Thermosensitive copolymer with cobalt phthalocyanine and catalytic behavior based on adjustable LCST
Wangyang Lu a ,Baoyan Zhao b ,Nan Li a ,Yuyuan Yao a ,Wenxing Chen a,*
a Key Laboratory of Advanced Textile Materials and Manufacturing Technology,Ministry of Education of China,Zhejiang Sci-Tech University,Hangzhou 310018,China b
Zhejiang Textile and Fashion College,Ningbo 315211,China
a r t i c l e i n f o Article history:
Received 19June 2009
Received in revised form 9November 2009Accepted 13November 2009
Available online 18November 2009Keywords:
Phthalocyanine
Thermosensitive copolymers N -isopropylacrylamide Acrylamide
Phase separation
a b s t r a c t
Thermosensitive polymers with metallophthalocyanine were prepared by immobilizing cobalt tetra(2,4-dichloro-1,3,5-triazine)aminophthalocyanine (Co-TDTAPc)on poly(N -isopropylacrylamide)(PNIPA)and copolymers of N -isopropylacrylamide (NIPA)with acrylamide (AM)(P(NIPA-co-AM))to obtain Co-TD-TAPc–PNIPA and Co-TDTAPc–P(NIPA-co-AM).Examination of the thermosensitive behavior of these poly-mers showed that the proportion of AM in Co-TDTAPc–P(NIPA-co-AM)had a signi?cant effect on the low critical solution temperature (LCST)in aqueous solution.The LCST of Co-TDTAPc–P(NIPA-co-AM)was adjustable from 34.5°C to 90.0°C by changing the AM molar fraction from 0%to 40%.The copolymers showed a high level of catalytic activity on the oxidation of 2-mercaptoethanol in the homogeneous phase when the reaction temperature was below the LCST,and the copolymers could be precipitated and recovered by heterogeneous separation when the temperature was above the https://www.doczj.com/doc/5815087551.html,pared to Co-TDTAPc–PNIPA,the catalytic system with Co-TDTAPc–P(NIPA-co-AM)is able to maintain homogene-ity at a higher temperature due to the higher LCST of the copolymers.In addition,strong salting-out salts,such as NaCl and Na 2SO 4,can decrease the LCST of the copolymers dramatically and obviate the need for more heat to drive the catalytic reaction system to achieve heterogeneous separation.Co-TDTAPc–P(NIPA-co-AM)was stable and remained ef?cient during repetitive test cycles with no obvious decrease of catalytic activity.
ó2009Elsevier Ltd.All rights reserved.
1.Introduction
Metallophthalocyanine derivatives (MtPc),which are structur-ally analogous to the active center of cytochrome P-450,have been used as an effective catalyst for a variety of organic reactions [1–5].As an important class of photosensitizers,MtPc can be used in pho-todynamic therapy for treatment of a range of cancers,macular degeneration,and infectious diseases [6–8],but wider application of MtPc is limited,mainly due to the tendency for aggregation and the dif?culty of catalyst recovery and recycling.The aggrega-tion tendency of the dendritic phthalocyanines decreases as the size of the dendrons increases [9–13];however,it is very dif?cult to realize catalyst recovery and recycling by this method.The strat-egy of immobilizing MtPc on selected insoluble supports (such as activated charcoal,zeolite or clay)has been introduced and used to prepare polymeric MtPc catalysts and thereby to facilitate cata-lyst separation and recycling,which reduces ef?uent contamina-tion [14–18].Unfortunately,the catalytic activity of these materials is reduced (compared with that of their nonsupported
soluble counterpart)and,as in the case of photodynamic therapy,if they are not amenable to immobilization of MtPc on an insoluble rigid support,the application cannot be realized.
Poly(N -isopropylacrylamide)(PNIPA)is one of the most popular thermosensitive polymers,and undergoes a sharp conformational transition from a water-soluble random coil into water-insoluble globule forms at 32–34°C in aqueous solution [19–22].To obtain MtPc catalysts that have a low aggregation tendency and can be recycled,our group has explored a general approach to the synthe-sis of polymeric MtPc catalysts by introducing a polymerizable N -acrylic carbonyl group into the side chains of cobalt tetraamin-ophthalocyanine (Co-APc)and then copolymerizing with N -isopro-pylacrylamide (NIPA)[23].This copolymer has a high level of catalytic activity in the homogeneous phase and could be recovered by simple heating and heterogeneous separation.The catalytic activity showed a marked decrease when the reaction temperature was above the lower critical solution temperature (LCST)of the copolymer ($32.6°C).Thus,the reaction temperature must be controlled below the LCST to achieve a high level of catalytic activ-ity.However,the environmental temperature in some catalytic applications of MtPc are naturally above this LCST,for instance,in studies of MtPc in the photodynamic therapy ?eld,in which the
1381-5148/$-see front matter ó2009Elsevier Ltd.All rights reserved.doi:10.1016/j.reactfunctpolym.2009.11.002
*Corresponding author.Tel./fax:+8657186843251.E-mail address:chenwxg@https://www.doczj.com/doc/5815087551.html, (W.Chen).
Reactive &Functional Polymers 70(2010)
135–141
Contents lists available at ScienceDirect
Reactive &Functional Polymers
j o ur na l h om e pa ge :w w w.e ls e v ie r.c o m/lo c a t e/re ac
t
reaction temperature must be maintained near the physiological temperature of37°C.In addition,other complicated environmental factors in photodynamic therapy,such as the mixture of salts in body?uids,must be taken into account.In the present study,we fo-cus our efforts on developing a novel approach to regulation and control of the LCST of these thermosensitive polymeric MtPc cata-lysts for catalytic applications in a wide range of temperature.
Here,thermosensitive polymers with MtPc were prepared by immobilizing highly reactive cobalt tetra(2,4-dichloro-1,3,5-tri-azine)aminophthalocyanine(Co-TDTAPc)[24]onto the homopoly-mer of NIPA or a copolymer of NIPA and acrylamide(AM)in different molar fractions to obtain Co-TDTAPc–PNIPA and Co-TDTAPc–P(NIPA-co-AM).We describe the thermosensitive proper-ties and catalytic activities of the water-soluble polymeric catalysts Co-TDTAPc–PNIPA and Co-TDTAPc–P(NIPA-co-AM).The copoly-mers were characterized by UV/vis spectra,Fourier transform infrared(FT-IR)spectra,nuclear magnetic resonance(1H NMR), atom absorption spectroscopy(AAS),and dynamic thermogravi-metric analysis(TGA).The LCST of these copolymers was measured by an UV/vis spectrophotometer in a constant-temperature water bath.Considering the importance of environmental factors in the application of MtPc,we focused on investigating the effects of var-ious salts on the LCST of these polymers.The catalytic activity of the polymers was estimated by measuring the ef?ciency of cata-lytic oxidation on2-mercaptoethanol at different temperatures. Due to the higher LCST of Co-TDTAPc–P(NIPA-co-AM),the temper-ature range for application of these polymers can be enlarged. These copolymers have potential applications in developing new water-soluble polymeric catalysts containing MtPc with thermo-sensitive properties.
2.Experiment
2.1.Materials
NIPA(Tokyo Kasei Kogyo Co.,Ltd.)was recrystallized from a1:1 (V/V)mixture of hexane and toluene.AM(Shanghai Lingfeng Chemical reagent Co.,Ltd.Shanghai,China),cobalt chloride hexa-hydrate,urea,and ammonium molybdate were purchased as ana-lytical grade reagents and used as received.Cyanuric chloride (2,4,6-trichloro-1,3,5-triazine,analytical grade)was purchased from Acros.Ammonium persulphate(APS,initiator)was obtained from Aldrich Chemical Co.,Inc.N,N,N0,N0-tetramethylethylenedi-amine(TEMED,accelerator)was purchased from Sigma–Aldrich Co.,Ltd.All the other chemicals were of reagent grade.Water was deionized with a Millipore Milli-Q system.
2.2.Synthesis of Co-TDTAPc
Cobalt tetraaminophthalocyanine(Co-APc)was synthesized from4-nitrophthalic acid,cobalt chloride hexahydrate,and urea as described[25].Co-TDTAPc was prepared by reaction of cyanuric chloride with Co-APc in N,N0-dimethylformamide(DMF)[24].
