Radical Ring Opening Research Articles

Theoretical studies on the kinetics of ring opening of 1-bicyclo[2.1.0]-pentanylmethyl, 1-bicyclo[3.1.0]-hexanylmethyl, and 1-bicyclo[4.1.0]-heptanylmethyl radicals

By carrying out B3LYP calculations, we have performed a detailed mechanism study on the 1-bicyclo[n.1.0] (1-bicyclo[2.1.0]-pentanylmethyl, 1-bicyclo[3.1.0]-hexanylmethyl, and 1-bicyclo[4.1.0]-heptanylmethyl) radicals ring opening reaction in THF solvent. We calculated the rate constants for the reactions. Our calculations are consistent with the experimental results that the expansion pathway is favored both kinetically and thermodynamically compared with the non-expansion pathway for the 1-bicyclo[n.1.0] radical ring opening reaction. Our calculated results also show that with the ring size decreasing, the ring-expansion for the 1-bicyclo[n.1.0]-hexanylmethyl radical ring opening reaction becomes easier kinetically and thermodynamically. We would expect that the accurate calculation results for the model systems will be useful for the experimental researchers working in this field.

ChemInform Abstract: Generation of a Low‐Valent Titanium Species from Titanatrane and Its Catalytic Reactions: Radical Ring Opening of Oxetanes.

AbstractThe first examples of the C—O bond cleavage of various oxetanes at the 2‐position using low valent titanium alkoxides, generated in situ from the titanatrane complex, Mg, and TmsCl, are presented.

Nitroxide‐Mediated Radical Ring‐Opening Copolymerization: Chain‐End Investigation and Block Copolymer Synthesis

Well-defined, degradable copolymers are successfully prepared by nitroxide-mediated radical ring opening polymerization (NMrROP) of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) or methyl methacrylate (MMA), a small amount of acrylonitrile (AN) and cyclic ketene acetals (CKAs) of different structures. Phosphorous nuclear magnetic resonance allows in-depth chain-end characterization and gives crucial insights into the nature of the copoly-mer terminal sequences and the living chain fractions. By using a small library of P(OEGMA-co-AN-co-CKA) and P(MMA-co-AN-co-CKA) as macroinitiators, chain extensions with styrene are performed to furnish (amphiphilic) block copolymers comprising a degradable segment.

Hydrogen Bonding Interaction Induced Complexation of mPEG-b-PAA and Star PDMAEMA-b-poly (HEMA-g-PCL) Hybrid Micelles in Water

A series of amphiphilic star-shaped copolymer, poly(dimethylaminomethyl methacrylate)-block-poly(2-hydroxyethyl methacrylate -graft- poly(ϵ-caplactone)), s(PDMAEMA-b-P(HEMA-g-PCL))4, were synthesized by atom transfer radical polymerization (ATRP) and ring opening polymerization (ROP) with PDMAEMA as hydrophilic star core and PCL as hydrophobic outer arms. The star copolymer micelles were formed in different pH values and the hybrid micelles were obtained from s(PDMAEMA-b-P(HEMA-g-PCL))4 and methoxy-poly(ethylene glycol)-block-polyacrylic acid (mPEG-b-PAA)by hydrogen bonding interaction between PDMAEMA and PAA. These copolymers were characterized by 1H-NMR spectroscopy and size exclusive chromatography(SEC). pH sensitive self-assembly behavior of these copolymers could be observed by increasing pH values, which was examined by fluorescence spectra, dynamic light scattering (DLS), zeta potential and transmission electron microscopy (TEM). As a result, these copolymers could form micelles with diameters under 500 nm from pH 2.0 to 8.0 but nanoparticles above pH 9.0. MTT assay exhibited that the addition of mPEG-b-PAA could increase the cell viability from 40% to 90%. The drug release assays of indometacin (IND) drug loaded star copolymer micelles and hybrid micelles were investigated in Phosphate Buffered Saline (pH 7.4) at 37°C. mPEG-b-PAA had less influence on the drug release and the cumulative releases of all the micelles were from 57.5% to 69.7% after 40 h.

