Micelles In Aqueous Solution Research Articles

Hybridization of Step-/Chain-Growth and Radical/Cationic Polymerizations Using Thioacetals as Key Components for Triblock, Periodic and Random Multiblock Copolymers with Thermoresponsiveness.

A novel strategy for synthesizing a series of multiblock copolymers is developed by combining radical/cationic step-growth polymerizations of dithiols and divinyl ethers and chain-growth cationic degenerative chain-transfer (DT) polymerizations of vinyl ethers using thioacetals as key components. The combination of radical step-growth polymerization and a cationic thiol-ene reaction or cationic step-growth polymerization enables the synthesis of a series of macro chain-transfer agents (CTAs) composed of poly(thioether) and thioacetal groups at different positions. The resulting products are 1) bifunctional macro CTAs with thioacetal groups at both chain ends, 2) periodic macro CTAs periodically having thioacetal groups in the main chain, and 3) random macro CTAs randomly having thioacetal groups in the main chain. Subsequently, the obtained macro CTAs are used for chain-growth cationic DT polymerization of methoxyethyl vinyl ether (MOVE) to result in 1) triblock, 2) periodic, and 3) random multiblock copolymers consisting of poly(thioether) and poly(MOVE) segments. All these triblock and multiblock copolymers composed of hydrophobic poly(thioether) and hydrophilic poly(MOVE) segments show an amphiphilic tendency to form characteristic micelles in aqueous solutions. In addition, due to the thermoresponsive poly(MOVE) segments, the obtained copolymers exhibit lower critical solution temperatures that depend on the segment sequences and lengths.

DPD simulations and experimental study on reduction-sensitive polymeric micelles self-assembled from PCL-SS-PPEGMA for doxorubicin controlled release

Delivery of anticancer drugs by amphiphilic polymeric micelles with disulfide bonds as the reduction-responsive groups has potential application in the field of drug-controlled release. In this study, three disulfide-linked polycaprolactone-b-polyethylene glycol methyl ether methacrylate (PCL-SS-PPEGMA) were synthesized and confirmed by 1H NMR and GPC, and then used for doxorubicin (DOX) delivery. The CMC values of the three PCL-SS-PPEGMA micelles were low (0.71–4.56 mg/L), indicative of the good stability of micelles in aqueous solution. The drug loading content (LC) and encapsulation efficiency (EE), together with the DOX accelerated release profiles were determined, with good drug loading capacity and well drug-controlled release performance. And to explore the mesoscopic behavior of reduction-responsive drug-loaded polymeric micelles, by using a dedicated disulfide bond-breaking model and script, dissipative particle dynamics (DPD) simulations were carried out on the three PCL-SS-PPEGMA polymers. Their self-assembled behavior, formation of DOX-loaded micelles, the disulfide bond-breaking process, as well as the DOX reduction-responsive release process were simulated and assessed. Comparing the DPD simulation results with the experimental data, we found that they were in good agreement, effectively demonstrating that the DPD simulation method developed can provide a practical mesoscopic approach for the reduction-responsive drug-loaded polymeric micelles that involved the cleavage of dynamic covalent bonds.

Schiff-Linked PEGylated Doxorubicin Prodrug Forming pH-Responsive Nanoparticles With High Drug Loading and Effective Anticancer Therapy.

Developing efficacious drug delivery systems for targeted cancer chemotherapy remains a major challenge. Here we demonstrated a kind of pH-responsive PEGylated doxorubicin (DOX) prodrug via the effective esterification and Schiff base reactions, which could self-assemble into the biodegradable micelles in aqueous solutions. Owing to low pH values inside the tumor cells, these PEG-Schiff-DOX nanoparticles exhibited high drug loading ability and pH-responsive drug release behavior within the tumor cells or tissues upon changes in physical and chemical environments, but they displayed good stability at physiological conditions for a long period. CCK-8 assay showed that these PEGylated DOX prodrugs had a similar cytotoxicity to the MCF-7 tumor cells as the free DOX drug. Moreover, this kind of nanoparticle could also encapsulate small DOX drugs with high drug loading, sufficient drug release and enhanced therapeutic effects toward MCF-7 cells, which will be benefited for developing more drug carriers with desirable functions for clinical anticancer therapy.

