Recent advances of Pd-π-allyl zwitterions in cycloaddition reactions

Palladium-catalyzed cycloaddition reactions via Pd-π-allyl zwitterions have been established as significant synthetic transformations to enable numerous carbon-or heterocycles compounds that are key constituents of various biologically active natural products and pharmaceuticals.In addition to the well-known Pd-π-allyl zwitterions,including palladium-trimethylenemethane and Pd-1,3/1,4-zwitterions,chemists have recently discovered new applications of several long ago reported but less-studied Pd-π-allyl zwitterions,which can straightforwardly and efficiently construct novel cyclic architectures.Meanwhile,some impressive newly designed zwitterions have been also developed.Those zwitterions are diverse and can serve as transient and highly reactive intermediates for the subsequent cyclization with various acceptors.In this review,we highlight recent advances in applications of these two types of zwitterions in the synthesis of complex polycyclics and medium-sized cyclic compounds.

Synergistic anionic/zwitterionic mixed surfactant system with high emulsification efficiency for enhanced oil recovery in low permeability reservoirs

Emulsification is one of the important mechanisms of surfactant flooding. To improve oil recovery for low permeability reservoirs, a highly efficient emulsification oil flooding system consisting of anionic surfactant sodium alkyl glucosyl hydroxypropyl sulfonate(APGSHS) and zwitterionic surfactant octadecyl betaine(BS-18) is proposed. The performance of APGSHS/BS-18 mixed surfactant system was evaluated in terms of interfacial tension, emulsification capability, emulsion size and distribution, wettability alteration, temperature-resistance and salt-resistance. The emulsification speed was used to evaluate the emulsification ability of surfactant systems, and the results show that mixed surfactant systems can completely emulsify the crude oil into emulsions droplets even under low energy conditions. Meanwhile,the system exhibits good temperature and salt resistance. Finally, the best oil recovery of 25.45% is achieved for low permeability core by the mixed surfactant system with a total concentration of 0.3 wt%while the molar ratio of APGSHS:BS-18 is 4:6. The current study indicates that the anionic/zwitterionic mixed surfactant system can improve the oil flooding efficiency and is potential candidate for application in low permeability reservoirs.

Bacterial Cellulose/Zwitterionic Dual-network Porous Gel Polymer Electrolytes with High Ionic Conductivity

Bacterial cellulose(BC)was innovatively combined with zwitterionic copolymer acrylamide and sulfobetaine methacrylic acid ester[P(AM-co-SBMA)]to build a dual-network porous structure gel polymer electrolytes(GPEs)with high ionic conductivity.The dual network structure BC/P(AM-co-SBMA)gels were formed by a simple one-step polymerization method.The results show that ionic conductivity of BC/P(AM-co-SBMA)GPEs at the room temperature are 3.2×10^(-2) S/cm@1 M H_(2)SO_(4),4.5×10^(-2) S/cm@4 M KOH,and 3.6×10^(-2) S/cm@1 M NaCl,respectively.Using active carbon(AC)as the electrodes,BC/P(AM-co-SBMA)GPEs as both separator and electrolyte matrix,and 4 M KOH as the electrolyte,a symmetric solid supercapacitors(SSC)(AC-GPE-KOH)was assembled and testified.The specific capacitance of AC electrode is 173 F/g and remains 95.0%of the initial value after 5000 cycles and 86.2%after 10,000 cycles.

Diradicals or Zwitterions: The Chemical States of m-Benzoquinone and Structural Variation after Storage of Li Ions

m-Benzoquinones are often regarded as unstable materials in the form of radicals.Herein,an air-stable small molecular m-benzoquinone[4,6-diamino-1,3-benzoquinone(4,6DA1,3BQ)]without bulky groups or large conjugated systems is reported,and its chemical structure and state are profoundly elucidated by a series of substantial investigations that indicate their presence as zwitterions rather than as diradicals.

Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers

Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

Synthesis of a pair of novel receptors and their properties of enantioselective recognition for amino acid zwitterions

A pair of artificial enantiotopic receptors la and lb composed of (S,S) or (R,R) chiral bicyclic guanidinium, azacrown ether and (t-butyldiphenylsilyloxy) methyl group for amino acid zwitterions have been synthesized. The liquid-liquid competition experiments and 1 H NMR studies indicate that the receptor 1a with (S, S) configuration and 1b with (R,R) configuration selectively recognize L- and D-aromatic amino acids & respectively.

A novel triple responsive smart fluid for tight oil fracturing-oil expulsion integration

The traditional multi-process to enhance tight oil recovery based on fracturing and huff-n-puff has obvious deficiencies,such as low recovery efficiency,rapid production decline,high cost,and complexity,etc.Therefore,a new technology,the so-called fracturing-oil expulsion integration,which does not need flowback after fracturing while making full use of the fracturing energy and gel breaking fluids,are needed to enable efficient exploitation of tight oil.A novel triple-responsive smart fluid based on“pseudo-Gemini”zwitterionic viscoelastic surfactant(VES)consisting of N-erucylamidopropyl-N,N-dimethyl-3-ammonio-2-hydroxy-1-propane-sulfonate(EHSB),N,N,N′,N′-tetramethyl-1,3-propanediamine(TMEDA)and sodium p-toluenesulfonate(NaPts),is developed.Then,the rheology of smart fluid is systematically studied at varying conditions(CO_(2),temperature and pressure).Moreover,the mechanism of triple-response is discussed in detail.Finally,a series of fracturing and spontaneous imbibition performances are systematically investigated.The smart fluid shows excellent CO_(2)-,thermal-,and pressure-triple responsive behavior.It can meet the technical requirement of tight oil fracturing construction at 140°C in the presence of 3.5 MPa CO_(2).The gel breaking fluid shows excellent spontaneous imbibition oil expulsion(∼40%),salt resistance(1.2×104 mg/L Na+),temperature resistance(140°C)and aging stability(30 days).

MP2 Study on the Proton Transfer Mechanism of Glycine Assisted by Water

The geometries of glycine-nH2O （n = 1-5） complexes and the transition states of proton transfer in glycine-H2O system were calculated at the MP2/6-31＋＋G＊＊//MP2/6-31G＊ level, upon which we discovered the proton transfer mechanisms, including the number of water molecules necessary for the stabilization of zwitterions and the effect of increasing water molecules on the proton transfer. To our interest, we found that only one water molecule can stabilize the zwitterions; in addition, with the increment of water molecules, the activation energy of positive reaction decreases and that of reverse reaction increases gradually. Glycine will be ionized completely while the water molecules reach to a certain number.

Thermodynamic solvation of a series of homologous α-amino acids in non-aqueous mixture of ethylene-glycol and N,N-dimethyl formamide

Standard free energies (ΔG0t(i) ) and entropies (ΔS0t(i)) of transfer of some homologous α-amino acids viz. glycine (gly), dl-alanine (ala), dl-α-amino butyric acid (aba) and dl-nor-valine (nor-val) from protic ethylene glycol (EG) to dipolar aprotic N,N-dimethyl formamide (DMF) have been evaluated from solubility measure-ments at five equidistant temperatures i.e from 15 to 350C. The observed ΔG0t(i) and TΔS0t(i) Vs composition profiles are complicated because of the various interaction effects. The chemical effects of the transfer Gibbs energies (ΔG0t.ch(i)) and entropies of transfer (ΔS0t.ch(i)) have been obtained after elimination of cavity effect, estimated by the scaled particle theory and dipole-dipole interaction effects, estimated by the use of Keesom-orientation expression. The chemical contributions of transfer energetics of homologous α-amino acids are guided by the composite effects of increased dispersion interaction, basicity and decreased acidity, hydrogen bonding effects and solvophobic solvation of ethylene glycol and N, N-dimethyl formamide mixed solvent as compared to that of reference solvent (ethylene glycol).

