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

submitted on 19.11.2019 and posted on 26.11.2019 by Anna Notaro, Gilles Gasser, Annie Castonguay
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.


Email Address of Submitting Author


Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences



ORCID For Submitting Author


Declaration of Conflict of Interest



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