Co-reporter:Kishore Raghupathi, Scott J. Eron, Francesca Anson, Jeanne A. Hardy, and S. Thayumanavan
Molecular Pharmaceutics December 4, 2017 Volume 14(Issue 12) pp:4515-4515
Publication Date(Web):October 20, 2017
DOI:10.1021/acs.molpharmaceut.7b00643
Therapeutic biologics have various advantages over synthetic drugs in terms of selectivity, their catalytic nature, and, thus, therapeutic efficacy. These properties offer the potential for more effective treatments that may also overcome the undesirable side effects observed due to off-target toxicities of small molecule drugs. Unfortunately, systemic administration of biologics is challenging due to cellular penetration, renal clearance, and enzymatic degradation difficulties. A delivery vehicle that can overcome these challenges and deliver biologics to specific cellular populations has the potential for significant therapeutic impact. In this work, we describe a redox-responsive nanoparticle platform, which can encapsulate hydrophilic proteins and release them only in the presence of a reducing stimulus. We have formulated these nanoparticles using an inverse emulsion polymerization (IEP) methodology, yielding inverse nanoemulsions, or nanogels. We have demonstrated our ability to overcome the liabilities that contribute to activity loss by delivering a highly challenging cargo, functionally active caspase-3, a cysteine protease susceptible to oxidative and self-proteolytic insults, to the cytosol of HeLa cells by encapsulation inside a redox-responsive nanogel.Keywords: caspase-3; inverse emulsion polymerization; inverse nanoemulsion; nanogel; protease protection; protein delivery; redox-responsive nanogels;
Co-reporter:Bo Zhao, Jiaming Zhuang, Mahalia A. C. Serrano, Richard W. Vachet, and S. Thayumanavan
Macromolecules December 26, 2017 Volume 50(Issue 24) pp:9734-9734
Publication Date(Web):December 7, 2017
DOI:10.1021/acs.macromol.7b02434
The effects of charge density on supramolecular host–guest interactions between peptides and reverse micelles are studied using an amphiphilic random copolymer scaffold. While our classical understanding of polyvalent electrostatic interactions suggests that the binding capacity should increase with charge density, our results indicate that this correlation does not necessarily hold within the nanoscale environment of reverse micelles. Using four series of different polymers, we show that peptide binding efficiency depends on the presence of an optimum charge density inside the reverse micelles. Interestingly, the distribution of charges does not have a significant effect on binding. Reverse micelle stability at high charge densities can be regained by tuning the hydrophilic–lipophilic balance of the polymer, yet an optimal density dependence remains. Our findings improve our understanding of host–guest chemistry in confined aqueous environments.
Co-reporter:Bin Liu and S. Thayumanavan
Biomacromolecules December 11, 2017 Volume 18(Issue 12) pp:4163-4163
Publication Date(Web):October 31, 2017
DOI:10.1021/acs.biomac.7b01220
In targeted drug delivery systems, it is desirable that the delivery of hydrophobic drugs to a cell or tissue is achieved with little to no side effects. To ensure that the drugs do not leak during circulation, encapsulation stability of the drug carrier in serum is critical. In this paper, we report on a modified FRET-based method to evaluate encapsulation stability of amphiphilic assemblies and cross-linked polymer assemblies in serum. Our results show that serum components can act as reservoirs for hydrophobic molecules. We also show that serum albumin is likely to be the primary determinant of this property. This work highlights the importance of assessing encapsulation stability in terms of dynamics of guest molecules, as it provides the critical distinction between hydrophobic molecules bound inside amphiphilic assemblies and the molecules that are bound to the hydrophobic pockets of serum albumin.
Co-reporter:Kingshuk Dutta, Ding Hu, Bo Zhao, Alexander E. Ribbe, Jiaming Zhuang, and S. Thayumanavan
Journal of the American Chemical Society April 26, 2017 Volume 139(Issue 16) pp:5676-5676
Publication Date(Web):April 13, 2017
DOI:10.1021/jacs.7b01214
Trafficking proteins inside cells is an emerging field with potential utility in basic cell biology and biological therapeutics. A robust and sustainable delivery strategy demands not only good protection of the cargo but also reversibility in conjugation and activity. We report a protein-templated polymer self-assembly strategy for forming a sheath around the proteins and then tracelessly releasing them in the cytosol. The versatility of the approach, demonstrated here, suggests that the strategy is compatible with a wide array of biologics.
Co-reporter:Piyachai Khomein
Chemical Communications 2017 vol. 53(Issue 37) pp:5190-5192
Publication Date(Web):2017/05/04
DOI:10.1039/C7CC00963A
Flat aromatic structures are ubiquitous in organic semiconducting molecules. The possibility of endowing these inherently anisotropic molecules with isotropic structures is explored using a polymeric nanoparticle attachment strategy. Preliminary findings, outlined in this manuscript, suggest that this might be a simple and effective strategy for organic semiconductors with consistent mobilities.
Co-reporter:Mahalia A. C. Serrano;Huan He;Bo Zhao;Rajasekhar R. Ramireddy;Richard W. Vachet
Analyst (1876-Present) 2017 vol. 142(Issue 1) pp:118-122
Publication Date(Web):2016/12/19
DOI:10.1039/C6AN01591C
A combination of donor–acceptor and electrostatic interactions in a three-component supramolecular system has been shown to form the basis for selective and sensitive detection of peptides. Different substituents in the polymer and the detection matrix were compared to demonstrate that the favorable donor–acceptor interactions explain the observed signal enhancement. The ternary supramolecular interactions discovered in this work are enabled by the self-packing behavior of amphiphilic homopolymers and their ability to mediate interactions between the detection matrix and peptide that facilitate sensitive detection of peptides.
