Demonstration of the Importance of Metal Ion Speciation in Bioactive Systems

Abstract

This paper gives insight into chemical speciation. After a brief introduction, the methods available to study solution state of metal ions and the importance of speciation in biology are discussed through different examples. Speciation of toxic Al III , beneficial Cu II and Ca II and potentially medicinal Pd II and VO IV in various biofluids and tissues is discussed in order to describe the solution state of these metal ions in an organism. The relevance of ternary complex formation with endogenous biomolecules is emphasised. The importance of the biospeciation of Al III ion in its transport and involvement in neurological disorders, of the actual chemical form of the insulin-mimetic VO IV complexes in its biological occurrence and Ca II in mineralization/demineralization processes is discussed. The role of time, i.e., the kinetic aspects of biospeciation, is discussed in the case of the transport of Al III and Cu II and some Pd II complexes (models of the anticancer Pt II complexes) in blood serum.

Development of the application of speciation in chemistry

“…[134,136] In mM total Al(III) concentrations, which correspond better to aluminum overload conditions and those when the thermodynamic equilibrium is reached (monitored by multinuclear NMR; see later), the amount of phosphate-bound Al(III) increases significantly and ternary Al(III)-citrate-phosphate complexes can also be detected (see Table 6) [32].…”

“…However, protein-metal equilibria cannot be excluded, especially in faster complexation processes with the proteins. Indeed, protein interactions were included in computer simulations of the distributions of Al(III) [32], V(IV)O [33], Zn(II) [34], Ga(III) [35], and Gd(III) [36] complexes in serum. In the case of speciation in natural/industrial waters, the redox processes, solubility properties, and adsorption interactions must also be considered (see Section 4.2).…”

“…The speciation model provided in Table 6 of Ref. [32] suggests that 93% of the total Al(III) is bound to Tf. Among the pool of LMM aluminum, 88% of Al(III) will be bound to citrate, 8% to hydroxide, and ~2% to phosphate.…”

Speciation of Metal Complexes of Medicinal Interest: Relationship between Solution Equilibria and Pharmaceutical Properties

“…In the past years we have published several reviews in this field [1,43,[101][102][103][104][105], and thus there may be significant similarity of this section with some of them. When a larger part of the text is very similar to one of these former reviews a reference number will be given.…”

DFT study of vanadyl (IV) complexes with low molecular mass ligands: Picolinate, oxalate, malonate, and maltolate

“…Kiss et al7 have pointed out that metal complexes prepared with potential biological activity may differ considerably from those in the living systems where they are intended to exert their biological effects. Recently, Kiss et al8 discussed the importance of the metal ion speciation in bioactive systems. The various molecules acting as ligands compete for the metal center and, hence, change drastically the equilibrium.…”