Dual‐Mode Antibacterial Conjugated Polymer Nanoparticles for Photothermal and Photodynamic Therapy

In this work, dual‐mode antibacterial conjugated polymer nanoparticles (DMCPNs) combined with photothermal therapy (PTT) and photodynamic therapy (PDT) are designed and explored for efficient killing of ampicillin‐resistant Escherichia coli (Amp^r E. coli). The DMCPNs are self‐assembled into nanoparticles with a size of 50.4 ± 0.6 nm by co‐precipitation method using the photothermal agent poly(diketopyrrolopyrrole‐thienothiophene) (PDPPTT) and the photosensitizer poly[2‐methoxy‐5‐((2‐ethylhexyl)oxy)‐p‐phenylenevinylene] (MEH‐PPV) in the presence of poly(styrene‐co‐maleic anhydride) which makes nanoparticles disperse well in water via hydrophobic interactions. Thus, DMCPNs simultaneously possess photothermal effect and the ability of sensitizing oxygen in the surrounding to generate reactive oxygen species upon the illumination of light, which could easily damage resistant bacteria. Under combined irradiation of near‐infrared light (550 mW cm^?2, 5 min) and white light (65 mW cm^?2, 5 min), DMCPNs with a concentration of 9.6 × 10^?4 µm could reach a 93% inhibition rate against Amp^r E. coli, which is higher than the efficiency treated by PTT or PDT alone. The dual‐mode nanoparticles provide potential for treating pathogenic infections induced by resistant microorganisms in clinic.     

Preparation of antibacterial cellulose with a monochloro‐s‐triazine‐based N‐halamine biocide

A novel monochloro‐s‐triazine‐based N‐halamine precursor, 4‐(4‐(5,5‐dimethylhydantoin‐3‐ethylamino)‐6‐chloro‐1,3,5‐triazinylamino)‐benzenesulfonate (HB), was synthesized and characterized by proton nuclear magnetic resonance. The reactive dyes dyeing method was applied to bond HB onto cotton fabrics, and the treated fabrics were confirmed by Fourier transform infrared spectrometer and scanning electron microscope. The chlorinated HB‐treated fabrics showed excellent antibacterial efficacies against Staphylococcus aureus and Escherichia coli O157:H7 and inactivated all inoculated bacteria within 1 min of contact. Interestingly, it was found that the finishing process and following chlorination caused smaller tensile strength loss of cotton fabrics than the traditional pad‐dry‐cure method. Furthermore, the antimicrobial cotton fabrics exhibited good stability and regenerability. Copyright © 2015 John Wiley & Sons, Ltd.     

Novel antibacterial fibers of amphiphilic N‐halamine polymer prepared by electrospinning

As a significant role in subcategory of halogen antibacterial field, amphiphilic N‐halamine polymers show a promise as potential antimicrobials having a broad spectrum of microorganisms, long‐term stability, and renewal of their antibacterial properties. By controlling the process parameters, electrospinning has been well recognized as a versatile and effective method being capable of making fibers and could be easily engineered with desired pore size and porosity to enhance the antimicrobial properties. The amphiphilic N‐halamine P (ADMH‐MMA‐HEMA) terpolymer fibers showed efficient antimicrobial properties against both Gram‐positive and Gram‐negative bacteria within brief contact time. The result meant that the polymer fibers of macromolecular architecture with control of structural parameters such as hydrophobicity/hydrophilicity balance achievement improved antimicrobial activities via electrospinning technique. In vitro cytotoxicity study demonstrated that the polymer was biocompatible. As a result, the integration of amphiphilic antibacterial materials and the electrospinning technique provided us a feasible method to fabricate biocompatible antimicrobial products easily with low manufacturing cost and would be applied in many promising application areas.     