Novel Therapeutic Platform of Micelles and Nanogels from Dopa-Functionalized Triblock Copolymers.

Multi-drug delivery systems constructed from a basic polymeric scaffold, and which have the ability to target a variety of biomedical applications, can streamline the development of nanomedicine to provide both environmental and economical relief. Herein, amphiphilic ABA-triblock copolymers are synthesized and assembled sequentially into micelles and nanogels as drug delivery systems following a thorough evaluation on advanced in vitro models to explore their potential for the treatment of cancer and bacterial infections. Short blocks of 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) are oligomerized from PEG6k and thereafter functionalized with dihydroxyphenylalanine (dopa)-functional thiols using thiol-ene coupling (TEC) click chemistry. The copolymers self-assemble into well-defined micelles in aqueous solution and are further formulated into nanogels via UV-induced TEC. The resulting spherical micelles and nanogels are stable nanoparticles, with sizes ranging between 100 and 200 nm. The nanogels are found to be non-toxic to a panel of cell lines and mask the toxicity of the potent drugs until their release. The nanogels would be superior to micelles for the elimination of cancer cells supported by both 2D cell culture and a 3D spheroid model. The opposite conclusion could be drawn for bacteria inhibition.

Self‐assembly mechanism of PEG‐b‐PCL and PEG‐b‐PBO‐b‐PCL amphiphilic copolymer micelles in aqueous solution from coarse grain modeling

AbstractWe followed the self‐assembly of high‐molecular weight MePEG‐b‐PCL (poly(methyl ethylene glycol)‐block‐poly(ε‐caprolactone)) diblock and MePEG‐b‐PBO‐b‐PCL (poly(methyl ethylene glycol)‐block‐poly(1,2‐butylene oxide)‐block‐poly(ε‐caprolactone)) into micelles using molecular dynamics simulation with a coarse grain (CG) force field based on quantum mechanics (CGq FF). The triblock polymer included a short poly(1,2‐butylene oxide) (PBO) at the hydrophilic‐hydrophobic interface of these systems. Keeping the hydrophilic length fixed (MePEG45), we considered 250 chains in which the hydrophobic length changed from PCL44 or PBO6‐b‐PCL43 to PCL62 or PBO9‐b‐PCL61. The polymers were solvated in explicit water for 2 μs of simulations at 310.15 K. We found that the longer diblock system undergoes a morphological transition from an intermediate rod‐like micelle to a prolate‐sphere, while the micelle formed from the longer triblock system is a stable rod‐like micelle. The two shorter diblock and triblock systems show similar self‐assembly processes, both resulting in slightly prolate‐spheres. The dynamics of the self‐assembly is quantified in terms of chain radius of gyration, shape anisotropy, and hydration of the micelle cores. The final micelle structures are analyzed in terms of the local density components. We conclude that the CG model accurately describes the molecular mechanisms of self‐assembly and the equilibrium micellar structures of hydrophilic and hydrophobic chains, including the quantity of solvent trapped inside the micellar core.

