Defining Stereochemistry in the Polymerization of Lactide by Aluminum Catalysts: Insights into the Dual-Stereocontrol Mechanism.

Aspects of the proposed pathway combining chain-end and enantiomorphic site control for the stereospecific polymerization of lactide (LA) were investigated through studies of aluminum complexes supported by enantiopure and racemic bipyrrolidine-based salan ligands, Lig1AlOBn and Lig2AlOBn. Spectroscopic analysis of stoichiometric initiation reactions and the definition of the stereochemistry of the selective formation of the "match" single-insertion products by X-ray crystallography led to key conclusions about the observed stereocontrol. Notably, it was determined to rely heavily on the preference for the trio of stereocenters around the metal to have a "match" formation (RR-ligand + S-polymer), which works synergistically with the enantiomorphic site preference of the catalyst to ring-open next to a stereocenter of a monomer of the same chirality as that of the ligand, resulting in highly heterotactic or syndiotactic PLA from rac- or meso-LA, respectively.

Stereogradient Poly(Lactic Acid) from meso-Lactide/L-Lactide Mixtures.

The production of L-lactide from L-lactic acid involves a substantial formation of meso-lactide as an impurity, and, upon polymerization with the industrial catalyst tin octanoate, results in poly(L-lactic acid) of reduced crystallinity due to stereoerrors randomly distributed along the polymer chains. We describe a new approach wherein, instead of avoiding stereoerrors by removing the meso-lactide prior to polymerization, the stereoerrors in the polymer are tolerated, by crowding them in a stereogradient copolymer. A zirconium complex of an amine tris(phenolate) ligand is found to exhibit very high syndioselectivity in the ring opening polymerization catalysis of meso-lactide at room temperature, and gives rise to stereogradient copolymers in the polymerization of mixtures of meso-lactide/L-lactide in the melt at 180 °C. Relative to the stereo-random copolymers obtained with tin octanoate, the stereogradient copolymers exhibit enhanced crystallinities manifested in lower solubilities and higher melting temperatures and enthalpies.

Master of Chaos and Order: Opposite Microstructures of PCL-co-PGA-co-PLA Accessible by a Single Catalyst.

One catalyst, two reaction set-ups, three monomers and unlimited macromolecular microstructural designs: The iron guanidine complex [FeCl2 (TMG5NMe2 asme)] (1) polymerizes lactide faster than the industrially used Sn(Oct)2 and shows high activity towards glycolide and ϵ-caprolactone. Its distinguished features enable the synthesis of both block and random-like copolymers in the melt by a simple change of the polymerization set-up. Sequential addition of monomers yields highly ordered block copolymers including the symmetrical PLA-b-PGA-b-PCL-b-PGA-b-PLA pentablock copolymers, while polymerizations of monomer mixtures feature enhanced transesterifications and pave the way to di- and terpolymers with highly dispersed repeating unit distributions. A robust catalyst active under industrially applicable conditions and producing copolymers with desired microstructures is a major step towards biocompatible polymers with tailor-made properties as alternatives for traditional plastics on the way towards a sustainable, circular material flow.

Aluminium complexes of salanol ligands: coordination chemistry and stereoselective lactide polymerization.

The tetradentate dianionic {ONNO}-type salanol ligands featuring phenolate and alcoholate arms and a chiral-bipyrrolidine core are introduced. The diastereoselectively-formed {ONNO}-Al-OBn complexes catalyze the ring-opening polymerization of rac-lactide and meso-lactide by either the dual stereocontrol or the chain-end stereocontrol mechanisms to give PLAs of all possible tacticities.

Isoselective Polymerization of rac-Lactide by Highly Active Sequential {ONNN} Magnesium Complexes.

The coordination chemistry and the activities in the ring-opening polymerization catalysis of racemic lactide (LA) of magnesium complexes of a series of {ONNN}-type sequential monoanionic ligands are described. All ligands include pyridyl and substituted-phenolate as peripheral groups. The ligands bearing either chiral or meso-bipyrrolidine cores led to single diastereomeric complexes, whereas the ligands bearing a diaminoethane core led to diastereomer mixtures. All {ONNN}Mg-X complexes [X=Cl, HMDS (hexamethyldisilazide)] led to highly active and isoselective catalysts. The complexes bearing the chiral bipyrrolidine core exhibited the highest activities (full consumption of 5000 equiv. of rac-LA at RT within 5 min) and highest isoselectivities (Pm =0.91), as well as a living character. The complexes of the meso-bipyrrolidine based ligands were almost as active and slightly less stereoselective, while those of the diaminoethane based ligands exhibited reduced activities and isoselectivities.

