In this study, the combined results of electrochemical, EPR, DFT, and biochemical experiments have established that the dirhodium complexes cis-[Rh2(O2CCH3)2(R1R2dppz)2]2+ (R1R2dppz = substituted dipyrido[3,2-a:2′,3′-c]phenazine) constitute a sensitive redox-regulated series of T7-RNAP inhibitors that are readily tuned by alternating the electron-withdrawing or -donating ability of the dppz substituents. Inhibition of transcription takes place via formation of intra- and inter-T7-RNAP disulfide bonds that affect the enzyme critical sulfhydryl cysteine groups.