2.3.Synthesis of Co-TDTAPc–PNIPA and Co-TDTAPc–P(NIPA-co-AM)
PNIPA and P(NIPA-co-AM)were synthesized essentially as de-scribed by Schild and co-workers but with modi?cations,and poly-mers were obtained after drying in vacuo[26].Co-TDTAPc–PNIPA was prepared as follows:2.8g of PNIPA was dissolved in80mL of water at room temperature under agitation.Thirty-three milli-gram of Na2CO3was added to this solution.The mixture was stir-red to ensure that all of the solutes had dissolved.Next,140mL of 0.388mmol/L Co-TDTAPc aqueous solution was added rapidly to the above system during the stirring process,which continued for1h before separation and puri?cation.After the reaction,the insoluble and hydrolyzed Co-TDTAPc was eliminated from the solution by centrifugation.The bottle-green supernatant was re-moved by keeping the solution above50°C,and the pellet was dis-solved in100mL of water.The same process was then repeated three times.The resulting solid was dried in vacuo and then dis-solved in50mL of acetone.The solution was centrifuged to remove Co-TDTAPc,which is insoluble in acetone.The polymer was precip-itated in hexane,then dried in vacuo at45°C for48h to yield Co-TDTAPc–PNIPA.In a similar manner,Co-TDTAPc–P(NIPA-co-AM) was synthesized with different molar fractions of AM,and the pre-cipitation and puri?cation process was done by keeping the solu-tion above50°C.When the AM molar fraction was greater than 17%,the copolymer obtained was dissolved in ethanol and then precipitated in hexane because Co-TDTAPc–P(NIPA-co-AM)is insoluble in acetone when the AM molar fraction is greater than 17%.Here the designation X in Co-TDTAPc–P(NIPA-co-XAM)de-notes the AM unit feed mole percentage in the copolymer,as shown in Table1.
2.4.Polymer characterization
The UV/vis spectra of these copolymers in water,ethanol and DMF were recorded with a Hitachi U-3010spectrophotometer.A Thermo solaar M6atomic absorption spectrometer was used for the determination of the cobalt weight fraction in Co-TDTAPc–PNI-PA and Co-TDTAPc–P(NIPA-co-AM).The FT-IR spectra of samples were recorded using a Thermo-Nicolet5700FT-IR spectrometer. 1H NMR spectra were measured on a Bruker AVANCE400 (400MHz)spectrophotometer using DMSO-d6as a solvent and tet-ramethylsilane(TMS)as an internal standard.The cobalt phthalo-cyanine(CoPc)molar fraction in polymers can be calculated according to the cobalt weight fraction.TGA analysis was done with a Perkin–Elmer Pyris1instrument under nitrogen atmo-sphere with a?ow rate of100mL/min and a heating rate of 10°C/min.In the solubility test,Co-APc,Co-TDTAPc,PNIPA,Co-TDTAPc–PNIPA and Co-TDTAPc–P(NIPA-co-AM)(0.01g)were placed into10mL of solvent(water,DMF,ethanol,acetone,tetra-hydrofuran(THF)and chloroform,respectively)and vibrated at 25°C for24h in a thermostatic vibrator.Next,the solution was?l-tered and the insoluble substrate was collected,dried and weighed. The molecular weight of PNIPA,P(NIPA-co-AM),Co-TDTAPc–PNI-PA,and Co-TDTAPc–P(NIPA-co-AM)was measured by gel perme-ation chromatography(GPC)with three series of aqueous phase columns(Waters Ultrahydrogel250,500and2000, 7.8?300mm)utilizing a Waters515pump,a Wyatt HELEOS18-angle light scattering detector,and a Wyatt Optilab rEX refractive index detector.H2O was used as the eluent at1mL/min.
2.5.LCST measurement
The phase transition of the aqueous polymer solution(1mg/ mL)was detected visually in a closed glass tube and the tempera-ture was controlled by immersion of the glass tube in a constant-temperature water bath.The aqueous solution was adjusted to pH6.7by a diluted aqueous solution of NaOH or HCl.The LCSTs were examined with a Lambda900UV/vis spectrophotometer (Perkin–Elmer)with a constant-temperature water bath by immersion of test tubes containing polymer solutions as a function of temperature.The phase transition was monitored by optical transmittance at500nm through a1-cm sample cell reference against distilled water.The temperature was altered manually, and the solution was allowed to equilibrate for at least5min at each temperature point.LCST is de?ned as the temperature point at which50%of the absorbance change occurred.The same method
136W.Lu et al./Reactive&Functional Polymers70(2010)135–141
was used to determine the LCST values of the polymers in the pres-ence of different salts,such as NaCl,Na2SO4,NaBr,and NaSCN. 2.6.Measurement of catalytic activity
The reaction rates of oxidation of2-mercaptoethanol in the presence of the catalyst were determined by measuring the oxygen consumption in the reaction mixture with a gas burette[27].The 2-mercaptoethanol solution was adjusted to pH11.0with NaOH. The system was equipped with a water jacket,and the reaction solution was stirred by a magnetic follower.The oxygen burette, the reactor,and the connection pipe were thermostatically con-trolled,and the temperature of the entire system was regulated by controlling the temperature of the water jacket.The initial reac-tion rate,V0=àd[HOCH2CH2SH]/d t,was taken from the slope of the tangent line of the concentration of HOCH2CH2SH consumption oxidized by oxygen versus time.The concentration of RSH oxidized by oxygen was calculated from the concentration of consumed oxygen in solution[23].
3.Results and discussion
3.1.Preparation of Co-TDTAPc–PNIPA and Co-TDTAPc–P(NIPA-co-AM)
PNIPA was prepared at room temperature(25°C)by aqueous redox polymerization and a high yield was achievable with further puri?cation by heating.A series of AM-modi?ed P(NIPA-co-AM) copolymers were synthesized via aqueous redox polymerization. Due to the high electrophilic reactivity of2,4-dichloro-1,3,5-tri-azine in Co-TDTAPc[24],Co-TDTAPc can react with imino or amido groups in PNIPA and P(NIPA-co-AM),respectively,in the presence of sodium carbonate in aqueous solution,as shown in https://www.doczj.com/doc/5815087551.html,-pared with the copolymer of cobalt tetra(N-carbonylacrylic)amin-ophthalocyanine and NIPA(if the weight ratio of CoPc to NIPA was above1%in the solution,an insoluble gel tended to form at room temperature,which would limit its application as a homoge-neous catalyst),the weight ratio of CoPc in this system could be improved without the existence of an insoluble gel because the steric extrusion of the macromolecular chain in PNIPA or P(NIPA-co-AM)can prevent cross-linking between Co-TDTAPc and poly-mers.The molar ratio of CoPc in Co-TDTAPc–PNIPA and in Co-TDTAPc–P(NIPA-co-AM)with different AM molar ratios are given in Table S1.In addition,the weight-average molecular weight (M w)and number-average molecular weight(M n)were measured by GPC combined with18-angle light scattering detector,as shown in Table https://www.doczj.com/doc/5815087551.html,pared with PNIPA and P(NIPA-co-AM),the molec-ular weight of Co-TDTAPc–PNIPA and Co-TDTAPc–P(NIPA-co-AM) increased very slightly,indicating that Co-TDTAPc was attached to these polymers but there was seldom cross-linking present in these polymers.
For structure characterization and measurement of the thermo-sensitive behavior of polymers,we tested the solubility of Co-APc, Co-TDTAPc,Co-TDTAPc–PNIPA,and Co-TDTAPc–P(NIPA-co-AM)in different solvents,as shown in Table1.The results revealed that Co-APc and Co-TDTAPc were soluble only in strong aprotic sol-vents,such as DMF.Co-TDTAPc immobilized on PNIPA exhibited excellent solubility in most solvents because Co-TDTAPc had little effect on the excellent solubility of PNIPA alone,and the polymer improved the solubility of Co-TDTAPc.However,when Co-TDTAPc was immobilized on P(NIPA-co-AM),the solubility changed with increased AM molar fraction.Co-TDTAPc–P(NIPA-co-AM)was highly soluble in strongly polar solvents,such as water,ethanol, and DMF.Co-TDTAPc–P(NIPA-co-AM)was dissolved selectively in solvents of relatively decreased polarity,such as acetone,THF, and chloroform.
