DFT Modeling of Organocatalytic Ring-Opening Polymerization of Cyclic Esters: A Crucial Role of Proton Exchange and Hydrogen Bonding

Abstract

Organocatalysis is highly efficient in the ring-opening polymerization (ROP) of cyclic esters. A variety of initiators broaden the areas of organocatalysis in polymerization of different monomers, such as lactones, cyclic carbonates, lactides or gycolides, ethylene phosphates and phosphonates, and others. The mechanisms of organocatalytic ROP are at least as diverse as the mechanisms of coordination ROP; the study of these mechanisms is critical in ensuring the polymer compositions and architectures. The use of density functional theory (DFT) methods for comparative modeling and visualization of organocatalytic ROP pathways, in line with experimental proof of the structures of the reaction intermediates, make it possible to establish these mechanisms. In the present review, which continues and complements our recent manuscript that focused on DFT modeling of coordination ROP, we summarized the results of DFT modeling of organocatalytic ROP of cyclic esters and some related organocatalytic processes, such as polyester transesterification. 4 of 49 were found to be polymerizable due to strain in the ester group. In addition, the predominance of high-energy coiled conformations in linear homopolymers the formed from PDO, εCL and GL was proportionately less than extended conformations, in comparison to the inactive monomer γBL. However, while the prevalence of coiled conformations over extended conformations was expected for poly(LA), this factor does not affected the reactivity of lactides. Very good agreement between the experimental and calculated data for ROP of GL, l-LA and (R,S)-lactide [47] should be separately noted. 4-(Dimethylamino)pyridine (DMAP) and Related CompoundsDMAP was the first employed organocatalyst in polymer synthesis. In 2001, Nederberg et al. [48] reported the "first organocatalytic living polymerization" (Ð M < 1.2) of L-lactide (l-LA) mediated by DMAP or 4-pyrrolidinopyridine in the presence of ROH initiators. Four years later [49], Feng and Dong reported polymerization of ε-caprolactone (εCL) catalyzed by DMAP in the presence of chitozane as an initiator. Bourissou et al. studied the mechanism of DMAP-catalyzed ROP of l-LA and five-membered lactic O-carboxylic anhydride (lacOCA) [50]. Two possible reaction pathways were analyzed at the B3LYP/6-31G(d) level of theory [39,40,51]; the solvent effect of dichloromethane was taken into account through the PCM/SCRF model [52]. The modeled reaction was the methanolysis of l-LA or lacOCA; alternative nucleophilic/monomer (Scheme 1a) and basic/alcohol (Scheme 1b) activation mechanisms were proposed for these reactions, and then analyzed by DFT optimization of the key reaction intermediates and transition states, if necessary. Scheme 1. Schematic representation of the nucleophilic/monomer (a) and basic/alcohol (b) mechanisms for (Dimethylamino)pyridine (DMAP)-catalyzed methanolysis of l-LA. Author Contributions: Conceptualization, P.I.; Methodology, I.N. and P.I.; Writing-Original draft preparation, P.I.; Writing-Review and editing, I.N. and P.I.; V...

Stereoselective ROP of rac- and meso-Lactides Using Achiral TBD as Catalyst

“…Considering the size and geometry of the achiral TBD molecule, along with its mode of action, proceeding through concurrent activation of both monomer and initiating/propagating alcohol [23], we postulated that the stereocontrol of the cryogenic-based ROP must come from a perfect imbrication of both chiral LA and propagating chiral end-group both in interaction with the TBD catalyst, which is facilitated at low temperatures. To confirm this hypothesis, the reaction profiles corresponding to the first step of the ROP process were simulated with a quantum-chemical approach, since earlier works [23,24], and a recent review devoted to organocatalytic ring-opening polymerization of cyclic esters [25], have pointed out that it is the rate-determining step. This step corresponds to the attack of the alcohol on the lactide activated by the TBD catalyst [23].…”

Functionalized Biodegradable Polymers via Termination of Ring-Opening Polymerization by Acyl Chlorides

“…Ring-opening polymerization of cyclic esters, phosphates and phosphonates ( Scheme 1 b) [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] results in the formation of polymers containing –OH end group. To date, a number of methods of the functionalization of –OH end group in separated polymers with a formation of NHS or MI derivatives have been implemented [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ].…”

Comparative Experimental and Theoretical Study of Mg, Al and Zn Aryloxy Complexes in Copolymerization of Cyclic Esters: The Role of the Metal Coordination in Formation of Random Copolymers

“…Catalytic ring-opening polymerization (ROP) of cyclic esters is the basis for the efficient synthetic approach to actual biodegradable and biocompatible materials [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Both organocatalysts [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ] and coordination catalysts [ 16 , 17 , 18 , 19 , 20 ] have been efficiently used in ROP. The reaction mechanism of the coordination ROP, catalyzed by metal alkoxy complexes, is traditionally viewed as a repeating sequence of monomer coordination, alkoxy insertion and ring-opening ( Scheme 1 ); these processes are influenced by both the metal nature and ligand environment at the metal center [ 16 , 17 , 18 , 19 , 20 , 21 ].…”

“…Polylactide (PLA) and poly(ε-caprolactone) (PCL), obtained by catalytic ROP of the corresponding cyclic esters, lactide (LA) and ε-caprolactone (εCL) ( Scheme 2 A) [ 1 , 4 , 8 , 15 , 20 , 22 , 23 , 24 ], have currently received great attention in biomedical applications [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Due to the contrasting physical properties of polylactide (PLA) and poly-ε-caprolactone (PCL), random copolymers of LA and εCL have generally proved useful for the development of polymer materials with desired mechanical characteristics and biodegradation rate [ 33 , 34 , 35 , 36 , 37 , 38 ].…”

“…The reaction mechanism of the coordination ROP, catalyzed by metal alkoxy complexes, is traditionally viewed as a repeating sequence of monomer coordination, alkoxy insertion and ring-opening (Scheme 1); these processes are influenced by both the metal nature and ligand environment at the metal center [16][17][18][19][20][21]. Polylactide (PLA) and poly(ε-caprolactone) (PCL), obtained by catalytic ROP of the corresponding cyclic esters, lactide (LA) and ε-caprolactone (εCL) (Scheme 2A) [1,4,8,15,20,[22][23][24], have currently received great attention in biomedical applications [25][26][27][28][29][30][31][32]. Due to the contrasting physical properties of polylactide (PLA) and poly-ε-caprolactone (PCL), random copolymers of LA and εCL have generally proved useful for the development of polymer materials with desired mechanical characteristics and biodegradation rate [33][34][35][36][37][38].…”