The symmetrical 2,2′‐disubstitued derivatives of diphenyl disulfide showing widely spanning rates of electrophilic attack of the HIV‐1 nucleocapsid protein p7 zinc fingers have been rationalized, based on the lowest unoccupied molecular orbital (LUMO)‐lowering approach, by the substituents' π‐effects and the hydrogen bond stabilization effects. In the 2,2′‐amide‐ and 4,4′‐N‐amide‐substituted derivatives, the extent of LUMO lowering has been reduced by the destabilization of lone‐pair bond orbital, lp(N), present on the nitrogen atom of N‐amide. From the natural bond orbital viewpoint, hydrogen bond stabilization of LUMO is mainly governed by stabilization of the σ*SS bond orbital.