These polymers have been characterized by FT-IR,1H NMR,and UV/vis spectroscopy.The absorbance of Co-TDTAPc in FT-IR spectra (Fig.S2)was not marked because the amount of CoPc in Co-TDTAPc–PNIPA was very small(about1–2wt.%).In addition,the 1H NMR of Co-TDTAPc–PNIPA(Fig.S3)and Co-TDTAPc–P(NIPA-co-AM)(Fig.S4)was almost identical to that of PNIPA and P(NIPA-co-AM),respectively,due to the paramagnetism of Co-TDTAPc.Therefore,the UV/vis spectra were used to prove whether Co-TDTAPc was supported on PNIPA or P(NIPA-co-AM).The UV/vis spectra of virgin and Co-TDTAPc-labeled thermosensitive polymers in different solvents are compared in Figs.1and2.We used water, ethanol,and DMF as solvents to determine the solubility of the polymers(Table1).It can be seen in Fig.1that Co-TDTAPc–PNIPA shows an absorption band at$300nm and another at600–700nm,corresponding to the B band and the Q band of metall-ophthalocyanines,respectively[28,29].These absorption bands were not present in the UV/vis spectrum of PNIPA.Since Co-APc and Co-TDTAPc were insoluble in ethanol,it could be con?rmed that Co-TDTAPc had been attached to PNIPA.Of course,Co-TDTAPc had also been attached to P(NIPA-co-AM),as shown in Fig.2.
As an important catalyst parameter to be evaluated,the thermal stability of phthalocyanine and polymers was investigated by TGA. Fig.S5presents the weight loss curves recorded for Co-TDTAPc, PNIPA,and Co-TDTAPc–PNIPA.The weight loss of Co-TDTAPc occurs at temperatures between230°C and375°C,which
Table1
Solubility test of Co-APc,Co-TDTAPc,PNIPA,and Co-TDTAPc–P(NIPA-co-AM)with different AM molar fractions(25°C).
Samples H2O DMF Ethanol Acetone THF CHCl3
Co-APcà+ààààCo-TDTAPc+a+ààààPNIPA++++++ Co-TDTAPc–PNIPA++++++ Co-TDTAPc–P(NIPA-co-1.06AM)++++++ Co-TDTAPc–P(NIPA-co-2.17AM)++++++ Co-TDTAPc–P(NIPA-co-3.23AM)++++++ Co-TDTAPc–P(NIPA-co-3.85AM)++++++ Co-TDTAPc–P(NIPA-co-4.76AM)+++++àCo-TDTAPc–P(NIPA-co-9.09AM)+++++àCo-TDTAPc–P(NIPA-co-16.67AM)+++++àCo-TDTAPc–P(NIPA-co-25.00AM)+++à+àCo-TDTAPc–P(NIPA-co-28.57AM)+++àààCo-TDTAPc–P(NIPA-co-33.33AM)+++àààCo-TDTAPc–P(NIPA-co-38.46AM)+++àààCo-TDTAPc–P(NIPA-co-40.00AM)+++ààà
+,soluble;à,insoluble.
a The solution of Co-TDTAPc can be obtained when the fresh sample of Co-TDTAPc was prepared in aqueous solution.
W.Lu et al./Reactive&Functional Polymers70(2010)135–141137
corresponds to decomposition of the side chains of cobalt phthalo-cyanine.The decomposition of the molecular chain of PNIPA starts from 345°C,while that of Co-TDTAPc–PNIPA starts from 425°C,showing that Co-TDTAPc–PNIPA is more stable than PNIPA at high-er temperature.This can be explained by the fact that phthalocya-nine molecules can form physical cross-linking points in the polymer matrix at high temperature,which can improve the stabil-ity of the polymer.Co-TDTAPc can also improve the stability of P(NIPA-co-AM)due to a similar mechanism.
3.2.Thermosensitive behavior of Co-TDTAPc–PNIPA and Co-TDTAPc–P(NIPA-co-AM)
Cloud-point temperature measurements have been used to study the effects of the hydrophilic/hydrophobic balance in a series of Co-TDTAPc–P(NIPA-co-AM)copolymers upon the smart thermal responses of these systems in dilute aqueous solution (Fig.S6).Fig.3shows the LCST of aqueous solutions of Co-TDTAPc–P(NIPA-co-AM)with different compositions.With increased AM molar ratio,a pronounced change was observed in the LCST
of
Fig. 1.UV/vis spectra of PNIPA and Co-TDTAPc–PNIPA in different solvents including:(a)water,(b)ethanol,and (c)
DMF.
Fig.2.UV/vis spectra of P(NIPA-co-28.57AM)and Co-TDTAPc–P(NIPA-co-28.57AM)in different solvents including:(a)water,(b)ethanol,and (c)DMF.
138W.Lu et al./Reactive &Functional Polymers 70(2010)135–141
Co-TDTAPc–P(NIPA-co-AM).The increase in the content of the more hydrophilic AM monomer will lead to an obvious increase of the LCST of the system.The results might be expected from the predictions of Taylor and Cerankowski [30]and other studies [31,32]in which the hydrophilic/hydrophobic balance of NIPA-based systems was altered.
The phase transition of Co-TDTAPc–P(NIPA-co-28.57AM)is shown in Fig.4.The transparent aqueous solution (A)is trans-formed into a turbid liquid (B)when it is warmed above the LCST of the polymer (55.8°C).This indicates a microphase separation,
but without obvious precipitation.Continuous heating causes the system morphology to undergo further changes and results in the formation of a granular deposit (C).As time increases,the precipita-tion process produces a separation between the polymer and the solution (D).With constant homotropic shaking,a shrunken sphere (E)can be observed that makes the system separation easier than it is by ?ltration or centrifugation.When the phase-separated system is cooled,it returns to the initial homogeneous state (A).3.3.Effect of salts on thermal phase transitions
The LCST of Co-TDTAPc–PNIPA or Co-TDTAPc–P(NIPA-co-AM)can be affected by various salts,such as Na 2SO 4,NaCl,and NaBr.Fig.S7shows the effect of different salts on the LCST of Co-TDTAPc–PNIPA.As can be seen,at the same concentration of an-ions,SO 2à4is ranked as a strong salting-out ion,Cl àand Br à
are mild
salting-out ions,and SCN à
is a strong salting-in ion.The results show that the effect of added salts on Co-TDTAPc–PNIPA depends on the kind of anion [33].The effects of different salts on the LCST of Co-TDTAPc–P(NIPA-co-AM)are given in Table 2,where it can be seen that Na 2SO 4decreased the LCST of Co-TDTAPc–P(NIPA-co-AM)dramatically.Due to the higher LCST of Co-TDTAPc–P(NIPA-co-AM),we chose the strong salting-out salt Na 2SO 4to investigate the effect of salt concentration on the LCST of Co-TDTAPc–P(NIPA-co-AM)(Fig.5).Signi?cant decreases in the LCST of Co-TDTAPc–P(NIPA-co-AM)were observed with an increased concentration of Na 2SO 4.This is probably because the existence of Na 2SO 4reduces the hydrogen bond between Co-TDTAPc–P(NIPA-co-AM)and water,destroys the hydration layer in the polymer surface,and causes an increase of hydrophobicity.Therefore,Na 2SO 4can poten-tially be used to precipitate the polymers from the catalytic reac-tion system at a high temperature.
3.4.Catalytic activity of Co-TDTAPc–PNIPA and Co-TDTAPc–P(NIPA-co-AM)on oxidation of 2-mercaptoethanol
It is well known that the homogeneous or heterogeneous cata-lytic oxidation of 2-mercaptoethanol by oxygen in the presence
of
Fig.3.LCST of Co-TDTAPc–P(NIPA-co-AM)as a function of AM molar fraction in monomer feeds (concentration of Co-TDTAPc–P(NIPA-co-AM):1mg/mL,pH
6.7).
Fig.4.Thermosensitive phase transition of Co-TDTAPc–P(NIPA-co-28.57AM).
Table 2
Effect of salt on the LCST of Co-TDTAPc–P(NIPA-co-38.46AM)solution (salt concen-tration:0.3168mol/L).Salt Without salt Na 2SO 4NaCl NaBr NaSCN LCST (°C)
81.0
31.0
58.2
63.8
85.0
Fig.5.Effect of concentration of Na 2SO 4on the LCST of Co-TDTAPc–P(NIPA-co-38.46AM).
W.Lu et al./Reactive &Functional Polymers 70(2010)135–141139
CoPc complexes results in the formation of disul?des,according to the oxidation reaction (Eq.1)[34,35].The catalytic activity of Co-TDTAPc–PNIPA and Co-TDTAPc–P(NIPA-co-AM)was determined by measuring the amount of O 2consumed.
