The reactivity of bulky alkylphosphino-thiol ligands (PSH) toward nitride-M(V, VI) (M = Tc/Re) precursors was investigated. Neutral five-coordinate monosubstituted complexes of the type [M(N)(PS)Cl(PPh3)] (Tc1-4, Re1-2) were prepared in moderate to high yields. It was found that these [M(N)(PS)Cl(PPh3)] species underwent ligand-exchange reactions under mild conditions when reacted with bidentate mononegative ligands having soft donor atoms such as dithiocarbamates (NaLn) to afford stable dissymmetrical mixed-substituted complexes of the type [M(N)(PS)(L-n)] (Tc5,8-10, Re5-9) containing two different bidentate chelating ligands bound to the [M N](2+) moiety. In these reactions, the dithiocarbamate replaced the two labile monodentate ligands (Cl and PPh3) leaving the [M(N)(PS)](+) building block intact. In the above reactions, technetium and rhenium were found to behave in a similar way. Instead, under more drastic conditions, reactions of PSH with [M(N)Cl-2(PPh3)(2)] gave a mixture of monosubstituted [M(N)(PS)Cl(PPh3)] and bis-substituted species [M(N)(PS)(2)] (Tc11-14) in the case of technetium, whereas only monosubstituted [M(N)(PS)Cl(PPh3)] complexes were recovered for rhenium. All isolated products were characterized by elemental analysis, IR and multinuclear (H-1, C-13, and P-31) NMR spectroscopies, ESI MS spectrometry, and X-ray crystal structure determination of the representative monosubstituted [Tc(N)(PStbu)Cl(PPh3)] (Tc4) and mixed-substituted [Re(N)(PScy)(L-3)] (Re7) and [Re(N)(PSiso)(L-4)] (Re9) complexes. The latter rhenium complexes represent the first example of a square-pyramidal nitrido Re species with the basal plane defined by a PS3 donor set. Monosubstituted [M(N)(PS)Cl(PPh3)] species bearing the substitution-inert [M(N)(PS)](+) moieties act as suitable building blocks proposed for the construction of new classes of dissymmetrical nitrido compounds with potential application in the development of essential and target specific Tc-19m and Re-188 radiopharmaceuticals for imaging and therapy, respectively.