The design of novel alkylated norcamphor derivatives that undergo cyclopolymerization is explored... more The design of novel alkylated norcamphor derivatives that undergo cyclopolymerization is explored; the resulting polymers incorporate suitable functional groups for chemical amplification and show excellent imaging characteristics under lithographic exposure at 193 nm.
The interest in imaging materials with improved environmental characteristics has led us to consi... more The interest in imaging materials with improved environmental characteristics has led us to consider imaging formulations coated from and developed in aqueous media, thus avoiding the need for both organic solvents and basic aqueous developer solutions. We have previously reported on the design of several negative-tone resists operating via radiation-induced crosslinking, and while the performance of these negative-tone systems met
Journal of Photopolymer Science and Technology, 1999
We have designed and synthesized a series of novel nortricyclene and other cycloaliphatic homo-an... more We have designed and synthesized a series of novel nortricyclene and other cycloaliphatic homo-and co-polymers incorporating at high carbon to hydrogen ratio and various structural units for use in 193 nm microlithography. The various macromolecules are prepared using a radical cyclopolymerization process involving norbornadienes or other suitable bis-olefinic moieties modified with an imageable functionality. The physical properties of the cyclopolymers may be tuned through copolymerization and simple modifications in the structure and composition of the monomers. The resulting materials may be formulated with a suitable photoacid generator to afford chemically amplified resists. The resists exhibit outstanding dry-etch resistance, good adhesion to silicon, good transparency at 193 nm and are uncontaminated by metal catalysts. Development with standard aqueous base affords positive-tone images with resolution of 0.16 pm and better. The concept of using self assembled monolayers of dendrimers for molecular scale imaging using scanning probe lithography is also outlined.
ABSTRACT A series of cyclopolymers designed for use in 193 nm photoresist materials has been synt... more ABSTRACT A series of cyclopolymers designed for use in 193 nm photoresist materials has been synthesized and characterized. These novel materials that provide both optical transparency at 193 nm and also reactive ion etch resistance are obtained via cyclopolymerization of suitably designed bifunctional monomers incorporating acrylic and olefinic double bonds. The approach is highly versatile and allows the preparation of a broad array of structurally related materials with different substituents providing the imaging function and the desired level of etch resistance. The cyclopolymerization process is experimentally forgiving, enabling control of the molecular weight as well as the incorporation of comonomers such as acrylic acid or maleic anhydride to fine-tune the lithographic properties.
Advances in Resist Technology and Processing XVII, Jun 23, 2000
ABSTRACT We report on the development and exploitation of a new type of chemically amplified resi... more ABSTRACT We report on the development and exploitation of a new type of chemically amplified resist for 193 nm microlithography. The approach has great versatility as it involves a general structure amenable to radical cyclopolymerization that contains easily interchanged ester functionalities. As the mechanism of polymerization involves free radicals, changes may be made either in the polymerization conditions or in the monomer feed to adjust variables such molecular weight or etch resistance. The latter property is favorably influenced by the formation of new ring structures during polymerization. Variations in the nature of the ester moieties contained in the monomer area easily accomplished to modify the imaging characteristics, surface properties, or etch resistance of the polymers. We report the preparation of a number of novel polymer and copolymer structures and their preliminary testing as resist candidates for 193 nm lithography.
... Jennifer M. Havard1, Dario Pasini1, Jean MJ Fréchet1,3, David Medeiros2, Shintaro Yamada2, an... more ... Jennifer M. Havard1, Dario Pasini1, Jean MJ Fréchet1,3, David Medeiros2, Shintaro Yamada2, and C. Grant Willson2 ... Microcircuit Eng., Grenoble 1982, 82, p. 260. 3. Lin, Q.; Simpson, L.; Steinhausler, T.; Wilder, M.; Willson, CG; Havard, JM; Fréchet, JMJ Proc. ...