HOCH 2CH 2tOH à!HOCH 2CH 2S àtH 2O
4HOCH 2CH 2S àtO 2t2H 2O !catalyst
2HOCH 2CH 2SSCH 2CH 2OH
t4OH à
e1T
According to our previous report,pH 11is optimal for oxidation on 2-mercaptoethanol catalyzed by CoPc derivatives [34].Fig.6presents the time-dependence of oxygen consumption in 2-mercaptoethanol oxidation catalyzed by Co-TDTAPc–PNIPA and Co-TDTAPc–P(NIPA-co-28.57AM)in water at pH 11.0and at 25°C or 50°C.The results showed that both Co-TDTAPc–PNIPA and Co-TDTAPc–P(NIPA-co-28.57AM)have good catalytic activity in aqueous solution at 25°C,based on the homogenous catalytic oxi-dation process.At 50°C,the oxygen consumption rate of the oxida-tion reaction catalyzed by Co-TDTAPc–PNIPA was markedly decreased.In contrast,the rate of oxygen consumption in the pres-ence of Co-TDTAPc–P(NIPA-co-28.57AM)increased markedly.These two catalytic processes present different super?cial phe-nomena at 50°C:the solution including Co-TDTAPc–PNIPA was clouded and had some deposits,while the solution including Co-TDTAPc–P(NIPA-co-28.57AM)was transparent and homoge-neous.At 50°C,Co-TDTAPc–PNIPA serves as a heterogeneous catalyst and Co-TDTAPc–P(NIPA-co-AM)serves as a homogeneous catalyst.
Some reactions were done at various temperatures to further investigate the temperature-dependence of oxidation of 2-mercap-toethanol catalyzed by these copolymers,as shown in Fig.7.When Co-TDTAPc–PNIPA was chosen as the catalyst,the initial reaction rate V 0increased in the range 20.0–32.0°C,showing that the cata-lytic oxidation of 2-mercaptoethanol is an endothermic reaction,and then a dramatic decline of V 0was observed at 34.0°C.The aqueous solution containing Co-TDTAPc–PNIPA became turbid at temperatures above 32.0°C,which is slightly lower than the LCST of Co-TDTAPc–PNIPA (34.5°C).This is mainly because the LCST of Co-TDTAPc–PNIPA is lowered to pH 11by the addition of alkali [36].Above the LCST,a dramatic decline in the catalytic activity of Co-TDTAPc–PNIPA appeared at 34.0°C.This can be explained in that the catalytic activity of the phthalocyanine molecule was in?uenced by its microenvironment.When the temperature is
above the LCST,a hydrophobic group can exist on the surface of Co-TDTAPc–PNIPA,and prevent àSCH 2CH 2OH,(the hydrophilic group)from coordinating with the active center of CoPc.This is why the catalytic activity decreases on oxidation of 2-mercap-toethanol.Fig.7shows that Co-TDTAPc–P(NIPA-co-AM)has a similar transformation trend.V 0was observed to increase in the range of 20.0to 54.0°C because the oxidation of 2-mercap-toethanol is an endothermic https://www.doczj.com/doc/5815087551.html,pared with Co-TDTAPc–PNIPA,a dramatic decline of V 0was observed at 56.0°C because the latter has a higher LCST than the former.From the LCST data for Co-TDTAPc–P(NIPA-co-AM)in Fig.3,the LCST of Co-TDTAPc–P(NIPA-co-28.57AM)is 55.8°C.Therefore,the catalytic activity of Co-TDTAPc–P(NIPA-co-AM)is correlated directly with the LCST.A higher reaction temperature is an important factor when trying to achieve a higher catalytic activity.The different AM molar frac-tions in the Co-TDTAPc–P(NIPA-co-AM)can meet the need for a higher reaction temperature by adjusting the LCST.In some catalytic or enzymatic reactions involving phthalocyanine,the temperature can be controlled by adjusting the AM molar fraction.Furthermore,cyclic utilization is essential to evaluation of a catalyst.The results show that the catalytic activity of Co-TDTAPc–P(NIPA-co-AM)was very slightly impaired by
four
Fig. 6.Oxidation of 2-mercaptoethanol catalyzed by Co-TDTAPc–PNIPA or Co-TDTAPc–P(NIPA-co-28.57AM)in aqueous solution (concentration of CoPc:1?10à5mol/L;concentration of 2-mercaptoethanol at time zero:0.1
mol/L).
Fig.7.Temperature-dependence of the initial rate V 0of oxidation of 2-mercap-toethanol catalyzed by Co-TDTAPc–PNIPA or Co-TDTAPc–P(NIPA-co-28.57AM)(concentration of CoPc:1?10à5mol/L;concentration of 2-mercaptoethanol at time zero:0.1
mol/L).
Fig.8.Recycling of oxidation of 2-mercaptoethanol catalyzed by Co-TDTAPc–P(NIPA-co-28.57AM)in aqueous solution (concentration of CoPc:1?10à5mol/L;concentration of 2-mercaptoethanol at time zero:0.1mol/L;50°C).
140W.Lu et al./Reactive &Functional Polymers 70(2010)135–141
repetitive experiments,as shown in Fig.8,and homogeneous catal-ysis and heterogeneous separation have been realized successfully by simple heating.
4.Conclusion
A series of water-soluble polymeric catalysts containing CoPc (Co-TDTAPc–PNIPA and Co-TDTAPc–P(NIPA-co-AM))with temper-ature-responsive properties were prepared.The LCST of these poly-meric catalysts with different AM molar fractions cover a wide temperature range.Co-TDTAPc–P(NIPA-co-AM)with a large AM molar fraction can more or less resist the in?uence of salting-out salts and exists as a transparent solution at high temperature.The copolymers showed a high level of catalytic activity on oxidation of2-mercaptoethanol in the homogeneous phase when the reaction temperature was below the LCST,and could be precipitated and recovered by heterogeneous separation when the temperature was above the LCST.Since the catalytic oxidation of2-mercap-toethanol is an endothermic reaction,the increasing AM content in the copolymer can enhance the catalytic activity of the copolymer via increase of the LCST to maintain homogeneous catalysis at the higher reaction temperature.In addition,the presence of strong salting-out salts,such as Na2SO4,bene?ts separation of the copoly-mer from the reaction system.Since the LCST of the copolymers is adjustable,we can choose a polymeric catalyst with a certain LCST and control the reaction temperature according to different needs, e.g.,the application of a polymeric catalyst with an LCST above 37°C in photodynamic therapy.These copolymers have potential applications in development of new water-soluble polymeric cata-lysts with thermosensitive properties containing MtPc.
Acknowledgements
This work was supported by theNational Natural Science Foun-dation of China(No.50872124and20574061),Program for Chang-jiang Scholars and Innovative Research Team in University(IRT 0654),and Zhejiang Provincial Natural Science Foundation of China (Y4080341).
Appendix A.Supplementary material
Supplementary data associated with this article can be found,in the online version,at doi:10.1016/j.reactfunctpolym.2009.11.002.References
[1]C.C.Leznoff,A.B.P.Lever,Phthalocyanines:Properties and Applications,vols.
1–4,VCH,New York,1989–1996.
[2]H.Shirai,N.Kobayashi,Phthalocyanines–Chemistry and Functions,IPC,
Tokyo,1997.
[3]N.B.McKeown,Phthalocyanine Materials:Synthesis,Structure and Function,
Cambridge University Press,Cambridge,1998.
[4]D.W?hrle,N.Baziakina,O.Suvorova,S.Makarov,V.Kutereva,E.Schupok,G.
Schnurpfeil,J.Porphyrins Phthalocyan.8(2004)1390.
[5]H.Shirai,H.Tsuiki,E.Masuda,T.Koyama,K.Hanabusa,J.Phys.Chem.95
(1991)417.
[6]H.Ali,J.E.van Lier,Chem.Rev.99(1999)2379.
[7]E.A.Lukyanets,J.Porphyrins Phthalocyan.3(1999)424.
[8]C.M.Allen,W.M.Sharman,J.E.van Lier,J.Porphyrins Phthalocyan.5(2001)
161.
[9]Z.Sheng,X.Ye,Z.Zheng,S.Yu,D.K.P.Ng,T.Ngai,C.Wu,Macromolecules35
(2002)3681.
[10]A.C.H.Ng,X.-Y.Li,D.K.P.Ng,Macromolecules32(1999)5292.
[11]X.-Y.Li,X.He,A.C.H.Ng,C.Wu,D.K.P.Ng,Macromolecules33(2000)2119.
[12]T.Ngai,G.-Z.Zheng,X.-Y.Li,D.K.P.Ng,C.Wu,Langmuir17(2001)1381.
[13]P.P.S.Lee,T.Ngai,J.-D.Huang,C.Wu,W.-P.Fong,D.K.P.Ng,Macromolecules36
(2003)7527.