Zwitterionic polymer-coated porous poly(vinyl acetate–divinyl benzene)microsphere: A new support for enhanced performance of immobilized lipase

Enzyme immobilization has attracted great attention for improving the performance of enzymes in industrial applications.This work was designed to create a new support for Candida rugosa lipase(CRL)immobilization.A porous poly(vinyl acetate–divinyl benzene)microsphere coated by a zwitterionic polymer,poly(maleic anhydride-alt-1-octadecene)and N,N-dimethylethylenediamine derivative,was developed for CRL immobilization via hydrophobic binding.The catalytic activity,reaction kinetics,stabilities and reusability of the immobilized CRL were investigated.It demonstrated the success of the zwitterionic polymer coating and subsequent CRL immobilization on the porous microsphere.The immobilized lipase(p2-MS-CRL)reached27.6 mg·g^-1 dry carrier and displayed a specific activity 1.5 times higher than free CRL.The increase of Vmax and decrease of Kmwere also observed,indicating the improvement of catalytic activity and enzyme-substrate affinity of the immobilized lipase.Besides,p2-MS-CRL exhibited significantly enhanced thermal stability and pH tolerance.The improved performance was considered due to the interfacial activation regulated by the hydrophobic interaction and stabilization effect arisen by the zwitterionic polymer coating.This study has thus proved the advantages of the zwitterionic polymer-coated porous carrier for lipase immobilization and its potential for further development in various enzyme immobilizations.

Fabrication and characterization of epoxylated zwitterionic copolymergrafted silica nanoparticle as a new support for lipase immobilization

Our previous work proved that the thermal stability of Candida rugosa lipase(CRL)immobilized on zwitterionic polymer(poly(carboxybetaine methacrylate))grafted silica nanoparticle(SNP)was much higher than that on poly(glycidyl methecrylate)(pGMA)grafted SNP,while the latter showed significantly increased activity.Inspired by the research,we have herein proposed to synthesize copolymers of zwitterionic sulfobetaine methacrylate(SBMA)and GMA for CRL immobilization.The copolymers were grafted onto SNP surface at three GMA/SBMA(G/S)molar ratios(G100/S0,G50/S50,G10/S90),followed by the covalent coupling of CRL to the surface copolymers.The immobilized CRLs on the corresponding supports were denoted as p(G100-S0)-CRL,p(G50-S50)-CRL and p(G10-S90)-CRL.The enzyme loading increased with the increase of GMA content in the copolymer,while the activity varied with the grafted copolymer composition.Kinetic study proved the improvement of enzyme-substrate affinity after immobilization.In comparison to p(G100-S0)-CRL,p(G50-S50)-CRL and p(G10-S90)-CRL presented remarkably enhanced thermal stability and pH tolerance,and p(G10-S90)-CRL showed the highest stability.These results suggest that the copolymer design is promising for development as a versatile platform for enzyme immobilization.

Structure and Magnetic Properties of a Manganese Complex with 1-Carboxymethylpyridinium-3-carboxylate

One complex with a zwitterionic dicarboxylate ligand, [Mn（L）（N3）]n 1 （L = 1-car- boxymethylpyridinium-3-carboxylate）, was synthesized and structurally characterized. Complex 1 crystallizes in triclinic, space group P1 with a = 7.570（2）, b = 7.808（2）, c = 9.232（3） A, β= 94.450（19）°, V= 489.0（3） A3, Z = 2, Mr = 277.11, Dc = 1.882 g/cm3, F（000） = 278,μ = 1.359 mm-1, S = 1.021, the final R = 0.0509 and wR = 0.1149 for 2236 observed reflections with 1 〉 2σ（I）. Complex 1 consists of two-dimensional coordination layers in which the anionic uniform chains with mixed triple bridges （one end-on （EO） azide and two syn-syn carboxylates） are cross-linked by the flexible cationic N-methylpyridinium spacers. Magnetic studies demonstrated that the triple bridge in 1 transmits antiferromagnetic coupling between the Mn（Ⅱ） ions.