Synthesis, characterisation and drug release properties of microspheres of polystyrene with aliphatic polyester side-chains

A series of graft copolymers consisting of polystyrene backbone with biocompatible side chains based on (co)polymers of l-lactic acid and glycolic acid were synthesised by combination two controlled polymerisations, namely, nitroxide mediated radical polymerisation (NMRP) and ring opening polymerisation (ROP) with “Click” chemistry. The main goal of this work was to design new biodegradable microspheres using obtained graft copolymers for long-term sustained release of imatinib mesylate (IMM) as a model drug. The IMM loaded microspheres of the graft copolymers, polystyrene-g-poly(lactide-co-glycolide) (PS-g-PLLGA), polystyrene-g-poly(lactic acid) (PS-g-PLLA) and poly(lactic-coglycolic acid) (PLLGA) were then prepared by a modified water-in-oil-in-water (w1/o/w2) double emulsion/solvent evaporation technique. The optimised microspheres were characterised by particle size, encapsulation efficiency, and surface morphology also; their degradation and release properties were studied in vitro. The degradation studies of three different types of microspheres showed that the PS backbone of the graft copolymers slows down the degradation rate compared to PLLGA.

Degradable and Comb-Like PEG-Based Copolymers by Nitroxide-Mediated Radical Ring-Opening Polymerization

Three cyclic ketene acetals, 2-methylene-1,3-dioxepane (MDO), 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), and 2-methylene-4-phenyl-1,3-dioxolane (MPDL), have been copolymerized with oligo(ethylene glycol) methyl ether methacrylate and a small amount of acrylonitrile (or styrene) at 90 °C by nitroxidemediated radical ring-opening polymerization, as a convenient way to prepare degradable PEG-based copolymers for biomedical applications. MPDL was the best candidate, enabling high monomer conversions to be reached and well-defined PEG-based copolymers with adjustable amount of ester groups in the main chain to be synthesized, leading to nearly complete hydrolytic degradation (5% KOH aqueous solution, ambient temperature). The noncytotoxicity of the obtained copolymers was shown on three different cell lines (i.e., fibroblasts, endothelial cells and macrophages), representing a promising approach for the design of degradable precursors for PEGylation and bioconjugation via the NMP technique.

Generation of a Low‐Valent Titanium Species from Titanatrane and its Catalytic Reactions: Radical Ring Opening of Oxetanes

AbstractTreatment of a titanatrane complex with trimethylsilyl chloride and magnesium powder in tetrahydrofuran generated a low‐valent titanium species. This species catalyzed the radical ring opening of epoxides and oxetanes to produce the corresponding less substituted alcohols. The reagent also catalyzed the deallylation and depropargylation of allylic and propargylic ethers, respectively, to provide the parent alcohols.magnified image

Polymers Composed of Alternating Anthracene and Pyridine Containing Units by Radical Ring-Opening Polymerization: Controlled Synthesis, Optical Properties, and Metal Complexes

Novel polymers composed of alternating anthracene and pyridine containing units were synthesized by radical ring-opening polymerization of pyridine-containing cyclic monomers via reversible addition–fragmentation chain transfer (RAFT) process. The ring-opening polymerization proceeded predominantly to afford well-defined polymers (Mw/Mn ∼ 1.30), which exhibited the characteristic absorption and fluorescence due to the anthracene unit. On the other hand, fluorescence quenching was observed in chloroform and acidic aqueous solutions. The quenching was explained by charge transfer from the excited anthracene units to the coordinated or protonated pyridine units. Additionally, fluorescence quenching independent of external ambient conditions was conducted by quaternization. In the thin film state, the obtained polymers exhibited fluorescence due to the formation of excimers. The formation of complexes between the anthracene-containing polymers and metal species (Zn, Cu, and Co) led to the change in the optical properties compared to those of pristine polymers. These results demonstrate that the unique optical properties could be developed under various conditions due to the interactions between the anthracene and pyridine units in the well-defined polymers.