[14]M.Ganschow,D.W?hrle,G.Schulz-Ekloff,J.Porphyrins Phthalocyan.3(1999)
299.
[15]K.J.Balkus Jr.,M.Eissa,R.Levado,J.Am.Chem.Soc.117(1995)10753.
[16]R.F.Parton,P.E.Neys,P.A.Jacobs,R.C.Sosa,P.G.Rouxhet,J.Catal.164(1996)
341.
[17]V.Iliev,A.Ileva,L.Bilyarska,J.Mol.Catal.A:Chem.126(1997)199.
[18]A.Hirth,A.K.Sobbi,D.W?hrle,J.Porphyrins Phthalocyan.1(1997)275.
[19]Y.Chen,M.Sone,K.Fuchise,R.Sakai,R.Kakuchi,Q.Duan,J.Sun,A.Narumi,T.
Satoh,T.Kakuchi,React.Funct.Polym.69(2009)463.
[20]X.Z.Zhang,R.X.Zhuo,Langmuir17(2001)12.
[21]T.Saitoh,Y.Sugiura,K.Asano,M.Hiraide,React.Funct.Polym.69(2009)792.
[22]J.Li,J.Ren,Y.Cao,W.Yuan,React.Funct.Polym.69(2009)870.
[23]W.X.Chen,B.Y.Zhao,Y.Pan,Y.Y.Yao,S.S.Lu,S.L.Chen,L.J.Du,J.Colloid Interf.
Sci.300(2006)626.
[24]W.X.Chen,W.Y.Lu,Y.Y.Yao,M.H.Xu,Environ.Sci.Technol.41(2007)6240.
[25]B.N.Achar,G.M.Fohlen,J.A.Parker,J.Keshavayya,Polyhedron6(1987)1463.
[26]H.G.Schild,D.A.Tirrell,J.Phys.Chem.94(1990)4352.
[27]H.Fischer,G.Schulz-Ekloff,D.W?hrle,Chem.Eng.Technol.20(1997)462.
[28]H.P.Xia,M.Nogami,Opt.Mater.15(2000)93.
[29]A.Hadasch,A.Sorokin,A.Rabion,B.Meunier,New J.Chem.22(1998)45.
[30]L.D.Taylor,L.D.Cerankowski,J.Polym.Sci.,Polym.Chem.Ed.13(1975)2551.
[31]H.Feil,Y.H.Bae,J.Feijen,S.W.Kim,Macromolecules26(1993)2496.
[32]M.Shibayama,S.Mizutani,S.Nomura,Macromolecules29(1996)2019.
[33]E.Krasovitski,Y.Cohen,H.Bianco-Peled,J.Polym.Sci.Part B:Polym.Phys.42
(2004)3713.
[34]Y.Pan,W.X.Chen,S.F.Lu,Y.F.Zhang,Dyes Pigm.66(2005)115.
[35]M.Sanchez,N.Chap,J.B.Cazaux,B.Meunier,Eur.J.Inorg.Chem.2001(2001)
1775.
[36]X.M.Liu,L.S.Wang,L.Wang,J.C.Huang,C.B.He,Biomaterials25(2004)5659.
W.Lu et al./Reactive&Functional Polymers70(2010)135–141141
英语介词用法大全 TTA standardization office【TTA 5AB- TTAK 08- TTA 2C】
介词（The Preposition）又叫做前置词，通常置于名词之前。它是一种虚词，不需要重读，在句中不单独作任何句子成分，只表示其后的名词或相当于名词的词语与其他句子成分的关系。中国学生在使用英语进行书面或口头表达时，往往会出现遗漏介词或误用介词的错误，因此各类考试语法的结构部分均有这方面的测试内容。 1. 介词的种类 英语中最常用的介词，按照不同的分类标准可分为以下几类： (1). 简单介词、复合介词和短语介词 ①.简单介词是指单一介词。如： at , in ,of ,by , about , for, from , except , since, near, with 等。②. 复合介词是指由两个简单介词组成的介词。如： Inside, outside , onto, into , throughout, without , as to as for , unpon, except for 等。 ③. 短语介词是指由短语构成的介词。如： In front of , by means o f, on behalf of, in spite of , by way of , in favor of , in regard to 等。 (2). 按词义分类 {1} 表地点（包括动向）的介词。如： About ,above, across, after, along , among, around , at, before, behind, below, beneath, beside, between , beyond ,by, down, from, in, into , near, off, on, over, through, throught, to, towards,, under, up, unpon, with, within , without 等。 {2} 表时间的介词。如： About, after, around , as , at, before , behind , between , by, during, for, from, in, into, of, on, over, past, since, through, throughout, till(until) , to, towards , within 等。 {3} 表除去的介词。如： beside , but, except等。 {4} 表比较的介词。如： As, like, above, over等。 {5} 表反对的介词。如： againt ,with 等。 {6} 表原因、目的的介词。如： for, with, from 等。 {7} 表结果的介词。如： to, with , without 等。 {8} 表手段、方式的介词。如： by, in ,with 等。 {9} 表所属的介词。如： of , with 等。 {10} 表条件的介词。如：
介词用法知多少 介词是英语中最活跃的词类之一。同一个汉语词汇在英语中可译成不同的英语介词。例如汉语中的“用”可译成：（1）用英语（in English）；（2）用小刀（with a knife）；（3）用手工（by hand）；（4）用墨水（in ink）等。所以，千万不要以为记住介词的一两种意思就掌握了这个介词的用法，其实介词的用法非常广泛，搭配能力很强，越是常用的介词，其含义越多。下面就简单介绍几组近义介词的用法及其搭配方法。 一. in, to, on和off在方位名词前的区别 1. in表示A地在B地范围之内。如： Taiwan is in the southeast of China. 2. to表示A地在B地范围之外，即二者之间有距离间隔。如： Japan lies to the east of China. 3. on表示A地与B地接壤、毗邻。如： North Korea is on the east of China. 4. off表示“离……一些距离或离……不远的海上”。如： They arrived at a house off the main road. New Zealand lies off the eastern coast of Australia. 二. at, in, on, by和through在表示时间上的区别 1. at指时间表示： （1）时间的一点、时刻等。如： They came home at sunrise （at noon, at midnight, at ten o’clock, at daybreak, at dawn）. （2）较短暂的一段时间。可指某个节日或被认为是一年中标志大事的日子。如： He went home at Christmas （at New Year, at the Spring Festival, at night）. 2. in指时间表示： （1）在某个较长的时间（如世纪、朝代、年、月、季节以及泛指的上午、下午或傍晚等）内。如： in 2004, in March, in spring, in the morning, in the evening, etc （2）在一段时间之后。一般情况下，用于将来时，谓语动词为瞬间动词，意为“在……以后”。如： He will arrive in two hours. 谓语动词为延续性动词时，in意为“在……以内”。如： These products will be produced in a month. 注意：after用于将来时间也指一段时间之后，但其后的时间是“一点”，而不是“一段”。如： He will arrive after two o’clock. 3. on指时间表示： （1）具体的时日和一个特定的时间，如某日、某节日、星期几等。如： On Christmas Day（On May 4th）, there will be a celebration. （2）在某个特定的早晨、下午或晚上。如： He arrived at 10 o’clock on the night of the 5th. （3）准时，按时。如： If the train should be on time, I should reach home before dark. 4. by指时间表示： （1）不迟于，在（某时）前。如：
With的用法全解 with结构是许多英语复合结构中最常用的一种。学好它对学好复合宾语结构、不定式复合结构、动名词复合结构和独立主格结构均能起很重要的作用。本文就此的构成、特点及用法等作一较全面阐述，以帮助同学们掌握这一重要的语法知识。 一、 with结构的构成 它是由介词with或without+复合结构构成，复合结构作介词with或without的复合宾语，复合宾语中第一部分宾语由名词或代词充当，第二部分补足语由形容词、副词、介词短语、动词不定式或分词充当，分词可以是现在分词，也可以是过去分词。With结构构成方式如下： 1. with或without-名词/代词+形容词； 2. with或without-名词/代词+副词； 3. with或without-名词/代词+介词短语； 4. with或without-名词/代词 +动词不定式； 5. with或without-名词/代词 +分词。 下面分别举例： 1、 She came into the room，with her nose red because of cold.（with+名词+形容词，作伴随状语）
2、 With the meal over ， we all went home.（with+名词+副词，作时间状语） 3、The master was walking up and down with the ruler under his arm。（with+名词+介词短语，作伴随状语。） The teacher entered the classroom with a book in his hand. 4、He lay in the dark empty house，with not a man ，woman or child to say he was kind to me.（with+名词+不定式，作伴随状语）He could not finish it without me to help him.（without+代词 +不定式，作条件状语） 5、She fell asleep with the light burning.（with+名词+现在分词，作伴随状语） Without anything left in the with结构是许多英 语复合结构中最常用的一种。学好它对学好复合宾语结构、不定式复合结构、动名词复合结构和独立主格结构均能起很重要的作用。本文就此的构成、特点及用法等作一较全面阐述，以帮助同学们掌握这一重要的语法知识。 二、with结构的用法 with是介词，其意义颇多，一时难掌握。为帮助大家理清头绪，以教材中的句子为例，进行分类，并配以简单的解释。在句子中with结构多数充当状语，表示行为方式，伴随情况、时间、原因或条件（详见上述例句）。 1.带着，牵着…… (表动作特征)。如： Run with the kite like this.
