Comparisons (25 degrees C) are made of substitution reactions, X replacing H2O, at the tetrahedral Ni of the heterometallic sulfide cuboidal cluster [Mo3NiS4(H2O)(10)](4+), I = 2.00 M (LiClO4). Stopped-flow formation rate constants (k(f)/M(-1) s(-1)) for six X reagents, including two water soluble air-stable phosphines, 1,3,5-triaza-7-phosphaadamantane PTA (119) and-tris(3-sulfonatophenyl)phosphine TPPTS3- (58), and CO (0.66), Br- (14.6), I- (32.3), and NCS- (44) are reported alongside the previous value for Cl- (9.4). A dependence on [H+] is observed with PTA, which gives an unreactive form confirmed by NMR as N-protonated PTA (acid dissociation constant K-a = 0.61 M), but in no other cases with [H+] in the range 0.30-2.00 M. The narrow spread of rate constants for all but the CO reaction is consistent with an I-d dissociative interchange mechanism. In addition NMR studies with (H2O)-O-17 enriched solvent are too slow for direct determination of the water-exchange rate constant indicating a value <10(3) s(-1). Equilibrium constants/M(-1) for 1:1 complexing with the different X groups at the Ni are obtained for PTA (2040) and TPPTS3- (8900) by direct spectrophotometry and from kinetic studies (k(f)/k(b)) for Cl- (97), Br- (150), NCS- (690), and CO (5150). No NCS- substitution at the Ni is observed in the case of the heterometallic cube [Mo3Ni(L)S-4(H2O)(9)](4+), with tridentate 1,4,7-triazacyclononane(L) coordinated to the Ni. Substitution of NCS- for H2O, at the Mo’s of [Mo3NiS4(H2O)(10)](4+) and [Mo-3(NiL)S-4(H2O)9](4+) are much slower secondary processes, with k(f) = 2.7 x 10(-4) M(-1) s(-1) and 0.94 x 10(-4) M(-1) s(-1) respectively. No substitution of H2O by TPPTS3- or CO is observed over similar to 1h at either metal on [Mo3FeS4(H2O)(10)](4+), on [Mo4S4(H2O)(12)](5+) or [Mo3S4(H2O)9](4+).