Co-reporter:Poornima Rangadurai; Mijanur Rahaman Molla; Priyaa Prasad; Matthew Caissy
Journal of the American Chemical Society 2016 Volume 138(Issue 24) pp:7508-7511
Publication Date(Web):June 3, 2016
DOI:10.1021/jacs.6b04099
An amphiphilic polymer with cleavable side chain and main chain functional groups has been designed and synthesized. Specific cleavage of either of its functional groups was found to have an effect on the morphology of the assembly. Degradation of the main chain is shown to cause morphology of the supramolecular assembly to evolve with time from a micelle-like assembly to a vesicular assembly. On the other hand, stimulus-induced cleavage of the side chains causes these nanoassemblies to disassemble. These temporal (main chain) and triggered (side chain) degradation processes have implications in the design of degradable polymers as supramolecular scaffolds for biological applications.
Co-reporter:Dr. Wei Bai;Ziwen Jiang;Dr. Alexer E. Ribbe; S. Thayumanavan
Angewandte Chemie 2016 Volume 128( Issue 36) pp:10865-10869
Publication Date(Web):
DOI:10.1002/ange.201605050
Abstract
Rational design of organic 2D (O2D) materials has made some progress, but it is still in its infancy. A class of self-assembling small molecules is presented that form nano/microscale supramolecular 2D materials in aqueous media. A judicial combination of four different intermolecular interactions forms the basis for the robust formation of these ultrathin assemblies. These assemblies can be programmed to disassemble in response to a specific protein and release its non-covalently bound guest molecules.
Co-reporter:Xiaochi Liu, Ding Hu, Ziwen Jiang, Jiaming Zhuang, Yisheng Xu, Xuhong Guo, and S. Thayumanavan
Macromolecules 2016 Volume 49(Issue 17) pp:6186-6192
Publication Date(Web):August 16, 2016
DOI:10.1021/acs.macromol.6b01397
A strategy to construct different stimuli-responsive polymers from postpolymerization modifications of a single polymer scaffold via thiol–disulfide exchange has been developed. Here, we report on a random copolymer that enables the design and syntheses of a series of dual or multi-stimuli-responsive nanoassemblies using a simple postpolymerization modification step. The reactive functional group involves a side chain monopyridyl disulfide unit, which rapidly and quantitatively reacts with various thiols under mild conditions. Independent and concurrent incorporation of physical, chemical, or biologically responsive properties have been demonstrated. We envision that this strategy may open up opportunities to simplify the synthesis of multifunctional polymers with broad implications in a variety of biological applications.
Co-reporter:Oyuntuya Munkhbat, Matteo Garzoni, Krishna R. Raghupathi, Giovanni M. Pavan, and S. Thayumanavan
Langmuir 2016 Volume 32(Issue 12) pp:2874-2881
Publication Date(Web):March 3, 2016
DOI:10.1021/acs.langmuir.5b04540
Aromatic interactions were found to greatly influence the temperature-dependent dynamic behavior within supramolecular assemblies. Using an amphiphilic dendron, we systematically changed the hydrophobic groups introducing increasing levels of aromaticity while keeping the hydrophilic part constant. We show that the supramolecular assemblies become less sensitive to temperature changes when aromatic interactions in the aggregate are increased. Conversely, the absence of aromaticity in the hydrophobic moieties produces temperature-sensitive aggregates. These results show that subtle molecular-level interactions can be utilized to control temperature-sensitive behavior in the nanoscale. These findings open up new design strategies to rationally tune the behavior of stimuli-responsive supramolecular assemblies on multiple spatiotemporal scales.
Co-reporter:Dr. Wei Bai;Ziwen Jiang;Dr. Alexer E. Ribbe; S. Thayumanavan
Angewandte Chemie International Edition 2016 Volume 55( Issue 36) pp:10707-10711
Publication Date(Web):
DOI:10.1002/anie.201605050
Abstract
Rational design of organic 2D (O2D) materials has made some progress, but it is still in its infancy. A class of self-assembling small molecules is presented that form nano/microscale supramolecular 2D materials in aqueous media. A judicial combination of four different intermolecular interactions forms the basis for the robust formation of these ultrathin assemblies. These assemblies can be programmed to disassemble in response to a specific protein and release its non-covalently bound guest molecules.
Co-reporter:Krishna R. Raghupathi; Uma Sridhar; Kevin Byrne; Kishore Raghupathi
Journal of the American Chemical Society 2015 Volume 137(Issue 16) pp:5308-5311
Publication Date(Web):April 20, 2015
DOI:10.1021/jacs.5b02108
Molecular design features that endow amphiphilic supramolecular assemblies with a unique temperature-sensitive transition have been investigated. We find that conformational rigidity in the backbone is an important feature for eliciting this feature. We also find that intramolecular hydrogen-bonding can induce such rigidity in amphiphile backbone. Guest encapsulation stability of these assemblies was found to be significantly altered within a narrow temperature window, which correlates with the temperature-sensitive size transition of the molecular assembly. Molecular design principles demonstrated here could have broad implications in developing future temperature-responsive systems.
