Bioinorganic Chemistry

GENERAL I ARTICLE Coordination Chemistry of Life Processes: Bioinorganic Chemistry R N Mukherjee Many enzymes and proteins have metal ions at their active sites that play key roles in catalysis. An important goal of an interdisciplinary field like bioinorganic chem istry is the development of small inorganic coordination complexes that not only reproduce structural and spec troscopic features, but also function in a manner similar to their natural counterparts. To highlight this burgeon The author is a Professor at the Department of ing field, some selected results on synthetic modelling of Chemistry, liT, Kanpur. (i) the electronic structure of manganese cluster of pho His major research tosystem II and (ii) functional modelling of the dinuclear interests include copper enzyme tyrosinase are described in this article. synthetic modelling of molecular Preamble and electronic structural and functional aspects of A Chakravorty has portrayed the life of Alfred Werner, the inven dinuc1ear iron, manga nese and copper tor of coordination theory, in this issue. Needless to say that containing today's inorganic chemistry research cen tres around Werner's co metalloproteins/enzymes ordination theory. Therefore it would be most appropriate to highlight how the discovery of structure and bonding ofcoordina tion compounds finds its expressi<?n in enriching our understand ing of the inorganic chemistry oflife processes. It is now well known that many inorganic elements and their compounds are essential or beneficial for life on earth. Organic compounds are of course essential, because they provide organ isms with such essential compounds as proteins, nuc1eotides, car bohydrates, vitamins and so forth. Inorganic compounds, particu larly metallic ions and complexes, are essential cofactors in a vari ety of enzymes and proteins. They provide essential services that cannot be or can only poorly be rendered by organic compounds. The roles played by essential inorganic elements and compounds are (i) structural, (ii) carrying and transporting electrons and oxygen, -R-ES-O-N-A-N-C-E--I-s-e-Pt-e-m-b-e-r--1-9-99---------~~-----------------------------53- GENERAL I ARTICLE Suggested Reading (iii) catalytic roles in oxidation-reduction (including oxygenation) re [1] J A Ibers and R H Holm, actions and (iv) catalytic roles in acid-base and other reactions. It has Science, 209, 223-235, also been known for a long time that excesses of these elements can 1980. [2] Bioinorganic Chemistry be very dangerous. In fact, a narrow concentration window exists -State of the Art, J. Chem. for most of the so-called trace elements. Educ., 62, 916-1001, 1985. [3] Bioinorganic Chemistry, Scie.nce,261,699.730,1993. Bioinorganic chemistry is a leading discipline at the interface of chem [4] S J Lippard and J M Berg, istry and biology. The field is undergoing a phase of explosive Principles of Bioinorganic Chemistry, University Sci growth, partly because of exposure and insights obtained by in ence Books 1995; Panima creasing numbers of metalloenzyme X-ray structures. There are Publishing Corporation: New Delhi, Bangalore three major avenues of investigation in bioinorganic chemistry. (First Indian Reprint, 1997). The first involves direct study of the structure and function of [5) Bioinorganic Enzymology 'metallobiomolecules', an area which is traditionally that of a bio (Guest Editors: R H Holm and E I Solomon), Chem. chemist. The second major avenue involves an indirect approach, Rev., 96, 2239-3042, 1996. commonly the domain of the inorganic or organic chemists. The [6] W Riittinger and G C Dismukes, Chem. Rev., 97, third involves the addition of metal ions or complexes as probes to 1-24, 1997. biochemical structure and function. [7] C W Hoganson and G T Babcock, Science, 277, 1953-1956, 1997. Similarity with Werner-type Coordination Com [8] C Tommos and G T plexes Babcock, Ace. Chem. Res., 31, 18-25, 1998. [9] J Limburg, V A Szalai and Intuitively, one can anticipate that the behaviour of metal ions in G W Brudvig,]. Chem. Soc., proteins cannot be vastly different from that governed by the Dalton Trans., 1353-1361, 1999. fundamental chemistry of the particular metal. The synthetic ana [10] G Blondin, R Davydov, C logue approach, the primary focus of this article, is based on the Philouze, M-F Charlot, S Styring, B Akemark, J-J premise that the chemistry of the metal-binding site ('active site') Girerd and A Boussac, ]. is dependent, for the most part, on the immediate coordination Chern. Soc., Dalton Trans., 4069-4074, 1997. environment of the metal ion. For most metalloproteins, the [11] T K Lal and R N Mu immediate coordination environment consists of donors from the kherjee, lnorg. Chem., 37, 2373-2382, 1998 and ref side-chains of amino acids. Sometimes, a prosthetic group (e.g., a erences therein. porphyrin ring) completes the coordination sphere of the metal [12] N Kitajima and Y Moro oka, Chem. Rev., 94, 737- ion. Thus it could be generalised that the 'metallo-biomolecules' 757, 1994. are highly elaborated coordination complexes whose metal-con [13] K D Karlin and Z Tyeklar, Adv. lnorg. Biochem., 