Introduction - Chemical Speciation of Complexes of l-phenylalanine and maleic acid with toxic metal ions in Dimethylformamide...

Introduction
Heavy metals are common in our environment and diet and many of them are essential to living organisms but some of them are highly toxic or become toxic given sufficient exposure and accumulation in the body. Metals such as Hg, Cd, Pb, Sn, Cr and As are generally not required for metabolic activity and are toxic to living organisms even at low concentrations [1]. The mechanism of the toxicity of metals is very complicated. Generally, toxicity of metals results from blocking the essential biological functional groups (-OH, -SH, and –N) or modifying the active conformation of biomolecules (enzyme, DNA, etc.,) through binding and displacing the essential metal ions from their natural binding sites of the bio-molecules with a foreign metal ion. Human civilization and the increase in industrial activity has gradually redistributed many toxic metals from the earth’s crust to the environment and increased the possibility of exposure. Lead, cadmium, and mercury are among the various toxic metals especially prevalent in nature due to their high industrial use. These metals serve no biological function and their presence in tissues reflects contact of the organism with its environment [2].
The main sources of lead pollution specially the bones and teeth, the kidneys, and the nervous, cardiovascular, immune and reproductive systems [3,4]. Lead also interferes with the normal metabolism of calcium in cells and causes it to build up within them [5].
The sources of Cd pollution in urban areas are metallurgical plants, Cd plating and battery fabricators. It can also enter the environment through natural causes, such as volcanic activity and forest fires [6]. Human exposure to cadmium mainly occurs through cigarette smoking [7]. but exposure can also occur through contaminated food [8], water or air [9]. Cadmium is a known carcinogen to mammals [10]. Cadmium interacts with calcium in the skeletal system to produce osteodystropies [11]. Due to their similarity in properties, cadmium displaces zincin many metallo-enzymes and many of the symptoms of cadmium toxicity can be traced to a cadmium-induced zinc deficiency [12]. Cd (II) binds strongly with the -SH groups of cysteine residues of enzymes [13], e.g. carbonic anhydrase, dipeptidase, carboxy peptidase etc., and effects the active conformation of bio -molecules due to this strong binding.
Mercury exposure is related to the release of mercury forms (Hg(0), inorganic Hg (II), and organic Hg into the environment by both natural and man -made activities [14]. Mercury is a highly toxic element because of its accumulative and persistent character in the environment and living organisms [15]. It affects the immune system, alters genetics and enzyme systems, damages the nervous affinity for the protonated forms of thiol ligands such as cysteine [16]. So, Hg (II) binds strongly with the thiol group of proteins, enzymes and other bio-molecules in which this binding changes the conformation of bio-molecules in their active site [13, 17].
Speciation studies of toxic and essential metal ion complexes are useful in order to understand the role played by the active site cavities in biological molecules and the bonding behavior of their residues with metal ions. The possible ligand groups in proteins are the amino acid side chains, the terminal amino, carboxyl and thiol groups and, in some cases, the amide group is the peptide backbone [18].
However, the study of metal-protein system may be difficult to construct in simple - like amino acids and peptides but such models may give a tremendous amount of information about the structure of proteins and function of bio-molecules in biological systems [19]. The interaction of metals with amino acids and peptides has been the subject of much research [20], due to the importance of metals in many biochemical processes [21], such as respiration, metabolism and nerve transmission [22]. Investigations of acid-base equilibria of amino acids and peptides and their interaction with metal ions at varying ionic strengths, temperatures and dielectric constant media throw light on the mechanism of enzyme catalyzed reactions. It is known that the polarity of the active site cavities in proteins is lower than that of the bulk but direct measurements of the dielectric constant is not possible.
Comparing the formation constants of acid-base equilibria and/or metal complex equilibria with those at biological centers offers a way to estimate the effective dielectric constant or equivalent solution dielectric constant for the active site cavity [23]. This has brought an important new approach to the study of complex equilibria in aqua-organic mixtures apart from its established utility in understanding solute-solvent interactions, increasing sensitivity of reactions of analytical and industrial importance and solubilizing ligands of their metal complexes.
Chemical speciation of metals is important for an understanding of their distribution, mobility, toxicity, and for setting environmental quality standards [24]. Bioavailability of a particular metal depends on its complex chemical reactions of dissolution, binding and complexation with the constituents of the environmental aquatic media [25]. To reveal the solvent effects on equilibrium processes involving charged species, we have studied the complex formation of L-phenylalanine and maleic acid with Pb (II), Cd (II) and Hg (II) as a good example in modelling of the bonding modes of peptides to toxic metal ions in mixtures containing Dimethyl formamide (DMF) and water.
|