Co-reporter:Mijanur Rahaman Molla; Priyaa Prasad
Journal of the American Chemical Society 2015 Volume 137(Issue 23) pp:7286-7289
Publication Date(Web):May 28, 2015
DOI:10.1021/jacs.5b04285
Mimicking noncovalent interaction based processes in nature has been an important goal of supramolecular chemistry. Here, we report on amphiphilic polypeptides that self-assemble to form nanoscale supramolecular assemblies and are programmed to disassemble in response to a specific protein. Benzenesulfonamide and carbonic anhydrase have been chosen as the ligand and protein, respectively, to demonstrate this possibility. Since the amphiphilic nanoassembly sequesters hydrophobic guest molecules, the protein-specific disassembly event provides a protein-sensitive molecular release as well. We envision that the binding induced disassembly and guest release might open up new opportunities for the next generation of supramolecular assemblies for protein-specific delivery and diagnostics.
Co-reporter:Conghui Yuan, Ying Chang, Jie Mao, Shirong Yu, Weiang Luo, Yiting Xu, S. Thayumanavan and Lizong Dai
Journal of Materials Chemistry A 2015 vol. 3(Issue 14) pp:2858-2866
Publication Date(Web):18 Feb 2015
DOI:10.1039/C4TB01880J
Intermolecular B–N coordination has been recognized as a promising driving force for molecular self-organization. However, direct utilization of this intermolecular interaction as a building bridge for the supramolecular self-assembly of chemical functionalities to form nano-sized architectures remains a daunting challenge. Here, we outline a multiple intermolecular B–N coordination based supramolecular system, where small boronate molecules can be brought together in solution to form nanoparticles with controllable sizes and morphologies. We not only demonstrate the intrinsic switchable fluorescence and the stimuli-responsive capabilities of designed boronate molecules, but also show that the stabilized or surface functionalized nanoparticles are degradable in response to pH and D-glucose and able to retain the fluorescence features of the boronate molecules. Additionally, the degraded nanoparticles can repair themselves through the reformation of B–N coordination.
Co-reporter:Longyu Li, Cunfeng Song, Matthew Jennings and S. Thayumanavan
Chemical Communications 2015 vol. 51(Issue 8) pp:1425-1428
Publication Date(Web):12 Nov 2014
DOI:10.1039/C4CC08000A
Reagent-free synthetic methods are of great interest because of their simplicity and implications in green chemistry. We have taken advantage of photoinduced heterodisulfide metathesis to generate crosslinked polymer nanoparticles. The method of development and the mechanistic basis for the synthetic approach are outlined in this communication.
Co-reporter:Hui Wang, Jiaming Zhuang, Krishna R. Raghupathi and S. Thayumanavan
Chemical Communications 2015 vol. 51(Issue 97) pp:17265-17268
Publication Date(Web):28 Sep 2015
DOI:10.1039/C5CC07408H
We report a simple, robust, and general strategy for protein detection based on supramolecular dissociation. The simplicity of the design is exemplified by the fact that the host assemblies can be widely varied and that these assemblies can be achieved from commercially available surfactants. An operating mechanism that is consistent with all the data has been proposed.
Co-reporter:Rajasekhar R. Ramireddy, P. Prasad, A. Finne and S. Thayumanavan
Polymer Chemistry 2015 vol. 6(Issue 33) pp:6083-6087
Publication Date(Web):07 Jul 2015
DOI:10.1039/C5PY00879D
Zwitterionic amphiphilic homopolymers can be conveniently prepared in one-pot using activated ester-based polymer precursors. We show that these zwitterionic polymers can (i) spontaneously self-assemble to form micelle-like and inverse micelle-like assemblies depending on the solvent environment; (ii) act as hydrophilic and hydrophobic nanocontainers in apolar and polar solvents respectively; (iii) undergo pH-responsive surface charge and size variations; and (iv) exhibit the least cytotoxicity compared to the structurally analogous amphiphilic homopolymers.
Co-reporter:Cunfeng Song, Longyu Li, Lizong Dai and S. Thayumanavan
Polymer Chemistry 2015 vol. 6(Issue 26) pp:4828-4834
Publication Date(Web):21 May 2015
DOI:10.1039/C5PY00600G
We report a facile approach to form ultra-fine single-chain polymer nanoparticles (SCPNs) via disulfide-based intrachain crosslinking of single polymer chains of a random copolymer poly(HEMA-co-PDSEMA). The SCPNs, which were prepared under mild reaction conditions and at normal reaction concentrations (up to 10 mg mL−1), have been characterized by 1H nuclear magnetic resonance (1H NMR) spectroscopy, atomic force microscopy (AFM), differential scanning calorimetry (DSC), gel permeation chromatography (GPC), and dynamic light scattering (DLS). The influences of the crosslinking density, the molecular weight and the initial concentration of the polymer upon the formation of SCPNs are also reported. In order to investigate the hydrophobic interior of SCPNs, we trace the emission spectrum of a pyrene probe. We highlight that these SCPNs exhibit host–guest properties to stably encapsulate hydrophobic guest molecules and release them in response to a redox stimulus.