Plasmid DNA was directly encapsulated into biocompatible polymer microparticles via radical polym... more Plasmid DNA was directly encapsulated into biocompatible polymer microparticles via radical polymerization in an inverse emulsion system. Acrylamide-based microspheres 0.2-1 µm in diameter were prepared using an acid-cleavable difunctional monomer. Retention of the DNA payload at physiological pH with complete release under acidic conditions at lysosomal pH was demonstrated. By trapping the plasmid DNA within the cross-linked microparticle, enzymatic degradation was prevented when exposed to serum nucleases. For vaccine development, these delivery vehicles were also investigated for their ability to generate immune responses when delivered to phagocytic cells of the immune system. Encapsulated plasmid DNA demonstrated immunostimulatory activity in macrophages, leading to cytokine secretion of IL-6 with a response ∼40-fold higher than that achieved with DNA alone.
Proceedings of the National Academy of Sciences, 2009
A biodegradable positron-emitting dendritic nanoprobe targeted at α v β 3 integrin, a biological ... more A biodegradable positron-emitting dendritic nanoprobe targeted at α v β 3 integrin, a biological marker known to modulate angiogenesis, was developed for the noninvasive imaging of angiogenesis. The nanoprobe has a modular multivalent core-shell architecture consisting of a biodegradable heterobifunctional dendritic core chemoselectively functionalized with heterobifunctional polyethylene oxide (PEO) chains that form a protective shell, which imparts biological stealth and dictates the pharmacokinetics. Each of the 8 branches of the dendritic core was functionalized for labeling with radiohalogens. Placement of radioactive moieties at the core was designed to prevent in vivo dehalogenation, a potential problem for radiohalogens in imaging and therapy. Targeting peptides of cyclic arginine–glycine–aspartic acid (RGD) motifs were installed at the terminal ends of the PEO chains to enhance their accessibility to α v β 3 integrin receptors. This nanoscale design enabled a 50-fold enhanc...
Proceedings of the National Academy of Sciences, 2009
Materials that combine facile synthesis, simple tuning of degradation rate, processability, and b... more Materials that combine facile synthesis, simple tuning of degradation rate, processability, and biocompatibility are in high demand for use in biomedical applications. We report on acetalated dextran, a biocompatible material that can be formed into microparticles with degradation rates that are tunable over 2 orders of magnitude depending on the degree and type of acetal modification. Varying the degradation rate produces particles that perform better than poly(lactic- co -glycolic acid) and iron oxide, two commonly studied materials used for particulate immunotherapy, in major histocompatibility complex class I (MHC I) and MHC II presentation assays. Modulating the material properties leads to antigen presentation on MHC I via pathways that are dependent or independent of the transporter associated with antigen processing. To the best of our knowledge, this is the only example of a material that can be tuned to operate on different immunological pathways while maximizing immunolog...
Acid-degradable particles containing a model protein antigen, ovalbumin, were prepared from a pol... more Acid-degradable particles containing a model protein antigen, ovalbumin, were prepared from a polyurethane with acetal moieties embedded throughout the polymer, and characterized by dynamic light scattering and transmission electron microscopy. The small molecule degradation by-product of the particles was synthesized and tested in vitro for toxicity indicating an LC 50 of 12,500 μg/ml. A new liquid chromatography-mass spectrometry technique was developed to monitor the in vitro degradation of these particles. The degradation by-product inside RAW macrophages was at its highest level after 24 hours of culture and was efficiently exocytosed until it was no longer detectable after four days. When tested in vitro, these particles induced a substantial increase in the presentation of the immunodominant ovalbumin-derived peptide SIINFEKL in both macrophages and dendritic cells. In addition, vaccination with these particles generated a cytotoxic T-lymphocyte response that was superior to both free ovalbumin and particles made from an analogous but slower-degrading acid-labile polyurethane polymer. Overall, we present a fully degradable polymer system with nontoxic by-products, which may find use in various biomedical applications including protein-based vaccines.