Di‐N‐Methylation of Anti‐Gram‐Positive Aminoglycoside‐Derived Membrane Disruptors Improves Antimicrobial Potency and Broadens Spectrum to Gram‐Negative Bacteria

The effect of di‐N‐methylation of bacterial membrane disruptors derived from aminoglycosides (AGs) on antimicrobial activity is reported. Di‐N‐methylation of cationic amphiphiles derived from several diversely structured AGs resulted in a significant increase in hydrophobicity compared to the parent compounds that improved their interactions with membrane lipids. The modification led to an enhancement in antibacterial activity and a broader antimicrobial spectrum. While the parent compounds were either modestly active or inactive against Gram‐negative pathogens, the corresponding di‐N‐methylated compounds were potent against the tested Gram‐negative as well as Gram‐positive bacterial strains. The reported modification offers a robust strategy for the development of broad‐spectrum membrane‐disrupting antibiotics for topical use.     

一步法制备PNIPAAm-g-PAN/PSt载银复合微球及其抗菌性能研究

以AgNO3为金属源,通过乙醇将与聚N-异丙基丙烯酰胺接枝聚丙烯腈/聚苯乙烯（PNIPAAm-g-PAN/PSt）聚合物微球表面酰胺基团配位的银离子（Ag+）还原,一步法制备了PNIPAAm-g-PAN/PSt载银复合微球。通过傅立叶变换红外（FTIR）和紫外-可见光光谱表征发现,由Ag+还原所得的Ag纳米颗粒被成功地固载在PNIPAAm-g-PAN/PSt 微球上;用透射电子显微镜（TEM）对载银微球的大小和形态进行了表征;热重分析（TGA）结果表明,固载在微球表面的银纳米颗粒的含量（质量分数）为12%;抗菌实验结果表明,所制备的载银微球具有抗革兰氏阴性菌的活性。     

Synthesis of N‐alkyl‐N′‐aryl or Alkenylpiperazines: A Copper‐Catalyzed C–N Cross‐Coupling in the Presence of Aryl and Alkenyl Triflates and DABCO

Unsymmetrical piperazines are key constituents of many pharmaceuticals. Given that the selective introduction of an aryl and alkyl motif onto the piperazine is not always straightforward, direct arylation and alkenylation of 1,4‐diaza‐bicyclo[2.2.2]octane would obviate the inefficiencies associated with the preparation of these target molecules. We have utilized alkyl halides, aryl or alkenyl triflates, and 1,4‐diaza‐bicyclo[2.2.2]octane for the synthesis of N‐alkyl‐N ′‐aryl or alkenylpiperazines. The optimum conditions are developed using CuCl, t‐BuOL i in NMP . Alkenyl triflates requires N ,N ′‐dimethylethylenediamine and higher temperature to afford the desired cross‐coupled product. Substrates bearing electron‐deficient and electron‐rich groups were successfully coupled under the optimum reaction conditions.     

N‐bromo‐hydantoin grafted polystyrene beads: Synthesis and nano‐micro beads characteristics for achieving controlled release of active oxidative bromine and extended microbial inactivation efficiency

N‐bromo‐hydantoin and N‐bromo‐5,5′‐dimethylhydantoin conjugated polystyrene beads were synthesized from chloromethyl polystyrene beads which differ in their particles size, crosslinking, nano‐micro porosity, and tunnels size on the surface, in order to study the effect of these parameters on oxidative halogen release and resultant activity, for water purification applications. The synthesized beads were characterized using elemental analysis, FT‐IR, solid state ¹³C‐NMR, and scanning electron microscope (SEM). The conjugation yield and kinetics in different solvents and bromine loading capacity were studied. The N‐bromoamine polystyrene beads were tested for water decontamination according to NSF 231 protocol. The release of active bromine was analyzed by spectrophotometer using a DPD‐1 kit and also studied the antimicrobial activity against Escherichia coli and MS2 phages. Bead's nano‐micro characteristics were found critical for oxidative halogen release control: rate stabilization and modulation, extension and also influences antimicrobial activity. The synthesized beads exhibited extended and stable release of bromine, 6 and 4 log reduction for E. coli and MS2, respectively for 250 L of passing contaminated water. Thus, N‐halamine hydantoins conjugated polystyrenes, chemically or kinetically release modified should have applications as disinfectants in water purification systems as well as medical field. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 596–610     