Copper catalyzed ring opening copolymerization of a vinyl cyclopropane and methyl methacrylate

Vinyl cyclopropanes are an important class of monomers which on radical ring opening polymerization (RROP) lead to polymers having cyclic moieties, carbon-carbon unsaturation and different other functional groups inside its backbone as in the pendant group. This investigation reports controlled radical ring opening polymerization (CRROP) of 1,1-bis (ethoxy carbonyl)-2-vinylcyclopropane (BCVCP) catalyzed by Cu catalyst. In this case homo and co-polymerization of BCVCP was carried out via ATRP using ethyl-2-bromoisobutyrate as initiator and CuBr as catalyst in combination with Me6-TREN ligand. Radical polymerization of BCVCP and its copolymerization with methyl methacrylate (MMA) via ATRP led to predominantly 1,5 ring opening polymerization leading to linear polymers with >CC< in the main chain of the polymer. Conventional free radical co-polymerization of BCVCP and MMA led to polymers predominantly with cyclic rings in the main chain. The polymers were characterized by NMR, FT-IR, GPC, DSC and TGA analysis.

Physical Tuning of Cellulose-Polymer Interactions Utilizing Cationic Block Copolymers Based on PCL and Quaternized PDMAEMA

In this work, the objective was to synthesize and evaluate the properties of a compatibilizer based on poly(ε-caprolactone) aimed at tuning the surface properties of cellulose fibers used in fiber-reinforced biocomposites. The compatibilizer is an amphiphilic block copolymer consisting of two different blocks which have different functions. One block is cationic, quaternized poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and can therefore electrostatically attach to anionic reinforcing materials such as cellulose-based fibers/fibrils under mild conditions in water. The other block consists of poly(ε-caprolactone) (PCL) which can decrease the surface energy of a cellulose surface and also has the ability to form physical entanglements with a PCL surface thereby improving the interfacial adhesion. Atom Transfer Radical Polymerization (ATRP) and Ring-Opening Polymerization (ROP) were used to synthesize three block copolymers with the same length of the cationic PDMAEMA block but with different lengths of the PCL blocks. The block copolymers form cationic micelles in water which can adsorb to anionic surfaces such as silicon oxide and cellulose-model surfaces. After heat treatment, the contact angles of water on the treated surfaces increased significantly, and contact angles close to those of pure PCL were obtained for the block copolymers with longer PCL blocks. AFM force measurements showed a clear entangling behavior between the block copolymers and a PCL surface at about 60 °C, which is important for the formation of an adhesive interface in the final biocomposites. This demonstrates that this type of amphiphilic block copolymer can be used to improve interactions in biocomposites between anionic reinforcing materials such as cellulose-based fibers/fibrils and less polar matrices such as PCL.

Synthesis and evaluation of star-shaped poly(ϵ-caprolactone)-poly(2-hydroxyethyl methacrylate) as potential anticancer drug delivery carriers

Novel star-shaped poly(ϵ-caprolactone)-b-poly(2-hydroxyethyl methacrylate) (sPCL-b-PHEMA) with 3 arm and 6 arm was synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization. The structure of copolymers was confirmed by nuclear magnetic resonance (1H and 13C NMR) and Fourier transform infrared spectroscopy. The thermal behavior was measured by differential scanning calorimetry. The results showed that Tc, Tm, and Xc of the sPCL-b-PHEMA were reduced along with the increase in the length of the PHEMA block. The copolymers could self-assemble into dispersed micelles with quite low (×10−4 mg/mL) critical micelle concentration. The size and morphology of the micelles were characterized by dynamic light scattering and HAADF scanning transmission electron microscopy. It was found that the micelles were around 20–70 nm with a regular spherical shape. Moreover, drug loading content and encapsulation efficiency of paclitaxel by 3sPCL-b-PHEMA micelles were much lower than the values of 6sPCL-b-PHEMA micelles. The drug release experiments demonstrated that paclitaxelrelease was two-phase release profile and relative to the structure of sPCL-b-PHEMA.The in vitro cytotoxicity of sPCL-b-PHEMA micelles was evaluated using methylthiazoletetrazolium assay. The results showed no apparent inhibition effect on the Hela cells. These preliminary studies suggest that sPCL-b-PHEMA has a possible application as anticancer drug delivery carriers.

