Analysis of Dimer Impurity in Polyamidoamine Dendrimer Solutions by Small-angle Neutron Scattering
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摘要
Dimer impurity in the solution of a generation five(G5) polyamidoamine(PAMAM) dendrimer has been investigated by small-angle neutron scattering(SANS). The existence of dimer impurity in dendrimer solution was evidenced by indirect Fourier transform(IFT) analysis of the SANS data, in which the maximum dimension of particles in solution was found to be about twice the diameter of G5 dendrimer. We then developed an analytical model which accounts for the scattering contribution from both dendrimer monomer and dimer. The experimental data were well fitted by using the established model. The results showed that the amount of dimer impurities is significant for the measured three batches of G5 PAMAM dendrimers.
Dimer impurity in the solution of a generation five(G5) polyamidoamine(PAMAM) dendrimer has been investigated by small-angle neutron scattering(SANS). The existence of dimer impurity in dendrimer solution was evidenced by indirect Fourier transform(IFT) analysis of the SANS data, in which the maximum dimension of particles in solution was found to be about twice the diameter of G5 dendrimer. We then developed an analytical model which accounts for the scattering contribution from both dendrimer monomer and dimer. The experimental data were well fitted by using the established model. The results showed that the amount of dimer impurities is significant for the measured three batches of G5 PAMAM dendrimers.
Dimer impurity in the solution of a generation five(G5) polyamidoamine(PAMAM) dendrimer has been investigated by small-angle neutron scattering(SANS). The existence of dimer impurity in dendrimer solution was evidenced by indirect Fourier transform(IFT) analysis of the SANS data, in which the maximum dimension of particles in solution was found to be about twice the diameter of G5 dendrimer. We then developed an analytical model which accounts for the scattering contribution from both dendrimer monomer and dimer. The experimental data were well fitted by using the established model. The results showed that the amount of dimer impurities is significant for the measured three batches of G5 PAMAM dendrimers.
引文
1 Tomalia,D.A.; Khanna,S.N.A systematic framework and nanoperiodic concept for unifying nanoscience:Hard/soft nanoelements,superatoms,meta-atoms,new emerging properties,periodic property patterns,and predictive mendeleev-like nanoperiodic tables.Chem.Rev.2016,116,2705-2774.
2 Tomalia,D.A,Birth of a new macromolecular architecture:Dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry.Prog.Polym.Sci.2005,30,294-324.
3 Tomalia,D.A.Interview:An architectural journey:From trees,dendrons/dendrimers to nanomedicine.Nanomedicine 2012,7,953-956.
4 Zhao,L.;Wu, Q.;Cheng,Y.;Zhang,J.; Wu,J.;Xu,T.Highthroughput screening of dendrimer-binding drugs.J.Am.Chem.Soc.2010,132,13182-13184.
5 Wang,H.;Huang,Q.;Chang,H.;Xiao,J.;Cheng,Y.Stimuliresponsive dendrimers in drug delivery.Biomater.Sci. 2016,4,375-390.
6 Hu,J.;Xu,T.; Cheng,Y.NMR insights into dendrimer-based host-guest systems.Chem.Rev.2012,112,3856-3 891.
7 Svenson,S.Dendrimers in biomedical applications-reflections on the field.Adv.Drug Deliv.Rev.2005,57,2 106-2 129.
8 Wang,H.;Wang,Y.;Wang,Y.;Hu,J.;Li,T.;Liu,H.;Zhang,Q.; Cheng,Y.Self-assembled fluorodendrimers combine the features of lipid and polymeric vectors in gene delivery.Angew.Chem.Int.Ed.2015,54,1 1647-1 1651.
9 Wang,M.;Liu,H.; Li,L.;Cheng,Y.A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios.Nat.Commun.2014,5,3053.
10 Cheng,Y.Fluorinated polymers in gene delivery.Acta Polymerica Sinica(in Chinese)2017,8,1234-1245.
11 Kallos,G.J.; Tomalia,D.A.; Hedstrand,D.M.; Lewis,S.;Zhou,J.Molecular weight determination of a polyamidoamine starburst polymer by electrospray ionization mass spectrometry.Rapid Commun.Mass Spectrom.1991,5,383-386.
12 Tomalia,D.A.; Baker,H.; Dewald,J.; Hall,M.; Kallos,G.;Martin,S.;Roeck,J.;Ryder,J.;Smith,P.A new class of polymers:Starburst-dendritic macromolecules.Polym.J.1985,17,117-132.
13 Tolic,L.P.;Anderson,G.A.; Smith,R.D.; Brothers,H.M.;Spindler,R.; Tomalia,D.A.Electrospray ionization fourier transform ion cyclotron resonance mass spectrometric characterization of high molecular mass StarburstTM dendrimers.Int.J.Mass Spectrom.1997,165/166,405-418.
