Nitrile hydration to amides catalyzed by [Cp2Mo(OH)(OH2)]+ has been theoretically investigated by using acrylonitrile as a model and performing density functional theory calculations (B3LYP), both in the gas phase and in water solution. In both media, our results confirm the experimental belief that, among four plausible proposals, the intramolecular nucleophilic mechanism is the most favored for this kind of process. A hydrogen migration from oxygen to nitrogen atoms is the rate-limiting step in the gas phase. In the continuum solvation model the most significant energy barriers become larger than in the gas phase due to the relatively large solvation of the [Cp2Mo(OH)]+ complex, which is taken as reference to measure such barriers. However, the inclusion of explicit water molecules in the hydrogen migration between oxygen and nitrogen atoms notably stabilizes this step; thus the attack of the catalyst hydroxide to the nitrile becomes the rate-limiting step in water solution with a Gibbs energy barrier of 33.8 kcal/mol, in agreement with the slow reaction rate experimentally observed. The replacement of acrylonitrile by lactonitrile, isobutyronitrile, acetonitrile, propionitrile, and 3-hydroxypropionitrile also gives rise to rate-determining Gibbs energy barriers in water solution consistent with experimental trends for the effect of electron-withdrawing substituents and for the effect of enlargement of the backbone of the nitrile, thus corroborating the reaction mechanism found for the title hydration process investigated.

Density functional theory methodologies combined with continuum and discrete-continuum descriptions of solvent effects were used to investigate the [Pd(OH2)4](2+)-catalyzed acrylonitrile hydration to yield acrylamide. According to our results, the intramolecular hydroxide attack mechanism and the external addition mechanism of a water molecule with rate-determining Gibbs energy barriers in water solution of 27.6 and 28.3 kcal/mol, respectively, are the most favored. The experimental kinetic constants of the hydration started by hydroxide, k(OH), and water, k(H2O), attacks for the cis-[Pd(en)(OH2)2](2+)-catalyzed dichloroacetonitrile hydration rendered Gibbs energy barriers whose energy difference, 0.7 kcal/mol, is the same as that obtained in the present study. Our investigation reveals the nonexistence of the internal attack of a water ligand for Pd-catalyzed nitrile hydration. At the low pHs used experimentally, the equilibrium between [Pd(OH2)3(nitrile)](2+) and [Pd(OH2)2(OH)(nitrile)](+) is completely displaced to [Pd(OH2)3(nitrile)](2+). Experimental studies in these conditions stated that water acts as a nucleophile, but they could not distinguish whether it was a water ligand, an external water molecule, or a combination of both possibilities. Our theoretical explorations clearly indicate that the external water mechanism becomes the only operative one at low pHs. On the basis of this mechanistic proposal it is also possible to ascribe an (1)H NMR signal experimentally detected to the presence of a unidentate iminol intermediate and to explain the influence of nitrile concentration reported experimentally for nitriles other than acrylonitrile in the presence of aqua-Pd(II) complexes. Therefore, our theoretical point of view on the mechanism of nitrile hydration catalyzed by aqua-Pd(II) complexes can shed light on these relevant processes at a molecular level as well as afford valuable information that can help in designing new catalysts in milder and more efficient conditions.

Density functional calculations have been performed to rationalize the oxidation of carbon monoxide by [Cp2Mo(OH)(OH2)]+ (Cp = η5‐C5H5) to give carbon dioxide and [Cp2MoH(CO)]+. Our results show that the intramolecular nucleophilic mechanism is the most favored both in the gas phase and in water solution, which is in good agreement with experimental results. The rearrangement that takes place during the nucleophilic hydroxide attack with a simultaneous hydrogen migration to the molybdenum center is the rate‐determining step in the gas phase with a Gibbs energy barrier of 48.7 kcal mol–1. In water medium, however, this combined process takes place separately and passes through a new [Cp2Mo(COOH)]+‐type intermediate. The inclusion of one explicit water molecule in the continuum solvent model computations plays a crucial role to make the nucleophilic hydroxide attack the rate‐determining step in the overall reactive process with a Gibbs energy barrier in solution of 21.2 kcal mol–1. Besides this, our results have allowed us to rationalize the relatively low conversion of [Cp2Mo(OH)(OH2)]+ that was experimentally found.