The photophysical and hydrodynamic properties of dendrimers (GnPZn and GnTPPH2) with zinc porphyr... more The photophysical and hydrodynamic properties of dendrimers (GnPZn and GnTPPH2) with zinc porphyrin (PZn) and tetraphenylporphyrin (TPP) cores are studied in tetrahydrofuran (THF) and dimethylformamide (DMF). UV-vis absorption spectra of GnPZn exhibit a small red shift of the Soret band upon increasing the generation as a result of interactions between the dendrons and the core. All fluorescence decays obtained from global analysis show a monoexponential profile. The intrinsic viscosity obtained for GnPZn from the hydrodynamic volume (V h) passes through a maximum as a function of generation (G) in agreement with earlier experimental findings and calculations suggesting that the internal density profile of dendrimers decrease monotonically outward from the center of the molecule. Within the investigated range (G) 1-3), GnTPPH2 exhibits an approximately constant intrinsic viscosity due to the linear dependence between the hydrodynamic volume and the molecular weight. The differences observed between GnPZn and GnTPPH2 are correlated to structural differences in their cores. The additional phenyl group of the TPP in GnTPPH2 increases the distance between the branches and the porphyrin moiety compared to GnPZn, resulting in a more flexible structure. The enhanced flexibility allows the terminal groups to sample more conformational space and therefore decreases the volume of the dendrimer as compared to the theoretical fully extended structure where Vh ∝ G 3. A comparison of the results obtained from analysis of fluorescence anisotropy decays with previously reported viscometry measurements shows a dependence of the structural collapse on the core size.
The zero shear melt viscosity, η0, for a variety of dendritic poly(benzyl ether) macromolecules h... more The zero shear melt viscosity, η0, for a variety of dendritic poly(benzyl ether) macromolecules has been measured. The viscosity of low generation dendrimers exhibits a strong molecular mass, M, dependence, yet, direct proportionality between η0 and M is observed at higher generations. The viscosity scales with M for mono-and tridendrons rather than generation number. Hypercore dendrimers continue this scaling although the viscosity is slightly greater. A large deviation from the master curve for the mono-and tridendrons is found for an end-substituted monodendron. The viscosity for the end-substituted monodendron is also much more temperature dependent than virgin dendrimers, and it is concluded that end groups have a much larger effect on the viscosity than the core. Reexamination of literature data for intrinsic viscosity and glass transition temperature is performed, and these quantities also scale with molecular mass. Comparison with free volume theory indicates that the theory is extremely robust although some question of its validity is made when applied to dendrimers.
One essential requirement for more sensitive gadolinium-based MRI contrast agents is to slow the ... more One essential requirement for more sensitive gadolinium-based MRI contrast agents is to slow the molecular tumbling of the gadolinium(III) ion, which increases the gadolinium's relaxivity, or the ability to speed up the NMR relaxation of nearby water molecules. One route to this is through conjugation to high-molecular weight polymers such as dendrimers. In this work, amine functionalized TREN-bis(1,2-HOPO)-TAM-ethylamine and TREN-bis(1-Me-3,2-HOPO)-TAMethylamine ligands have been synthesized and attached to biocompatible 40 kDa esteramide (EA) and poly-L-lysine based (PLL) dendrimers capable of binding up to eight gadolinium complexes. These conjugates have T 1 relaxivities of up to 38.14 ± 0.02 mM-1 s-1 per gadolinium at 37 °C, corresponding to relaxivities of up to 228 mM-1 s-1 per dendrimer molecule. This relaxivity expressed on a "per Gd" basis is several times that of the small molecule complexes, and an order of magnitude higher than that of current commercial agents. Due to their high performance and low toxicity these macromolecules may constitute an attractive complement to currently available gadolinium(III) based contrast agents. Supporting Information Available: All conjugation procedures, characterization, cytotoxicity and experimental details; This material is available free of charge via the Internet at http://pubs.acs.org.