An AIE‐Active Conjugated Polymer with High ROS‐Generation Ability and Biocompatibility for Efficient Photodynamic Therapy of Bacterial Infections

New, biocompatible materials with favorable antibacterial activity are highly desirable. In this work, we develop a unique conjugated polymer featuring aggregation‐induced emission (AIE) for reliable bacterial eradication. Thanks to the AIE and donor‐π‐acceptor structure, this polymer shows a high reactive oxygen species (ROS)‐generation ability compared to a low‐mass model compound and the common photosensitizer Chlorin E6. Moreover, the selective binding of pathogenic microorganisms over mammalian cells was found, demonstrating its biocompatibility. The effective growth inhibition of bacteria upon polymer treatment under light irradiation was validated in vitro and in vivo. Notably, the recovery from infection after treatment with our polymer is faster than that with cefalotin. Thus, this polymer holds great promise in fighting against bacteria‐related infections in practical applications.     

Temperature‐Correlated Afterglow of a Semiconducting Polymer Nanococktail for Imaging‐Guided Photothermal Therapy

Nanoparticles for photothermal therapy: Real‐time temperature monitoring is critical to reduce the nonspecific damage during photothermal therapy (PTT); however, PTT agents that can emit temperature‐related signals are rare and limited to few inorganic nanoparticles. We herein synthesize a semiconducting polymer nanococktail (SPN_CT) that can not only convert photo‐energy to heat but also emit temperature‐correlated luminescence after cessation of light excitation. Such an afterglow luminescence of the SPN_CT detects tumors more sensitively than fluorescence as a result of the elimination of tissue autofluorescence, while its temperature‐dependent nature allows tumor temperature to be optically monitored under near‐infrared (NIR) laser irradiation. Thus, SPN_CT represents the first organic optical nanosystem that enables optical‐imaging guided PTT without real‐time light excitation.     

Highly Efficient Drug Delivery Nanosystem via L‐Phenylalanine Triggering Based on Supramolecular Polymer Micelles

An intelligent drug delivery nanosystem has been developed based on biodegradable supramolecular polymer micelles (SMPMs). The drug release can be triggered from SMPMs responsively by a bioactive agent, L ‐phenylalanine in a controlled fashion. The SMPMs are constructed from ethylcellulose‐graft‐poly(ε‐caprolactone) (EC‐g‐PCL) and α‐cyclodextrin (α‐CD) derivate via host–guest and hydrophobic interactions. It has been found that these SMPMs have disassembled rapidly in response to an additional L ‐phenylalanine, due to great affinity discrepancy to α‐CD between L ‐phenylalanine and PCL. Experiments have been carried out on trigger‐controlled in vitro drug release of the SMPMs loaded with a model porphyrin based photosensitizer THPP. The result shows that the SMPMs released over 85% THPP in 6 h, which is two orders magnitudes faster than that of control. Also investigated is the photodynamic therapy (PDT) of THPP‐loaded SMPMs with and without L ‐phenylalanine on MCF‐7 carcinoma cell line. An effective trigger‐concentration dependent lethal effect has been found showing promise in clinical photodynamic therapy.

     

Functionalization of poly(lactide) with N‐phenyl maleimide using N‐acetoxy‐phthalimide during reactive extrusion

Radical grafting of poly(lactide) (PLA) during postpolymerization reactive extrusion is usually done with peroxide initiation, leading to undesirable side reactions (branching or crosslinking) and to difficulties to control the process parameters as well as the final macromolecular structure. The use of N‐acetoxy‐phthalimide (NAPI) was investigated as an alternative to peroxides for the functionalization in the melt of PLA with N‐phenylmaleimide (PhM) monomer. The use of NAPI was found to lead to similar grafting rates in comparison to peroxides, with a better control of the PLA macromolecular structure, due to the formation of nitroxide radicals that combine with the produced macroradicals. Also, the grafting site on PLA backbone was identified after hydrolysis of grafted PLA. Above an optimal PhM concentration, homopolymerization of the monomer was also highlighted. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 917–928     

