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

Abstract

In the present study the dependenceo ft he reaction rate of carbon-carbon reductivee limination from R 3 PAu(MeOH)(CH 3 ) 2 (R = Me, Et) complexes inside [Ga 4 L 6 ] 12À 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. Classicalm olecular dynamics simulations reveal that the smallert he gold complex (which depends on the phosphine ligand size) the larger the number of solvent molecules encapsulated. The size of the phosphine ligandsd efines the space that is left available inside the cavity that can be occupied by solvent molecules.T he 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. Supramolecular catalysis is av ery rapid expanding discipline that joins catalysis and supramolecular chemistry. [1][2][3][4][5][6][7][8] Several supramolecular hosts have been designeda sn anoreactors and appliedt ot he host-guestc atalysis, with metallocages playing ap rominent role. [9][10][11][12] Metallocages (M x L y )a re synthesized from metal ions and organic ligands( linkers) and offer well defined cavities in size and shape to host molecules and chemical reactions. [13,14] Examples include Raymond's Ga 4 L 6 (L = (L = N,N'bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene), [15] Fujita's Pd 6 L 4 (L = 1,3,5-tris(4-pyridyl)triazine), [16] Nitschke'st erphenyl edged Fe 4 L 6 , [17] Lusby's Pd 2 L 4 (L = 2,6-bis(3-pyridinylethynyl)pyridine), [18] among others. [19,20] The tetrahedron supramolecular metallocage, K 12 [Ga 4 L 6 ]d evelopedb yR aymonda nd co-workers,h as been applied to many reactions as the CÀCr eductive elimination from Au III and Pt IV complexes, [21] the orthoformate hydrolysis, [22] Nazarov cyclization, [23] the hydroalkylation, [24] etc. [25][26][27] The great catalytic power of the metallocage, [Ga 4 L 6 ] 12À ,f or the CÀCr eductive elimination has been studied in detail by Bergman,R aymond and To ste. [21,28] One of the most interesting findings regarding the relationship between the metallocage and the hostedcatalytic system is related to the dependence of the catalytic kinetics in function of the nature of the phosphine ligand. Indeed, the presence of PEt 3 versus PMe 3 as goldligand significantly influences the Gibbs energy barrier of the reductive elimination inside the metallocage, but not in solution. The ratio between measured Michaelis-Menten rate constants, k cat (PEt 3 )/ k cat (PMe 3 ), is calculated to be 103, whereas the ratio between observed uncatalyzed rate constants, k uncat (PEt 3 )/ k uncat (PMe 3 ), is around2 .7 (Scheme 1). Understanding the origin of such ad ifferent behavior is ac hallenge from both chemical and computationalp oint of view but could lead to major improvement in developing novel metallocagesa nd/orl ookingf or new guest reactions.Theor...

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

“…Computing reliable binding affinities can be a precious tool for designing supramolecular hosts. Based on previous studies on supramolecular systems, 14 , 15 , 18 , 32 , 33 , 65 , 72 several variables could relate to such prediction: (1) the cavity volume of the host alone, (2) the volume of the guest, (3) the packing values, that is, the ratio between the volume of the guest in front of the volume of the cavity of the host, and (4) the possible involvement of solvent molecules. It is likely although that the real relationship lies as a combination of these different factors.…”

“… 14 − 19 So far, the works performed were based on quantum chemistry approaches combined with limited conformational sampling performed via molecular dynamics (MD) (either based on force fields or quantum approaches). 14 , 15 , 17 − 20 These works were focused at decoding the particularities of the host–guest catalytic mechanism compared to the reaction taking place in solution. Among the most striking results was the identification that the few solvent molecules that access the host cavity are fundamental for the catalytic effect provided by the supramolecular assembly.…”

Origin of the Rate Acceleration in the C−C Reductive Elimination from Pt(IV)‐complex in a [Ga4L6]12− Supramolecular Metallocage

“…[38][39][40][41][42][43][44][45][46][47] In the case of highly anionic hosts, as the [Ga 4 L 6 ] 12À metallocage, all computational studies show that electrostatic effects are crucial for the rate acceleration. [30][31][32][33]48,49] In our previous works, we studied the reductive eliminations from the Au(III) complexes, [R 3 PAu (MeOH)(CH 3 ) 2 ] + , in the [Ga 4 L 6 ] 12À and showed that not only encapsulation by the host, but also microsolvation plays an important role for lowering the Gibbs energy barrier of the reductive elimination from the Au(III) complexes inside [Ga 4 L 6 ] 12À . [30,31] In the present study, we investigate computationally the origin of the catalysis observed for alkyl-alkyl reductive elimination from the Pt(IV)-complex, [trans-(Me 3 P) 2 Pt-(MeOH)(CH 3 ) 3 ] + , 2P.…”

“…[30][31][32][33]48,49] In our previous works, we studied the reductive eliminations from the Au(III) complexes, [R 3 PAu (MeOH)(CH 3 ) 2 ] + , in the [Ga 4 L 6 ] 12À and showed that not only encapsulation by the host, but also microsolvation plays an important role for lowering the Gibbs energy barrier of the reductive elimination from the Au(III) complexes inside [Ga 4 L 6 ] 12À . [30,31] In the present study, we investigate computationally the origin of the catalysis observed for alkyl-alkyl reductive elimination from the Pt(IV)-complex, [trans-(Me 3 P) 2 Pt-(MeOH)(CH 3 ) 3 ] + , 2P. The analysis is performed first in solution and then inside the metallocage, [Ga 4 L 6 ] 12À , 3, (Scheme 1).…”

“…Theoretical studies are essential to understand catalytic processes; [34–37] however, computational works on supramolecular catalysis are still scarce [38–47] . In the case of highly anionic hosts, as the [Ga 4 L 6 ] 12− metallocage, all computational studies show that electrostatic effects are crucial for the rate acceleration [30–33,48,49] . In our previous works, we studied the reductive eliminations from the Au(III) complexes, [R 3 PAu(MeOH)(CH 3 ) 2 ] + , in the [Ga 4 L 6 ] 12− and showed that not only encapsulation by the host, but also microsolvation plays an important role for lowering the Gibbs energy barrier of the reductive elimination from the Au(III) complexes inside [Ga 4 L 6 ] 12− [30,31] …”