Co-reporter:Hui Wang, Krishna R. Raghupathi, Jiaming Zhuang, and S. Thayumanavan
ACS Macro Letters 2015 Volume 4(Issue 4) pp:422
Publication Date(Web):April 1, 2015
DOI:10.1021/acsmacrolett.5b00199
We describe a novel activatable probe for fluorine-19 NMR based on self-assembling amphiphilic dendrons. The dendron probe has been designed to be spectroscopically silent due to the formation of large aggregates. Upon exposure to the specific target enzyme, the aggregates disassemble to give rise to a sharp 19F NMR signal. The probe is capable of detecting enzyme concentrations in the low nanomolar range. Response time of the probe was found to be affected by the hydrophilic–lipophilic balance of dendrons. Understanding the structural factors that underlie this design principle provides the pathway for using this strategy for a broad range of enzyme-based imaging.
Co-reporter:Mallory R. Gordon, Mine Canakci, Longyu Li, Jiaming Zhuang, Barbara Osborne, and S. Thayumanavan
Bioconjugate Chemistry 2015 Volume 26(Issue 11) pp:2198
Publication Date(Web):August 26, 2015
DOI:10.1021/acs.bioconjchem.5b00399
Antibody–drug conjugates have attracted a great amount of attention as a therapeutic strategy for diseases where targeting specific tissues and cells are critical components, such as in cancer therapy. Although promising, the number of approved ADC drugs is relatively limited. This emanates from the challenges associated with generating the conjugates and the complexities associated with the stability requirements for these conjugates during circulation and after reaching the target. Here, we provide a comprehensive overview of the design challenges facing the ADC field. These challenges also provide several unique research and development opportunities, which are also highlighted throughout the review.
Co-reporter:Judy Ventura, Scott J. Eron, Daniella C. González-Toro, Kishore Raghupathi, Feng Wang, Jeanne A. Hardy, and S. Thayumanavan
Biomacromolecules 2015 Volume 16(Issue 10) pp:
Publication Date(Web):September 2, 2015
DOI:10.1021/acs.biomac.5b00779
Conjugation of biologically active proteins to polymeric materials is of great interest in the treatment of cancer and other diseases of protein deficiency. The conjugation of such biomacromolecules is challenging both due to their hydrophilicity and propensity to denature under non-native conditions. We describe a novel reactive self-assembly approach to “wrap” a protein with polymers, simultaneously protecting its delicate folded state and silencing its enzymatic activity. This approach has been demonstrated using caspase-3, an apoptosis-inducing protein, as the first case study. The protein–polymer conjugation is designed to be reversed under the native conditions for caspase-3, that is, the reducing environment found in the cytosol. The current strategy allowed release and recovery of up to 86% of caspase activity and nanogel–caspase-3 conjugates induced 70–80% apoptotic cell death shortly thereafter. This approach is widely generalizable and should be applicable to the intracellular delivery of a wide range of therapeutic proteins for treatment of complex and genetic diseases.
Co-reporter:Ambata Poe;Andrea DellaPelle;Sean Byrnes ; S. Thayumanavan
Chemistry - A European Journal 2015 Volume 21( Issue 21) pp:7721-7725
Publication Date(Web):
DOI:10.1002/chem.201406625
Abstract
A series of ketocyanine derivatives possessing bis(diarylamino)fluorenyl donors and variable acceptors installed at the bridging carbon atom were synthesized to investigate how the electronic structure of the dye can be systemically tuned through stabilization of the cyanine-like character of the donor by increasing the acceptor strength. Analysis of the 1H NMR spectra indicates that the “charge-separated” species dominates in these dyes, given that carbons possessing a positive or negative charge in the resonance structures of this state purposefully shift downfield or upfield, respectively, depending on the strength of the acceptor moiety. In DAA-Fl-PI, the acceptor strength and the gain of acceptor aromaticity indicates a predisposition of the separated state, indicated by asymmetry in the 1H NMR spectrum, as well as uneven distribution of the HOMO on the fluorenyl donor.
Co-reporter:Priyaa Prasad, Mijanur Rahaman Molla, Wei Cui, Mine Canakci, Barbara Osborne, Jesse Mager, and S. Thayumanavan
Biomacromolecules 2015 Volume 16(Issue 11) pp:
Publication Date(Web):September 14, 2015
DOI:10.1021/acs.biomac.5b00900
Safe delivery systems that can not only encapsulate hydrophobic drug molecules, but also release them in response to specific triggers are important in several therapeutic and biomedical applications. In this paper, we have designed a nanogel based on molecules that are generally recognized as safe (GRAS). We have shown that the resultant polymeric nanogels exhibit responsive molecular release and also show high in vitro cellular viability on HEK 293T, HeLa, MCF 7, and A549 cell lines. The toxicity of these nanogels was further evaluated with a highly sensitive assay using mouse preimplantation embryo development, where blastocysts were formed after 4 days of in vitro culture, and live pups were born when morulae/early blastocysts were transferred to the uteri of surrogate recipients. Our results indicate that these nanogels are nontoxic during mammalian development and do not alter normal growth or early embryo success rate.
Co-reporter:Longyu Li;Dr. Conghui Yuan;Dongming Zhou;Dr. Alexer E. Ribbe; Kevin R. Kittilstved; S. Thayumanavan
Angewandte Chemie International Edition 2015 Volume 54( Issue 44) pp:12991-12995
Publication Date(Web):
DOI:10.1002/anie.201505242
Abstract
The use of reversible linkers in polymers has been of interest mainly for biomedical applications. Herein, we present a novel strategy to utilize reversible interactions in polymeric nanoparticles to generate hollow metal–organic nanoparticles (MOPs). These hollow MOPs are synthesized from self-assembled polymeric nanoparticles using a simple metal–comonomer exchange process in a single step. The control over the size of the polymer precursor particles translates into a straightforward opportunity for controlling MOP sizes. The shell thickness of the MOPs could be easily tuned by the concentration of metal ions in solution. The underlying mechanism for the formation of these hollow MOPs has been proposed. Evidence for the generality of the method is provided by its application to a variety of metal ions with different coordination geometries.