Anti‐Adhesive,Platelet Gathering Effects of c‐RGD Modified Poly(p‐dioxanone‐co‐l‐Phe) Electrospun Membrane and Its Comprehensive Application in Intestinal Anastomosis

Intestinal resection and anastomosis are performed in over a million people with various bowel diseases annually. Excessive fibrosis and anastomotic site leakage are the main complications of anastomosis surgery, despite great improvements in operative technique and equipment in recent years. In this study, cRGD modified poly(p‐dioxanone‐co‐l ‐Phe) (PDPA) membranes are designed and applied in intestinal anastomosis to simultaneously solve the two aforementioned complications. cRGD is modified onto PDPA membranes through both physical absorption and π–π accumulation between d ‐Phe of cRGD and l ‐Phe of PDPA. Although cRGD modification enhanced the biocompatibility of PDPA membranes, cRGD modified PDPA membrane suppresses fibroblast proliferation both in vitro and in vivo as a result of degradation and subsequent release of fibroblast suppressive l ‐Phe from PDPA. Meanwhile, platelets are entrapped by cRGD modified PDPA membranes through the specific binding of cRGD and platelet GP_IIbIIIa. cRGD modified PDPA membranes are applied in rat intestinal anastomosis, and both adhesion and stenosis are successfully prevented at anastomotic sites. At the same time, bursting pressure, which represents healing intensity at anastomotic sites, is promoted. The gathering and activation of platelets on PDPA membranes induce secretion of autologous PDGF and VEGF to facilitate angiogenesis and subsequent healing of anastomotic sites.     

Synthesis and characterization of κ‐carrageenan/poly(N,N‐diethylacrylamide) semi‐interpenetrating polymer network hydrogels with rapid response to temperature

In this study, a novel classical thermo‐ and salt‐sensitive semi‐interpenetrating polymer network (semi‐IPN) hydrogel composed of poly(N,N‐diethylacrylamide) (PDEAm) and κ‐carrageenan (KC) was synthesized by free radical polymerization. The structure of the hydrogels was studied by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). FTIR and SEM revealed that the semi‐IPN hydrogels possessed the structure of H‐bonds and larger number of pores in the network. Compared to the PDEAm hydrogel, the prepared semi‐IPN hydrogels exhibited a much faster response rate to temperature changes and had larger equilibrium swelling ratios at temperatures below the lower critical solution temperature (LCST). The salt‐sensitive behavior of the semi‐IPN hydrogels was dependent on the content of KC. In addition, during the reswelling process, semi‐IPN hydrogels showed a non‐sigmoidal swelling pattern. Copyright © 2008 John Wiley & Sons, Ltd.     

Time‐Dependent Photodynamic Therapy for Multiple Targets: A Highly Efficient AIE‐Active Photosensitizer for Selective Bacterial Elimination and Cancer Cell Ablation

Pathogen infections and cancer are two major human health problems. Herein, we report the synthesis of an organic salt photosensitizer (PS), called 4TPA‐BQ, by a one‐step reaction. 4TPA‐BQ presents aggregation‐induced emission features. Owing to the aggregation‐induced reactive oxygen species generated and a sufficiently small ΔE_ST, 4TPA‐BQ shows a satisfactorily high ¹O₂ generation efficiency of 97.8 %. In vitro and in vivo experiments confirmed that 4TPA‐BQ exhibited potent photodynamic antibacterial performance against ampicillin‐resistant Escherichia coli with good biocompatibility in a short time (15 minutes). When the incubation duration persisted long enough (12 hours), cancer cells were ablated efficiently, leaving normal cells essentially unaffected. This is the first reported time‐dependent fluorescence‐guided photodynamic therapy in one individual PS, which achieves ordered and multiple targeting simply by varying the external conditions. 4TPA‐BQ reveals new design principles for the implementation of efficient PSs in clinical applications.     

