Inspired by the recently proposed cooperative mechanism of hydrotropy, where water molecules
mediate the aggregation of hydrotrope around the solute, this work studies the impact of apolar volume
and polar group position on the performance of hydrotropes. To do so, the ability of two different
families of alkanediols (1,2-alkanediols and 1,n-alkanediols) to increase the aqueous solubility of syringic
acid is initially investigated. Interestingly, it is observed that in the dilute region (low hydrotrope
concentration), the relative position of the hydroxyl groups of the alkanediols does not impact their
performance. Instead, their ability to increase the solubility of syringic acid correlates remarkably well
with the size of their alkyl chains. However, this is not the case for larger hydrotrope concentrations,
where 1,2-alkanediols are found to perform, in general, better than 1,n-alkanediols. These seemingly
contradictory findings are reconciled using theoretical and experimental techniques, namely the
cooperative model of hydrotropy and chemical environment probes (Kamlet–Taft and pyrene polarity
scales). It is found that the number of hydrotropes aggregated around a solute molecule does not
increase linearly with the apolar volume of the former, reaching a maximum instead. This maximum is
discussed in terms of competing solute–hydrotrope and hydrotrope–hydrotrope interactions. The
results suggest that hydrotrope self-aggregation is more prevalent in 1,n-alkanediols, which negatively
impacts their performance as hydrotropes. The results reported in this work support the cooperative
model of hydrotropy and, from an application perspective, show that hydrotropes should be designed
taking into consideration not only their apolar volume but also their ability to stabilize their selfaggregation
in water, which negatively impacts their performance as solubility enhancers.
This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, and CIMO-Mountain Research Center, UIDB/00690/2020, financed by national funds through the FCT/MEC, and when appropriate, cofinanced by FEDER under the PT2020
Partnership Agreement. B. P. S. acknowledges FCT for her PhDgrant SFRH/BD/138439/2018.
