The mechanism of Mo-catalyzed cyclodehydration was also probed computationally. We first evaluated four representative structures that correspond to complexes 2 based on the available crystallographic data (Figure ). Bis-oxo complexes 2 exist in two distinct and stable conformers schematically depicted as Z(N) (where two phenolic arms of the tripod ligand face the pyridine group) and Z(O) (where both the phenoxide groups are located closer the oxo group). Regardless of the substitution of the phenolic group, the Z(N) structures are more stable (DG 9.3-11.7 kcal•mol -1 ), but their relative stabilities vary depending on the size of the R 1 group located on the spectator pyridine ligand. The calculated barriers for interconversion of these structures are low (DG # 1.2-2.4 kcal•mol -1 ), and at the reaction conditions, both conformers are readily available. This unique feature allows for accommodation of a broad selection of substrates as the catalyst can adopt optimal conformation in response to the geometry of the reactants. Next, we analyzed the reaction profile with model amides 51 and the Z(N) isomer of 52 (Figure ). The removal of water from amides is a thermodynamically unfavorable process that requires at least two challenging steps to take place: rotation to an amide with Z configuration and breakage of the carbonyl group. The DFT study supports the notion that the pyridine group can help to recruit the substrates to bind to the molybdenum center (53 and 54), but in the reactive conformer 55 that undergoes cyclization the assistance of pyridine moiety is not required. Furthermore, intermediate 55 shows favorable enthalpic binding (1.3-2 kcal•mol -1 ) which is sufficient to overcomes the barrier for amide rotation and supports the notion that two binding sites in the substrates are required for cyclization. It is also intriguing to note that the most stable structure 55 originates from hydrogen bonding between OH/SH groups and one of the phenolic ligands. Subsequent steps lead to two intermediates 56 and 57 that are stabilized by pyridine and the oxo ligand. From these two structures, the loss of water can proceed with the assistance of catalyst scaffolding (e.g., pyridine) but can also take place after dissociation of oxazolidine/thiazolidine from molybdenum.