Effect of Substitution Degree and Homogeneity on Cyclodextrin-Ligand Complex Stability: Comparison of Fenbufen and Fenoprofen Using CD and NMR Spectroscopy

Int J Mol Sci. 2023 Apr 19;24(8):7544. doi: 10.3390/ijms24087544.

Abstract

The stability of host-guest complexes of two NSAID drugs with similar physicochemical properties, fenbufen and fenoprofen, was investigated by comparing induced circular dichroism and 1H nuclear magnetic resonance methods using eight cyclodextrins of different degrees of substitution and isomeric purity as guest compounds. These cyclodextrins include native β-cyclodextrin (BCyD), 2,6-dimethyl-β-cyclodextrin 50 (DIMEB50), 80 (DIMEB80) and 95% (DIMEB95) isomerically pure versions, low-methylated CRYSMEB, randomly methylated β-cyclodextrin (RAMEB) and 4.5 and 6.3 average substitution grade hydroxypropyl-β-cyclodextrin (HPBCyD). The stability constants obtained by the two methods show good agreement in most cases. For fenbufen complexes, there is a clear trend that the stability constant increases with the degree of substitution while isomer purity has a smaller effect on the magnitude of stability constants. A significant difference was found in the case of DIMEB50 when compared to DIMEB80/DIMEB95, while the latter two are similar. In the fenbufen-fenoprofen comparison, fenbufen, with its linear axis, gives a more stable complex, while fenoprofen shows lower constants and poorly defined trends.

Keywords: NMR; cyclodextrin; fenbufen; fenoprofen; host–guest complex stability; induced circular dichroism.

Publication types

  • Comparative Study

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Cyclodextrins* / chemistry
  • Fenoprofen / chemistry
  • Ligands
  • Magnetic Resonance Spectroscopy / methods
  • beta-Cyclodextrins* / chemistry

Substances

  • 2-Hydroxypropyl-beta-cyclodextrin
  • beta-Cyclodextrins
  • Cyclodextrins
  • fenbufen
  • Fenoprofen
  • Ligands

Grants and funding

The research was financed by the Higher Education Institutional Excellence Programme within the framework of the molecular biology thematic programme of Semmelweis University (TKP2021-EGA-24), and the ÚNKP-22-5-SE-3 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund. Arash Mirzahosseini is grateful for the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.