An estrogen-platinum terpyridine conjugate: DNA and protein binding and cellular delivery.

A platinum metal complex in which terpyridine joins estradiol (via an ethynyl link) to a platinum with a labile ligand (chloride) has been designed, synthesised and its X-ray crystal structure determined. The aim of this work was to link a targeting motif (in this case estrogen) to a metal-based biomolecule recognition unit (the platinum moiety). The target molecule: 17alpha-[4'-ethynyl-2,2':6',2'-terpyridine]-17beta-estradiol platinum(II) chloride (PtEEtpy) has been shown to bind to both human and bovine serum albumin (SA) and to DNA. FTICR mass spectrometry shows that the bimolecular units are in each case linked through coordination to the platinum with displacement of the chloride ligand. Circular dichroism indicates that a termolecular entity involving PtEEtpy, SA and DNA is formed. A range of electrospray mass spectrometry experiments showed that the PtEEtpy complex breaks and forms coordination bonds relatively easily. A whole cell estrogen receptor assay in an estrogen receptor positive cell (MCF-7) confirms binding of both EEtpy and PtEEtpy to the estrogen receptor in cells. The work demonstrates the concept of linking a targeting moiety (in this case estrogen) to a DNA binding agent.

Intramolecular DNA Coiling Mediated by a Metallo-Supramolecular Cylinder.

In the groove! A tetracationic supramolecular cylinder, [Fe2 L3 ]4+ (L=C25 H20 N4 ), with a triple-helical architecture is just the right size to fit into the major groove of DNA and too big to fit into the minor groove. NMR spectroscopic data confirm that the cylinder binds in the major groove. Linear dichroism shows that very low loadings of [Fe2 L3 ]4+ have a dramatic bending effect on the DNA and atomic force microscopy images show that this is an intramolecular effect resulting in coils of DNA.