Metal Complexation with Biological Molecules

One of the major ways in which metals interact with biological molecules is via complexation. The formation of metal complexes can be described by this simple equilibrium equation  

How Does the Nature of the Metal Ion Influence Complexation If the metal-ligand complex is the result of electrostatic attraction between the metal ion and the ligand, then both charge and metal ion size are influential. For example, the stability constants (KM]) for phosphate complexes are as follows  

the charge density of the metal ion plays a pivotal role in the stability constants. The first series contains metal ions of similar size but different charges, while the ions in the second series increase with size from Mg2+ to Ba2+. In both cases, ions with higher charge densities form stronger complexes. Sometimes ions with similar sizes and charge densities can be transported by the same transport proteins. For example, Cd2+ (0.97 A) can be transported via Ca2+ (0.99 A) channels. 

Not all complexes are purely electrostatic. In fact, many metal complexes in biological systems have covalent interactions as well. In these cases, the ligand donates a pair of electrons (acting as a Lewis base) to the metal, which functions as a Lewis acid. Therefore, metals can be evaluated based on their abilities to accept electron pairs. Alkali metal ions (Na+, K+) and alkaline earth metals (Mg2+, Ca2+) tend to not form stable complexes with Lewis base ligands. Transition metal ions, particularly those with vacant ri-orbitals, will form more stable complexes with Lewis base-acting ligands. 

A Note about Chelation Therapies. Chelation therapies are used to prevent or treat metal-induced toxicities. They are often used in acute poisoning scenarios, but can also be used to assess exposure. One of the major challenges in the management of chelation therapies is the tendency for chelating agents to interact with essential metals, particularly calcium and zinc. Chelation therapies should only be administered by a physician due to the potential to disrupt essential metal functions. The Food and Drug Administration does not regulate dietary supplements, and several do it yourself chelation therapies are available. These are not advisable. 

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On the other hand, the interaction of metal complexes with biological molecules can be used as an approach to improve their anticancer activity. Most biological molecules are electron-rich, for example, DNA or proteins therefore, polynuclear organometallics can establish different types of interactions with... 

V. Interaction of Metal Complexes with Biological Ligands and Macro-molecules... 

As should be evident from various chapters in this volume, the theoretical description of NMR shieldings and chemical shifts has seen a tremendous development during the past few years, and a number of methods are now at a point to be truly useful to experimental researchers as well as to answer fundamental questions. DFT based methods are a major aspect of these developments. The particular strength of DFT is perhaps its computational expedience, paired with accuracy and reliability. Hence, DFT applications are particularly useful for large and/or heavy systems including metal complexes or biological molecules. 

This chapter does not cover the use of metal ions as allosteric effectors (3), skeletal components (4) (see Crystal Engineering, Supramolecular Materials Chemistry), or sensing elements (5) (see Molecular Redox Sensors, Colorimetric Sensors and Luminescent Sensing, Supramolecular Devices). It also does not address the interaction of metal complexes with biological systems (see Synthetic Peptide-Based Receptors, Biological Small Molecules as Receptors, Molecular Recognition and Supramolecular Bioinorganic Chemistry, Supramolecular Aspects... 

In this section we summarise the manner in which i -metals. Fig. 6, and where possible specifically the platinum complexes of concern here, interact with biological molecules. Some radio-tracer studies have been carried out on the distribution of platinum complexes in whole bacteria grown in media inocculated with the metal ion. The results are summarised in Table 11. It is noteworthy that the bacteriocidal complex [PtClg]2- was taken up almost entirely by the cytoplasmic protein whereas the filamentous forming neutral species, [Pt(NHs)2Cl4], was... 

Experimental investigation of the factors that control the rates of biological redox reactions has not come as far as the study of the electron transfers of metal complexes, because many more variables must be dealt with (e.g., asymmetric surface charge, nonspherical shape, uncertain details of structures of proteins complexed with small molecules or other proteins). Many experimental approaches have been pursued, including the covalent attachment of redox reagents to the surfaces of metalloproteins. 

Ion-binding studies with biological molecules can be important in elucidating fundamental biochemical reaction systems in relation to bioenergetics, enzyme activation and membrane transport [182]. For example, the adenosine triphosphate (ATP)—adenosine diphosphate (ADP) cycle is one of the processes of primary importance to cellular energy systems and association constants determined [427—430] for metal—ATP and metal—ADP complexes are therefore of considerable interest Table 2.5). The constants may be obtained from measure-... 

The uranyl ion (UO ) is the most stable species, easily forms complexes, which are both well dissolved in water and represent the form present in the mammalian body [154]. It may react with biological molecules to produce cellular necrosis (cell death) and/or atrophy in the tubular walls in the kidneys, resulting in a diminished ability to filter impurities from the blood. There is no data available for long-term effects of uranium-induced developmental toxicity on humans. The information from intermediate-term studies on animals using the uranyl ion, oxides and rarely the metal [155, 156] demonstrate that DU is mutagenic and has neurotoxic properties [157]. 

Trefoil knots, and therefore the molecular knots discussed in this section, are chiral (Figure 4-29). The resolution of a dicopper(I) knot prepared from a helical precursor containing the 1,3-phenylene-linked bis-phenanthroline ligand described above (LI 198) has been achieved by crystallisation of the racemic cation with (5)-(+)-l,l -binaphthyl-2,2 -diyl phosphate [343]. As commented by these authors, the preparation of optically pure knot complexes is of great potential interest in relation both to interactions with biological molecules and, where the complexed metal has more than one accessible oxidation state, to enantioselective electron transfer [344]. 

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