Self-assembly behavior and conformation of amphiphilic hemicellulose-graft-fatty acid micelles

In this work, a series of amphiphilic hemicellulose-based grafting polymers are synthesized by homogeneous esterification with various hydrophobic chain fatty acids. With the flexible chain conformation of hemicelluloses, the hemicellulose-graft-fatty acid is self-assembled into hard sphere micelles in aqueous solution through hydrophobic interactions. The resultant micelles show apparent hydrodynamic radius (Rh) varying in the range of 34–57 nm and radius of gyration (Rg) varying from 30 to 44 nm. Moreover, the Rh, Rg, zeta potential and critical micelle concentration (CMC) of the micelles gradually decreases with the increasing hydrophobic chain length. The aggregation number of micelles can be tuned by varying alkyl chain lengths. Taking curcumin (Cur) as a model drug, the hemicellulose micelles were investigated as drug carriers, which exhibit a chain length-controlled drug release behavior. Taken together, structure and property tunable hemicellulose-based micelles were obtained, and showed potential of application in pharmaceutical, food, and cosmetics fields.

New GSH-responsive amphiphilic zinc(II) phthalocyanine micelles as efficient drug carriers for combinatorial cancer therapy

Combination therapies for the treatment of cancer have attracted wide attention. The poor selectivity and biocompatibility of photosensitizers (PS) limit the use of combination therapies in chemotherapy and photodynamic therapy (PDT) for cancer. In this work, the Gender PS (mPEG-[Formula: see text]-PLA-S-S-ZnPC), asymmetric zinc(II) phthalocyanine (ZnPC) and mono-methoxy oxygen-based polyethylene glycol-polylactic acid (mPEG-b-PLA) were designed and synthesized for PDT through disulfide bond (-S-S-). The amphipathic PS could be self-assembled into a micelle in aqueous solution, and paclitaxel (PTX) was encapsulated in the core of the micelle for chemotherapy (PTX/mPEG-[Formula: see text]-PLA-S-S-ZnPc). The PTX/mPEG-[Formula: see text]-PLA-S-S-ZnPc micelle was spherical with a uniform diameter of about 184 nm. At the first 48 h, the release behaviors of ZnPC and PTX at 10 mmol / L GSH were 30% and 75.2%, respectively. These results suggested that GSH-responsive PTX/mPEG-[Formula: see text]-PLA-S-S-ZnPc micelle was an active ingredient in combination therapies for cancer.

Hydrophobically modified PEGylated glycol chitosan nanoparticles: synthesis, characterisation and anticancer properties

A novel palmitoylated glycol chitosan polymer grafted with PEG (PGC-PEG) was successfully developed to form amphiphilic micelles in aqueous solution.

Diatom-inspired self-assembly for silica thin sheets of perpendicular nanochannels

HypothesisMultistage silicate self-organization into light-weight, high-strength, hierarchically patterned diatom frustules carries hints for innovative silica-based nanomaterials. With sodium silicate in a biomimetic sol-gel system templated by a tri-surfactant system of hexadecyltrimethylammonium bromide, sodium dodecylsulfate, and poly(oxyethylene-b-oxypropylene-b-oxyethylene) (P123), mesoporous silica nanochannel plates with perpendicular channel orientation are synthesized. The formation process, analogous to that of diatom frustules, is postulated to be directed by an oriented self-assembly of the block copolymer micelles shelled with charged catanionic surfactants upon silication. ExperimentsThe postulated formation process for the oriented silica nanochannel plates was investigated using time-resolved small-angle X-ray and neutron scattering (SAXS/SANS) and freeze fracture replication transmission electron microscopy (FFR-TEM). FindingsWith fine-tuned molar ratios of the anionic, cationic, and nonionic surfactants, the catanionic combination and the nonionic copolymer form charged, prolate ternary micelles in aqueous solutions, which further develop into prototype monolayered micellar plates. The prolate shape and maximized surfactant adsorption of the complex micelles, revealed from combined SAXS/SANS analysis, are of critical importance in the subsequent micellar self-assembly upon silicate deposition. Time-resolved SAXS and FFR-TEM indicate that the silicate complex micelles coalesce laterally into the prototype micellar nanoplates, which further fuse with one another into large sheets of monolayered silicate micelles of in-plane lamellar packing. Upon silica polymerization, the in-plane lamellar packing of the micelles further transforms to 2D hexagonal packing of vertically oriented silicate channels. The unveiled structural features and their evolution not only elucidate the previously unresolved self-assembly process of through-thickness silica nanochannels but also open a new line of research mimicking free-standing frustules of diatoms.

