Room-temperature stable Perillaldehyde—Natural cyclodextrin inclusion complexes: Preparation, characterization, thermal stability, water solubility, antioxidant activity and slow–release performance

Abstract

The compound Perillaldehyde (PA) is a bioactive constituent found in natural Perilla oil, exhibiting remarkable antibacterial and antioxidant activity. However, the instability of this compound caused by the easy oxidation of its aldehyde and olefin groups imposes limitations on its extensive applications. Therefore, it is crucial to develop effective strategies for enhancing the stability of PA. This study focuses on utilizing a series of natural cyclodextrins (CDs) to synthesize inclusion complexes (ICs) with PA, aiming to improve water solubility and achieve exceptional stability at room temperature, which is essential for their potential applications in biomedicine or food industries. The hydrophobic cavity of CDs can accommodate the hexatomic ring and hydrophobic chains of PA based on the well-known size-matching effect and hydrophobic interaction, thereby forming stable ICs. Additionally, the hydrophilic outer wall of CDs imparts excellent water solubility to ICs. Phase solubility investigations demonstrate successful construction of α-CD-PA IC and β-CD-PA IC with an inclusion ratio of 1:1. Their respective stability constant (KC) are determined as 342 L/mol and 180 L/mol, indicating superior stability for α-CD-PA IC compared to β-CD-PA IC. Conversely, γ-CD with a larger cavity fails to form a stable inclusion complex with PA due to inadequate size matching. Nuclear Magnetic Resonance Hydrogen Spectroscopy (1H and 2D NMR) studies reveal that PA enters the CDs cavity (α-CD or β-CD) from its wide rim with almost the entire molecule being obliquely embedded within it. Thermogravimetry Analysis (TGA) confirm that after inclusion with CDs, PA exhibits expected stability at 25 ℃. Furthermore, CDs-PA ICs demonstrate significantly improved water solubility compared to pure PA along with enhanced antioxidant activity and slow-release performance, rendering them highly favorable for various applications.