14 Peterson,J.;Allikmaa,V.;Subbi,J.;Pehk,T.;Lopp,M.Structural deviations in poly(amidoamine)dendrimers:A MALDITOF MS analysis.Eur.Polym.J.2003,39,33-42.
15 Aura,T.;Ungaro,R.;Liu,X.;Chen,C.;Giordano,L.;Peng,L.;Charles,L.Structural characterization of new defective molecules in poly(amidoamide)dendrimers by combining mass spectrometry and nuclear magnetic resonance.Anal.Chin.Acta 2015,853,451-459.
16 Mohammad,T.I.;Shi,X.;Balogh, L.;Baker, J.R.HPLC Separation of different generations of poly(amidoamine)dendrimers modified with various terminal groups.Anal.Chew.2005,77,2063-2070.
17 Mullen,D.G.; Desai,A.; van Dongen,M.A.; Barash,M.;Baker,J.R.; Banaszak Holl,M.M.Best practices for purification and characterization of PAMAM dendrimer.Macromolecules 2012,45,5316-5320.
18 van Dongen,M.A.; Desai,A.; Orr,B.G.; Baker,J.R.;Banaszak Hol,M.M.Quantitative analysis of generation and branch defects in G5 poly(amidoamine)dendrimer.Polymer2013,54.4126-4133.
19 Likos,C.N.Soft matter with soft particles.Soft Matter 2006,2,478-498.
20 Caminade,A.M.; Laurent,R.; Majoral,J.P.Characterization of dendrimers.Adv.Drug Deliv.Rev.2005,5 7,2130-2146.
21 Wang,X.Characterizations of polyamidoamine dendrimers with scattering techniques.Polymers 2012,4,600-61 6.
22 Topp,A.;Bauer,B.J.;Kilmash,K.W.;Spindler,R.;Tomalia,D.A.;Amis,E.J.Effect of solvent quality on the molecular dimensions of PAMAM dendrimers.Macromolecules 1999,32,7226-7231.
23 Imae,T.;Funayama,K.;Aoi,K.;Tsutsumiuchi,K.;Okada,M.;Furusaka,M.Small-angle neutron scattering and surface force investigations of poly(amido amine)dendrimer with hydroxyl end groups.Langmuir 1999,15,4076-4084.
24 Potschke,D.;Ballauff,M.;Lindner,P.;Fischer,M.;Vogtle,F.Analysis of the structure of dendrimers in solution by smallangle neutron scattering including contrast variation.Macro molecules 1999,32,4079-4087.
25 Rosenfeldt,S.; Dingenouts,N.; Ballauff,M.; Werner,N.;Vogtle,F.; Lindner,P.Distribution of end groups within a dendritic structure:A SANS study including contrast variation.Macromolecules 2002,35,8098-8105.
26 Rathgeber,S.; Monkenbusch,M.; Kreitschmann,M.; Urban,V.;Brulet,A.Dynamics of star-burst dendrimers in solution in relation to their structural properties.J.Chem.Phys.2002,11 7,4047-4062.
27 Huang,Q.R.; Dubin,P. L.; Lal,J.; Moorefield,C. N.;Newkome,G.R.Small-angle neutron scattering studies of charged carboxyl-terminated dendrimers in solutions.Lang muir 2005,21,2737-2742.
28 Porcar,L.;Liu,Y.;Verduzco,R.;Hong,K.;Butler,P.D.;Magid,L.J.;Smith,G.S.;Chen,W.R.Structural investigation of PAMAM dendrimers in aqueous solutions using small-angle neutron scattering:Effect of generation.J.Phys.Chem.B 2008,112,14772-14778.
29 Li,T.; Shao,N.; Liu,Y.;Hu,J.;Wang,Y.; Zhang,L.;Wang,H.; Chen,D.; Cheng,Y.Poly(amidoamine)and poly(propyleneimine)dendrimers show distinct binding behaviors with sodium dodecyl sulfate:Insights from SAXS and NMR analysis.J.Phys.Chem.B 2014,118,3074-3084.
30 Li,T.;Hong,K.;Porcar,L.;Verduzco,R.;Butler,P.D.;Smith,G.S.;Liu,Y.;Chen,W.R.Assess the intramolecular cavity of a PAMAM dendrimer in aqueous solution by small-angle neutron scattering.Macromolecules 2008,41,8916-8920.
31 Chen,W.R.; Porcar,L.; Liu,Y.; Butler,P.D.; Magid,L.J.Small-angle neutron scattering studies of the counterion effects on the molecular conformation and structure of charged G4PAMAM dendrimers in aqueous solutions.Macromolecules2007,40,5887-5898.