Controlling polymer topology presents challenging synthetic obstacles as well as exciting opportu... more Controlling polymer topology presents challenging synthetic obstacles as well as exciting opportunities for tuning macromolecular properties. 1 In particular, nanoscale molecular architectures with well-defined shapes and dimensions may provide significant advancements in areas such as drug delivery and nanotechnology. Over the last decade, breakthroughs in polymer syntheses have greatly increased the variety of macromolecular architectures that may be obtained, including dendronized, cylindrical, star, hyperbranched, and cyclic polymers as well as various block copolymers. 2,3 However, the synthesis of circular nanostructures remains challenging due in large part to the difficulty in preparing functionalized cyclic polymers. 4 Furthermore, reliance on macrocyclization routes to cyclic polymers restricts attachment of large side chains or dendrons to post-polymerization, and an efficient route to cyclic hybrid architectures of high purity is yet to be realized. Following recent developments in ringexpansion metathesis polymerization (REMP) 5 and linear dendronized polymers, 6 we aimed to interface these two areas to achieve a direct, efficient route to cyclic organic nanostructures. 7 Herein, we report the REMP of a dendronized macromonomer (MM) as well as confirmation of cyclic polymer topology via atomic force microscopy (AFM). REMP utilizes Ru-based metathesis catalysts (Figure 1) capable of producing cyclic polymers directly from cyclic olefin monomers, thus avoiding linear polymeric synthons. Earlier studies revealed that N-heterocyclic carbene backbone saturation greatly increased overall catalyst activity, while tether length influenced the relative rates of propagation vs catalyst release. With access to a range of catalyst activities, we envisioned that REMP of dendronized MMs may achieve dendronized cyclic polymers in a single operation. In addition, REMP can produce high molecular weight (MW) cyclic polymers, a goal not easily accomplished using macrocyclization processes. While the polymerization of sterically hindered MMs presents an inherent challenge, it was shown that 1 (Figure 1) could be efficiently polymerized via ROMP using a highly active Rubased metathesis catalyst. This approach to dendritic polymers is particularly attractive, in that post-polymerization modifications are unnecessary, ensuring that complete dendron functionality is present along the polymer backbone. 2c Thus, we examined the efficiency of REMP using 1 in combination with cyclic catalysts SC-5 and UC-6.
Near-field scanning optical microscopy (NSOM) has been used to investigate the photophysical char... more Near-field scanning optical microscopy (NSOM) has been used to investigate the photophysical characteristics of first-to fourth-generation (G1 to G4) light-harvesting dendrimer thin films containing coumarin-343 and coumarin-2 as the core and peripheral chromophores, respectively. Thin film photoluminescence (PL) spectra exhibit a significant red shift in the lower generations (G1, G2, and G3) as compared to their respective solution PL spectra, implying the formation of excimers. Spatially resolved PL NSOM images exhibit pronounced nanoscopic domains in G1, which become more homogeneous in higher generations due to site-isolation of the core chromophore. G4 exhibits complete site-isolation for these light-harvesting dendrimer films.
Commercial gadolinium magnetic resonance imaging (MRI) contrast agents are limited by low relaxiv... more Commercial gadolinium magnetic resonance imaging (MRI) contrast agents are limited by low relaxivity (r 1) and coordination to only a single water molecule (q = 1). Consequently, gram quantities of these agents must be injected to obtain sufficient diagnostic contrast. In this study, MRI contrast agents for T 1 and T 2 relaxivity were synthesized using hydroxypyridinone (HOPO) and terephthalamide (TAM) chelators with mesityl and 1,4,7-triazacyclononane (TACN) capping moieties. When covalently conjugated to a highly biocompatible esteramide dendrimer, T 2 relaxation rates up to 52 mM-1 s-1 and T 1 relaxation rates up to 31 mM-1 s-1 per gadolinium are observed under clinically relevant conditions. These values are believed to be brought about by using a dendritic macromolecule to decrease the molecular tumbling time of the small molecule complexes. These agents also show high aqueous solubility and low toxicity in vitro. In this study we report six new compounds: three discrete complexes and three dendrimer conjugates.
Novel chromophore-labeled dendrimers with penta-and heptathiophene cores and coumarin-2 chromopho... more Novel chromophore-labeled dendrimers with penta-and heptathiophene cores and coumarin-2 chromophores at their periphery have been shown to be very efficient lightharvesting systems. Excitation of the peripheral coumarin-2 chromophores results in energy transfer to the oligothiophene cores as a result of the large overlap between the donor emission spectrum and the acceptor absorption spectrum, as well as the large transition dipole moments of the oligothiophenes. Although these core dyes have low fluorescence quantum yields, their emission intensity is significantly enhanced by the ability of the large light-harvesting dendron to funnel absorbed energy to the core. Because of the large Stokes shift of the oligothiophenes, the emission spectrum of the dendrimers was red-shifted by 200 nm from the excitation wavelength. Additionally, it was found that oligothiophene orientationsend functionalization vs central functionalizationsdid not have a significant effect on energy-transfer efficiency.