PH-sensitive curcumin conjugated micelles for tumor triggered drug delivery

Development of new drugs are confronted with some barriers and challenges, since these projects are mainly expensive, complex, time consuming with lack of success, there is an urgent need to reformulate the current poorly water soluble anti-cancer drugs. In this study, a new type of polymer–curcumin conjugates based on glycidyl azide polymer (GAP) was developed for cancer therapy. The copolymer was used for delivery of curcumin (CUR) as an anticancer drug to cancer cells. Our method is based on the facile conjugation of CUR to amine-containing polymeric vehicles through imine linkage bonds, which could remain stable in normal physiological condition while readily dissociate by an acidic environment and make the prodrug active to liberate its payload CUR to inhibit cell growth. The results demonstrated that fabricated amphiphilic PDCs were self-assembled into nanosized micelles in aqueous solution and the micelles showed an average size of 180 nm with a good polydispersity index. Drug release studies demonstrated that this nano-conjugate is fairly stable at physiologic environments but prone to mild acidic conditions which would trigger the release of conjugated CUR. Moreover, the PDCs micelles exhibited excellent cytotoxicity effect on 4T1 mouse breast cancer cell line but no significant toxicity was observed for the copolymer. In addition, the copolymer did not display remarkable toxicity against A. salina even at high doses of copolymer. In addition, the synthesized PDCs exhibited hemolysis lowers than 6%. The safety of copolymers as a drug vehicle was also confirmed by LD50, since all mice which treated with 5000 mg/Kg (limited dose) were still alive after one week. Our findings revealed that these unique pH-sensitive PDCs may provide a promising approach for delivery of the anticancer drugs to cancer cells.

Adenine-Functionalized Supramolecular Micelles for Selective Cancer Chemotherapy.

Functional supramolecular micelles containing self-complementary multiple hydrogen bonding adenine groups (A-PPG) can spontaneously self-assemble into stable nanosized micelles in aqueous solution. These micelles can be used to selectively deliver anticancer drugs to cancer cells and effectively promote tumor cell death via apoptosis, without harming normal cells. The drug-loaded micelles exhibit tunable drug-loading capacity and rapid pH-triggered drug release under acidic conditions, as well as a high drug-entrapment stability in serum-rich media due to the reversible hydrogen-bonded adenine-adenine interactions within the micellar interior; these properties are critical to achieving effective chemotherapeutic drug delivery and controlled drug release. In vitro assays show that the drug-loaded micelles exert significant cytotoxic effects on cancer cells, with minimal effects on normal cells under physiological conditions. Cytotoxicity assays using A-PPG micelles loaded with different anticancer drugs confirm these effects. Importantly, cellular internalization and flow cytometric analyses demonstrate that the adenine moieties within A-PPG micelles significantly increase selective endocytic uptake of the supramolecular micelles by cancer cells, which in turn induce apoptotic cell death and substantially enhance the response to chemotherapy. Thus, A-PPG micelles can improve the safety and efficacy of cancer chemotherapy.

Pure and mixed aqueous micellar solutions of Sodium Dodecyl sulfate (SDS) and Dimethyldodecyl Amine Oxide (DDAO): Role of temperature and composition