精神分裂症的病因及发病机理 精神分裂症病因：尚未明，近百年来的研究结果也仅发现一些可能的致病因素。（一）生物学因素1．遗传遗传因素是精神分裂症最可能的一种素质因素。国内家系调查资料表明：精神分裂症患者亲属中的患病率比一般居民高6.2倍，血缘关系愈近，患病率也愈高。双生子研究表明：遗传信息几乎相同的单卵双生子的同病率远较遗传信息不完全相同 的双卵双生子为高，综合近年来11项研究资料：单卵双生子同病率（56.7%），是双卵双生子同病率（12.7%）的4.5倍，是一般人口患难与共病率的35-60倍。说明遗传因素在本病发生中具有重要作用，寄养子研究也证明遗传因素是本症发病的主要因素，而环境因素的重要性较小。以往的研究证明疾病并不按类型进行遗传，目前认为多基因遗传方式的可能性最大，也有人认为是常染色体单基因遗传或多源性遗传。Shields发现病情愈轻，病因愈复杂，愈属多源性遗传。高发家系的前瞻性研究与分子遗传的研究相结合，可能阐明一些问题。国内有报道用人类原癌基因Ha-ras-1为探针，对精神病患者基因组进行限止性片段长度多态性的分析，结果提示11号染色体上可能存在着精神分裂症与双相情感性精神病有关的DNA序列。2．性格特征：约40%患者的病前性格具有孤僻、冷淡、敏感、多疑、富于幻想等特征，即内向
型性格。3．其它：精神分裂症发病与年龄有一定关系，多发生于青壮年，约1/2患者于20～30岁发病。发病年龄与临床类型有关，偏执型发病较晚，有资料提示偏执型平均发病年龄为35岁，其它型为23岁。80年代国内12地区调查资料：女性总患病率（7.07%。）与时点患病率（5.91%。）明显高于男性（4.33%。与3.68%。）。Kretschmer在描述性格与精神分裂症关系时指出：61%患者为瘦长型和运动家型，12.8%为肥胖型，11.3%发育不良型。在躯体疾病或分娩之后发生精神分裂症是很常见的现象，可能是心理性生理性应激的非特异性影响。部分患者在脑外伤后或感染性疾病后发病；有报告在精神分裂症患者的脑脊液中发现病毒性物质；月经期内病情加重等躯体因素都可能是诱发因素，但在精神分裂症发病机理中的价值有待进一步证实。（二）心理社会因素1．环境因素①家庭中父母的性格，言行、举止和教育方式（如放纵、溺爱、过严）等都会影响子女的心身健康或导致个性偏离常态。②家庭成员间的关系及其精神交流的紊乱。③生活不安定、居住拥挤、职业不固定、人际关系不良、噪音干扰、环境污染等均对发病有一定作用。农村精神分裂症发病率明显低于城市。2．心理因素一般认为生活事件可发诱发精神分裂症。诸如失学、失恋、学习紧张、家庭纠纷、夫妻不和、意处事故等均对发病有一定影响，但这些事件的性质均无特殊性。因此，心理因素也仅属诱发因
with的用法大全----四级专项训练with结构是许多英语复合结构中最常用的一种。学好它对学好复合宾语结构、不定式复合结构、动名词复合结构和独立主格结构均能起很重要的作用。本文就此的构成、特点及用法等作一较全面阐述，以帮助同学们掌握这一重要的语法知识。 一、 with结构的构成 它是由介词with或without+复合结构构成，复合结构作介词with或without的复合宾语，复合宾语中第一部分宾语由名词或代词充当，第二部分补足语由形容词、副词、介词短语、动词不定式或分词充当，分词可以是现在分词，也可以是过去分词。With结构构成方式如下： 1. with或without-名词/代词+形容词; 2. with或without-名词/代词+副词; 3. with或without-名词/代词+介词短语; 4. with或without-名词/代词+动词不定式; 5. with或without-名词/代词+分词。 下面分别举例：
1、 She came into the room，with her nose red because of cold.(with+名词+形容词，作伴随状语) 2、 With the meal over ， we all went home.(with+名词+副词，作时间状语) 3、The master was walking up and down with the ruler under his arm。(with+名词+介词短语，作伴随状语。) The teacher entered the classroom with a book in his hand. 4、He lay in the dark empty house，with not a man ，woman or child to say he was kind to me.(with+名词+不定式，作伴随状语) He could not finish it without me to help him.(without+代词 +不定式，作条件状语) 5、She fell asleep with the light burning.(with+名词+现在分词，作伴随状语) 6、Without anything left in the cupboard， she went out to get something to eat.(without+代词+过去分词，作为原因状语) 二、with结构的用法 在句子中with结构多数充当状语，表示行为方式，伴随情况、时间、原因或条件(详见上述例句)。
1.I don`t like a ___(rain) day. 2.Please tell Tom ___(call)me back. 3.____ is the weather like? It`s snowy. How. What. Where. Why. 4.____ ia it going? It`s great. How. What. Where. When. 5.Is he____? No, he’s ___ in the river. A. swims,fishing B. swimming, running C. swim,walking D. running, swimming 6.Hello!is that Linda speaking? Yes.______ Who’s that? Who’s it? Who are you? I’m Linda. 7.He often ____(watch)TV in the evening. But now he _____(read)a book. 8.My uncle is a ___(cook). 9.It’s a nice ____. A weather photo salad rice 10.After supper Mary often ___ along the river. Take a walk takes walk taking a walk takes a walk 11.How’s it going? _____. The weather is so cold. Preety good. Great. Terrible. Not bad. 12.Beijing ___ (have)a long history. 13.I am having a great time ____(visit)my grandmother. 14.We feel very ___ after the ___ (relax) vacation. 15.We are ___ vacation in Dalian. A in B on C at Dof 16.What ____ when it’s sunny? Aare you doing B do you do C does you D is he do 17.Tom like to go ___(skate) 18.Kate is very tired, so she needs ____(relax) 19.Would you like to ____ a photofor us? Sure. Agive B make C take Dget 20.Could you help me put up the maps on the wall?_____ A.No problem B. I hope so C. That’s all right D.That’s a good idea. 21.China plan to let Jim ____the Xisha Islands> Visit visits visiting visited 22.Where is Grace? She ____ IN THE yard. Reads read is reading was reading 23.Britain is ___ European country and Singapore is ___ Asian country A,a,a a, an the , an a ,the 1.I don`t like a ___(rain) day. 2.Please tell Tom ___(call)me back. 3.____ is the weather like? It`s snowy. How. What. Where. Why. 4.____ ia it going? It`s great. How. What. Where. When. 5.Is he____? No, he’s ___ in the river. A. swims,fishing B. swimming, running C. swim,walking D. running, swimming 6.Hello!is that Linda speaking? Yes.______ Who’s that? Who’s it? Who are you? I’m Linda. 7.He often ____(watch)TV in the evening. But now he _____(read)a book. 8.My uncle is a ___(cook). 9.It’s a nice ____. A weather photo salad rice 10.After supper Mary often ___ along the river. Take a walk takes walk taking a walk takes a walk 11.How’s it going? _____. The weather is so cold. Preety good. Great. Terrible. Not bad. 12.Beijing ___ (have)a long history. 13.I am having a great time ____(visit)my grandmother. 14.We feel very ___ after the ___ (relax) vacation. 15.We are ___ vacation in Dalian. A in B on C at Dof 16.What ____ when it’s sunny? Aare you doing B do you do C does you D is he do 17.Tom like to go ___(skate) 18.Kate is very tired, so she needs ____(relax) 19.Would you like to ____ a photofor us? Sure. Agive B make C take Dget 20.Could you help me put up the maps on the wall?_____ A.No problem B. I hope so C. That’s all right D.That’s a good idea. 21.China plan to let Jim ____the Xisha Islands> Visit visits visiting visited 22.Where is Grace? She ____ IN THE yard. Reads read is reading was reading 23.Britain is ___ European country and Singapore is ___ Asian country A,a,a a, an the , an a ,the