Preparation and characterization of quaternized poly (2,2,2‐trifluoroethyl methacrylate‐co‐N‐vinylimidazole) membrane for vanadium redox flow battery

Aiming to develop a suitable ion exchange membrane for vanadium redox flow battery (VRB), a new kind of imidazolium salt type anion exchange membrane based on the copolymer of N‐vinylimidazole and 2,2,2‐trifluoroethyl methacrylate has been prepared. The membrane is characterized by means of water uptake, ion‐exchange capacity, ionic conductivity, and thermal stability. Furthermore, a VRB with this membrane is assembled, and the performance of such VRB is evaluated. The permeability experiments show that this membrane has reasonable low permeability of vanadium ions. The coulombic efficiency (CE) and energy efficiency (EE) of VRB with the synthesized membrane are 99.5% and 75.0%, whereas the CE and EE of the VRB with Nafion® 117 membrane are 82.6% and 72.6%, respectively. The synthesized membrane shows good chemical stability in VRB via more than 4000 cycles test. Therefore, this membrane shows good applicable potential in VRB. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis and Evaluation of Novel 5‐cyclohexyl‐2‐(4″‐substitutedphenyl)‐3‐(2″‐substitutedphenyl)4H‐2,3,3a,5,6,6a‐hexahydropyrrolo[3,4‐d]isoxazole‐4,6‐dione Derivatives for Their In Vitro Antioxidant and Antibacterial Activities

1,3‐Dipolar cycloaddition reactions of N‐cyclohexyl maleimide ( 1 ) with azomethine N‐oxide ( 2 ) have afforded novel isoxazolidine ( 3 ) in excellent yield. Their structures have been characterized from their IR, ¹H‐NMR, ¹³C‐NMR, ¹H,¹H‐COSY, MS(ESI), and elemental analysis techniques. In vitro antibacterial activity of the synthesized compounds were investigated against a representative panel of pathogenic strains specifically two Gram‐positive bacteria (Staphylococcus aureus and Streptococcus pyogenes ) and two Gram‐negative bacteria (Pseudomonas aeruginosa and Escherichia coli ) using agar‐well diffusion assay. Some of the compounds ( 3a , 3k , 3n , and 3o ) exhibited promising antibacterial activities. All the synthesized compounds have also been screened for their antioxidant activities and were found to be significantly active.     

Synthesis and characterization of a poly(N‐isopropylacrylamide) with β‐cyclodextrin as pendant groups

A novel linear poly(N‐isopropylacrylamide) (PNIPA) with β‐cylodextrin (β‐CD) moiety (PNIPA‐β‐CD) was synthesized by the conjugation of β‐CD carrying amino groups (EDA‐β‐CD) onto PNIPA with epoxy groups (P(NIPA‐co‐GMA), M_n = 3.86 × 10⁴), and the related reaction conditions are investigated. PNIPA‐β‐CD was characterized by means of IR, NMR and UV spectroscopes, element analysis, and differential scanning calorimetry (DSC). The number‐average molecular weight (M_n) and the β‐CD content of the obtained PNIPA‐β‐CD are 4.87 × 10⁴ and 18.8 wt %, respectively. PNIPA‐β‐CD can not only respond to temperature stimuli but also include guest molecules. Lower critical solution temperature (LCST) of aqueous PNIPA‐β‐CD solution is similar to that of PNIPA. The association constant (K_a) for PNIPA‐β‐CD with methyl orange (MO) is 2.4 × 10³ L mol^?1 at pH 1.4, which is comparable to that of EDA‐β‐CD (K_a = 2.9 × 10³ L mol^?1). © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3516–3524, 2005     

Construction of a Highly Selective and Sensitive La(III) Sensor Based on N‐(2‐Pyridyl)‐N′‐(4‐methoxyphenyl)‐thiourea for Nano Level Monitoring of La(III) Ions

