Conclusions
In conclusion, this study takes advantage of our previous work on
1,3-dipolar cycloaddition where we synthesized 36 novel polyheterocyclic
1,2,4-oxadiazolindolone compounds by a one-step
reaction.31 The 6-31G(d) basis set and B3LYP, M052X,
M062X, and APFD functionals were used to optimize the geometries and
determine the vibrational frequencies of 5 reactants, 5 intermediates,
and 36 products. The results showed symmetry matching between the LUMO
of substituted chloroxime compounds and HOMO of substituted isatin in
the LUMO-controlled reaction. Furthermore, the presence of a phenyl
group in chloroxime is more conducive to the reaction because an
electron-withdrawing substituent on the phenyl group can reduce the LUMO
energy level of the reactant and thus facilitate the reaction. When
isatin is substituted with an electron-donating group, the HOMO energy
level increases, which is also beneficial to the reaction. In this
study, the applicability of the B3LYP functional to this system was
determined, and the reaction mechanism was discussed at the
B3LYP/6-31G(d) level. The three main elementary reactions and
corresponding transition states, TS1, TS2, and TS3, in the liquid and
gas phases were calculated and discussed. Using the IRC method, the
accuracy of the transition states was confirmed, and the advantages and
disadvantages of LQA, HPC, and GS2 in producing the IRC were compared.
HPC produced an IRC curve with higher accuracy, and the two ends of the
curve were closer to the structure of the product. The reaction process
was calculated. Finally, by comparing the ΔE avalues for the gas- and liquid-phase reactions, it was proven that the
solvent only has a minor effect on the reaction process. This study is
expected to have a long-term significance by providing useful ideas for
the design of more effective drugs of this kind in the future.
ASSOCIATED CONTENT
Supporting Information .
The following files are available free of charge.
The specific experimental steps, the energy difference between the
lowest unoccupied molecular orbital (LUMOs) and the highest occupied
molecular orbital (HOMOs) of the reactants at different levels, the ΔG
of each reaction in the gas phase at different levels. And the Cartesian
coordinates (Å) of the optimal structure of the fixed point in the
liquid phase reaction can be seen in the attachment support information.
(file type, i.e., PDF)
Notes
The authors declare no competing financial interest.