The design of novel alkylated norcamphor derivatives that undergo cyclopolymerization is explored... more The design of novel alkylated norcamphor derivatives that undergo cyclopolymerization is explored; the resulting polymers incorporate suitable functional groups for chemical amplification and show excellent imaging characteristics under lithographic exposure at 193 nm.
The interest in imaging materials with improved environmental characteristics has led us to consi... more The interest in imaging materials with improved environmental characteristics has led us to consider imaging formulations coated from and developed in aqueous media, thus avoiding the need for both organic solvents and basic aqueous developer solutions. We have previously reported on the design of several negative-tone resists operating via radiation-induced crosslinking, and while the performance of these negative-tone systems met
Journal of Photopolymer Science and Technology, 1999
We have designed and synthesized a series of novel nortricyclene and other cycloaliphatic homo-an... more We have designed and synthesized a series of novel nortricyclene and other cycloaliphatic homo-and co-polymers incorporating at high carbon to hydrogen ratio and various structural units for use in 193 nm microlithography. The various macromolecules are prepared using a radical cyclopolymerization process involving norbornadienes or other suitable bis-olefinic moieties modified with an imageable functionality. The physical properties of the cyclopolymers may be tuned through copolymerization and simple modifications in the structure and composition of the monomers. The resulting materials may be formulated with a suitable photoacid generator to afford chemically amplified resists. The resists exhibit outstanding dry-etch resistance, good adhesion to silicon, good transparency at 193 nm and are uncontaminated by metal catalysts. Development with standard aqueous base affords positive-tone images with resolution of 0.16 pm and better. The concept of using self assembled monolayers of dendrimers for molecular scale imaging using scanning probe lithography is also outlined.
ABSTRACT A series of cyclopolymers designed for use in 193 nm photoresist materials has been synt... more ABSTRACT A series of cyclopolymers designed for use in 193 nm photoresist materials has been synthesized and characterized. These novel materials that provide both optical transparency at 193 nm and also reactive ion etch resistance are obtained via cyclopolymerization of suitably designed bifunctional monomers incorporating acrylic and olefinic double bonds. The approach is highly versatile and allows the preparation of a broad array of structurally related materials with different substituents providing the imaging function and the desired level of etch resistance. The cyclopolymerization process is experimentally forgiving, enabling control of the molecular weight as well as the incorporation of comonomers such as acrylic acid or maleic anhydride to fine-tune the lithographic properties.
Advances in Resist Technology and Processing XVII, Jun 23, 2000
ABSTRACT We report on the development and exploitation of a new type of chemically amplified resi... more ABSTRACT We report on the development and exploitation of a new type of chemically amplified resist for 193 nm microlithography. The approach has great versatility as it involves a general structure amenable to radical cyclopolymerization that contains easily interchanged ester functionalities. As the mechanism of polymerization involves free radicals, changes may be made either in the polymerization conditions or in the monomer feed to adjust variables such molecular weight or etch resistance. The latter property is favorably influenced by the formation of new ring structures during polymerization. Variations in the nature of the ester moieties contained in the monomer area easily accomplished to modify the imaging characteristics, surface properties, or etch resistance of the polymers. We report the preparation of a number of novel polymer and copolymer structures and their preliminary testing as resist candidates for 193 nm lithography.
... Jennifer M. Havard1, Dario Pasini1, Jean MJ Fréchet1,3, David Medeiros2, Shintaro Yamada2, an... more ... Jennifer M. Havard1, Dario Pasini1, Jean MJ Fréchet1,3, David Medeiros2, Shintaro Yamada2, and C. Grant Willson2 ... Microcircuit Eng., Grenoble 1982, 82, p. 260. 3. Lin, Q.; Simpson, L.; Steinhausler, T.; Wilder, M.; Willson, CG; Havard, JM; Fréchet, JMJ Proc. ...
