Preparation, stability, and molecular modeling of nitro-oleic acid/ cyclodextrin complexes under aqueous conditions

Nitro-oleic acid (NO2-OA) is an endogenously produced pleiotropic modulator involved in cell redox homeo-stasis. The intrinsic property of NO2-OA is a decay reaction under aqueous conditions. This aqueous instability is simultaneously a problematic issue for NO2-OA sample handling and NO2-OA application in general. In this work NO2-OA (eq. mol. 9/10-NO2 isomers) was encapsulated with 8-cyclodextrin (8-CD). The formation of the 8-CD/ NO2-OA complex was determined based on 1H NMR. The QM calculations revealed that dispersion forces are crucial for the stability of the complex. Based on thermogravimetry-differential scanning calorimetry, free NO2- OA was less thermally stable than its inclusion 8-CD complex. The electrochemical reduction of the nitro group was investigated to determine the degradation kinetics of 8-CD/NO2-OA. Under aqueous conditions, 8-CD/NO2- OA degrades at a similar rate to NO2-OA alone. However, when 8-CD/NO2-OA is stored in solid (lyophilized) form, no degradation was observed for a one-month period.

Automated summary

The study shows that the complex formed by 8-cyclodextrin (8-CD) and NO2-OA is more stable in aqueous solution, while NO2-OA alone is less stable. Under solid-state conditions, the degradation rate of 8-CD/NO2-OA is slower and has a longer storage time.