Co-reporter:Longyu Li;Dr. Conghui Yuan;Dongming Zhou;Dr. Alexer E. Ribbe; Kevin R. Kittilstved; S. Thayumanavan
Angewandte Chemie 2015 Volume 127( Issue 44) pp:13183-13187
Publication Date(Web):
DOI:10.1002/ange.201505242
Abstract
The use of reversible linkers in polymers has been of interest mainly for biomedical applications. Herein, we present a novel strategy to utilize reversible interactions in polymeric nanoparticles to generate hollow metal–organic nanoparticles (MOPs). These hollow MOPs are synthesized from self-assembled polymeric nanoparticles using a simple metal–comonomer exchange process in a single step. The control over the size of the polymer precursor particles translates into a straightforward opportunity for controlling MOP sizes. The shell thickness of the MOPs could be easily tuned by the concentration of metal ions in solution. The underlying mechanism for the formation of these hollow MOPs has been proposed. Evidence for the generality of the method is provided by its application to a variety of metal ions with different coordination geometries.
Co-reporter:Krishna R. Raghupathi, Jing Guo, Oyuntuya Munkhbat, Poornima Rangadurai, and S. Thayumanavan
Accounts of Chemical Research 2014 Volume 47(Issue 7) pp:2200-2211
Publication Date(Web):June 17, 2014
DOI:10.1021/ar500143u
Similarly, the propensity of these molecules to form inverse micelles in apolar solvents and thus bind polar guest molecules, combined with the fact that these assemblies do not thermodynamically equilibrate in biphasic mixtures, was used to predictably simplify peptide mixtures. The structure–property relationships developed from these studies have led to a selective and highly sensitive detection of peptides in complex mixtures. Selectivity in peptide extraction was achieved using charge complementarity between the peptides and the hydrophilic components present in inverse micellar interiors. These findings will have implications in areas such as proteomics and biomarker detection.
Co-reporter:Diego Amado Torres ; Matteo Garzoni ; Ayyagari V. Subrahmanyam ; Giovanni M. Pavan
Journal of the American Chemical Society 2014 Volume 136(Issue 14) pp:5385-5399
Publication Date(Web):March 18, 2014
DOI:10.1021/ja500634u
We use monodisperse dendrons that allow control over functional group presentation to investigate the influence of the location of a ligand on protein-induced disassembly and release of encapsulated small molecules. Based on both experiments and molecular dynamics simulations, we demonstrate that ligand location greatly influences release of guest molecules from the dendron-based supramolecular assembly. We show that a ligand moiety grafted to the dendron periphery is more accessible for the target protein in aqueous solution. On the other hand, the ligand moiety placed at the focal point or at the intermediate layer within the dendritic scaffold is less accessible, since it is surrounded by an environment rich in PEG chains, which hinders binding and even influences nonspecific interactions. We also demonstrate that the specific binding between one ligand and the target protein can destabilize the dendritic assembly. Furthermore, if more ligands are available, multivalent interactions are also possible with extravidin, which speed up disassembly and trigger the release of hydrophobic guests.
Co-reporter:Jing Guo ; Jiaming Zhuang ; Feng Wang ; Krishna R. Raghupathi
Journal of the American Chemical Society 2014 Volume 136(Issue 6) pp:2220-2223
Publication Date(Web):January 21, 2014
DOI:10.1021/ja4108676
An amphiphilic nanoassembly was designed to respond to the concurrent presence of a protein and an enzyme. We present herein a system, where in the presence of these two stimuli supramolecular disassembly and molecular release occur. This molecular release arises in the form a fluorescence response that has been shown to be specific. We also show that this system can be modified to respond only if light stimulus is also present in addition to the protein and the enzyme. Demonstration of such supramolecular disassembly principles could have broad implications in a variety of biological applications.
Co-reporter:Conghui Yuan, Kishore Raghupathi, Bhooshan C. Popere, Judy Ventura, Lizong Dai and S. Thayumanavan
Chemical Science 2014 vol. 5(Issue 1) pp:229-234
Publication Date(Web):26 Sep 2013
DOI:10.1039/C3SC52347K
Nanoscale assemblies with stimuli-sensitive features have attracted significant attention due to implications in a variety of areas ranging from materials to biology. Recently, there have been excellent developments in obtaining nanoscale structures that are concurrently sensitive to multiple stimuli. Such nanostructures are primarily focused on a single nanostructure containing an appropriate combination of functional groups within the nanostructure. In this work, we outline a simple approach to bring together two disparate supramolecular assemblies that exhibit very different stimuli-sensitive characteristics. These composite nanostructures comprise a block copolymer micelle core and nanogel shell, both of which can preserve their respective morphology and stimulus sensitivities. The block copolymer is based on poly(2-(diisopropylamino)ethylmethacrylate-b-2-aminoethylmethacrylate hydrochloride), which contains a pH-sensitive hydrophobic block. Similarly, the redox-sensitive nanogel is derived from a poly(oligoethyleneglycolmonomethylethermethacrylate-co-glycidylmethacrylate-co-pyridyldisulfide ethylmethacrylate) based random copolymer. In addition to the independent pH-response of the micellar core and redox-sensitivity of the nanogel shell in the composite nanostructures, the synergy between the micelles and the nanogels have been demonstrated through a robust charge generation in the nanogels during the disassembly of the micelles. The supramolecular assembly and disassembly have been characterized using transmission electron microscopy, dynamic light scattering, zeta potential measurements, fluorescence spectroscopy and cellular uptake.