32 Keiderling,U.; Wiedenmann,A.New SANS instrument at the Berll Reactor in Berlin,Germany.Physica B 1995,213/214,895-897.
33 Helmholtz-Zentrum Berlin fiir Materialien und Energie.V4:The small-angle scattering instrument(SANS)at BERⅡ.JLSKF 2016,2,A97.
34 Keiderling,U.The new'BerSANS-PC'software for reduction and treatment of small-angle neutron scattering data.Appl.Phys.A 2002,74,1455-1457.
35 Glatter,O.A new method for the evaluation of small-angle scattering data.J.Appl. Cryst.1977,10,415-421.
36 Svergun,D.Determination of the regularization parameter in indirect-transform methods using perceptual criteria.J.Appl.1992,25,495-503.
37 Chen,S.H.Small-angle neutron scattering studies of the structure and interaction in micellar and microemulsion systems.Annu.Rev.Phys.Chem.1986,3 7,351-399.
38 Guinier,A.;Fournet,G.S,mall-angle scattering of X-rays.John Wiley&Sons,New York,1955,p.1-78.
2 Tomalia,D.A,Birth of a new macromolecular architecture:Dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry.Prog.Polym.Sci.2005,30,294-324.
3 Tomalia,D.A.Interview:An architectural journey:From trees,dendrons/dendrimers to nanomedicine.Nanomedicine 2012,7,953-956.
4 Zhao,L.;Wu, Q.;Cheng,Y.;Zhang,J.; Wu,J.;Xu,T.Highthroughput screening of dendrimer-binding drugs.J.Am.Chem.Soc.2010,132,13182-13184.
5 Wang,H.;Huang,Q.;Chang,H.;Xiao,J.;Cheng,Y.Stimuliresponsive dendrimers in drug delivery.Biomater.Sci. 2016,4,375-390.
6 Hu,J.;Xu,T.; Cheng,Y.NMR insights into dendrimer-based host-guest systems.Chem.Rev.2012,112,3856-3 891.
7 Svenson,S.Dendrimers in biomedical applications-reflections on the field.Adv.Drug Deliv.Rev.2005,57,2 106-2 129.
8 Wang,H.;Wang,Y.;Wang,Y.;Hu,J.;Li,T.;Liu,H.;Zhang,Q.; Cheng,Y.Self-assembled fluorodendrimers combine the features of lipid and polymeric vectors in gene delivery.Angew.Chem.Int.Ed.2015,54,1 1647-1 1651.
9 Wang,M.;Liu,H.; Li,L.;Cheng,Y.A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios.Nat.Commun.2014,5,3053.
10 Cheng,Y.Fluorinated polymers in gene delivery.Acta Polymerica Sinica(in Chinese)2017,8,1234-1245.
11 Kallos,G.J.; Tomalia,D.A.; Hedstrand,D.M.; Lewis,S.;Zhou,J.Molecular weight determination of a polyamidoamine starburst polymer by electrospray ionization mass spectrometry.Rapid Commun.Mass Spectrom.1991,5,383-386.
12 Tomalia,D.A.; Baker,H.; Dewald,J.; Hall,M.; Kallos,G.;Martin,S.;Roeck,J.;Ryder,J.;Smith,P.A new class of polymers:Starburst-dendritic macromolecules.Polym.J.1985,17,117-132.
13 Tolic,L.P.;Anderson,G.A.; Smith,R.D.; Brothers,H.M.;Spindler,R.; Tomalia,D.A.Electrospray ionization fourier transform ion cyclotron resonance mass spectrometric characterization of high molecular mass StarburstTM dendrimers.Int.J.Mass Spectrom.1997,165/166,405-418.
14 Peterson,J.;Allikmaa,V.;Subbi,J.;Pehk,T.;Lopp,M.Structural deviations in poly(amidoamine)dendrimers:A MALDITOF MS analysis.Eur.Polym.J.2003,39,33-42.
15 Aura,T.;Ungaro,R.;Liu,X.;Chen,C.;Giordano,L.;Peng,L.;Charles,L.Structural characterization of new defective molecules in poly(amidoamide)dendrimers by combining mass spectrometry and nuclear magnetic resonance.Anal.Chin.Acta 2015,853,451-459.
16 Mohammad,T.I.;Shi,X.;Balogh, L.;Baker, J.R.HPLC Separation of different generations of poly(amidoamine)dendrimers modified with various terminal groups.Anal.Chew.2005,77,2063-2070.
17 Mullen,D.G.; Desai,A.; van Dongen,M.A.; Barash,M.;Baker,J.R.; Banaszak Holl,M.M.Best practices for purification and characterization of PAMAM dendrimer.Macromolecules 2012,45,5316-5320.