Synthesis and pyrolysis of ABC type miktoarm star copolymers with polystyrene, poly(lactic acid) and poly(ethylene glycol) arms

An ABC type miktoarm star copolymer possessing polystyrene (PS), poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) arms was synthesized by combining Atom Transfer Radical Polymerization (ATRP) and Ring Opening Polymerization (ROP) with two click chemistries, namely thiol–ene and copper catalyzed azide–alkyne cycloaddition (CuAAC). For this purpose, a core 1-(allyloxy)-3-azidopropan-2-ol with allyl and azide functionalities was synthesized in two steps. Then, clickable polymers, polystyrene with thiol functionality (PS–SH) and poly(ethylene glycol) with alkyne functionality (PEG–acetylene) were independently prepared. As the first step of the grafting onto process, PS–SH was thiol–ene clicked onto the core to yield PS–N3–OH. The second arm was then incorporated onto the core by the Ring Opening Polymerization (ROP) of l-(−)-Lactide (LA) using as PS–N3–OH initiator and tin(II) 2-ethylhexanoate as catalyst. Finally, alkyne–PEG–acetylene was bonded to the resulting PLA–PS–N3 using CuAAC click reaction. All intermediates, related polymers at different stages and final PS–PLA–PEG miktoarm star copolymer were characterized by 1H NMR, FT-IR, SEC and DP-MS analyses. Direct pyrolysis mass spectrometry, (DP-MS) analyses of PS–PLA–PEG and all intermediate polymers indicated that the decomposition of PS and PEG chains occurred almost independently, following the degradation mechanisms of the corresponding homopolymers. On the other hand, during the pyrolysis of PS–PLA–PEG, elimination of H2O during the decomposition of PEG chains at the early stages of pyrolysis caused hydrolysis of PLA chains and increased the yields of CO2, CO and units involving unsaturation and/or crosslinked structure.

Search for conical intersection points (CI) by Newton trajectories

Recently, valley–ridge inflection points on the potential energy surface for the ring opening of the cyclopropyl radical have been determined using Newton trajectories (NTs) [W. Quapp, J.M. Bofill, A. Aguilar-Mogas, Theor. Chem. Acc. 129 (2011) 803]. This Letter is the report about the utilization of NTs for the search for conical intersection (CI) points. These points play a main role in the understanding of intersections of different electronic surfaces which open the door for photochemical reactions. We explain the reason why Newton trajectories can find CI points, and report a CI seam on the CASSCF (3,3) surface of the allyl radical ring closure.

Topography of cyclopropyl radical ring opening to allyl radical on the CASSCF(3,3) surface: valley-ridge inflection points by Newton trajectories