Plasmid DNA was directly encapsulated into biocompatible polymer microparticles via radical polym... more Plasmid DNA was directly encapsulated into biocompatible polymer microparticles via radical polymerization in an inverse emulsion system. Acrylamide-based microspheres 0.2-1 µm in diameter were prepared using an acid-cleavable difunctional monomer. Retention of the DNA payload at physiological pH with complete release under acidic conditions at lysosomal pH was demonstrated. By trapping the plasmid DNA within the cross-linked microparticle, enzymatic degradation was prevented when exposed to serum nucleases. For vaccine development, these delivery vehicles were also investigated for their ability to generate immune responses when delivered to phagocytic cells of the immune system. Encapsulated plasmid DNA demonstrated immunostimulatory activity in macrophages, leading to cytokine secretion of IL-6 with a response ∼40-fold higher than that achieved with DNA alone.
Proceedings of the National Academy of Sciences, 2009
A biodegradable positron-emitting dendritic nanoprobe targeted at α v β 3 integrin, a biological ... more A biodegradable positron-emitting dendritic nanoprobe targeted at α v β 3 integrin, a biological marker known to modulate angiogenesis, was developed for the noninvasive imaging of angiogenesis. The nanoprobe has a modular multivalent core-shell architecture consisting of a biodegradable heterobifunctional dendritic core chemoselectively functionalized with heterobifunctional polyethylene oxide (PEO) chains that form a protective shell, which imparts biological stealth and dictates the pharmacokinetics. Each of the 8 branches of the dendritic core was functionalized for labeling with radiohalogens. Placement of radioactive moieties at the core was designed to prevent in vivo dehalogenation, a potential problem for radiohalogens in imaging and therapy. Targeting peptides of cyclic arginine–glycine–aspartic acid (RGD) motifs were installed at the terminal ends of the PEO chains to enhance their accessibility to α v β 3 integrin receptors. This nanoscale design enabled a 50-fold enhanc...
Proceedings of the National Academy of Sciences, 2009
Materials that combine facile synthesis, simple tuning of degradation rate, processability, and b... more Materials that combine facile synthesis, simple tuning of degradation rate, processability, and biocompatibility are in high demand for use in biomedical applications. We report on acetalated dextran, a biocompatible material that can be formed into microparticles with degradation rates that are tunable over 2 orders of magnitude depending on the degree and type of acetal modification. Varying the degradation rate produces particles that perform better than poly(lactic- co -glycolic acid) and iron oxide, two commonly studied materials used for particulate immunotherapy, in major histocompatibility complex class I (MHC I) and MHC II presentation assays. Modulating the material properties leads to antigen presentation on MHC I via pathways that are dependent or independent of the transporter associated with antigen processing. To the best of our knowledge, this is the only example of a material that can be tuned to operate on different immunological pathways while maximizing immunolog...
Acid-degradable particles containing a model protein antigen, ovalbumin, were prepared from a pol... more Acid-degradable particles containing a model protein antigen, ovalbumin, were prepared from a polyurethane with acetal moieties embedded throughout the polymer, and characterized by dynamic light scattering and transmission electron microscopy. The small molecule degradation by-product of the particles was synthesized and tested in vitro for toxicity indicating an LC 50 of 12,500 μg/ml. A new liquid chromatography-mass spectrometry technique was developed to monitor the in vitro degradation of these particles. The degradation by-product inside RAW macrophages was at its highest level after 24 hours of culture and was efficiently exocytosed until it was no longer detectable after four days. When tested in vitro, these particles induced a substantial increase in the presentation of the immunodominant ovalbumin-derived peptide SIINFEKL in both macrophages and dendritic cells. In addition, vaccination with these particles generated a cytotoxic T-lymphocyte response that was superior to both free ovalbumin and particles made from an analogous but slower-degrading acid-labile polyurethane polymer. Overall, we present a fully degradable polymer system with nontoxic by-products, which may find use in various biomedical applications including protein-based vaccines.