MOLECULAR ENGINEERING STUDIES ON NONTHROMBOGENIC BIOMATERIALS——A NOVEL CLASS OF NONTHROMBOGENIC BIOMATERIALS WITH ZWITTERIONIC STRUCTURE OF CARBOXYBETAINES

N,N-dimethyl-N-methacryloyloxyethyl-N-carboxyethyl ammonium(DMMCA)was graft-copolymerized onto thesurface of segmented poly(ether urethane)(SPEU)and PE film.The carboxybetaine structure on SPEU and PE filmsurfaces was confirmed by ATR-FTIR,XPS and water contact angle measurements.Through the experiments with plateletadhesion and protein adhesion assay in vitro,the two materials studied,including poly-DMMCA gel,all show excellentnonthrombogenicity.This confirms once again that the zwitterionic molecular structure on the surfaces of materials isessential for improving their nonthrombogenicity and biocompatibility.

Preparation of antifouling ultrafiltration membranes from copolymers of polysulfone and zwitterionic poly(arylene ether sulfone)s

The past few decades have witnessed rapid gains in our demands of antifouling membranes such as water purification membranes and hemodialysis membranes.A variety of methodologies have been proposed for improving the antifouling performance and the hemocompatibility of the membranes.In this study,a series of copolymers(PSF-PESSB)containing polysulfone(PSF)and poly(arylene ether sulfone)bearing pendant zwitterionic sulfobetaine groups(PESSB)were prepared via one-pot polycondensation.Subsequently,the ultrafiltration(UF)membranes were prepared from different zwitterion-containing copolymers.The prepared membranes showed high thermal stability and mechanical properties.Besides,it also displayed attractive antifouling performance and blood compatibility.Compared with the original PSF membrane,the amount of protein absorption on the modified membrane was reduced;the flux recovery ratio and the resistance to blood cells were significantly improved.The results of this work suggest that PSF-PESSB membranes are expected to be applied in blood purification.The introduction of zwitterion-containing polymers to membranes paves ways for developing advanced hemodialysis technologies for crucial process.

Hand-holding and releasing between the anion and cation to change their macroscopic behavior in water

Despite the similarity of ionic liquid and zwitterion, their some properties such as conductivity and hydrophobicity are different. Here we developed a novel phosphonium salt having a dynamic covalent bond between anion and cation, enabling reversible structural shift between free ion pair and zwitterion. With the phosphonium salt, control of the macroscopic phase behavior in aqueous solution, i.e. forming mono-or biphasic systems, upon exposure to an acid or base was reversibly achieved, based on the structural shift of the phosphonium salt. CO_2/N_2 bubbling reversibly changed the phase behavior as well as acid/base, leading to green separation systems.

Zwitterionic monolayer grafted ceramic membrane with an antifouling performance for the efficient oil-water separation

Enormous demands on the separation of oil/water(O/W)emulsions in various industries,such as petrochemical,food and pharmaceutical industries,are looking for high performance and energy-efficient separation methods.Ceramic membranes have been used to deal with O/W emulsions,for its outstanding characteristics of easy-operation,high-flux,and long-term stability.However,membrane fouling is still a challenge in the industrial application of ceramic membranes.Herein,antifouling ceramic membranes were fabricated by grafting zwitterions on the membrane surface via an environment-friendly two-step grafting method,which improves the antifouling property and permeability.Successful grafting of such zwitterion on the ceramic surface was assessed by the combination of FTIR and XPS characterization.More importantly,the hydration can be formed by electrostatic interactions layer on the modified membrane,which was confirmed by TGA characterization.The antifouling performance of prepared zwitterionic ceramic membranes in the separation of O/W emulsions was systematically tested.The results suggested that zwitterion can significantly improve the flux of ceramic ultrafiltration membrane,and can also improve antifouling property dramatically by reducing the irreversible fouling in the separation of O/W emulsions.Therefore,zwitterionic ceramic membranes hold promising potentials as an antifouling,highly efficient and green method in the practical purification of the O/W emulsions.

