Synthesis and analysis of platinum(II) sequence selective complexes

Abstract

The aim of this work was to synthesise two platinum-(II)-polyamide complexes, [B- ala-Py-Py-Py-L6-Pt]Cl and [B-ala-Py-Py-Py-B-ala-terpy-Pt]PF6, and assess them for specific DNA base binding affinity using a variety of spectroscopic techniques. [B- Ala-Py-Py-Py-L6-Pt]Cl and [B-ala-Py-Py-Py-B-ala-terpy-Pt]PF6 are similarly composed of a B-alanine terminal attached to three linked pyrrole molecules. They are differentiated by the platinum(II) complex attached (transplatin and terpyridine platinum, respectively) and also the linker separating the pyrrole and platinum(II) moiety (a long aliphatic chain abbreviated as L6 compared with a short B-alanine molecule, respectively). The two platinum(II) complexes were prepared in high yield (~70%) using solid phase synthesis by coupling derivatised imidazole and pyrrole monomers and platinum moieties using 2-(1H-benzotriazol-1-yl)-1,1,3,3- tetramethyluronium hexafluoro- phosphate and diisopropylethylamine. The derivatisation of the imidazole and pyrrole monomers required five synthetic steps to functionalise the monomers at position 2 with a carboxylic acid, whilst position 4 was protected using 9-fluorenylmethyl chloroformate. Modification of the imidazole and pyrrole functionalised compounds were originally reported by Dervan and co- workers, however the synthetic method has been substantially modified in our laboratory. This specific functionalisation was necessary in order for the monomers to be used in solid phase synthesis. The monomers were synthesised in an overall yield of ~20%, for each. The addition of the platinum complexes to the resin- polyamide via solid phase was found to be advantageous in terms of time and purity. This solid phase method has allowed such complexes to be synthesised in days, rather than months when compared to solution phase synthesis. The purity of these complexes was confirmed by nuclear magnetic resonance, electrospray ionisation- mass spectroscopy and elemental analysis.

Date of Award	2011
Original language	English