Co-reporter:Longyu Li, Kishore Raghupathi, Cunfeng Song, Priyaa Prasad and S. Thayumanavan
Chemical Communications 2014 vol. 50(Issue 88) pp:13417-13432
Publication Date(Web):04 Jul 2014
DOI:10.1039/C4CC03688C
Self-assembly of random copolymers has attracted considerable attention recently. In this feature article, we highlight the use of random copolymers to prepare nanostructures with different morphologies and to prepare nanomaterials that are responsive to single or multiple stimuli. The synthesis of single-chain nanoparticles from random copolymers and their potential applications are also discussed in some detail. We aim to draw more attention to these easily accessible copolymers, which are likely to play an important role in translational polymer research.
Co-reporter:Ambata M. Poe, Andrea M. Della Pelle, Ayyagari V. Subrahmanyam, William White, Guillaume Wantz and S. Thayumanavan
Chemical Communications 2014 vol. 50(Issue 22) pp:2913-2915
Publication Date(Web):22 Jan 2014
DOI:10.1039/C3CC49648A
A series of acceptor–donor–acceptor molecules containing terminal BODIPY moieties conjugated through the meso position were synthesized. Deep LUMO energy levels and good visible absorption led to their use as acceptors in bulk heterojunction solar cells. Inverted devices were fabricated, reaching efficiencies as high as 1.51%.
Co-reporter:Akshay Kokil, Ambata M. Poe, Youngju Bae, Andrea M. Della Pelle, Paul J. Homnick, Paul M. Lahti, Jayant Kumar, and S. Thayumanavan
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 13) pp:9920
Publication Date(Web):June 19, 2014
DOI:10.1021/am5021759
Polymer solar cells fabricated in air under ambient conditions are of significant current interest, because of the implications in practicality of such devices. However, only moderate performance has been obtained for the air-processed devices. Here, we report that enhanced short circuit current density (JSC) and open circuit voltage (VOC) in air-processed poly(3-hexylthiophene) (P3HT)-based solar cells can be obtained by using a series of donor–acceptor dyes as the third component in the device. Power conversion efficiencies up to 4.6% were obtained upon addition of the dyes which are comparable to high-performance P3HT solar cells fabricated in controlled environments. Multilayer planar solar cells containing interlayers of the donor–acceptor dyes, revealed that along with infrared sensitization, an energy level cascade architecture and Förster resonance energy transfer could contribute to the enhanced performance.Keywords: bulk heterojunction solar cells; donor−acceptor dyes; planar multilayer solar cells; polymer solar cells
Co-reporter:Supravat Karak, Paul J. Homnick, Andrea M. Della Pelle, Youngju Bae, Volodimyr V. Duzhko, Feng Liu, Thomas P. Russell, Paul M. Lahti, and S. Thayumanavan
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 14) pp:11376
Publication Date(Web):July 14, 2014
DOI:10.1021/am501965d
2,4-Bis[4′-(N,N-di(4″-hydroxyphenyl)amino)-2′,6′-dihydroxyphenyl]squaraine (Sq-TAA-OH, optical bandgap 1.4 eV, HOMO level −5.3 eV by ultraviolet photoelectron spectroscopy) is used as an active layer material in solution processed, bulk-heterojunction organic photovoltaic cells with configuration ITO/PEDOT:PSS/Sq-TAA-OH:PC71BM/LiF/Al. Power conversion efficiencies (PCEs) up to 4.8% are obtained by a well-reproducible procedure using a mixture of good and poor Sq-TAA-OH solubilizing organic solvents, with diiodooctane (DIO) additive to make a bulk heterojunction layer, followed by thermal annealing, to give optimized VOC = 0.84–0.86 V, JSC = 10 mA cm–2, and FF = 0.53. X-ray diffraction and scattering studies of pristine, pure Sq-TAA-OH solution-cast films show d-spacing features similar to single-crystal packing and spacing. The DIO additive in a good solvent/poor solvent mixture apparently broadens the size distribution of Sq-TAA-OH crystallites in pristine films, but thermal annealing provides a narrower size distribution. Direct X-ray diffraction and scattering morphological studies of “as-fabricated” active layers show improved Sq-TAA-OH/PC71BM phase separation and formation of crystallites, ∼48 nm in size, under conditions that give the best PCE.Keywords: molecule-based solar cells; N,N-diarylanilinosquaraines; organic bulk heterojunctions; solution-processed photovoltaic devices; squaraines; triarylamines
Co-reporter:Jiaming Zhuang, Reuben Chacko, Diego F. Amado Torres, Hui Wang, and S. Thayumanavan
ACS Macro Letters 2014 Volume 3(Issue 1) pp:1
Publication Date(Web):December 9, 2013
DOI:10.1021/mz400515s
A dual stimuli responsive nanogel–polyelectrolyte complex based on electrostatic coating has been developed. The nanoassembly is designed to elicit two disparate responses (viz., surface property change and guest encapsulation stability) from two different stimuli (viz., pH and redox variations). The components of the nanogel and the polyelectrolyte have been conveniently achieved from a simple homopolymer, poly(pentafluorophenylacrylate).