N‐(2‐Pyridyl)‐N′‐(4‐methoxyphenyl)‐thiourea (PMPT) was found to be a suitable neutral ion carrier for the construction of a highly selective and sensitive La(III) membrane sensor. Poly(vinyl chloride) (PVC) based membranes of PMPT with potassium tetrakis (p‐chlorophenyl) borate (KTpClPB) as an anionic excluder and oleic acid (OA), dibutyl phthalate (DBP), benzyl acetate (BA) and o‐nitrophenyloctyl ether (NPOE) as plasticizing solvent mediators were constructed and investigated as La(III) membrane sensors. A membrane composed of PMPT‐PVC‐KTpClPB‐BA with the ratio 8.0 : 35.0 : 3.0 : 54.0 works well over a very wide concentration range (4.0×10^?8 to 1.0×10^?1 M) with a Nernstian slope of 19.6±0.2 mV per decade of activity between pH values of 4.0 and 9.0. The detection limit of the sensor was calculated to be 2.0×10^?8 M (ca. 3.0 ppb). The sensor displays very good discrimination toward La(III) ions with regard to most common metal ions and lanthanide ions. The proposed sensor shows a short response time for whole concentration range (ca. 12 s). For evaluation of the analytical applicability of the La(III) sensor, it was successfully used as an indicator electrode for the titration of La(III) ions with EDTA. It was also applied to the determination of fluoride content of two mouth wash preparation samples and monitoring of La(III) ions in some binary and ternary mixtures.     

An Efficient Synthesis of a (−)‐Physostigmine's Library for Identifying Potential Anti‐Alzheimer's Agents

An efficient route for the synthesis of (?)‐physostigmine analogs 1a – 1g and 2a – 2k is described. Analogs 1a – 1g were synthesized via copper(I)‐catalyzed cycloaddition between the optically pure azide 10 and a variety of alkynes. Similarly, analogs 2a – 2k were prepared through ‘three‐component Huisgen cycloaddition’ using various amines, propargyl bromine, and 10 in H₂O. Facile preparation of 10 via MacMillan's organocatalysis has made it possible to generate a great diversity of natural product‐like compounds that can be screened for anti‐Alzheimer's effects.     

Radical heterogeneous polymerization behavior of N‐methyl‐α‐fluoroacrylamide in benzene

The polymerization of N‐methyl‐α‐fluoroacrylamide (NMFAm) initiated with dimethyl 2,2′‐azobisisobutyrate (MAIB) in benzene was studied kinetically and with electron spin resonance. The polymerization proceeded heterogeneously with the highly efficient formation of long‐lived poly(NMFAm) radicals. The overall activation energy of the polymerization was 111 kJ/mol. The polymerization rate (R_p) at 50 °C is given by R_p = k[MAIB]^0.75±0.05 [NMFAm]^0.44±0.05. The concentration of the long‐lived polymer radical increased linearly with time. The formation rate (R_p?) of the long‐lived polymer radical at 50 °C is expressed by R_p? = k[MAIB]^1.0±0.1 [NMFAm]^0±0.1. The overall activation energy of the long‐lived radical formation was 128 kJ/mol, which agreed with the energy of initiation (129 kJ/mol), which was separately estimated. A comparison of R_p? with the initiation rate led to the conclusion that 1‐methoxycarbonyl‐1‐methylethyl radicals (primary radicals from MAIB), escaping from the solvent cage, were quantitatively converted into the long‐lived poly(NMFAm) radicals. Thus, this polymerization involves completely unimolecular termination due to polymer radical occlusion. ¹H NMR‐determined tacticities of resulting poly(NMFAm) were estimated to be rr = 0.34, mr = 0.48, and mm = 0.18. The copolymerization of NMFAm(M₁) and St(M₂) with MAIB at 50 °C in benzene gave monomer reactivity ratios of r₁ = 0.61 and r₂ = 1.79. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2196–2205, 2001