Over the past several years, after numerous negative aspects of aluminum biological activity were reported the presence of aluminum in biological systems has gained in interest significantly. Most of these works concern aluminum toxicity. In general, the toxic effects of aluminum result from its competition with other metal ions in enzymes and proteins. As the aluminum ion substitutes at the normal metal binding site, the function of the protein changes and alters the metabolism of the cell, and consequently gravely affects the organism. MacDonald and Martin showed that the functions of magnesium (II) more than any other metal are affected by the competition with aluminum (III).
The nervous system is especially susceptible in humans. Alzheimer's disease, dialysis encephalopathy and Parkinson-dementia complex of Guam are some examples of maladies linked to aluminum (III) interference. Recently, Fasman's group reported two mechanisms for aluminum (III) interactions with the Neurofibrilar peptide (NF), in which aluminum may bind to carboxylate residues, forming intra-chain complexes, or to phosphorilated residues of the NF, where inter-chain bonds are created.
In addition to magnesium (II), iron (III) and calcium (II) are also susceptible to competition with aluminum (III). Size similarity is a dominant factor over the charge identity concerning metal ion competition . Thus, aluminum (III) substitution for magnesium (II), calcium (II) or iron (III) in physiological settings is possible. Magnesium (II) is the simplest metal that competes with aluminum (III). Thus, in this work we focus on the competition between magnesium (II) and aluminum (III).
The interactions of some metals with biologically relevant model ligands have been studied with ab initio methods, e.g. magnesium (II) calcium (II) cadmium (II) and zinc (II). In these works, the aminoacids are reduced to their functional groups, i.e. HCOO- for glutamic acid and aspartic acid, CH3O- for serine, CH3SH for cysteine, etc. Magnesium (II) metal ion has also been studied in model protein environment with different bioligands, again representing the aminoacids. Despite the quantity of these relevant theoretical works and the extensive experimental study concerning aluminum interacting with these biologically relevant ligands no ab initio work exploring these critical features has yet appeared in the literature.
To understand better the interactions of aluminum (III) with any relevant biological peptide it is important to analyze first the interactions of the metal with the aminoacids. In the present project we are studying the binding properties of magnesium (II) and aluminum (III) with the acidic aminoacid chains, represented in the anionic form because both aminoacids pK's are lower than the physiological pH.
Our hope in this investigation is not only to elucidate binding characteristics in these complexes, but also to provide detailed data which may be useful to develop force fields for aluminum, thereby facilitating molecular modeling studies which may be helpful to study the biotoxicity of aluminum. With the data provided by our ongoing investigation, a better understanding of the interactions between the aluminum (III) cation and the carboxylate containing residues will be obtained, along with data that should be useful in the creation of force field parameters for the aluminum (III) cation.
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