Co-reporter:Kishore Raghupathi, Longyu Li, Judy Ventura, Matthew Jennings and S. Thayumanavan
Polymer Chemistry 2014 vol. 5(Issue 5) pp:1737-1742
Publication Date(Web):18 Oct 2013
DOI:10.1039/C3PY01277H
Size and surface properties of a drug delivery vehicle play a very crucial role in determining its biological fate. The success of nanotherapeutic systems depends on several features such as deeper tumor tissue penetration, good retention and rapid cellular uptake. These properties are strongly influenced by the size and surface properties of the delivery vehicles. In this study, we demonstrate a polymeric nanoparticle that exhibits the size and surface charge variation features in response to slight changes in pH, which are biologically relevant (pH 7.4 to 6.5). These features have been demonstrated using a pH sensitive interparticle crosslinking by dynamic covalent imine bond formation between nanogels. The pH sensitive interparticle crosslinking is demonstrated using DLS, TEM, SEC, fluorescamine assay and cell uptake study.
Co-reporter:Sompit Wanwong, Ambata Poe, Ganapathy Balaji and S. Thayumanavan
Organic & Biomolecular Chemistry 2014 vol. 12(Issue 15) pp:2474-2478
Publication Date(Web):13 Feb 2014
DOI:10.1039/C3OB41648H
Cyclopentadithiophene (CPDT) derivatives with different heteroatom conformations have been synthesized. The optical, electrochemical and charge transport properties of these molecules are reported. The CPDT-anti-ketone not only exhibits the lowest optical and electronic bandgaps, but also exhibits reasonable hole mobility, 3 × 10−3 cm2 (V s)−1. Changing the carbonyl conformation to the syn position or incorporating the imine functionality results in a blue-shift in the lower energy band of the absorption spectrum indicative of the increased bandgaps.
Co-reporter:Andrea M. Della Pelle ; Paul J. Homnick ; Youngju Bae ; Paul M. Lahti
The Journal of Physical Chemistry C 2014 Volume 118(Issue 4) pp:1793-1799
Publication Date(Web):January 3, 2014
DOI:10.1021/jp410362d
A series of squaraine dyes was synthesized with electron-donating (OH, C6H13) and electron-withdrawing (F, CF3) groups allowing for tuning of the optical and electrochemical properties of the dyes. The squaraines exhibited strong absorbance (ε = 104–105 M–1 cm–1) at long wavelengths (λmax = 660–690 nm), attributed to an intramolecular charge transfer (ICT). As the electron-donating character of the dyes increases, the absorbance of the dyes red shifts and the band gap decreases. Interestingly, the ICT band seemed to be strongly dependent on the nature of the solvent, providing insights into the importance of hydrogen-bonding-induced coplanarity in these molecules. The squaraines were investigated for their charge-carrier mobility in FET configuration. Dyes with fluorine functional groups were found to exhibit either ambipolar (−F) or n-type (−CF3) charge-carrier characteristics, although the molecules themselves are made of traditionally p-type triarylamines.
Co-reporter:Mijanur Rahaman Molla, Tyler Marcinko, Priyaa Prasad, Derrick Deming, Scott C. Garman, and S. Thayumanavan
Biomacromolecules 2014 Volume 15(Issue 11) pp:
Publication Date(Web):October 7, 2014
DOI:10.1021/bm501091p
A polymeric nanogel has been used to sequester and turn off a lysosomal protein, acid α-glucosidase (GAA). The nanogel contains a β-thiopropionate cross-linker, which endows the nanogel with pH-sensitivity. While encapsulation of the enzyme fully turns off its activity, approximately 75% of the activity is recovered upon reducing the pH to 5.0. The recovered activity is ascribed to pH-induced degradation of the β-thiopropionate cross-linker causing the swelling of the nanogel and ultimately causing the release of the enzyme. We envision that strategies for sequestering protein molecules and releasing them at lysosomal pH might open up new directions for therapeutic treatment of lysosomal storage diseases.
Co-reporter:Longyu Li and S. Thayumanavan
Langmuir 2014 Volume 30(Issue 41) pp:12384-12390
Publication Date(Web):2017-2-22
DOI:10.1021/la502760c
Dynamic exchange of guest molecules, encapsulated in host assemblies, is a phenomenon in supramolecular chemistry that has important implications in several applications. While the mechanism of exchange in micellar assemblies has been previously investigated, the effect of host and guest environment upon the guest-exchange dynamics has received little attention, if any. In this paper, we study the guest-exchange mechanism in pH-sensitive nanogels along with pH-insensitive nanogels as a control. By systematically comparing the behavior of these nanogels, we show that size, concentration, and hydrophobicity can all play a critical role in guest-exchange dynamics. More importantly, these studies reveal that the dominant mechanism of guest exchange can intimately depend on environmental factors.
