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Molecular modelling in the School has focused largely on the modelling of metal complexes.
In situations where the coordination number of the metal ion/s is in little doubt, a useful approach is that of molecular mechanics, where the molecule is represented by a classical ?ball and springs? model. Since application of the methods of molecular mechanics to metal-ligand systems is relatively new, such applications often require that the model be parameterised for introduction of metal ions. Professor Marsicano and colleagues have developed and published computer software for the parameterisation of force fields involving metal ions in a bonded-atom model where the metal ion may be up to 12-coordinate. Such force-fields represent an extension of the MM(87) force-field to accommodate metal ion-containing species. Parameter optimisations may be carried out either on isolated molecules or in the full crystal environment. Molecular mechanics techniques are often useful in instances where the stability of the complexes is determined by the development of steric strain within the metal-ligand complex. Applications include systems used in solvent extraction separation of metal ions.
Professor Marques has made extensive used of molecular mechanics methods to model a number of bioinorganic systems. His group has developed a force field specifically for the modelling of the cobalt corrinoids (derivative of vitamin B12) and the force field is able to predict structures very accurately. By incorporating nOe data from 2D-NMR experiments, he is able to examine the structure of these complexes in solution.
Professor Marques has also developed force field parameters for the modelling of all metalloporphyrin complexes of the first transition series. Other projects include the modelling of tetraza macrocylic and acyclic complexes of several metal ions, and the interaction of bisphosphonate ligands with bone, of interest in the development of novel reagents for the treatment of bone cancer.
For modelling problems involving systems in which the coordination number of the metal ion is either variable or in doubt, useful approaches include ab-initio quantum mechanical or DFT-based calculations. Such techniques may be applied to systems involving ion exchange equilibria involving metal ion species and anionic ion exchange functional groups, where the stability of cation-anion interactions may depend crucially on inner-sphere / outer sphere relationships between metal ions and anionic functional groups.
During 2001 a new M.Sc. project (Mr Ziad S d, supervised by Professor Marsicano) was initiated involving development of a force field for the modelling, by the methods of molecular mechanics, of lanthanide complexes involving salicylic acids and neutral bifunctional ligands. The literature survey work has been completed and construction of the force field is under way, starting with the neutral oxygen donor of coordinated water molecules. In an Honours project (Bafana Hlatshwayo) carried during the second term of 2001 the effect of introduction of a N-methyl substituent on the stability of complexes of Ni(II), Cu(II) and Cd(II) with iminoacetate chelating ligands was studied by semi-empirical quantum mechanical methods. Calculations indicate that introduction of the substituent onto the ligand iminodiacetate should lead to less destabilisation of the complex formed than introduction of a similar substituent onto the ligand glycine. This is in line with earlier experimental observations of the relative stabilities of complexes of Ni(II) with the ligand pairs glycine/sarcosine, and iminodiacetate/N-methyliminodiacetate and supports the view developed in a previous honours project (Claudette Serge) that the methods of molecular mechanics provide a valid approach for investigating quite subtle steric effects in metal-ligand complex formation reactions.
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