Aqueous mixtures of anionic and nonionic/cationic surfactants can form non-trivial self-assemblies in solution and exhibit macroscopic responses. Here, we investigate the micellar phase of pure and mixed aqueous solutions of Sodium Dodecyl Sulfate (SDS) and Dimethyldodecyl Amine Oxide (DDAO) using a combination of Small Angle Neutron Scattering (SANS), Fourier-Transform Infrared Spectroscopy (FTIR) and rheological measurements. We examine the effect of temperature (0–60 °C), on the 20 wt% SDS micellar solutions with varying DDAO (⩽5 wt%), and seek to correlate micellar structure with zero-shear solution viscosity. SANS establishes the formation of prolate ellipsoidal micelles in aqueous solutions of pure SDS, DDAO and SDS/DDAO mixtures, whose axial ratio is found to increase upon cooling. Elongation of the ellipsoidal micelles of pure SDS is also induced by the introduction of the non-anionic DDAO, which effectively reduces the repulsive interactions between the anionic SDS head-groups. In FTIR measurements, the formation of elongated mixed ellipsoidal micelles is confirmed by the increase of ordering in the hydrocarbon chain tails and interaction between surfactant head-groups. We find that the zero-shear viscosity of the mixed surfactant solutions increases exponentially with decreasing temperature and increasing DDAO content. Significantly, a master curve for solution viscosity can be obtained in terms of micellar aspect ratio, subsuming the effects of both temperature and DDAO composition in the experimental range investigated. The intrinsic viscosity of mixed micellar solutions is significantly larger than the analytical and numerical predictions for Brownian suspensions of ellipsoidal colloids, highlighting the need to consider interactions of soft micelles under shear, especially at high concentrations.

Abstract 2881: Injectable thermoresponsive hydrogel for the sustained delivery of triptolide in breast cancer treatment

Abstract To avoid the narrow therapeutic window and take advantage of the anticancer efficacy of triptolide (TP), a major active component of Tripterygium wilfordii Hook.F., a novel thermo-responsive nano-micelle hydrogel was fabricated in present study for the sustained release of TP in breast tumor tissue. Briefly, the amphiphilic poloxamer 188-g-poly (N-isopropylacrylamide-co-acrylic acid) copolymer was synthesized by atomic transfer radical polymerization reaction and self-assembled into micelles in aqueous solution with CMC value of 2.6×10-3 mg/mL. TP encapsulated nanogel (TP/F68-g-(PNIPAAm-co-AAC)) exhibited the sol-gel phase transition at 32°C with a narrow size distribution (about 50.16 nm) and sustained drug release in vitro. And then, the TP-loaded nanogel significantly inhibited the cell proliferation against human breast cancer MDA-MB-231 and MCF-7 cells, as well as the induction of cell apoptosis and cell cycle arrest activity. Moreover, we also found the superior anti-angiogenic activities of TP nanogel in both HUVEC and rat aortic ring model when compared to free TP. As expected, mediated by the 4T1 mouse breast cancer model, we demonstrated that a single injection of the TP-loaded nanogel system resulted in the long detention time in tumor tissue due to its thermo-responsive capacity. Moreover, the novel nanogel remarkably enhanced anticancer efficacy and reduced the side effects, when compared with the multiple injections of free TP. Therefore, the injectable thermo-responsive nanogel provided a potential strategy for the efficient delivery of TP with a sustained release manner in breast cancer treatment. Citation Format: Jingjing Li, Jinming Zhang, George Pak-Heng Leung. Injectable thermoresponsive hydrogel for the sustained delivery of triptolide in breast cancer treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2881.

A comparison of β-casein complexes and micelles as vehicles for trans-/cis-resveratrol

Bovine β-casein is an amphiphilic protein that exists as a monomer and self-organizes into micelles in aqueous solution. The protein has been used as natural vehicles for bioactives. Trans-resveratrol has received significant attention due to its vast health benefits and conversion to cis-isomer during processing and storage. However, cis-isomer has not yet gained as much attention as that of trans-isomer. In this study, the interaction of β-casein with trans- and cis-resveratrol was characterized. Trans-resveratrol exhibited a higher affinity for β-casein than cis-isomer, and β-casein could bind two isomers simultaneously to form protein-diligand complexes. Both trans- and cis-isomers could be encapsulated into β-casein micelles with encapsulation efficiencies of ~69% and ~57%, respectively. The β-casein micelles could delay photo-isomerization of trans-isomer to cis-isomer, while β-casein-ligand complex showed a better protective effect for both isomers during storage than β-casein micelles. These results might be useful for the development of protein-based carriers for the polyphenols.

