Differential azobenzene solubility increases equilibrium cis/trans ratio in water

Abstract

Abstract We have determined aqueous solubility (Sw) for purified cis and trans isomers of azobenzene (AB) and ABn derivatives. Sw for trans-ABn is 0.05–0.15 mM and the cis isomer is 6–40× more soluble. The effect of differential solubility is important for aqueous sample concentration >Sw (trans) where cis/trans ratios >1 were observed via 1H and 19F NMR. This phenomenon is general for ABn(aq) that included semifluorinated ABn and peptide conjugates. The van’t-Hoff-Dimroth relationship predicts the equilibrium cis/trans ratio is proportional to the ratio of Sw values. Comparing NMR data to Sw values confirms the trend observed in the cis/trans ratios, but the magnitude of the ratio is lower. This phenomenon is observed in μmol concentration and may be a factor in photopharmacology. We have also studied the thermal cis-to-trans isomerization as a function of temperature for eight ABn compounds. Ea values ABn(aq) are ∼25 kJ mol−1 lower compared to Ea measured in nonpolar solvents and ΔS‡ values in water are more negative so that aqueous rates are 2–5 times greater in water. This class of ABn compounds generally show little solvent effect and this change in Ea is small compared to the behavior of donor-acceptor ABs. The inversion mechanism for this isomerization is supported by density functional theory.