The kinetics of exchange of phenylethanethiolate ligands (PhC2S) of monolayer-protected clusters (MPCs, average formula Au-140(PhC2S)(53)) by para-substituted arylthiols (p-X-ArSH) are described. H-1 NMR measurements of thiol concentrations show that the exchange reaction is initially rapid and gradually slows almost to a standstill. The most labile ligands, exchanging at the shortest reaction times, are thought to be those at defect sites (edges, vertexes) on the nanoparticle core surface. The pseudo-first-order rate constants derived from the first 10% of the exchange reaction profile vary linearly with in-coming arylthiol concentration, meaning that the labile ligands exchange in a second-order process, which is consistent with ligand exchange being an associative process. A linear Hammett relationship with slope rho = 0.44 demonstrates a substituent effect in the ligand place exchange reaction, in which the bimolecular rate constants increase for ligands with electron-withdrawing substituents (1.4 x 10(-2) and 3.8 x 10(-3) M-1 s(-1) for X = NO2 and 4-OH, respectively). This is interpreted as the more polar Au-S bonds at the defect sites favoring bonding with more electron deficient sulfur moieties. At longer reaction times, where ligands exchange on nondefect (terrace) as well as defect sites, the extent of ligand exchange is higher for thiols with more electron-donating substituents. The difference between short-time kinetics and longer-time pseudoequilibria is rationalized based on differences in Au-S bonding at defect vs nondefect MPC core sites. The study adds substance to the mechanisms of exchange of protecting ligands on nanoparticles. The scope and limitations of H-1 NMR spectroscopy for determining rate data are also discussed.