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Intramolecular charge transfer effects on flutamide drug
A Anton Smith1, R Manavalan, K Kannan
1Department of Pharmacy, Annamalai University, Annamalai nagar, 608 002, Tamilnadu, India.
Flutamide drug exhibits dual fluorescence, with its intramolecular charge transfer (ICT) emission enhanced in beta-cyclodextrin (beta-CD) inclusion complexes. This study elucidates the 1:1 inclusion mechanism and drug
Area of Science:
- Pharmaceutical Chemistry
- Physical Chemistry
- Supramolecular Chemistry
Background:
- Flutamide is an antiandrogen drug used in cancer therapy.
- Understanding drug-excipient interactions is crucial for drug formulation and delivery.
- Beta-cyclodextrin (beta-CD) is a common host molecule for forming inclusion complexes.
Purpose of the Study:
- To investigate the spectral characteristics of flutamide in various solvents and its inclusion complex with beta-CD.
- To elucidate the fluorescence behavior and the nature of intramolecular charge transfer (ICT) in flutamide.
- To determine the binding mode and mechanism of the flutamide-beta-CD inclusion complex.
Main Methods:
- Spectroscopic techniques: UV-visible absorption, fluorimetry, Fourier-transform infrared (FT-IR) spectroscopy, and proton nuclear magnetic resonance (1H NMR).
- Thermal analysis: Differential scanning calorimetry (DSC).
- Morphological analysis: Scanning electron microscopy (SEM).
- Computational methods: Austin Model 1 (AM1) calculations.
Main Results:
- Flutamide displayed dual fluorescence in all solvents, attributed to locally excited (B band, ~285 nm) and intramolecular charge transfer (A band, ~380 nm) states.
- Formation of the flutamide-beta-CD inclusion complex significantly enhanced the fluorescence intensity of the A band, indicating facilitated ICT emission.
- Beta-CD studies revealed the isopropyl group of flutamide resides within the beta-CD cavity, while amino and CF(3) groups are external.
Conclusions:
- The study confirms the formation of a 1:1 inclusion complex between flutamide and beta-CD.
- Beta-CD enhances the ICT emission of flutamide, suggesting potential applications in drug delivery systems.
- A detailed inclusion mechanism involving the orientation of flutamide within the beta-CD cavity is proposed.
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