Synthesis of Enantiopure Lanthanide Complexes Supported by Hexadentate N,N'-Bis(methylbipyridyl)bipyrrolidine and Their Circularly Polarized Luminescence.

We report the synthesis of lanthanide complexes supported by enantiopure N,N'-bis(methylbipyridyl)bipyrrolidine and subsequent characterization through luminescence studies. Complexes of this ligand with the visibly emissive lanthanides Sm, Eu, Tb, and Dy are luminescent (ϕf of ≤0.32) and demonstrate strong preferential emission of circularly polarized light in all four cases (|glum| of ≤0.26). Notably, all four possess at least one transition with a |glum| of >0.2, and the strongest preferential emission is measured from the complexes of Sm and Dy.

The Dual-Stereocontrol Mechanism: Heteroselective Polymerization of rac-Lactide and Syndioselective Polymerization of meso-Lactide by Chiral Aluminum Salan Catalysts.

We describe alkoxo-aluminum catalysts of chiral bipyrrolidine-based salan ligands that follow the dual-stereocontrol mechanism wherein a given combination of stereogeneities at the metal site and the proximal center of the last inserted lactidyl ("match") is active towards lactide having a proximal stereogenic center of the opposite configuration, while the diastereomeric combination of stereogeneities ("mismatch") is inactive towards any lactide. Polymerization of rac-LA by the enantiomerically pure catalysts was sluggish and gave stereoirregular poly(lactic acid) (PLA) because selective insertion to a match diastereomer gives a mismatch diastereomer. The racemic catalysts showed higher activity and led to highly heterotactic PLA following polymeryl exchange between two mismatched catalyst enantiomers. A succession of match diastereomers in selective meso-LA insertions led to syndiotactic PLAs reaching a syndiotacticity degree of α=0.96. This polymer featured a Tm of 153 °C matching the highest reported value, and the highest crystallinity (ΔHm =56 J g-1 ) ever reported for syndiotactic PLA.

Block-Stereoblock Copolymers of Poly(ϵ-Caprolactone) and Poly(Lactic Acid).

A magnesium complex of the type {ONNN}Mg-HMDS wherein {ONNN} is a sequential tetradentate monoanionic ligand is introduced. In the presence of an alcohol initiator this complex catalyzes the living and immortal homopolymerization of the lactide enantiomers and ϵ-caprolactone at room-temperature with exceptionally high activities, as well as the precise block copolymerization of these monomers in a one-pot synthesis by sequential monomer addition. Copolymers of unprecedented microstructures such as the PCL-b-PLLA-b-PDLA and PDLA-b-PLLA-b-PCL-b-PLLA-b-PDLA block-stereoblock microstructures that feature unique thermal properties are readily accessed.

Mechanism of the Polymerization of rac-Lactide by Fast Zinc Alkoxide Catalysts.

The ring-opening transesterification polymerization (ROTEP) of rac-lactide (rac-LA) using LXZn catalysts (LX = ligand having phenolate, amine, and pyridine donors with variable para substituents X on the bound phenolate donor; X = NO2, Br, t-Bu, OMe) was evaluated through kinetics experiments and density functional theory, with the aim of determining how electronic modulation of the ligand framework influences polymerization rate, selectivity, and control. After determination that zinc-ethyl precatalysts required 24 h of reaction with benzyl alcohol to convert to active alkoxide complexes, the subsequently formed species proved to be active and fairly selective, polymerizing up to 300 equiv of rac-LA in 6-10 min while yielding isotactic (Pm = 0.72-0.78) polylactide (PLA) with low dispersities: D = 1.06-1.17. In contrast to previous work with aluminum catalysts for which electronic effects of ligand substituents were significant (Hammett ρ = +1.2-1.4), the LXZn systems exhibited much less of an effect (ρ = +0.3). Density functional calculations revealed details of the initiation and propagation steps, enabling insights into the high isotacticity and the insensitivity of the rate on the identity of X.

Divergent [{ONNN}Mg-Cl] complexes in highly active and living lactide polymerization.

Chloro-magnesium complexes of divergent tetradentate-monoanionic {ONNN}-type ligands which formed as either mononuclear or dinuclear complexes are reported. These complexes catalyze the ring-opening polymerization of lactide with high activity and in a living manner, and enable the synthesis of well-defined stereo-diblock copolymers with Mn > 200 kDa, as well as stereo-n-block copolymers (n = tri, tetra) with high molecular weights by sequential monomer addition. Thermal and crystallographic characterizations revealed that even the very high molecular weight PLA copolymers crystallized in a stereocomplex phase, and that their degradation temperature was as high as 354 °C.

