Biological molecules, containing metals

FIGURE 1-11 Biological Molecules Containing Metal Ions, (a) Chlorophyll a, the active agent in photosynthesis, (b) Vitamin B12 coenzyme, a naturally occurring organometallic compound. 

Many biological molecules contain iron and Mossbauer spectroscopy is a useful tool for the study of proteins and enzymes. The measurement of the magnetic properties of transition metal elements in biological molecules by MS, NMR and EPR is an important way of characterizing the electronic state of the metal ion, and hence of providing a clue to the structure and function of the molecule. Mossbauer spectroscopy may be used to study their chemical state and bonding and to obtain qualitative data on the local structure and symmetry in their neighbourhood. 

On the other hand, as biological molecules become larger their tendency to be associated with water molecules, metal ions, and other materials increases. Crystalline proteins, for example, routinely contain 27-65 % of the solvent used for their crystallisation 183). Such associated materials may be difficult to locate by crystallography and it may become a question of terminology whether such molecules should be regarded as inclusion complexes, non-specific aggregates, or merely contaminated biomolecules. 

Although there has heen a great deal of research concerning how platinum(II) complexes hind to biological molecules and the hkely mechanism of antitumor activity of these platinum-containing species, far less attention has heen paid to the properties of other metal complexes in this arena. Recent attention has fallen on cohalt(II)-Schiff hase complexes, as several have heen discovered to have promise as antiviral agents. A review of recent work has appeared elsewhere [64], so the topic will not he covered here however, in addition to focusing on recent developments, emphasis is placed on the introduction of the new head unit, 3,6-diformylpyridazine (13), into Schiff-hase macrocyclic electrochemistry. 

The NMR investigations involved studies of the spectra of ferro-cytochrom.es c, ferricytochromes c, and the complexes with cyanide ion. For the interpretation of the data it was particularly important that methionine is the only potential hemochrome-forming amino acid which contains a methyl group. Since some of the arguments used might also apply to NMR studies of metal-ion coordination in other biological molecules a rather detailed account of these experiments is presented. 

A model of a flavin-based redox enzyme was prepared.[15] Redox enzymes are often flavoproteins containing flavin cofactors flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN). They mediate one- or two-electron redox processes at potentials which vary in a range of more than 500 mV. The redox properties of the flavin part must be therefore tuned by the apoenzyme to ensure the specific function of the enzyme. Influence by hydrogen bonding, aromatic stacking, dipole interactions and steric effects have been so far observed in biological systems, but coordination to metal site has never been found before. Nevertheless, the importance of such interactions for functions and structure of other biological molecules make this a conceivable scenario. 

Introduction of external chemical contamination from the sampling devices into the sample should be avoided because binding of metals to biological molecules is possible in vitro, and this can change the distribution of metal-containing species in the sample. Heavy metal contaminants could cause protein precipitation as well as irreversible deactivation of enzymes. 

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