engleski

The Computational Modelling of Disubstituted Ferrocene Amino Acids and Dipeptides

The 1, n’-disubstituted ferrocene amino acids and peptides are commonly used as peptidomimetics. Due to the inherent flexibility of ferrocene unit with two cyclopentadienyl rings that are able to rotate around the common axis and the specific distance between them (ca. 3.3 Å), the ferrocene derivatives are ideal to adapt to form intramolecular hydrogen bonds between the substituents mimicking turns observed in natural peptides. The conformational analysis of such ferrocene disubstituted derivatives is quite difficult due to inability of majority of available force fields to adequately model ferrocene unit. Formation of hydrogen bonds in different solvents (more or less polar) usually provides additional experimental information about the conformations of ferrocene derivatives. Consequently, the appropriate computational modelling with accurately described solvent effects could be of great help in understanding of intramolecular hydrogen bond patterns. We employed our own custom method to explore the conformational space of the simple disubstituted 1’-acetyl ferrocene derivatives I and II. The combination of molecular mechanics with restricted movements of some molecular parts was used to generate starting geometries optimized with quantum mechanics afterward. The obtained most stable conformers were analysed by the means of quantum theory of atoms in molecules (QTAIM) and hydrogen bonds were verified according to the formalism suggested by Koch and Popelier. Thus obtained conformational analysis of disubstituted derivatives I and II corroborate the experimental data.

ferrocene; molecular modelling; conformation; hydrogen bond

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