Group†4 Metal Complexes of Phenylene-Salalen Ligands in rac-Lactide Polymerization Giving High Molecular Weight Stereoblock Poly(lactic acid).

Phenylene-salalens-sequential tetradentate dianionic {ONNO}-type ligands that include an ortho-phenylene group bridging between an imine and amine internal donors bound to phenol arms with a broad variety of substitution patterns are described. Zirconium and hafnium complexes of the type [{ONNO}M(O-tBu)2 ] were formed as single diastereomers, which, according to crystallographic structures, featured the fac(around the amine)-mer(around the imine) wrapping mode. The reactivity and stereoselectivity in rac-lactide (rac-LA) polymerizations were found to depend on the substitution pattern: complexes featuring small groups on the imine-side phenol and bulky groups on the amine-side phenol exhibited the favorable combination of high activity and high isoselectivity (Pm ≤0.91). Isotactic stereoblock copolymers of high molecular weights were prepared. The polymers crystallized in the stereocomplex phase according to thermal (differential scanning calorimetry) and crystallographic analysis.

Tailor-Made Stereoblock Copolymers of Poly(lactic acid) by a Truly Living Polymerization Catalyst.

Poly(lactic acid) (PLA) is a biodegradable polymer prepared by the catalyzed ring opening polymerization of lactide. An ideal catalyst should enable a sequential polymerization of the lactide enantiomers to afford stereoblock copolymers with predetermined number and lengths of blocks. We describe a magnesium based catalyst that combines very high activity with a true-living nature, which gives access to PLA materials of unprecedented microstructures. Full consumption of thousands of equivalents of L-LA within minutes gave PLLA of expected molecular weights and narrow molecular weight distributions. Precise PLLA-b-PDLA diblock copolymers having block lengths of up to 500 repeat units were readily prepared within 30 min, and their thermal characterization revealed a stereocomplex phase only with very high melting transitions and melting enthalpies. The one pot sequential polymerization was extended up to precise hexablocks having "dialed-in" block lengths.

Multitask Imidazolium Salt Additives for Innovative Poly(l-lactide) Biomaterials: Morphology Control, Candida spp. Biofilm Inhibition, Human Mesenchymal Stem Cell Biocompatibility, and Skin Tolerance.

Candida species have great ability to colonize and form biofilms on medical devices, causing infections in human hosts. In this study, poly(l-lactide) films with different imidazolium salt (1-n-hexadecyl-3-methylimidazolium chloride (C16MImCl) and 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16MImMeS)) contents were prepared, using the solvent casting process. Poly(l-lactide)-imidazolium salt films were obtained with different surface morphologies (spherical and directional), and the presence of the imidazolium salt in the surface was confirmed. These films with different concentrations of the imidazolium salts C16MImCl and C16MImMeS presented antibiofilm activity against isolates of Candida tropicalis, Candida parapsilosis, and Candida albicans. The minor antibiofilm concentration assay enabled one to determine that an increasing imidazolium salt content promoted, in general, an increase in the inhibition percentage of biofilm formation. Scanning electron microscopy micrographs confirmed the effective prevention of biofilm formation on the imidazolium salt containing biomaterials. Lower concentrations of the imidazolium salts showed no cytotoxicity, and the poly(l-lactide)-imidazolium salt films presented good cell adhesion and proliferation percentages with human mesenchymal stem cells. Furthermore, no acute microscopic lesions were identified in the histopathological evaluation after contact between the films and pig ear skin. In combination with the good morphological, physicochemical, and mechanical properties, these poly(l-lactide)-based materials with imidazolium salt additives can be considered as promising biomaterials for use in the manufacturing of medical devices.

Zinc Complexes of Sequential Tetradentate Monoanionic Ligands in the Isoselective Polymerization of rac-Lactide.

Zinc complexes of {ONNN}-type sequential tetradentate monoanionic ligands reacted with diethylzinc to give the mononuclear ethylzinc complexes. The benzyloxy complexes were formed readily and were found to be highly active as well as living/immortal catalysts for ring-opening polymerization of rac-lactic acid with a clear isospecific inclination. Chiral gas chromatography analysis revealed a mild preference for a given lactide enantiomer by the chiral catalysts.

The stereoselectivity of bipyrrolidine-based sequential polydentate ligands around Ru(ii).