The photophysical and hydrodynamic properties of dendrimers (GnPZn and GnTPPH2) with zinc porphyr... more The photophysical and hydrodynamic properties of dendrimers (GnPZn and GnTPPH2) with zinc porphyrin (PZn) and tetraphenylporphyrin (TPP) cores are studied in tetrahydrofuran (THF) and dimethylformamide (DMF). UV-vis absorption spectra of GnPZn exhibit a small red shift of the Soret band upon increasing the generation as a result of interactions between the dendrons and the core. All fluorescence decays obtained from global analysis show a monoexponential profile. The intrinsic viscosity obtained for GnPZn from the hydrodynamic volume (V h) passes through a maximum as a function of generation (G) in agreement with earlier experimental findings and calculations suggesting that the internal density profile of dendrimers decrease monotonically outward from the center of the molecule. Within the investigated range (G) 1-3), GnTPPH2 exhibits an approximately constant intrinsic viscosity due to the linear dependence between the hydrodynamic volume and the molecular weight. The differences observed between GnPZn and GnTPPH2 are correlated to structural differences in their cores. The additional phenyl group of the TPP in GnTPPH2 increases the distance between the branches and the porphyrin moiety compared to GnPZn, resulting in a more flexible structure. The enhanced flexibility allows the terminal groups to sample more conformational space and therefore decreases the volume of the dendrimer as compared to the theoretical fully extended structure where Vh ∝ G 3. A comparison of the results obtained from analysis of fluorescence anisotropy decays with previously reported viscometry measurements shows a dependence of the structural collapse on the core size.
The zero shear melt viscosity, η0, for a variety of dendritic poly(benzyl ether) macromolecules h... more The zero shear melt viscosity, η0, for a variety of dendritic poly(benzyl ether) macromolecules has been measured. The viscosity of low generation dendrimers exhibits a strong molecular mass, M, dependence, yet, direct proportionality between η0 and M is observed at higher generations. The viscosity scales with M for mono-and tridendrons rather than generation number. Hypercore dendrimers continue this scaling although the viscosity is slightly greater. A large deviation from the master curve for the mono-and tridendrons is found for an end-substituted monodendron. The viscosity for the end-substituted monodendron is also much more temperature dependent than virgin dendrimers, and it is concluded that end groups have a much larger effect on the viscosity than the core. Reexamination of literature data for intrinsic viscosity and glass transition temperature is performed, and these quantities also scale with molecular mass. Comparison with free volume theory indicates that the theory is extremely robust although some question of its validity is made when applied to dendrimers.
One essential requirement for more sensitive gadolinium-based MRI contrast agents is to slow the ... more One essential requirement for more sensitive gadolinium-based MRI contrast agents is to slow the molecular tumbling of the gadolinium(III) ion, which increases the gadolinium's relaxivity, or the ability to speed up the NMR relaxation of nearby water molecules. One route to this is through conjugation to high-molecular weight polymers such as dendrimers. In this work, amine functionalized TREN-bis(1,2-HOPO)-TAM-ethylamine and TREN-bis(1-Me-3,2-HOPO)-TAMethylamine ligands have been synthesized and attached to biocompatible 40 kDa esteramide (EA) and poly-L-lysine based (PLL) dendrimers capable of binding up to eight gadolinium complexes. These conjugates have T 1 relaxivities of up to 38.14 ± 0.02 mM-1 s-1 per gadolinium at 37 °C, corresponding to relaxivities of up to 228 mM-1 s-1 per dendrimer molecule. This relaxivity expressed on a "per Gd" basis is several times that of the small molecule complexes, and an order of magnitude higher than that of current commercial agents. Due to their high performance and low toxicity these macromolecules may constitute an attractive complement to currently available gadolinium(III) based contrast agents. Supporting Information Available: All conjugation procedures, characterization, cytotoxicity and experimental details; This material is available free of charge via the Internet at http://pubs.acs.org.