Conjugation of a zwitterionic polymer with dimethyl chains to lipase significantly increases the enzyme activity and stability

Enzyme-polymer conjugates are complex molecules with great practical significance.This work was designed to develop a novel enzyme-polymer conjugate by covalently coupling a zwitterionic polymer with side dimethyl chains(pID)to Candida rugosa lipase(CRL)via the reaction between the anhydrides of polymer chains with the amino groups of the enzyme.The resulting two CRL-pID conjugates with different pID grafting densities were investigated in term of the catalytic activity,stability and structural changes.In comparison with native CRL,both the CRL conjugates displayed 2.2 times higher activity than the native enzyme,and showed an increase in the maximum reaction rate(V_(max))and a decrease in the Michaelis constant(K_(m)),thus resulting in about three-fold increases in the catalytic efficiency(k_(cat)/K_(m)).These are mainly attributed to the activation of lipase by the hydrophobic alky side chains.Moreover,the thermostability and pH tolerance of the lipase conjugates were significantly enhanced due to the stabilizing effect of the zwitterion moieties.For instance,a five-fold increase of the enzyme half-life at 50℃ for the high-pID conjugated CRL was observed.Spectroscopic studies reveal that the pID conjugation protected the enzyme in the changes in its microenvironment and conformation,well correlating with enhanced activity and stability of lipase conjugates.The findings indicate that enzyme conjugation to the zwitterionic polymer is promising for improving enzyme performance and deserves further development.

Synthesis and Crystal Structure of Dimethyl-3-(4-bromophenyl)-1-phenyl-4,5-dihydro-1H-pyrazole-4,5-dicarboxylate

The title compound （C19H17BrN2O4） was synthesized via a one-pot procedure starting from 4-bromobenzaldehyde, dimethyl acetylenedicarboxylate （DMAD） and phenylhydrazine with pyridine as the catalyst. Its structure was determined by single-crystal X-ray diffraction analysis. The crystal belongs to the monoclinic system, space group P21/c with a = 11.115（3）, b = 8.090（2）, c = 20.211（5） , β = 97.032（5）°, V = 1803.7（8） 3, Z = 4, Mr = 417.25, Dc = 1.536 g/cm3, μ = 2.306 mm-1, F（000） = 852, the final R = 0.0403 and wR = 0.0895 for 2215 observed reflections with I 2σ（I）.

A zwitterionic polymer-inspired material mediated efficient CRISPR-Cas9 gene editing

The typeⅡ prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR/Cas9) adaptive immune system is a cutting-edge genome-editing toolbox.However,its applications are still limited by its inefficient transduction.Herein,we present a novel gene vector,the zwitterionic polymer-inspired material with branched structure (ZEBRA) for efficient CRISPR/Cas9 delivery.Polo-like kinase 1 (PLK1) acts as a master regulator of mitosis and overexpresses in multiple tumor cells.The Cas9 and single guide sgRNA (sgRNA)-encoded plasmid was transduced to knockout Plk1 gene,which was expected to inhibit the expression of PLK1.Our studies demonstrated that ZEBRA enabled to transduce the CRISPR/Cas9 system with large size into the cells efficiently.The transduction with ZEBRA was cell line dependent,which showed~10-fold higher in CD44-positive cancer cell lines compared with CD44-negative ones.Furthermore,ZEBRA induced highlevel expression of Cas9 proteins by the delivery of CRISPR/Cas9 and efficient gene editing of Plk1 gene,and inhibited the tumor cell growth significantly.This zwitterionic polymerinspired material is an effective and targeted gene delivery vector and further studies are required to explore its potential in gene delivery applications.

Novel Zwitterionic Surfactants: Synthesis and Surface Active Properties of N-(3-Alkoxy-2-Hydroxypropyl)-N, N-Dimethyl glycine Betaines

Five new zwitterionic surfactants with long chain alkyl betaine structure incorporated with hydroxylpropyl group have been synthesized. Their structures were identified by elemental analysis, IR (HNMR)-H-1, and (CNMR)-C-13. Surface tension experiments showed that these surfactants have higher surface activity than those without hydroxypropyl group. The values of CMC and gamma(CMC) of these surfactants have been determined.