9, taining sites (coordination units), comprising one or more metal 123- 172, 1993. atoms and their ligands, are usually the loci of electron transfer, [14] D Ghosh and R N Mukher jee,lnorg. Chern., 37, 6597- binding of exogenous molecules and catalysis. Two major factors 6605, 1998. control the properties of metal ions in biological systems: (i) the stereochemistry of the metal site and the nature of the ligands 54--------~------- RESONANCE I September 1999 GENERAL I ARTICLE attached to the metal and (ii) the protein environment, which Two major factors plays a crucial role in controlling the reactivity of the metal site. In control the some cases the protein can force metal ions into unusual geom properties of metal etries; the protein environment may be the determining factor ions in biological controlling the activity of the increasing number of functionally systems: (i) the distinct metalloproteins that have essentially identical metal cen stereochemistry of tres. From the aforesaid discussion, it is understandable that the metal site and inorganic chemists can contribute considerably to the under the nature of the standing of the structural, electronic and mechanistic aspects of ligands attached to metal ions in metalloproteins, by syn thesizing small coordination the metal and (ii) compounds, which mimic the specific properties of those metal the protein sites. These synthetic models are usually intended to serve as environment, stereochemical and electronic analogues of these sites and have which plays a the substantial advantage of being amenable to characterization crucial role in at a very high level of detail. In fact, these synthetic models could controlling the be used to investigate the effects of systematic variations in coor reactivity of the dination geometry, ligand, local environment and other factors. metal site. Simultaneous attainment of biological structure and function in a synthetic system has proven more difficult. The problem be comes more demanding when catalysis is involved. The purpose of models is not necessarily to duplicate natural properties but to sharpen or focus certain questions. A synergistic approach (Fig ure 1) to the study of metalloproteins can and has provided in sights that cannot be easily attained from protein studies. In this article, the present day views on the functioning of two metalloenzymes,photosystem II and tyrosinase, are discussed. The Figure 1. The synergistic important concepts of coordination chemistry have been pointed relationship between stud out. Many unfulfilled goals and current attempts to chemically ies involving metalloprotein duplicate such properties are also highlighted. biochemistry and inorganic modelling. Photosynthesis Human beings require reduced organic com pounds - carbohydrates, fats and protein - as a Synthetic models Metalloprotelns food source. Stored in these molecules is a great amount of useful energy. Humans can tap the /l'---__----ll \ establish relevant Active site energy from these food sources and can use it to coordination chemistry -R-ES-O-N-A-N--CE--I-s-e-p-te-m-b-e-r---19-9-9---------~----------------------------------" GENERAl. I ARTICl.E Figure2. A cycleofdioxygen metabolism that is critical to both plant and animal life ~ on earth. 2 ~.---\__ -,-- __o_rg--..,.c products + 0 1 I Aerobic ",spiration L C02 + H20 .---J build up their own complex molecules, to move about, to sense the environment and to keep warm. Without this input ofenergy, they would soon die. Fortunately, this external source of energy does grow on trees and elsewhere. However, plants do not ingest large fuel molecules themselves, but are capable of synthesizing glucose and other such molecules from CO2 and H20, which are waste products of animal metabolism. However, a large increase in free energy (a positive flG) is required for the production of glucose and oxygen. This endergonic process is accomplished through the use of an external energy source - sunlight. Plants release 02 as a by-product of the splitting of water (Figure 2). Photosynthesis is the system of reactions by which green plants, blue-green algae and some cyanobacteria capture solar energy, convert it to chemical energy and use this energy in the reduction of CO 2 to carbohydrates. Most of the oxygen in the atmosphere, which supports aerobic life on earth, is generated by the photo induced oxidation of water to dioxygen: (1) Through photosynthesis, energy-poor compounds such as CO2 and H20 are converted to energy-rich compounds, carbohydrates and Oz. The overall process in photosynthesis is expressed as 6CO 6H O --+- 60 (2) z + z + light C6H 1Z0 6 (glucose) + z' Photosynthesis can be divided into three steps: 1) Light collection. via chlorophyll and other pigments and con- 56--------~-------- RESONANCE I September 1999 GENERAL I ARTICLE veying the energy to a reaction centre. The absorption of light energy by 2) The oxidation of HzO to 0z leads to a series of reactions that photosynthetic generate biological energy in the form of ATP and the reduction pigments, the ofNADP+ to NADPH.

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