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Note of Caution for the Aqueous Behavior of Metal-based Drug Candidates
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Poor aqueous solubility is one of the recurrent drawbacks of many compounds in
medicinal chemistry. To overcome this limitation, the dilution of drug candidates from
stock solutions is common practice. However, the precise characterisation of these
compounds in aqueous solutions is often neglected, leading to some uncertainties
regarding the nature of the actual active species. In this communication, we demonstrate
that two ruthenium complexes previously reported by our group for their
chemotherapeutic potential against cancer, namely [Ru(DIP)2(sq)](PF6) and
[Ru(DIP)2(3-methoxysq)](PF6), where DIP is 4,7-diphenyl-1,10-phenanthroline, sq =
semiquinonate and 3-methoxysq = 3-methoxysemiquinonate, form colloids in waterDMSO (1% v/v) mixtures that are invisible to the naked eyes. [Ru(DIP)2(3-
methoxysq)](PF6) was found to form a highly stable and monodispersed colloid with
nanoaggregates of ~25 nm. In contrast, [Ru(DIP)2(sq)](PF6) was found to form large
reticulates of mostly spherical aggregates which size was found to increase over time.
The difference in size and shape distribution of drug candidates is of tremendous
significance as the study of their biological activity might be severely affected. Overall,
we strongly believe that these observations should be taken into account by the
scientific community working on the development of metal-based drugs with poor