Modeling Amine Methylation in Methyl Ester Cavitand.

Methylation of amines inside an introverted resorcinarene-based deep methyl ester cavitand is investigated by means of molecular dynamics simulations and quantum chemical calculations. Experimentally, the cavitand has been shown to bind a number of amines and accelerate the methylation reaction by more than four orders of magnitude for some of them. Eight different amines are considered in the present study, and the geometries and energies of their binding to the cavitand are first characterized and analyzed. Next, the methyl transfer reactions are investigated and the calculated barriers are found to be in generally good agreement with experimental results. In particular, the experimentally-observed rate acceleration in the cavitand as compared to the solution reaction is well reproduced by the calculations. The origins of this rate acceleration are analyzed by computational modifications made to the structure of the cavitand, and the role of the solvent is discussed.

Catalysis by [Ga4 L6 ]12- Metallocage on the Nazarov Cyclization: The Basicity of Complexed Alcohol is Key.

The Nazarov cyclization is investigated in solution and within K12 [Ga4 L6 ] supramolecular organometallic cage by means of computational methods. The reaction needs acidic condition in solution but works at neutral pH in the presence of the metallocage. The reaction steps for the process are analogous in both media: (a) protonation of the alcohol group, (b) water loss and (c) cyclization. The relative Gibbs energies of all the steps are affected by changing the environment from solvent to the metallocage. The first step in the mechanism, the alcohol protonation, turns out to be the most critical one for the acceleration of the reaction inside the metallocage. In order to calculate the relative stability of protonated alcohol inside the cavity, we propose a computational scheme for the calculation of basicity for species inside cavities and can be of general use. These results are in excellent agreement with the experiments, identifying key steps of catalysis and providing an in-depth understanding of the impact of the metallocage on all the reaction steps.

Origin of the Rate Acceleration in the C-C Reductive Elimination from Pt(IV)-complex in a [Ga4 L6 ]12- Supramolecular Metallocage.

The reductive elimination on [(Me3 P)2 Pt(MeOH)(CH3 )3 ]+ , 2P, complex performed in MeOH solution and inside a [Ga4 L6 ]12- metallocage are computationally analysed by mean of QM and MD simulations and compared with the mechanism of gold parent systems previously reported [Et3 PAu(MeOH)(CH3 )2 ]+ , 2Au. The comparative analysis between the encapsulated Au(III) and Pt(IV)-counterparts shows that there are no additional solvent MeOH molecules inside the cavity of the metallocage for both systems. The Gibbs energy barriers for the 2P reductive elimination calculated at DFT level are in good agreement with the experimental values for both environments. The effect of microsolvation and encapsulation on the rate acceleration are evaluated and shows that the latter is far more relevant, conversely to 2Au. Energy decomposition analysis indicates that the encapsulation is the main responsible for most of the energy barrier reduction. Microsolvation and encapsulation effects are not equally contributing for both metal systems and consequently, the reasons of the rate acceleration are not the same for both metallic systems despite the similarity between them.

Modeling Kinetics and Thermodynamics of Guest Encapsulation into the [M4L6]12- Supramolecular Organometallic Cage.

The encapsulation of molecular guests into supramolecular hosts is a complex molecular recognition process in which the guest displaces the solvent from the host cavity, while the host deforms to let the guest in. An atomistic description of the association would provide valuable insights on the physicochemical properties that guide it. This understanding may be used to design novel host assemblies with improved properties (i.e., affinities) toward a given class of guests. Molecular simulations may be conveniently used to model the association processes. It is thus of interest to establish efficient protocols to trace the encapsulation process and to predict the associated magnitudes ΔGbind and ΔGbind⧧. Here, we report the calculation of the Gibbs energy barrier and Gibbs binding energy by means of explicit solvent molecular simulations for the [Ga4L6]12- metallocage encapsulating a series of cationic molecules. The ΔGbind⧧ for encapsulation was estimated by means of umbrella sampling simulations. The steps involved were identified, including ion-pair formation and naphthalene rotation (from L ligands of the metallocage) during the guest's entrance. The ΔGbind values were computed using the attach-pull-release method. The results reveal the sensitivity of the estimates on the force field parameters, in particular on atomic charges, showing that higher accuracy is obtained when charges are derived from implicit solvent quantum chemical calculations. Correlation analysis identified some indicators for the binding affinity trends. All computed magnitudes are in very good agreement with experimental observations. This work provides, on one side, a benchmarked way to computationally model a highly charged metallocage encapsulation process. This includes a nonstandard parameterization and charge derivation procedure. On the other hand, it gives specific mechanistic information on the binding processes of [Ga4L6]12- at the molecular level where key motions are depicted. Taken together, the study provides an interesting option for the future design of metal-organic cages.

Peptide Hydrolysis by Metal (Oxa)cyclen Complexes: Revisiting the Mechanism and Assessing Ligand Effects.

