Pulsed gradient spin-echo nuclear magnetic resonance diffusion measurements have been used to show that platinum(II)-based intercalating agents self-stack in solution and form nanorods 0.45-3.9 nm in length (at 25 mM); their lengths are dependent on metal complex concentration, salt concentration and solution temperature.The anticancer agent 56MESS [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] 2+ , Fig. 1a, is our lead candidate in a family of over 60 platinum(II)-based DNA intercalating complexes. [1][2][3][4] It has demonstrated significant in vitro cytotoxicity in cisplatin sensitive and resistant human cancer cell lines. 5 56MESS is thought to induce cellular apoptosis by intercalating double-stranded DNA, thereby preventing DNA transcription and replication. 1 Drug transport, cellular uptake and intracellular glutathione degradation 6 are also thought to play a significant role in the structure-activity relationship of this family of platinum complexes. 1 A number of new platinum(II)-based DNA intercalator complexes are also being developed that contain terpyridine intercalating groups (e.g. [(2,2 0 :6 0 ,2 00 -terpyridine)chloro-platinum(II)] + [Pt(terpy)Cl] + ; Fig. 1b). 7-9 A number of these compounds display activity similar to, or greater than, cisplatin in several cell lines. 10 It is widely accepted that compounds that contain fused aromatic rings are capable of forming dimers in solution through favourable p-p stacking. 11 Platinum(II) complexes containing planar aromatic ligands have been shown to stack and form dimers in aqueous solvents; however, these investigations have been limited to one-dimensional 1 H nuclear magnetic resonance (NMR) and electronic spectroscopy. [11][12][13][14] The formation of higher order aggregates (i.e. greater than two molecules) of these compounds has not been well demonstrated. The self-assembly of these complexes, particularly under physiological-like conditions, is of great importance, as aggregation may influence the ability of the complex to intercalate with DNA. In addition, the formation of large aggregates may influence the rate of drug transport/uptake. 15 56MESS and [Pt(terpy)Cl] + serve as excellent model compounds for initial investigations of such aggregation mechanisms. Thus, we have studied the self-aggregation of 56MESS and [Pt(terpy)Cl] + at varying metal complex/salt concentrations and solution temperatures using pulsed gradient spin-echo (PGSE) NMR diffusion measurements. 16 X-Ray crystal structures have shown that platinum(II)-based DNA intercalators can p-p stack in three different configurations; a head-to-head, 17 head-to-tail 18 or pinwheel configuration, where alternate intercalator molecules are rotated B901 compared to the molecule stacked above it. 2 In any configuration, the resultant macromolecule forms a cylinder or rod-like structure. We have employed the simple model of an ellipsoid (oblate or prolate, ESIw, Fig. S5) for the determination of macromolecule length. By substituting the observed diffusion coef...