Controlling polymer topology presents challenging synthetic obstacles as well as exciting opportu... more Controlling polymer topology presents challenging synthetic obstacles as well as exciting opportunities for tuning macromolecular properties. 1 In particular, nanoscale molecular architectures with well-defined shapes and dimensions may provide significant advancements in areas such as drug delivery and nanotechnology. Over the last decade, breakthroughs in polymer syntheses have greatly increased the variety of macromolecular architectures that may be obtained, including dendronized, cylindrical, star, hyperbranched, and cyclic polymers as well as various block copolymers. 2,3 However, the synthesis of circular nanostructures remains challenging due in large part to the difficulty in preparing functionalized cyclic polymers. 4 Furthermore, reliance on macrocyclization routes to cyclic polymers restricts attachment of large side chains or dendrons to post-polymerization, and an efficient route to cyclic hybrid architectures of high purity is yet to be realized. Following recent developments in ringexpansion metathesis polymerization (REMP) 5 and linear dendronized polymers, 6 we aimed to interface these two areas to achieve a direct, efficient route to cyclic organic nanostructures. 7 Herein, we report the REMP of a dendronized macromonomer (MM) as well as confirmation of cyclic polymer topology via atomic force microscopy (AFM). REMP utilizes Ru-based metathesis catalysts (Figure 1) capable of producing cyclic polymers directly from cyclic olefin monomers, thus avoiding linear polymeric synthons. Earlier studies revealed that N-heterocyclic carbene backbone saturation greatly increased overall catalyst activity, while tether length influenced the relative rates of propagation vs catalyst release. With access to a range of catalyst activities, we envisioned that REMP of dendronized MMs may achieve dendronized cyclic polymers in a single operation. In addition, REMP can produce high molecular weight (MW) cyclic polymers, a goal not easily accomplished using macrocyclization processes. While the polymerization of sterically hindered MMs presents an inherent challenge, it was shown that 1 (Figure 1) could be efficiently polymerized via ROMP using a highly active Rubased metathesis catalyst. This approach to dendritic polymers is particularly attractive, in that post-polymerization modifications are unnecessary, ensuring that complete dendron functionality is present along the polymer backbone. 2c Thus, we examined the efficiency of REMP using 1 in combination with cyclic catalysts SC-5 and UC-6.
Near-field scanning optical microscopy (NSOM) has been used to investigate the photophysical char... more Near-field scanning optical microscopy (NSOM) has been used to investigate the photophysical characteristics of first-to fourth-generation (G1 to G4) light-harvesting dendrimer thin films containing coumarin-343 and coumarin-2 as the core and peripheral chromophores, respectively. Thin film photoluminescence (PL) spectra exhibit a significant red shift in the lower generations (G1, G2, and G3) as compared to their respective solution PL spectra, implying the formation of excimers. Spatially resolved PL NSOM images exhibit pronounced nanoscopic domains in G1, which become more homogeneous in higher generations due to site-isolation of the core chromophore. G4 exhibits complete site-isolation for these light-harvesting dendrimer films.
Commercial gadolinium magnetic resonance imaging (MRI) contrast agents are limited by low relaxiv... more Commercial gadolinium magnetic resonance imaging (MRI) contrast agents are limited by low relaxivity (r 1) and coordination to only a single water molecule (q = 1). Consequently, gram quantities of these agents must be injected to obtain sufficient diagnostic contrast. In this study, MRI contrast agents for T 1 and T 2 relaxivity were synthesized using hydroxypyridinone (HOPO) and terephthalamide (TAM) chelators with mesityl and 1,4,7-triazacyclononane (TACN) capping moieties. When covalently conjugated to a highly biocompatible esteramide dendrimer, T 2 relaxation rates up to 52 mM-1 s-1 and T 1 relaxation rates up to 31 mM-1 s-1 per gadolinium are observed under clinically relevant conditions. These values are believed to be brought about by using a dendritic macromolecule to decrease the molecular tumbling time of the small molecule complexes. These agents also show high aqueous solubility and low toxicity in vitro. In this study we report six new compounds: three discrete complexes and three dendrimer conjugates.
Novel chromophore-labeled dendrimers with penta-and heptathiophene cores and coumarin-2 chromopho... more Novel chromophore-labeled dendrimers with penta-and heptathiophene cores and coumarin-2 chromophores at their periphery have been shown to be very efficient lightharvesting systems. Excitation of the peripheral coumarin-2 chromophores results in energy transfer to the oligothiophene cores as a result of the large overlap between the donor emission spectrum and the acceptor absorption spectrum, as well as the large transition dipole moments of the oligothiophenes. Although these core dyes have low fluorescence quantum yields, their emission intensity is significantly enhanced by the ability of the large light-harvesting dendron to funnel absorbed energy to the core. Because of the large Stokes shift of the oligothiophenes, the emission spectrum of the dendrimers was red-shifted by 200 nm from the excitation wavelength. Additionally, it was found that oligothiophene orientationsend functionalization vs central functionalizationsdid not have a significant effect on energy-transfer efficiency.
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Papers by Jean Fréchet