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

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. (C) 2017 Elsevier B.V. All rights reserved.