Porphyrin chelate effect

Hence, dissociation of tiron occurs in a concerted fashion when the porphyrin is incorporated into the first coordination sphere. Obviously, if proton transfer from H2P has been established, the series of substitutions occurring at MA are rather fast steps dominated by kinetic chelate effects. 

The chelate effect is important in biochemistry and molecular biology. The additional thermodynamic stabilization provided by entropy effects helps stabilize biological metal-chelate complexes, such as porphyrins, and can allow changes in the oxidation state of the metal ion while retaining the structural integrity of the complex. 

Chelation itself is sometimes useful in directing the course of synthesis. This is called the template effect (37). The presence of a suitable metal ion facihtates the preparation of the crown ethers, porphyrins, and similar heteroatom macrocycHc compounds. Coordination of the heteroatoms about the metal orients the end groups of the reactants for ring closure. The product is the chelate from which the metal may be removed by a suitable method. In other catalytic effects, reactive centers may be brought into close proximity, charge or bond strain effects may be created, or electron transfers may be made possible. 

A first example is represented by the Mn(III)/Mn(II) redox switch. The complexes of Mn(II) and Mn(III) with the water-soluble tetraphenylsulpho-nate porphyrin (TPPS, Chart 13) display significantly different ri values at low magnetic field strength (lower than 1 MHz), but very similar values at the fields currently used in the clinical practice (> 10 MHz) (141). However, the longer electronic relaxation rates of the Mn(II) complex makes its relaxivity dependent on the rotational mobility of the chelate. In fact, upon interacting with a poly-p-cyclodextrin, a 4-fold enhancement of the relaxivity of [Mn(H)-TPPS(H20)2] at 20 MHz has been detected, whereas little effect has been observed for the Mn(III)-complex. The ability of the Mn(II)/Mn(III)... 

Chelation with metal ions dramatically affects the reactivity of the porphyrin macrocycle, and this can be used to advantage in many cases. For example, for efficient electrophilic substitution of the ring, metals can be chosen (vide infra) which effectively release electron density to the organic porphyrin ligand, while reductions are best carried out on metallo-porphyrins in which the metal tends to deplete the porphyrin ligand of its electron density by way of back-bonding. 

Early workers appeared to show that electrophilic substitution reactions could not be carried out on porphyrins, and began to question the aromaticity of porphyrins since this classical pre-requisite of aromatic character could not be accomplished. However, they had concentrated on reactions of metal-free systems, and since many electrophilic substitution reactions utilize acidic conditions (nitration, sulfonation), they were actually dealing with the non-nucleophilic porphyrin dication. But, as early as 1929, H. Fischer had realised that diacetylation of deuteroporphyrin-IX (Table 1) had to be carried out on a metal complex, such as the iron (III) derivative chelation with a metal ion which cannot be removed under the acid conditions of the subsequent reaction, effectively eliminates dication formation. A judicious choice of metal complex therefore needs to be made for any particular reaction. For example, though magnesium(II) produces an extremely reactive substrate for electrophilic substitution reactions, it is removed by contact with the mildest of acids and is, consequently, of little use for this purpose. 

These BCAs chelate metal atoms by holding them in the center of their nitrogenous ring structure, in a manner similar to the chelation of iron at the core of a porphyrin prosthetic group. The excellent stability of this complex allows the use of DOTA, NOTA, and TETA conjugates in vivo with minimal potential for leaching and deleterious side effects. 

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