A molecular mechanics study for selective complexation of metal ions in medical applications
Date
1994
Authors
Chantson, Tracy, Elizabeth
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Abstract
Molecular mechanics calculations are used to interpret and predict metal ion
discrimination by coordinating ligands. Of particular interest are chelates exhibiting
characteristics that Single them out for potential medical application;
Selectivity patterns for several series of ligands are investigated with the help of strain
energy profiles as a function of metal-donor atom bond distance. Ligands include
simple; open-chain oxygen- and nitrogen-donors ana triaza- and tetraazamacrocyeles.
Results are compared with X-ray crystallographic and solution data. Factors such as
chelate ring size, conformational flexibility and preferred metal coordination geometry
are found to influence metal specificity. Addition of pendent donor groups to
macrocyoles leads to rigid structures and selectivity predictions according to cavity size.
Interpretation of specific. metal ion recognition by polyetner antibiotics is attempted.
Structural and steric factors are probed as possible determinants of metal choice.
both covalent and ionic bonding models are explored. The covalent approach results
in predictions of metal selectivity which correlate with mown selectivity patterns.
Unfortunately, inability to optimise force field parameters in the ionic bonding
approach forced us to abandon this model.
The main force field used is the TRIPOS (1992,1993) force field. It performs well in
calculations involving a univariate scanning technique but has to be modified to obtain
reasonable structure reproduction with the large antibiotics, Errors in thermodynamic
data predictions are obtained, nonbonding parameters have yet to be properly
parameterized and the allocation of partial atomic charges warrants closer
examination . All of these factors contribute to the poor performance of the force
field when ionic interactions between metal and donor atoms of the polyethers are
assumed.
Description
A dissertation submitted to the Faculty of Science University of the Witwatersrand, Johannesburg for the degree of Master of Science. Johannesburg, 1994.
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Citation
Chantson, Tracy, Elizabeth (1994) A molecular mechanics study for selective complexation of metal ions in medical applications, University of the Witwatersrand, Johannesburg, <http://hdl.handle.net/10539/22402>