Effect of Water Microsolvation on the Excited-State Proton Transfer of 3-Hydroxyflavone Enclosed in γ-Cyclodextrin

Abstract

The effect of microsolvation on excited-state proton transfer (ESPT) reaction of 3-hydroxyflavone (3HF) and its inclusion complex with γ-cyclodextrin (γ-CD) was studied using computational approaches. From molecular dynamics simulations, two possible inclusion complexes formed by the chromone ring (C-ring, Form I) and the phenyl ring (P-ring, Form II) of 3HF insertion to γ-CD were observed. Form II is likely more stable because of lower fluctuation of 3HF inside the hydrophobic cavity and lower water accessibility to the encapsulated 3HF. Next, the conformation analysis of these models in the ground (S₀) and the first excited (S₁) states was carried out by density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations, respectively, to reveal the photophysical properties of 3HF influenced by the γ-CD. The results show that the intermolecular hydrogen bonding (interHB) between 3HF and γ-CD, and intramolecular hydrogen bonding (intraHB) within 3HF are strengthened in the S₁ state confirmed by the shorter interHB and intraHB distances and the red-shift of O-H vibrational modes involving in the ESPT process. The simulated absorption and emission spectra are in good agreement with the experimental data. Significantly, in the S₁ state, the keto form of 3HF is stabilized by γ-CD, explaining the increased quantum yield of keto emission of 3HF when complexing with γ-CD in the experiment. In the other word, ESPT of 3HF is more favorable in the γ-CD hydrophobic cavity than in aqueous solution.

Keywords: 3-hydroxyflavone (3HF); density functional theory (DFT); excited-state proton transfer (ESPT); molecular dynamics (MD); γ-cyclodextrin (γ-CD).

Figure 1

(A) Chemical structure of 3-Hydroxyflavone, 3HF. (B) Docked structures of the two possible 3HF/γ-CD complexes, Form I and Form II, where their percentage of occurrence and the lowest interaction energy retrieved from 100 independent docking runs are also given.

Figure 2

The plots of distance measured from the C_m of each 3HF ring to the C_m of the primary rim of γ-CD (all 7 O6 atoms) for the four MD simulations MD1-MD4 with different initial structures of complexes in Form I and Form II.

Figure 3

(A) Radial distribution function (RDF or g(r)) of water oxygen atoms around the O1-O3 atoms of 3HF encapsulated in the γ-CD cavity over the last 50-ns MD simulations for Form I (MD3-MD4) and Form II (MD1-MD4 with initial structures in this form and additional MD1-MD2 from re-encapsulation process found in Form I). (B) Average integration number, n(r), up to the first minimum derived from RDF plots, corresponding to the number of water molecules pointing toward the focused oxygens of 3HF.

Figure 4

All S₀ optimized structures of 3HF, 3HFW, and the different conformations of the 3HF/γ-CD inclusion complexes (Form I and Form II) as well as its inclusion complex with a water molecule (Form I-W and Form II-W) computed by PBE0/def2-SVP level of theory. The blue and green dot lines represent intraHB in 3HF and interHBs between 3HF and a water molecule, respectively.

Figure 5

Frontier MOs of all studied compounds.