Valley-ridge inflection points (VRI) on the potential energy surface for the ring opening of the cyclopropyl radical to the allyl radical are determined using the tool of Newton trajectories (NTs) (Quapp and Schmidt in Theor Chem Acc 128:47, 2011). The UHF surface is treated in a former paper (Quapp et al. in Theor Chem Acc 129:803, 2011). This paper is the extension to the more expensive CASSCF(3,3) surface. We compare the results on the UHF surface with the more appropriate calculation: there are quantitative as well as qualitative changes, of course. But many fundamental relations are the same on both surfaces. However, we could detect new pathways on the CASSCF(3,3) surface which highlight the bifurcation problem of this radical. VRIs play a role in the understanding of bifurcating reactions. The region where the bifurcation takes place is governed by a VRI point. Because the transition state of the ring opening is not symmetric, the steepest descent (SD) from the transition state is not along a symmetry axis either, and in this case the SD usually fails a downhill VRI point. The SD from the transition state of the ring opening goes to the disrotatory minimum of the allyl radical. In contrast, we find some pathways which end at the conrotatory minimum, and which go along so-called non steepest descent paths, at least in parts. The region of interest (around the SP of the ring opening) is crossed by electronic intersection seams. Conical intersection points on the seam can be detected by NTs. We use the possibility to explore parts of the intersection seam of the lower CAS surface and we determine connected VRI points being the corner stones of the possible ring opening channels in the disrotatory and the conrotatory case.

Amphiphilic copolymer brush with random pH-sensitive/hydrophobic structure: synthesis and self-assembled micelles for sustained drug delivery

A random hydrophobic/pH-sensitive copolymer brush poly(polylactide methacrylate-co-methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether methacrylate) [P(PLAMA-co-MAA)-b-PPEGMA] and its self-assembled micelles were developed for oral administration of hydrophobic drugs. The polymer was synthesized by the combination of activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and ring opening polymerization (ROP). The CMC of P(PLAMA-co-MAA)-b-PPEGMA in aqueous solution was extremely low (about 1.5 mg L−1). The self-assembled blank and drug-loaded micelles were spherical in morphology and had an average size of 160–220 nm, determined by DLS and SEM. Ibuprofen (IBU) was selected as the model drug and encapsulated into the core of micelles via a dialysis method. The in vitro release behavior of IBU from these micelles was pH-dependent. In simulated gastric fluid (SGF, pH 1.2), the cumulative release of IBU was less than 25% of the initial drug content over 24 h, suggesting that the drug can be well protected from the harsh environment in stomach. While in simulated intestinal fluid (SIF, pH 7.4), the ionization of carboxyl groups of MAA contributed to the swelling of the micelle structure, which could accelerate the IBU release from the micelles. 35–45% of IBU was released in 8 h, 60% in 24 h, and 100% after 56 h for P(PLAMA6.3k-co-MAA3k)-b-PPEGMA4k micelles, and it was 50% in 2 h, 90% in 10 h, and 100% after 14 h for P(PLAMA6.3k-co-MAA4.5k)-b-PPEGMA4k micelles with an increased content of MAA. All the results indicate that the pH-sensitive P(PLAMA-co-MAA)-b-PPEGMA micelles may be a potential oral drug delivery carrier for hydrophobic drugs with sustained release.

Effects of Sericite Modified by Macromolecular Dispersant on the Thermal, Mechanical and Electrical Properties of the NR/SBR Composites

A new hydrosoluble macromolecular dispersant and modifier, poly(ethylene glycol)-maleic anhydride-acrylic acid (PEG-MA-AA) terpolymer was synthesized via ring-opening reaction and free radical polymerization. The chemical structure of the PEG-MA-AA terpolymer was confirmed by Fourier transform infrared (FTIR) spectra and nuclear magnetic resonance spectroscopy (NMR), and its average molecular weight was determined by gel permeation chromatography (GPC). Modified sericite (MSE) was synthesized from sericite (SE) by the surface modification with PEG-MA-AA. The NR/SBR/MSE composites were prepared via the blending of the modified sericite and NR/SBR rubber. The thermal, mechanical and electrical properties of the composites were investigated by TGA, tensile test machine and high-insulation resistance meter. The results showed that the thermal stability and the mechanical and electrical insulation properties of NR/SBR/MSE composites were improved significantly. SEM also revealed that modified sericite possessed good dispersibility.