A supramolecular diagnosis and treatment integrated agent: Synthesis and self-assembly of stimulus-responsive star-shaped copolymer

We now report a star-shaped supramolecular copolymer for diagnosis and treatment by chelated with Gd3+ ion as magnetic resonance imaging (MRI) contrast agent and drug-carried for controlling release agent. The copolymer is prepared by the host-guest inclusion complexation between the host polymer polycaprolactone-β-cyclodextrin (4sPCL-CD) and the guest polymer adamantylamine-poly-L-lactic-block-poly(N-isopropylacrylamide-co-2-hydroxyethylmethacrylate-diethylenetriamine penta acetic acid) (AD-PLLA-b-P(NIPAM-co-HEMA-DTPA)) and can self-assemble into spherical micelles in aqueous solution. By adding 2-adamantylamine hydrochloride (AD-NH2), the supramolecular copolymer can be disassembled to the host and guest polymers and its molecular weight will be decreased. When the polymeric micelles are chelated with Gd3+ ion, they exhibit T1 relaxivity as a kind of contrast agent for MRI. This contrast agent can maintain a large molecular size to stay in vivo and also can reduce its molecular size quickly and metabolize rapidly from the body by disassembled. Also, as the copolymer carries drugs, it displays burst release and thermal-response release behaviors, due to its dis-assembly and thermal-response PNIPAM chain respectively. Thus, the supramolecular copolymer from the host-guest inclusion complexation is expected to realize diagnosis and treatment feature for clinic.

A smart drug delivery system responsive to pH/enzyme stimuli based on hydrophobic modified sodium alginate

A biocompatible dual-stimuli responsive drug delivery for hydrophobic drugs based on self-assembled polymeric micelles was presented. Hydrophobic modified alginate (HMA), used dodecyl glycidyl ether as a hydrophobic group, could form self-assembled micelles in aqueous solution above the critical micelle concentration. Doxorubicin (DOX) was chosen as a model drug and successfully loaded in HMA micelles. The percentage of drug loading efficiency of the HMA was determined as 65.4% by using fluorescence measurement. The pH-triggered and enzyme-triggered release behavior of DOX from DOX-HMA micelles indicated that the release of DOX was accelerated in acidic medium and that the release rate was dramatically enhanced in the presence of Alpha-L-fucosidase. It was found that almost 80% DOX was released from the DOX-HMA micelles in the presence of AFU at pH 5.5. Moreover, in vitro drug release studies exhibited that the DOX-HMA was effectively taken up by the cancer cells, and the blank micelles showed low toxicity toward the cancer cells, while the drug loaded micelles had high toxicity, even than the free drugs. These results demonstrate that HMA may serve as a general platform for therapeutic delivery.

Synthesis and characterization of castor oil-derived oxidation-responsive amphiphilic block copolymers: Poly(ethylene glycol)-b-poly(11-((2-hydroxyethyl)thio)undecanoate)

The synthesis of oxidation-responsive biodegradable amphiphilic block copolymers by Candida Antarctica Lipase B (CALB)-catalyzed self-polycondensation of 11-((2-hydroxyethyl)-thio)undecanoic acid (TEHA) initiated by methoxy polyethyleneglycol (mPEG-OH) of different molecular weights has been described. SEC and mono and bidimensional NMR have been used to confirm the molecular weight and structure of the polymers and copolymers. DSC and TGA have been employed to characterize their thermal properties. The oxidation behaviour in front of H2O2 as well as the structure of the oxidized products has been established using NMR, FTIR and Raman spectroscopies. The different block copolymers could self-assemble to form nanosized micelles in aqueous solution with low critical micelle concentration (CMC), showing potential application as dual responsive systems in drug delivery. Micellar characteristics were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). These micelles are prone to undergo a H2O2-triggered disassembly due to the oxidizable thioether groups in the hydrophobic core. Nile Red was used as model for hydrophobic drugs to test the oxidative triggered release of a copolymer, which showed progressive release in few hours upon the addition of H2O2.

