2 Method
The processes of the calculation were as follows:
(1) Generate initial conformations of probes with Confab;10
(2) Use Crest to call xtb to do batch structural optimization under the GFN2-xTB method,11 and then call isostat in Molclus12 program to screen out several conformations with the lowest energy for next step;
(3) Use Molclus to call ORCA13 to perform optimization and vibrational frequency analysis on the conformations generated from step (2) under PBE0/def2-TZVP,14, 15 and then single point energy and TDDFT calculation under wB2GP-PLYP/def2-TZVP so as to obtain the free energy with high precision.16, 17