the design of ligands with a specific architecture and the utilization of organic chemistry methodology to synthesize them is the heart of this enterprise. The ligand defines the coordination sphere, bringing control to the intrinsic kinetic and thermodynamic properties of metal ions in their various oxidation states in solvents ranging from noncoordinating hydrocarbons to water. The ligand used in these bioinorganic studies replaces protein residues surrounding a metalloprotein active site. The goal is to achieve the physical properties, chemistry, and functions of the natural systems in a manner to elucidate some of the secrets by which nature manages the seemingly impossible. The 26 Accounts in this special issue come from research laboratories around that world that are very active in bioinorganic modeling via synthesis. Still, they represent only a fraction of the work currently being undertaken. Late 20th and 21st century advancements, such as those in structural methodology, spectroscopy, theory and computation, and experimental procedures, have provided greater information on living systems and thus about how chemical transformations that are very difficult to carry out in the laboratory occur in biology. Directly related to this topic are the recently highlighted societal concerns in the sphere of energy, which have helped to focus activity on chemistry for the public good. Consider the perhaps most important chemical reactions of societal interest; these include dioxygen reduction (the fuel cell reaction), water oxidation to O2, carbon dioxide reduction to give potential fuels as products, water (proton) reduction giving dihydrogen, hydrocarbon functionalization (e.g., methane to methanol conversion), and nitrogen fixation (nitrogen reduction to ammonia). Every one of these reactions occurs in nature and involves metalloenzyme active sites. Of related interest is that in a quite recent discovery, certain copper enzymes are found to be capable of the oxidative breakdown of biomass, polysaccharides, and chitins. The Accounts in this special issue cover many of the important topics discussed above. Among the small molecules whose “activation” or transformations are discussed are molecular oxygen (O2) and its reduced derivatives, dihydrogen, water, hydrogen sulfide (H2S), dinitrogen, and several nitrogen oxides, that is, nitric oxide (NO, nitrogen monoxide), nitrite ion, and HNO (nitroxyl). The metal ions discussed include Fe, Cu, Co, Mn, Ni, and Ru, the latter in connection with the process of water oxidation or in anticancer drug development. We hope the readers of these Accounts will find the range of subjects to be of great interest and hold the excitement of the field of synthetic biological inorganic chemistry, which we ourselves share. Kenneth D. Karlin, Guest Editor Johns Hopkins University Stephen J. Lippard, Guest Editor Massachusetts Institute of Technology Joan S. Valentine, Guest Editor University of California, Los Angeles Cynthia J. Burrows, Editor University of Utah

DOI: 10.1021/acs.accounts.5b00447

Cite this paper

@article{Karlin2015Solving2C, title={Solving 21st Century Problems in Biological Inorganic Chemistry Using Synthetic Models.}, author={Kenneth D Karlin and Stephen J Lippard and Joan Selverstone Valentine and Cynthia J Burrows}, journal={Accounts of chemical research}, year={2015}, volume={48 10}, pages={2659-60} }