Direct Photoreduction and Ketone-Sensitized Reduction of Nitrospirobenzopyranindolines by Aliphatic Amines

The photoreduction of 6-nitrospiro[2H-1-benzopyran-2,2'-indoline] (N1) and two derivatives (N2 and N3) by diethylamine or triethylamine (TEA) in solution was studied by pulsed and steady-state photolysis. The quantum yield of coloration of the ring-closed Sp form, due to photoinduced ring opening, decreases in acetonitrile with increasing the TEA concentration. The main reason is reaction of TEA with the triplet-excited open merocyanine form. Quenching of this triplet state by amines is rather inefficient for N1-N3; the rate constant for triplet quenching by TEA is k(6) = (2-3) × 10(6) M(-1) s(-1). The secondary transient with an absorption maximum at 420 nm is ascribed to the radical anion. This and the corresponding α-aminoethyl radical subsequently undergo slow termination reactions, yielding a relatively stable product with a maximum at 420-450 nm, which is attributed to a ring-opened dihydromerocyanine (MH(-)). The mechanisms of the two subsequent reduction reactions are discussed. Using acetone as sensitizer the same dihydroproduct was obtained with the Sp form as acceptor, indicating a reaction sequence from photogenerated radicals via a ring-opened radical to MH(-)/MH(2). The effect of TEA concentration on the direct and ketone-sensitized reduction mechanisms was analyzed. Photoreduction by amines, due to competing triplet quenching, is strongly decreased on admission of oxygen.

Exploration of cyclopropyl radical ring opening to allyl radical by Newton trajectories: importance of valley-ridge inflection points to understand the topography

Valley-ridge inflection points (VRI) on the potential energy surface for the ring opening of the cyclopropyl radical to allyl radical are determined using the tool of Newton trajectories (Quapp and Schmidt in Theor Chem Acc 128:47, 2011). VRIs play a role in the understanding of bifurcating reactions. The region where the bifurcation takes place is usually governed by a VRI point. For this important ring opening, the knowledge of the VRI point after the transition state was demanded some years ago (Mann and Hase in J Am Chem Soc 124:3208, 2002). Because the transition state is not symmetric, also the steepest descent from the transition state is not along a symmetry axis, and in such cases the steepest descent can fail the VRI point. That is the case here, indeed, though the pathway of the steepest descent goes near to a VRI point downhill. However, an electronic intersection seam disturbs the relations. The exploration of the notorious curvilinear potential energy surface of this ring opening has delivered some further VRI points, which are reported. They give a frame for possible ring-opening channels including the conrotatory case.

A Novel Photopolymerization Initiating System Based on an Iridium Complex Photocatalyst

The use of a photocatalyst (tris(2-phenylpyridine)iridium [Ir(ppy)(3)]) being able to generate both radicals and cations to initiate free radical polymerization and ring opening polymerization is presented. Remarkably, under soft irradiations (fluorescence bulb, sunlight), excellent cationic polymerization profiles and final conversions are obtained. The involved mechanisms are investigated by ESR experiments.

ABA2-type triblock copolymer composed of PCL and PSt: synthesis and characterization

ABA2-type (Y-shaped) triblock copolymer made from poly(e-caprolactone) (PCL) and polystyrene were synthesized by the combination of enzymatic ring-opening polymerization (eROP) and atom transfer radical polymerization (ATRP). First, CCl3-terminated PCL were synthesized by eROP of e-caprolactone in the presence of initiator 2,2,2-trichloroethanol and biocatalyst Novozyme 435, followed by the esterification of the resulting PCL with 2,2-dichloro acetyl chloride to obtain trifunctional macroinitiator. The well-defined Y-shaped block copolymer was then synthesized by ATRP of styrene. The systems display characteristics of a living radical polymerization as indicated by linear first-order kinetics, linearly increasing molecular weight with conversion, and low polydispersities. The macromolecular structures and composition were characterized by HNMR, GPC, and FTIR. The thermal properties were characterized by differential scanning calorimetry.