18 van Dongen,M.A.; Desai,A.; Orr,B.G.; Baker,J.R.;Banaszak Hol,M.M.Quantitative analysis of generation and branch defects in G5 poly(amidoamine)dendrimer.Polymer2013,54.4126-4133.
19 Likos,C.N.Soft matter with soft particles.Soft Matter 2006,2,478-498.
20 Caminade,A.M.; Laurent,R.; Majoral,J.P.Characterization of dendrimers.Adv.Drug Deliv.Rev.2005,5 7,2130-2146.
21 Wang,X.Characterizations of polyamidoamine dendrimers with scattering techniques.Polymers 2012,4,600-61 6.
22 Topp,A.;Bauer,B.J.;Kilmash,K.W.;Spindler,R.;Tomalia,D.A.;Amis,E.J.Effect of solvent quality on the molecular dimensions of PAMAM dendrimers.Macromolecules 1999,32,7226-7231.
23 Imae,T.;Funayama,K.;Aoi,K.;Tsutsumiuchi,K.;Okada,M.;Furusaka,M.Small-angle neutron scattering and surface force investigations of poly(amido amine)dendrimer with hydroxyl end groups.Langmuir 1999,15,4076-4084.
24 Potschke,D.;Ballauff,M.;Lindner,P.;Fischer,M.;Vogtle,F.Analysis of the structure of dendrimers in solution by smallangle neutron scattering including contrast variation.Macro molecules 1999,32,4079-4087.
25 Rosenfeldt,S.; Dingenouts,N.; Ballauff,M.; Werner,N.;Vogtle,F.; Lindner,P.Distribution of end groups within a dendritic structure:A SANS study including contrast variation.Macromolecules 2002,35,8098-8105.
26 Rathgeber,S.; Monkenbusch,M.; Kreitschmann,M.; Urban,V.;Brulet,A.Dynamics of star-burst dendrimers in solution in relation to their structural properties.J.Chem.Phys.2002,11 7,4047-4062.
27 Huang,Q.R.; Dubin,P. L.; Lal,J.; Moorefield,C. N.;Newkome,G.R.Small-angle neutron scattering studies of charged carboxyl-terminated dendrimers in solutions.Lang muir 2005,21,2737-2742.
28 Porcar,L.;Liu,Y.;Verduzco,R.;Hong,K.;Butler,P.D.;Magid,L.J.;Smith,G.S.;Chen,W.R.Structural investigation of PAMAM dendrimers in aqueous solutions using small-angle neutron scattering:Effect of generation.J.Phys.Chem.B 2008,112,14772-14778.
29 Li,T.; Shao,N.; Liu,Y.;Hu,J.;Wang,Y.; Zhang,L.;Wang,H.; Chen,D.; Cheng,Y.Poly(amidoamine)and poly(propyleneimine)dendrimers show distinct binding behaviors with sodium dodecyl sulfate:Insights from SAXS and NMR analysis.J.Phys.Chem.B 2014,118,3074-3084.
30 Li,T.;Hong,K.;Porcar,L.;Verduzco,R.;Butler,P.D.;Smith,G.S.;Liu,Y.;Chen,W.R.Assess the intramolecular cavity of a PAMAM dendrimer in aqueous solution by small-angle neutron scattering.Macromolecules 2008,41,8916-8920.
31 Chen,W.R.; Porcar,L.; Liu,Y.; Butler,P.D.; Magid,L.J.Small-angle neutron scattering studies of the counterion effects on the molecular conformation and structure of charged G4PAMAM dendrimers in aqueous solutions.Macromolecules2007,40,5887-5898.
32 Keiderling,U.; Wiedenmann,A.New SANS instrument at the Berll Reactor in Berlin,Germany.Physica B 1995,213/214,895-897.
33 Helmholtz-Zentrum Berlin fiir Materialien und Energie.V4:The small-angle scattering instrument(SANS)at BERⅡ.JLSKF 2016,2,A97.
34 Keiderling,U.The new'BerSANS-PC'software for reduction and treatment of small-angle neutron scattering data.Appl.Phys.A 2002,74,1455-1457.
35 Glatter,O.A new method for the evaluation of small-angle scattering data.J.Appl. Cryst.1977,10,415-421.
36 Svergun,D.Determination of the regularization parameter in indirect-transform methods using perceptual criteria.J.Appl.1992,25,495-503.
37 Chen,S.H.Small-angle neutron scattering studies of the structure and interaction in micellar and microemulsion systems.Annu.Rev.Phys.Chem.1986,3 7,351-399.
38 Guinier,A.;Fournet,G.S,mall-angle scattering of X-rays.John Wiley&Sons,New York,1955,p.1-78.