**4. Conclusions**

The effect of water microsolvation on the strength of hydrogen bonding, ESIntraPT and ESInterPT reactions as well as photophysical behaviors of 3HF and its inclusion complexes in γ-CD has been systematically studied using MD simulations and DFT/TD-DFT at PBE0/TD-PBE0 with def2-SVP basis set. Two possible 3HF/γ-CD inclusion complexes; C-ring and P-ring insertions (Form I and Form II), were observed from molecular docking. From MD results, a lower 3HF mobility in the hydrophobic cavity and a lower water accessibility to the encapsulated 3HF in Form II suggest that this form is favorably more stable. From the static calculation results, the strength of hydrogen bonding of all studied compounds increases upon photoexcitation into the S<sup>1</sup> state leading to being easier deprotonation, confirmed by the change of important bond lengths (the increasing of the covalent O–H bond length of proton donor, together with decreasing of the O· · · H intraHBs and interHBs), the red shift of the O–H stretching modes, and the bond energy from the topology analysis. In addition, frontier MOs confirm that the main contribution for vertical S<sup>0</sup> to S<sup>1</sup> transition is π to π\* attributed from HOMO (π) to LUMO (π\*). For simulated spectra, the λabs of E, the λemis of E\* and the λemis of K\* are in good agreement with the experimental data (in the range of 0.52–0.61 eV relative differences) indicating that the present method is adequate to provide the information on their spectra and the possibility of ESPT processes. Besides, the ESIntraPT processes of the inclusion complexes (Form I and Form II) can occur easily like in the case of 3HF in aprotic solvents. Furthermore, the ESInterPT processes via interHBs of Form I-W and Form II-W inclusion complexes are

feasible to take place. In addition, K\* of Form II/Form II-W is more stable than that of Form I/Form I-W due to the lower energy and the higher oscillator strength. Consequently, the ESIntraPT and ESInterPT might be likely to occur in P-ring insertion in accordance with the MD results, in which P-ring insertion is the majority of the 3HF/γ-CD inclusion complexes with lower water accessibility. However, it is already known that the ESInterPT of 3HF in aqueous solution is hard to occur due to the higher ESInterPT barrier and the higher fluctuation of the water-rearrangement surrounding 3HF, which leads to a decrease of the fluorescence intensity. Thus, from the present work, we found that 3HF is stable inside the γ-CD hydrophobic cavity and promotes ESIntraPT by suppressing the 3HF-water network. This leads to the increment of fluorescent intensity. In the other word, the fluorescence intensity of K\* could be efficiently tuned via host-guest complexation.

**Supplementary Materials:** The following are available online. Figure S1: RMSD plots for all atoms and Rgyr of the two orientations of C-ring insertion (Form I), and P-ring insertion (Form II) inclusion complexes for four different MD runs of each system, Figure S2: The plots of distance measured from the C<sup>m</sup> of each 3HF ring to the C<sup>m</sup> of the secondary rim of γ-CD (all 7 O2 atoms) for the four MD simulations MD1-MD4 with different initial structures of complexes in Form I and Form II, Figure S3: The simulated absorption spectra of E, and the simulated emission spectra of E\* and K\* for all studied compounds computed at TD-PBE0/def2-SVP level of theory, Table S1: Electron density ρ(r), the Lagrangian kinetic energy G(r), potential energy density V(r), the Hamiltonian kinetic energy density H(r), the Laplacian of the electron density <sup>∇</sup>2ρ(r), the electron delocalization index (DI), and hydrogen-bonded energy (EHB) at selected BCPs in the S<sup>1</sup> state (a.u.) for all compounds.

**Author Contributions:** Conceptualization, N.K., T.R., and S.H.; methodology, K.K.; validation, N.K., T.R., and S.N.; formal analysis, K.K., and C.S.; data curation, K.K.; writing—original draft preparation, K.K.; writing—review and editing, R.D., N.K., T.R., and S.N.; visualization, K.K.; supervision, P.W., N.K., T.R., S.N., and S.H.; project administration, N.K., and S.H.; funding acquisition, N.K., T.R., and S.H. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research is supported by Ratchadapisek Somphot Fund for Postdoctoral Fellowship, Chulalongkorn University (CU).

**Acknowledgments:** The authors gratefully acknowledge the financial support from the Center of Excellence in Computational Chemistry (CECC) from Chulalongkorn University, the Center of Excellence in Materials Science and Technology, Chiang Mai University and the Office of National Higher Education Science Research and Innovation Policy Council (NXPO) in Global Partnership Project. N.K. thanks the Thailand Research Fund (Grant No. RSA6180044). Computational resources are provided by the Center of Excellence in Computational Chemistry (CECC), Computational Chemistry Laboratory Chiang Mai University (CCL-CMU), and NSTDA Supercomputer center (ThaiSC).

**Conflicts of Interest:** The authors declare no conflict of interest.

**Sample Availability:** Samples of the compounds are not available from the authors.
