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

Abstract

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.

Reaction Rate Inside the Cavity of [Ga4L6]12− Supramolecular Metallocage is Regulated by the Encapsulated Solvent

“…[32][33][34][35][36][37][38][39] In the case of highly charged hosts, as the [Ga 4 L 6 ] 12À metallocage,a ll theoretical investigations indicate that electrostatic effects are essential for the rate acceleration. [40][41][42][43] In our previous study,w es howed that not only encapsulation by the host, but also microsolvation is important for lowering the Gibbs energy barriero ft he reductivee limination from the cationic Au III complex, R 3 PAu(MeOH)(CH 3 ) 2 ,i nside [Ga 4 L 6 ] 12À . [43] We here investigate computationally the origin of the different catalytic behavior observede xperimentallyf or CÀCr eductivee limination using PEt 3 and PMe 3 as ligands for the same gold complex( Scheme 1).The CÀCr eductivee limination reactioni se valuated computationally for [Me 3 PAu(I)(CH 3 ) 2 ] 1M as starting reactanti n MeOH solution( Scheme1)i ncludingt he first solvation shell explicitly (12 MeOH molecules;F igure 1b lack profile).…”

“…[40][41][42][43] In our previous study,w es howed that not only encapsulation by the host, but also microsolvation is important for lowering the Gibbs energy barriero ft he reductivee limination from the cationic Au III complex, R 3 PAu(MeOH)(CH 3 ) 2 ,i nside [Ga 4 L 6 ] 12À . [43] We here investigate computationally the origin of the different catalytic behavior observede xperimentallyf or CÀCr eductivee limination using PEt 3 and PMe 3 as ligands for the same gold complex( Scheme 1).The CÀCr eductivee limination reactioni se valuated computationally for [Me 3 PAu(I)(CH 3 ) 2 ] 1M as starting reactanti n MeOH solution( Scheme1)i ncludingt he first solvation shell explicitly (12 MeOH molecules;F igure 1b lack profile). [44] Assumingt he formation of the cationic species 2M-12 ([Me 3 PAu(MeOH)(CH 3 ) 2 ] + )t he calculated Gibbs energy barrieri s 26.2 kcal mol À1 (Figure1), in excellent agreementw ith the estimated value of 27.2 kcal mol À1 obtained experimentally from the measuredr ate constant of 6.6 10 À8 s À1 at 298 K. [21] In the transition state, TS_2M-12,t he formingC ÀCb ond distance is 2.176 .F or comparison, the results for complex 2E with PEt 3 lead to aG ibbs energy barrier is 25.0 kcal mol À1 , [43] TS_2E-12, also in very good agreement with the experimental value of 26.7 kcal mol À1 .T herefore, the difference in calculated Gibbs energy barriers for gold complexesw ith PMe 3 and PEt 3 ligands in solution is 1.2 kcal mol À1 (26.2 vs. 25.0 kcal mol À1 ,f rom the startingg old complexes) which is also close to the experimen-[a] G.Communication doi.org/10.1002/chem.201905608 tal difference of 0.5 kcal mol À1 (FigureS4b).…”

“…1M:R= Me; 1E:R= Et.Figure 1. Gibbs energy profiles (in kcal mol À1 )for the reductive elimination of [(R 3 P)Au III (CH 3 ) 2 ]i nMeOHsolution and in metallocage.Communication doi.org/10.1002/chem.201905608 tion): [43] removing explicit solvent MeOH molecules aroundt he cationic gold complex decreases the Gibbs energy barrier of the reductive elimination.To proceed with the study of the encapsulated reaction we first performed classical molecular dynamics (MD) simulations of the gold complex inside metallocage 3. [44] Calculations were carried out within ap eriodic box of explicit solvent MeOH molecules.…”

“…The effects of microsolvation ande ncapsulation for 2E (containing PEt 3 )w eref ound to be ad iminishing the barrier by 5.7 and 3.1 kcal mol À1 ,r espectively. [43] The main difference comes from the microsolvation process:i n2M-2,t he gold complex (with PMe 3 )i ss urrounded by two MeOH solventm olecules (one coordinated and one not) whereas in 2E the gold complex (with PEt 3 )c ontains only one EtOH (the one coordinated).A ccording to the calculatedb arriers, the presence of the second MeOH solventm olecule for the complex with the smaller phosphine ligand hasadecisive role in hampering the reaction.So far,o ur study points out that the difference in microsolvation between 2M&3 and 2E&3 is likely to be the main reason responsible for the change in acceleration rate observed experimentally.W ed ecided to investigate further the origin and the impact of such changes in the solvation profiles. First, as eries of calculations werec arried out on 2M&3;a system where the square-planar gold complex 2M inside the metallocage has no additional solvent molecules apart from the coordinated one ( Figure S3).…”

“…[40][41][42][43] In our previous study,w es howed that not only encapsulation by the host, but also microsolvation is important for lowering the Gibbs energy barriero ft he reductivee limination from the cationic Au III complex, R 3 PAu(MeOH)(CH 3 ) 2 ,i nside [Ga 4 L 6 ] 12À . [43] We here investigate computationally the origin of the different catalytic behavior observede xperimentallyf or CÀCr eductivee limination using PEt 3 and PMe 3 as ligands for the same gold complex( Scheme 1).…”