Behavior of Curcumin in micellar biomimetic systems and its protolytic and tautomeric equilibria elucidated by multivariate analysis

• Published in: Journal of molecular liquids Vol. 394; p. 123729
• Main Authors: Lazzarotto Braga, Thais, Irineu Dias Pereira, Christhian, Schuvinski Ricken, Yara, Braga, Gustavo, Luiz Tessaro, André, Hioka, Noboru, Caetano, Wilker, Fabiano de Freitas Marin, Camila
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.01.2024
• Subjects: Keto-enol tautomerism; Multivariate analysis; pKa values; Protolytic equilibrium; Surfactants; pKa values; Keto-enol tautomerism; Multivariate analysis; Surfactants; Protolytic equilibrium
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2023.123729

[Display omitted] •CUR's versatile biomedical applications, overcome hydrophobicity and low bioavailability.•Successful interaction of CUR with various micellar systems, revealing pH-dependent behavior.•Notable impact of hydrophobic and electrostatic factors on CUR binding constants.•Efficient CUR incorporation in micelles, validated through spectral analysis and in-silico assays.•Multivariate analysis unveils the intriguing “chameleon effect” in CUR behavior. Curcumin (CUR), a natural compound originating from Asia, has found widespread application in the field of biomedicine. CUR shows significant results in its applications, despite its high hydrophobicity and low bioavailability. In general, success depends mainly on the interaction between CUR and the target cell, microbial membrane, cell wall, or protein capsule. Associated with this, solid tumors, gastric or stomach regions, as well as regions affected by wounds, have very different pH conditions. In this scenario, micellar biomimetic systems obtained from cationic (CTAB), anionic (SDS), zwitterionic (HPS), and non-ionic (TX-100) surfactants emerge as an interesting alternative within this type of investigation. Thus, in the present study, the interaction of CUR with CTAB, SDS, HPS, and TX-100 micelles was evaluated first under physiological conditions (pH 7.4). The results showed that CUR interacts very well with the most distinct environments, as demonstrated by experimental and computational analysis. The binding constant, Kb, was higher for TX-100 micelles and lower for SDS in the presence or absence of the ionic strength control, appointing the influence of hydrophobic and electrostatic effects. The spectral properties show the efficient incorporation of CUR in micelles, also confirmed by in-silico assays. Multivariate analysis based on Q-Imbrie's factor and the K-matrix method on the electronic absorption spectroscopy data in different pHs ranging from 0 to 14 allowed for the understanding of the complex protolytic/tautomeric equilibrium, and the influence of the microenvironment on the CUR at each pH. Thus, the CUR tends to prevail in the photolytic form of better interaction, a chemically explained fact here called the “chameleon effect”. So, in SDS the pKa values tend to increase to favor the interaction between CUR0 and SDS-. On the other hand, in CTAB the pKa values tend to decrease to favor the interaction between CUR-1/CUR-2 and CTA+. The multivariate analysis also allowed the pure spectra separation and the molar absorptivity determination of each species. These interactions were also confirmed by the estimated electrical potential ψo from ΔpKa-el determined using the Boltzmann equation.