Studies of the Characteristic Nature of Disulfide Bond in Unsaturated Systems by Natural Bond Orbital Method

Abstract

Analysis of compositions of a molecular orbital (MO) expanded in the bond orbital (BO) space provided by the natural bond orbital (NBO) method exhibits information based on the familiar Lewis structure It is therefore straightforward to explain observations through chemical substitution on MO energies obtained by experimental chemists The electron densities on BOs obtained by NBO calculations reveal the electron distributions on all chemical bonds and supply electron delocalization patterns described in the Lewis structure For a CF3 group both stabilization of the MO exerted by σ*CF BO and destabilization of MO by lp(F) BO have been found by the NBO method Since these two competing pi-effects are nearly counterbalanced as indicated by the vanishing values of crystal orbital overlap population the chemical substitution strategy originated from lowering of MOs by using electron-withdrawing group has been found effective in color-tuning to blue region Those orbital-based rationalizations give insight of color-tuning results observed for phosphorescent derivatives of Ir(III)-complexes The common feature involved in the anti-HIV activity study and the reductive cleavage of the disulfide bond performed on symmetrical disubstituted derivatives diphenyl disulfide (DPDS) is apparently pointed to the lowest unoccupied MO (LUMO) properties of DPDS The LUMO energy is considered in the anti-HIV activity study while the LUMO compositions are critical concerning the formation of the σ-type radical anion in the stepwise mechanism associated with the reductive cleavage of the disulfide bond The symmetrical 2 2’-disubstituted DPDS-derivatives showing widely spanning rates of electrophilic attack of the HIV-1 nucleocapsid protein p7 zinc fingers have been rationalized based on the LUMO-lowering approach by the substituents’ π-effects and the hydrogen bond (HB) stabilization effects In the NBO viewpoint hydrogen bond stabilization of the LUMO is primarily governed by intramolecular HB-stabilization of the σ*SS BO The larger composition of σ*SS BO compared to π*CC BOs of phenyl groups to the LUMO of DPDS lays the foundation for the formation of σ-type radical anion found by studies of reductive cleavage of disulfide bond performed on 4 4’-disubstitued DPDS-derivatives The weakening of disulfide bond in DPDS and its derivatives is attributed to the increasing electron density on σ*SS BO through negative hyperconjugation

Date of Award	2020
Original language	English
Supervisor	Fu-Yung Huang (Supervisor)