Nonionic and anionic surfactant-washing of polycyclic aromatic hydrocarbons in estuarine sediments around an industrial harbor in southern Taiwan

Various surfactants, such as nonionic Triton X-100 and Simple Green™ (SG), and anionic sodium dodecylsulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) were utilized to remove polycyclic aromatic hydrocarbons (PAHs) from heavily contaminated harbor sediments dredged from Kaohsiung Harbor in Taiwan. Desorption/re-sorption equilibrium, kinetics, and washability of PAHs using the selected surfactant were evaluated under different critical micelle concentrations (CMC). Experimental results revealed that the desorption rate of high molecular weight PAHs was greater than those of low molecular weight PAHs, and the anionic SDS was relatively effective in the removal of total PAHs (>50%) compared to the other surfactants. The correlation between the effectiveness of the surfactant washing processes and the physicochemical properties of individual PAH was statistically analyzed. The resulting data suggested that hydrophobic factors (Kow, Koc and Sw) affected PAH treatability more than the reactivity of PAH (electron affinity and ionization potential). Since the adsorption of anionic surfactant altered the hydrophobicity of organic matter in the sediment, PAHs preferred transferring from the sediment to the hydrophobic core of micelles in aqueous solution. Nevertheless, the nonionic surfactant enhanced the PAH partition in the aqueous phase, thus increasing the micellar solubilization of PAH.

Stereoselective self-aggregation of zinc bacteriochlorophyll-d analogs possessing an O-substituted oxime moiety at the 13-position

Zinc methyl 3-hydroxymethyl-131-deoxo-pyropheophorbides-a possessing a variety of O-substituted oxime moieties at the 13-position were prepared as models of bacteriochlorophyll-d, which could be found in the main light-harvesting system of green photosynthetic bacteria by chemical modification of naturally occurring chlorophyll-a. The E/Z-stereoisomers of the synthetic O-substituted oximes were successfully separated by silica gel column chromatography. Most of these zinc bacteriochlorophyll-d analogs formed J-type self-aggregates in an aqueous Triton X-100 micelle solution, affording large oligomers whose Soret and Qy bands were red-shifted, compared with those of their monomers in tetrahydrofuran. The self-aggregation was dependent on their E/Z-stereochemistry. Thus, the E-stereoisomers showed the red-shifted electronic absorption bands, which were similar to those of the original bacteriochlorophyll-d bearing the 131-oxo group. On the other hand, the Z-stereoisomers exhibited the less red-shifted absorption bands than did the E-stereoisomers, to give different self-aggregates. In addition, the self-aggregation could be controlled by the size of the O-substituents in the oxime moiety.

Asymmetric Reactions in Water Catalyzed by L-Proline Tethered on Thermoresponsive Ionic Copolymers

L-Proline was covalently tethered on thermoresponsive ionic block copolymers that formed micelles in aqueous solutions. The block copolymers consisted of a poly(N-isopropylacrylamide) (PNIPAAm) segment and an anionic or cationic polymer segment. These copolymers exhibited lower critical solution temperature (LCST) behavior at ca. 35-40°C, and achieved thermal stimuli-induced formation and dissociation of micelles. The copolymer generated micelles in aqueous solution at a higher temperature, where a catalytic aldol reaction proceeded with high diastereo- and enantioselectivities. The micelles dissociated at lower temperature to form a clear solution such that the products could be efficiently extracted from the aqueous reaction mixture. Extraction of the aldol product with an organic solvent from the aqueous solution of the anionic copolymer was more efficient than from the nonionic copolymer solution.