The Ru(ii) coordination chemistry of the sequential hexadentate, tetradentate and the novel hybrid pentadentate ligands assembled around the chiral bipyrrolidine core and including bipyridyl and pyridyl periphery units is described. The bipyridine group exhibited priority in binding over the bipyrrolidine group, which led to a diastereomer mixture in the case of the hexadentate ligand 1. Employing only monopyridyl or a combination of monopyridyl and bipyridyl peripheral groups restored the chiral induction ability to the bipyrrolidine core resulting in predetermined chiral-at-metal complexes for the ligands 3 and 4.

Assembling Quasi-enantiomeric Octahedral Complexes of Different Metals via Quasi-racemate Crystallization.

Aiming at a general methodology for binary co-assembly of complexes of different metals through quasiracemate crystallization, the hexadentate ligand 1 comprised of the chiral bipyrrolidine core and two bipyridine peripheral arms is introduced. Ligand 1 was found to bind in a fully diastereoselective and uniform mode around Zn(II), Fe(II) and Cd(II) giving coordinatively inert octahedral "chiral-at-metal" complexes with the Δ4Λ2/Λ4 Δ2 wrapping mode. Equimolar mixtures of quasienantiomeric pairs of these complexes exhibited a clear tendency to pack as quasiracemates as was revealed from the crystallographic structures of [(R,R)-1-Zn](PF6)2/[(S,S)-1-Fe](PF6)2 and [(R,R)-1-Zn](PF6)2/[(S,S)-1-Cd](PF6)2, in an isomorphous fashion to that of the racemic compound [rac-1-Zn](PF6)2 in space group C2/c.

Mechanistic Insight into the Stereochemical Control of Lactide Polymerization by Salan-Aluminum Catalysts.

Alkyl aluminum complexes of chiral salan ligands assembled around the 2,2'-bipyrrolidine core form as single diastereomers that have identical configurations of the N donors. Active catalysts for the polymerization of lactide were formed upon the addition of benzyl alcohol. Polymeryl exchange between enantiomorphous aluminum species had a dramatic effect on the tacticity of the poly(lactic acid) (PLA) in the polymerization of racemic lactide (rac-LA): The enantiomerically pure catalyst of the nonsubstituted salan ligand led to isotactic PLA, and the racemic catalyst exhibited lower stereocontrol. The enantiomerically pure catalyst of the chloro-substituted salan ligand led to PLA with a slight tendency toward heterotacticity, whereas the racemic catalyst led to PLA of almost perfect heterotacticity following an insertion/auto-inhibition/exchange mechanism.

Ring-opening homo- and co-polymerization of lactides and ε-caprolactone by salalen aluminum complexes.

Aluminum complexes of non-chiral-salalen ligands were investigated in the catalysis of ring-opening polymerization (ROP) of lactide and ε-caprolactone and in their copolymerization. The aluminum-salalen complexes were found to polymerize all varieties of lactide, namely: l-, d-, rac- and meso-lactide, and showed moderate productivities. rac-LA gave rise to isotactic polylactides (with Pm up to 72%), while meso-LA gave rise to heterotactic polylactides (with a Pm of 79%). An experiment was designed for distinguishing between chain-end control and enantiomorphic-site control combined with polymeryl exchange for the isotactic stereoblock microstructure observed for the PLA produced from rac-LA; it gave strong evidence for polymeryl exchange between propagating species. Finally, this class of catalysts promoted the copolymerization of ε-caprolactone and lactides. In particular, compound allowed controlled random copolymerization of ε-caprolactone and l-lactide.

Zirconium complexes of phenylene-bridged {ONSO} ligands: coordination chemistry and stereoselective polymerization of rac-lactide.

Sequential tetradentate dianionic thio-imine diphenolate ligands featuring an ortho-phenylene core and their zirconium complexes are described for the first time. Ligands that include different combinations of bulky-alkyl groups and halo groups on the two phenol arms were prepared by a substitution/condensation reaction sequence. An unexpected fac-fac wrapping mode was found in the solid state for the ligands in the octahedral [{ONSO}Zr(O(t)Bu)2] complexes. The complexes were all fluxional, and the barrier for enantiomer interconversion was found to depend on the phenolate substituents. The complexes were found to catalyze the polymerization of rac-lactide to poly(lactic acid) in solution with polymer tacticities varying from heterotactic to atactic which showed correlation to the nature of phenolate substituents but not to the degree of complex fluxionality.

Gradient isotactic multiblock polylactides from aluminum complexes of chiral salalen ligands.

Aluminum complexes of enantiomerically pure aminomethylpyrrolidine-based salalen ligands and their application in the stereoselective polymerization of lactide are described. Poly(lactic acid) featuring the new gradient isotactic multiblock microstructure was synthesized by isoselective catalysts, which operate by a combination of enantiomorphic-site and chain-end control mechanisms.