Differential azobenzene solubility increases equilibrium cis/trans ratio in water

Abstract

We have determined aqueous solubility (S w) for purified cis and trans isomers of azobenzene (AB) and AB n derivatives. S w for trans-AB n is 0.05-0.15 mM and the cis isomer is 6-40x more soluble. The effect of differential solubility is important for aqueous sample concentration > S w (trans) where cis/trans ratios >1 were observed via 1 H and 19 F NMR. This phenomenon is general for AB n (aq) that included semifluorinated AB n and peptide conjugates. The van't-Hoff-Dimroth relationship predicts the equilibrium cis/trans ratio is proportional to the ratio of S w values. Comparing NMR data to S w 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 AB n compounds. E a values AB n (aq) are ~ 25 kJ mol-1 lower compared to E a 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 AB n compounds generally show little solvent effect and this change in E a is small compared to the behavior of donor-acceptor ABs. The inversion mechanism for this isomerization is supported by density functional theory.

Photoresponsive molecular tools for emerging applications of light in medicine

“…This effect can shi the cis-trans equilibrium in favour of the cisisomer. 109 Another way to turn the change in solubility to an advantage was shown with DASA photoswitches that, upon photoswitching, turn form planar, linear, hydrophobic form to a cyclic, zwitterionic one. Helmy et al incorporated a monomethyl PEG chain into the DASA photoswitch through azidealkyne cycloaddition reaction.…”

Glutamate Transporter Inhibitors with Photo‐Controlled Activity

“…Photo‐control over biological activity can be achieved by the introduction of a molecular photoswitch, such as azobenzene, into the structure of the molecule. Thermally stable trans ‐azobenzene (See Figure in blue) is a linear, (near) flat molecule; irradiation with UV light results in the isomerization of the azo bond and gives cis ‐azobenzene, which is less stable, non‐planar, has a higher dipole moment and is more soluble in aqueous solutions then the trans isomer . Trans to cis isomerization can be reversed by irradiation with visible light; however, the cis ‐ trans isomerization also happens spontaneously on a time scale of milliseconds to years, depending on the azobenzene structure .…”

Light‐Triggered, Non‐Centrosymmetric Self‐Assembly of Aqueous Arylazopyrazoles at the Air–Water Interface and Switching of Second‐Harmonic Generation

“…In addition, compounds 1 , 2 display considerably large electric dipole moments ( trans ‐ 1 , 1.27 D, cis ‐ 1 , 3.64 D, trans ‐ 2 , 2.54 D, cis ‐ 2 , 3.55 D, calculated by B3LYP/6‐31G*, Spartan′14) as compared to those of the unsubstituted azobenzene. In the case of unsubstituted azobenzene, trans ‐ and cis ‐isomers have been reported to give limited solubility in water of 20–50 μM and 0.65–2 mM, respectively [42] …”