Interpreting the effect of confined cyclodextrin media on the FRET efficacy between Naproxen and a bio-active 3-pyrazolyl-2-pyrazoline derivative on the light of spectroscopic investigation appended by TD-DFT simulations and molecular docking analysis

- Applicability of Naproxen (NPX) and a bio-active 3-pyrazolyl-2-pyrazoline derivative (PYZ) as an efficient FRET pair.
- CD induced environmental changes controls the variation in FRET efficacy values of NPX-PYZ in different cyclodextrin media.
- TD-DFT calculations provided information about the medium dependent energy changes in the HOMO-LUMO of the NPX-PYZ FRET pair.
- Molecular docking outlined the most favorable orientation of the donor (NPX) inside different cyclodextrin nanocavities.

Significant Fluorescence Resonance Energy Transfer (FRET) process was observed between Naproxen (NPX) and a pharmaceutically important 3-pyrazolyl-2-pyrazoline derivative (PYZ) in bulk aqueous and heterogeneous cyclodextrin medium. The FRET efficacy of NPX-PYZ pair varied considerably in different cyclodextrin environments. Variation in the FRET efficacy mainly occurs due to a change in microenvironment of the fluorophores from bulk to a confined one. The structures of the FRET-pair and their interactions with cyclodextrins invoke a change in their spatial arrangement and proximity, which noticeably affects the FRET efficacy. The plausible explanations for this modulation in FRET efficacy has been established by employing steady state and time resolved fluorescence techniques in which simultaneous time-correlated analysis of the donor decay was observed to be reduced through FRET rather than some other relaxation pathway. Molecular Docking Analysis provided evidence of the possible modes of spatial orientation of the FRET pair in different cyclodextrin nano-cavities. Further TD-DFT calculations using B3LYP/6-31G/(d,p) method provided an intriguing insight about the medium dependent changes in the energies of the frontier molecular orbitals (HOMO-LUMO) associated with the corresponding FRET pair.

Variation of FRET efficacy between Naproxen and PYZ within the Cyclodextrin cavities.125