with用法归纳 （1）“用……”表示使用工具，手段等。例如： ①We can walk with our legs and feet. 我们用腿脚行走。 ②He writes with a pencil. 他用铅笔写。 （2）“和……在一起”，表示伴随。例如： ①Can you go to a movie with me? 你能和我一起去看电影'>电影吗？ ②He often goes to the library with Jenny. 他常和詹妮一起去图书馆。 （3）“与……”。例如： I’d like to have a talk with you. 我很想和你说句话。 （4）“关于，对于”，表示一种关系或适应范围。例如： What’s wrong with your watch? 你的手表怎么了？ （5）“带有，具有”。例如： ①He’s a tall kid with short hair. 他是个长着一头短发的高个子小孩。 ②They have no money with them. 他们没带钱。 （6）“在……方面”。例如： Kate helps me with my English. 凯特帮我学英语。 （7）“随着，与……同时”。例如： With these words, he left the room. 说完这些话，他离开了房间。 [解题过程] with结构也称为with复合结构。是由with+复合宾语组成。常在句中做状语，表示谓语动作发生的伴随情况、时间、原因、方式等。其构成有下列几种情形： 1.with+名词(或代词)+现在分词 此时，现在分词和前面的名词或代词是逻辑上的主谓关系。 例如:1)With prices going up so fast, we can't afford luxuries. 由于物价上涨很快，我们买不起高档商品。（原因状语） 2)With the crowds cheering, they drove to the palace. 在人群的欢呼声中，他们驱车来到皇宫。（伴随情况） 2.with+名词(或代词)+过去分词 此时，过去分词和前面的名词或代词是逻辑上的动宾关系。
in，on ，at，by ，of ，with 介词区别与用法 in用在年月季节前，还有上午、下午等固定习语里 at用于传统的节日前，如at Christmas等；还有固定词组：at noon, at night;在点时间前用at 如at 7.15 on 用于具体的日期前，星期几，几号，包括那天的上午下午晚上等，如on Friday afternoon with: 一、with表拥有某物 Mary married a man with a lot of money . 马莉嫁给了一个有着很多钱的男人。 I often dream of a big house with a nice garden . 我经常梦想有一个带花园的大房子。 The old man lived with a little dog on the lonely island . 这个老人和一条小狗住在荒岛上。 二、with表用某种工具或手段 I cut the apple with a sharp knife . 我用一把锋利的刀削平果。 Tom drew the picture with a pencil . 汤母用铅笔画画。 三、with表人与人之间的协同关系 make friends with sb talk with sb quarrel with sb struggle with sb fight with sb play with sb work with sb cooperate with sb I have been friends with Tom for ten years since we worked with each other , and I have never quarreled with him . 自从我们一起工作以来，我和汤母已经是十年的朋友了，但我们从没有吵过架。 四、with 表原因或理由 John was in bed with high fever . 约翰因发烧卧床。 He jumped up with joy . 他因高兴跳起来。 Father is often excited with wine . 父亲常因白酒变的兴奋。 五、with 表“带来”，或“带有,具有”，在…身上，在…身边之意 The girl with golden hair looks beautiful . 那个金头发的女孩看起来漂亮。 The famous director will come to the meeting with the leading actor and actress .
精神分裂症的发病原因是什么 精神分裂症是一种精神病，对于我们的影响是很大的，如果不幸患上就要及时做好治疗，不然后果会很严重，无法进行正常的工作和生活，是一件很尴尬的事情。因此为了避免患上这样的疾病，我们就要做好预防，今天我们就请广州协佳的专家张可斌来介绍一下精神分裂症的发病原因。 精神分裂症是严重影响人们身体健康的一种疾病，这种疾病会让我们整体看起来不正常，会出现胡言乱语的情况，甚至还会出现幻想幻听，可见精神分裂症这种病的危害程度。 (1)精神刺激：人的心理与社会因素密切相关，个人与社会环境不相适应，就产生了精神刺激，精神刺激导致大脑功能紊乱，出现精神障碍。不管是令人愉快的良性刺激，还是使人痛苦的恶性刺激，超过一定的限度都会对人的心理造成影响。 (2)遗传因素：精神病中如精神分裂症、情感性精神障碍，家族中精神病的患病率明显高于一般普通人群，而且血缘关系愈近，发病机会愈高。此外，精神发育迟滞、癫痫性精神障碍的遗传性在发病因素中也占相当的比重。这也是精神病的病因之一。 (3)自身：在同样的环境中，承受同样的精神刺激，那些心理素质差、对精神刺激耐受力低的人易发病。通常情况下，性格内向、心胸狭窄、过分自尊的人，不与人交往、孤僻懒散的人受挫折后容易出现精神异常。 (4)躯体因素：感染、中毒、颅脑外伤、肿瘤、内分泌、代谢及营养障碍等均可导致精神障碍，。但应注意，精神障碍伴有的躯体因素，并不完全与精神症状直接相关，有些是由躯体因素直接引起的，有些则是以躯体因素只作为一种诱因而存在。 孕期感染。如果在怀孕期间，孕妇感染了某种病毒，病毒也传染给了胎儿的话，那么，胎儿出生长大后患上精神分裂症的可能性是极其的大。所以怀孕中的女性朋友要注意卫生，尽量不要接触病毒源。 上述就是关于精神分裂症的发病原因，想必大家都已经知道了吧。患上精神分裂症之后，大家也不必过于伤心，现在我国的医疗水平是足以让大家快速恢复过来的，所以说一定要保持良好的情绪。
介词with的用法大全 With是个介词，基本的意思是“用”，但它也可以协助构成一个极为多采多姿的句型，在句子中起两种作用；副词与形容词。 with在下列结构中起副词作用： 1.“with+宾语+现在分词或短语”，如： (1) This article deals with common social ills, with particular attention being paid to vandalism. 2.“with+宾语+过去分词或短语”，如： (2) With different techniques used, different results can be obtained. (3) The TV mechanic entered the factory with tools carried in both hands. 3.“with+宾语+形容词或短语”，如： (4) With so much water vapour present in the room, some iron-made utensils have become rusty easily. (5) Every night, Helen sleeps with all the windows open. 4.“with+宾语＋介词短语”，如： (6) With the school badge on his shirt, he looks all the more serious. (7) With the security guard near the gate no bad character could do any thing illegal. 5.“with+宾语＋副词虚词”，如： (8) You cannot leave the machine there with electric power on. (9) How can you lock the door with your guests in? 上面五种“with”结构的副词功能，相当普遍，尤其是在科技英语中。 接着谈“with”结构的形容词功能，有下列五种： 一、“with+宾语+现在分词或短语”，如： (10) The body with a constant force acting on it. moves at constant pace. (11) Can you see the huge box with a long handle attaching to it ? 二、“with+宾语+过去分词或短语” (12) Throw away the container with its cover sealed. (13) Atoms with the outer layer filled with electrons do not form compounds. 三、“with+宾语+形容词或短语”，如： (14) Put the documents in the filing container with all the drawers open.