A thoroughly mechanistic investigation on the [Cp2Mo(OH)(OH2)](+)-catalyzed hydrolysis of ethyl acetate has been performed using density functional theory methodology together with continuum and discrete-continuum solvation models. The use of explicit water molecules in the PCM-B3LYP/aug-cc-pVTZ (aug-cc-pVTZ-PP for Mo)//PCM-B3LYP/aug-cc-pVDZ (aug-cc-pVDZ-PP for Mo) computations is crucial to show that the intramolecular hydroxo ligand attack is the preferred mechanism in agreement with experimental suggestions. Besides, the most stable intermediate located along this mechanism is analogous to that experimentally reported for the norbornenyl acetate hydrolysis catalyzed by molybdocenes. The three most relevant steps are the formation and cleavage of the tetrahedral intermediate immediately formed after the hydroxo ligand attack and the acetic acid formation, with the second one being the rate-determining step with a Gibbs energy barrier of 36.7 kcal/mol. Among several functionals checked, B3LYP-D3 and M06 give the best agreement with experiment as the rate-determining Gibbs energy barrier obtained only differs 0.2 and 0.7 kcal/mol, respectively, from that derived from the experimental kinetic constant measured at 296.15 K. In both cases, the acetic acid elimination becomes now the rate-determining step of the overall process as it is 0.4 kcal/mol less stable than the tetrahedral intermediate cleavage. Apart from clarifying the identity of the cyclic intermediate and discarding the tetrahedral intermediate formation as the rate-determining step for the mechanism of the acetyl acetate hydrolysis catalyzed by molybdocenes, the small difference in the Gibbs energy barrier found between the acetic acid formation and the tetrahedral intermediate cleavage also uncovers that the rate-determining step could change when studying the reactivity of carboxylic esters other than ethyl acetate substrate specific toward molybdocenes or other transition metal complexes. Therefore, in general, the information reported here could be of interest in designing new catalysts and understanding the reaction mechanism of these and other metal-catalyzed hydrolysis reactions.

Replacement of [Pd(H 2 O) 4 ] 2? by cis-[Pd(en) (H 2 O) 2 ] 2? , [PdCl 4 ] 2-, and [Pd(NH 3) 4 ] 2? on the hydrolytic cleavage of the Ace-Ala-Lys-Tyr-Gly-Gly-Met-Ala-Ala-Arg-Ala peptide is theoretically investigated by using different quantum chemical methods both in the gas phase an in water solution. First, we carry out a series of validation calculations on small Pd(II) complexes by computing highlevel ab initio [MP2 and CCSD(T)] and Density Functional Theory (B3LYP) electronic energies while solvent effects are taken into account by means of a Poisson-Boltzmann continuum model coupled with the B3LYP method. After having assessed the actual performance of the DFT calculations in predicting the stability constants for selected Pd(II)-complexes, we compute the relative free energies in solution of several Pd(II)-peptide model complexes. By assuming that the reaction of the peptide with cis-[Pd(en)(H 2 O) 2 ] 2? , [Pd(Cl) 4 ] 2-, and [Pd(NH 3) 4 ] 2? would lead to the initial formation of the respective peptide-bound complexes, which in turn would evolve to afford a hydrolytically active complex [Pd(peptide)(H 2 O) 2 ] 2? through the displacement of the en, Cl-, and NH 3 ligands by water, our calculations of the relative stability of these complexes allow us to rationalize why [Pd(H 2 O) 4 ] 2? and [Pd(NH 3) 4 ] 2? are more reactive than cis-[Pd(en)(H 2 O) 2 ] 2? and [PdCl 4 ] 2as experimentally found.