Note of Caution for the Aqueous Behavior of Metal-based Drug Candidates

26 November 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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 water solubility.


Bioinorganic Chemistry
Medicinal Inorganic Chemistry
Aqueous Behavior


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.