with用法小结 一、with表拥有某物 Mary married a man with a lot of money . 马莉嫁给了一个有着很多钱的男人。 I often dream of a big house with a nice garden . 我经常梦想有一个带花园的大房子。 The old man lived with a little dog on the lonely island . 这个老人和一条小狗住在荒岛上。 二、with表用某种工具或手段 I cut the apple with a sharp knife . 我用一把锋利的刀削平果。 Tom drew the picture with a pencil . 汤母用铅笔画画。 三、with表人与人之间的协同关系 make friends with sb talk with sb quarrel with sb struggle with sb fight with sb play with sb work with sb cooperate with sb I have been friends with Tom for ten years since we worked with each other, and I have never quarreled with him . 自从我们一起工作以来，我和汤姆已经是十年的朋友了，我们从没有吵过架。 四、with 表原因或理由 John was in bed with high fever . 约翰因发烧卧床。 He jumped up with joy . 他因高兴跳起来。 Father is often excited with wine . 父亲常因白酒变的兴奋。 五、with 表“带来”，或“带有,具有”，在…身上，在…身边之意
精神分裂症的病因是什么 精神分裂症是一种精神方面的疾病，青壮年发生的概率高，一般 在16～40岁间，没有正常器官的疾病出现，为一种功能性精神病。 精神分裂症大部分的患者是由于在日常的生活和工作当中受到的压力 过大，而患者没有一个良好的疏导的方式所导致。患者在出现该情况 不仅影响本人的正常社会生活，且对家庭和社会也造成很严重的影响。 精神分裂症常见的致病因素： 1、环境因素：工作环境比如经济水平低低收入人群、无职业的人群中，精神分裂症的患病率明显高于经济水平高的职业人群的患病率。还有实际的生活环境生活中的不如意不开心也会诱发该病。 2、心理因素：生活工作中的不开心不满意，导致情绪上的失控，心里长期受到压抑没有办法和没有正确的途径去发泄，如恋爱失败， 婚姻破裂，学习、工作中不愉快都会成为本病的原因。 3、遗传因素：家族中长辈或者亲属中曾经有过这样的病人，后代会出现精神分裂症的机会比正常人要高。 4、精神影响：人的心里与社会要各个方面都有着不可缺少的联系，对社会环境不适应，自己无法融入到社会中去，自己与社会环境不相
适应，精神和心情就会受到一定的影响，大脑控制着人的精神世界， 有可能促发精神分裂症。 5、身体方面：细菌感染、出现中毒情况、大脑外伤、肿瘤、身体的代谢及营养不良等均可能导致使精神分裂症，身体受到外界环境的 影响受到一定程度的伤害，心里受到打击，无法承受伤害造成的痛苦，可能会出现精神的问题。 对于精神分裂症一定要配合治疗，接受全面正确的治疗，最好的 疗法就是中医疗法加心理疗法。早发现并及时治疗并且科学合理的治疗，不要相信迷信，要去正规的医院接受合理的治疗，接受正确的治 疗按照医生的要求对症下药，配合医生和家人，给病人创造一个良好 的治疗环境，对于该病的康复和痊愈会起到意想不到的效果。
介词“with”的用法 1、同, 与, 和, 跟 talk with a friend 与朋友谈话 learn farming with an old peasant 跟老农学习种田 fight [quarrel, argue] with sb. 跟某人打架 [争吵, 辩论] [说明表示动作的词, 表示伴随]随着, 和...同时 change with the temperature 随着温度而变化 increase with years 逐年增加 be up with the dawn 黎明即起 W-these words he left the room. 他说完这些话便离开了房间。2 2、表示使用的工具, 手段 defend the motherland with one s life 用生命保卫祖国 dig with a pick 用镐挖掘 cut meat with a knife 用刀割肉3
3、说明名词, 表示事物的附属部分或所具有的性质]具有; 带有; 加上; 包括...在内 tea with sugar 加糖的茶水 a country with a long history 历史悠久的国家4 4、表示一致]在...一边, 与...一致; 拥护, 有利于 vote with sb. 投票赞成某人 with的复合结构作独立主格,表示伴随情况时，既可用分词的独立结构，也可用with的复合结构： with +名词(代词)+现在分词/过去分词/形容词/副词/不定式/介词短语。例如： He stood there, his hand raised. = He stood there, with his hand raise.他举手着站在那儿。 典型例题 The murderer was brought in, with his hands ___ behind his back A. being tied B. having tied C. to be tied D. tied 答案D. with +名词(代词)+分词+介词短语结构。当分词表示伴随状况时，其主语常常用
精神分裂症应该怎么治疗 1、坚持服药治疗 服药治疗是最有效的预防复发措施临床大量统计资料表明，大多数精神分裂症的复发与自行停药有关。坚持维持量服药的病人复发率为40%。而没坚持维持量服药者复发率高达80%。因此，病人和家属要高度重视维持治疗。 2、及时发现复发的先兆，及时处理 精神分裂症的复发是有先兆的，只要及时发现，及时调整药物和剂量，一般都能防止复发，常见的复发先兆为：病人无原因出现睡眠不好、懒散、不愿起床、发呆发愣、情绪不稳、无故发脾气、烦躁易怒、胡思乱想、说话离谱，或病中的想法又露头等。这时就应该及时就医，调整治疗病情波动时的及时处理可免于疾病的复发。 3、坚持定期门诊复查 一定要坚持定期到门诊复查，使医生连续地、动态地了解病情，使病人经常处于精神科医生的医疗监护之下，及时根据病情变化调整药量。通过复查也可使端正人及时得到咨询和心理治疗解除病人在生活、工作和药物治疗中的各种困惑，这对预防精神分裂症的复发也起着重要作用。 4、减少诱发因素 家属及周围人要充分认识到精神分裂症病人病后精神状态的薄弱性，帮助安排好日常的生活、工作、学习。经常与病人谈心，帮助病人正确对待疾病，正确对待现实生活，帮助病人提高心理承受能力，学会对待应激事件的方法，鼓励病人增强信心，指导病人充实生活，使病人在没有心理压力和精神困扰的环境中生活。 首先是性格上的改变，塬本活泼开朗爱玩的人，突然变得沉默寡言，独自发呆，不与人交往，爱干净的人也变的不注意卫生、生活
懒散、纪律松弛、做事注意力不集中，总是和患病之前的性格完全 相悖。 再者就是语言表达异常，在谈话中说一些无关的谈话内容，使人无法理解。连最简单的话语都无法准确称述，与之谈话完全感觉不 到重心。 第三个就是行为的异常，行为怪异让人无法理解，喜欢独处、不适意的追逐异性，不知廉耻，自语自笑、生活懒散、时常发呆、蒙 头大睡、四处乱跑，夜不归宿等。 还有情感上的变化，失去了以往的热情，开始变的冷淡、对亲人不关心、和友人疏远，对周围事情不感兴趣，一点消失都可大动干戈。 最后就是敏感多疑，对任何事情比较敏感，精神分裂症患者，总认为有人针对自己。甚至有时认为有人要害自己，从而不吃不喝。 但是也有的会出现难以入眠、容易被惊醒或睡眠不深，整晚做恶梦或者长睡不醒的现象。这些都有可能是患上了精神分裂症。 1.加强心理护理 心理护理是家庭护理中的重要方面，由于社会上普遍存在对精神病人的歧视和偏见，给病人造成很大的精神压力，常表现为自卑、 抑郁、绝望等，有的病人会因无法承受压力而自杀。家属应多给予 些爱心和理解，满足其心理需求，尽力消除病人的悲观情绪。病人 生活在家庭中，与亲人朝夕相处，接触密切，家属便于对病人的情感、行为进行细致的观察，病人的思想活动也易于向家属暴露。家 属应掌握适当的心理护理方法，随时对病人进行启发与帮助，启发 病人对病态的认识，帮助他们树立自信，以积极的心态好地回归社会。 2.重视服药的依从性 精神分裂症病人家庭护理的关键就在于要让病人按时按量吃药维持治疗。如果不按时服药，精神病尤其是精神分裂症的复发率很高。精神病人在医院经过一系统的治疗痊愈后，一般需要维持2~3年的
英语介词with的用法 with结构是许多英语复合结构中最常用的一种。学好它对学好复合宾语结构、不定式复合结构、动名词复合结构和独立主格结构均能起很重要的作用。本文就此的构成、特点及用法等作一较全面阐述，以帮助同学们掌握这一重要的语法知识。 一、 with结构的构成 它是由介词with或without+复合结构构成，复合结构作介词with或without的复合宾语，复合宾语中第一部分宾语由名词或代词充当，第二部分补足语由形容词、副词、介词短语、动词不定式或分词充当，分词可以是现在分词，也可以是过去分词。With结构构成方式如下： 1. with或without-名词/代词+形容词； 2. with或without-名词/代词+副词； 3. with或without-名词/代词+介词短语； 4. with或without-名词/代词+动词不定式； 5. with或without-名词/代词+分词。 下面分别举例： 1、 She came into the room，with her nose red because of cold.（with+名词+形容词，作伴随状语） 2、 With the meal over ， we all went home.（with+名词+副词，作时间状语） 3、The master was walking up and down with the ruler under his arm。（with+名词+介词短语，作伴随状语。） The teacher entered the classroom with a book in his hand. 4、He lay in the dark empty house，with not a man ，woman or child to say he was kind to me.（with+名词+不定式，作伴随状语） He could not finish it without me to help him.（without+代词 +不定式，作条件状语） 5、She fell asleep with the light burning.（with+名词+现在分词，作伴随状语） 6、Without anything left in the cupboard， she went out to get something to eat.（without+代词+过去分词，作为原因状语）