The mechanism responsible for peptide bond hydrolysis by Co(III) and Cu(II) complexes with (oxa)cyclen ligands has been revisited by means of computational tools. We propose that the mechanism starts by substrate coordination and an outer-sphere attack on the amide C atom of a solvent water molecule assisted by the metal hydroxo moiety as a general base, which occurs through six-membered ring transition states. This new mechanism represents a more likely scenario than the previously proposed mechanisms that involved an inner-sphere nucleophilic attack through more strained four-membered rings transition states. The corresponding computed overall free-energy barrier of 25.2 kcal mol-1 for hydrolysis of the peptide bond in Phe-Ala by a cobalt(III) oxacyclen catalyst (1) is consistent with the experimental values obtained from rate constants. Also, we assessed the influence of the nature of the ligand throughout a systematic replacement of N by O atoms in the (oxa)cyclen ligand. Increasing the number of coordinating O atoms accelerates the reaction by increasing the Lewis acidity of the metal ion. On the other hand, the higher reactivity observed for the copper(II) oxacyclen catalyst with respect to the analogous Co(III) complex can be attributed to the larger Brönsted basicity of the copper(II) hydroxo ligand. Ultimately, the detailed understanding of the ligand and metal nature effects allowed us to identify the double role of the metal hydroxo complexes as Lewis acids and Brönsted bases and to rationalize the observed reactivity trends.

Reaction Rate Inside the Cavity of [Ga4 L6 ]12- Supramolecular Metallocage is Regulated by the Encapsulated Solvent.

In the present study the dependence of the reaction rate of carbon-carbon reductive elimination from R3 PAu(MeOH)(CH3 )2 (R=Me, Et) complexes inside [Ga4 L6 ]12- metallocage on the nature of the phosphine ligand is investigated by computational means. The reductive elimination mechanism is analyzed in methanol solution and inside the metallocage. Classical molecular dynamics simulations reveal that the smaller the gold complex (which depends on the phosphine ligand size) the larger the number of solvent molecules encapsulated. The size of the phosphine ligands defines the space that is left available inside the cavity that can be occupied by solvent molecules. The Gibbs energy barriers calculated at DFT level, in excellent agreement with experiment both in solution and in the metallocage, show that the presence/absence of explicit solvent molecules inside the cavity significantly modifies the reaction rate.

A Reversible Phase Transition of 2D Coordination Layers by B-H∙∙∙Cu(II) Interactions in a Coordination Polymer.

Materials that combine flexibility and open metal sites are crucial for myriad applications. In this article, we report a 2D coordination polymer (CP) assembled from CuII ions and a flexible meta-carborane-based linker [Cu2(L1)2(Solv)2]•xSolv (1-DMA, 1-DMF, and 1-MeOH; L1: 1,7-di(4-carboxyphenyl)-1,7-dicarba-closo-dodecaborane). 1-DMF undergoes an unusual example of reversible phase transition on solvent treatment (i.e., MeOH and CH2Cl2). Solvent exchange, followed by thermal activation provided a new porous phase that exhibits an estimated Brunauer-Emmett-Teller (BET) surface area of 301 m2 g-1 and is capable of a CO2 uptake of 41 cm3 g-1. The transformation is reversible and 1-DMF is reformed on addition of DMF to the porous phase. We provide evidence for the reversible process being the result of the formation/cleavage of weak but attractive B-H∙∙∙Cu interactions by a combination of single-crystal (SCXRD), powder (PXRD) X-ray diffraction, Raman spectroscopy, and DFT calculations.

Microsolvation and Encapsulation Effects on Supramolecular Catalysis: C-C Reductive Elimination inside [Ga4L6]12- Metallocage.

The host effect of the supramolecular [Ga4L6]12- tetrahedral metallocage on reductive elimination of substrate by encapsulated Au(III) complexes is investigated by means of computational methods. The behavior of the reactants in solution and within the metallocage is initially evaluated by means of classical molecular dynamics simulations. These results guided the selection of proper computational models to describe the reaction in solution and inside the metallocage at the DFT level. The calculated Gibbs energy barriers are in very good agreement with experiment both in solution and inside the metallocage. The analysis in solution revealed that microsolvation around the Au(III) complex increases the Gibbs energy barrier. The analysis within the metallocage shows that its encapsulation favors the reaction. The process can be formally described as removing explicit microsolvation around the gold complex and encapsulating the metal complex inside the metallocage. Both processes are important for the reaction, but the removal of the solvent molecules surrounding the Au(III) metal complex is fundamental for the reduction of the reaction barrier. The energy decomposition analysis of the barrier among strain, interaction, and thermal terms shows that strain term is very low whereas the contribution of thermal (entropic) effects is moderate. Interestingly, the key term responsible for reducing the Gibbs energy barrier is the interaction. This term can be mainly associated with electrostatic interactions in agreement with previous examples in the literature.