Co-reporter:Longyu Li, Conghui Yuan, Lizong Dai, and S. Thayumanavan
Macromolecules 2014 Volume 47(Issue 17) pp:5869-5876
Publication Date(Web):August 21, 2014
DOI:10.1021/ma5015808
Cooperative polymerization, aided by the nucleation–elongation mechanism, has the promise of providing polymers and nanostructures that are otherwise inaccessible. The molecular origin of the cooperative growth of polymers is driven by a secondary interaction, often based on polarization, electrostatics, or sterics-driven secondary structure. Here, we demonstrate that covalent dative interactions can be used to achieve cooperative polymerization. Our results suggest that the initial polymer formation serves as the nucleus for monodisperse nanoparticle assembly. The dynamic nature of the dative interaction in this equilibrium self-assembly has been shown to endow these nanoparticles with thermal responsive characteristics.
Co-reporter:Jiaming Zhuang, Mallory R. Gordon, Judy Ventura, Longyu Li and S. Thayumanavan
Chemical Society Reviews 2013 vol. 42(Issue 17) pp:7421-7435
Publication Date(Web):13 Jun 2013
DOI:10.1039/C3CS60094G
In this review, we outline examples that illustrate the design criteria for achieving macromolecular assemblies that incorporate a combination of two or more chemical, physical or biological stimuli-responsive components. Progress in both fundamental investigation into the phase transformations of these polymers in response to multiple stimuli and their utilization in a variety of practical applications are highlighted. Using these examples, we aim to explain the origin of employed mechanisms of stimuli responsiveness which may serve as a guideline to inspire future design of multi-stimuli responsive materials.
Co-reporter:Jack M. Fuller ; Krishna R. Raghupathi ; Rajasekhar R. Ramireddy ; Ayyagari V. Subrahmanyam ; Volkan Yesilyurt
Journal of the American Chemical Society 2013 Volume 135(Issue 24) pp:8947-8954
Publication Date(Web):May 21, 2013
DOI:10.1021/ja402019c
Oligo(ethylene glycol)-decorated supramolecular assemblies have been of great interest due to their charge-neutral character and thus their propensity to avoid nonspecific interactions. These systems are known to exhibit a macroscopic temperature-sensitive transition, where the assembly phase-separates from the aqueous phase at higher temperatures. While this so-called lower critical solution temperature (LCST) behavior has been well-studied, there have been no studies on the fate of these supramolecular assemblies below this transition temperature. The work here brings to light the presence of a second, sub-LCST transition, observed well below the LCST of oligo(ethylene glycol) (OEG)-based dendrons, where the host–guest properties of the assembly are significantly altered. This sub-LCST transition is accompanied by changes in the guest encapsulation stability and dynamics of host exchange.
Co-reporter:Feng Wang ; Andrea Gomez-Escudero ; Rajasekhar R. Ramireddy ; Gladys Murage ; S. Thayumanavan ;Richard W. Vachet
Journal of the American Chemical Society 2013 Volume 135(Issue 38) pp:14179-14188
Publication Date(Web):August 23, 2013
DOI:10.1021/ja404940s
Supramolecular assemblies formed by amphiphilic homopolymers with negatively charged groups in the hydrophilic segment have been designed to enable high labeling selectivity toward reactive side chain functional groups in peptides. The negatively charged interiors of the supramolecular assemblies are found to block the reactivity of protonated amines that would otherwise be reactive in aqueous solution, while maintaining the reactivity of nonprotonated amines. Simple changes to the pH of the assemblies’ interiors allow control over the reactivity of different functional groups in a manner that is dependent on the pKa of a given peptide functional group. The labeling studies carried out in positively charged supramolecular assemblies and free buffer solution show that, even when the amine is protonated, labeling selectivity exists only when complementary electrostatic interactions are present, thereby demonstrating the electrostatically controlled nature of these reactions.
Co-reporter:Longyu Li, Kishore Raghupathi, Conghui Yuan and S. Thayumanavan
Chemical Science 2013 vol. 4(Issue 9) pp:3654-3660
Publication Date(Web):10 Jul 2013
DOI:10.1039/C3SC50899D
Nanocarriers that can be effectively transported across cellular membranes have potential in a variety of biomedical applications. Among these, materials that are capable of changing their surface properties and thus gain entry into a cell, in response to a specific tissue environment, are of particular interest. In this manuscript we report a facile route to prepare nanogels, which generate surface charge with pH as stimulus. This is achieved by designing a polymeric nanogel containing 2-diisopropylamino (DPA) moieties. The choice of DPA nanogel is based on its pKb, which causes this functional group to be rapidly protonated upon change in pH. It is noteworthy that the pH change at which the surface charge is generated in the nanogel corresponds to the slightly acidic conditions observed in the extracellular environment of solid tumor. We show that the pH at which the charge is generated, i.e. the isoelectric point (pI) of the nanogel, can be adjusted by varying the percentage of DPA units in the nanogel, its preparation process and crosslinking density. Intracellular delivery of these nanogels was greatly enhanced in an acidic pH environment due to the surface charge generation. This study demonstrates the versatile nature of the nanogels to introduce specific functionalities with relative ease to achieve desired functional behavior.
Co-reporter:Hui Wang, Jiaming Zhuang, and S. Thayumanavan
ACS Macro Letters 2013 Volume 2(Issue 10) pp:948
Publication Date(Web):October 7, 2013
DOI:10.1021/mz4004248
Surface functionalization of nanoparticles and host–guest properties of nanoassemblies are two critical features in the utilization of nanostructures in a variety of applications in materials, chemical, and biological nanotechnology. However, simultaneously incorporating these two features in one nanoparticle design is a rather challenging task. We have developed a simple and versatile nanoparticle platform that addresses this challenge. We have designed and characterized a polymer nanoparticle that provides the ability to encapsulate hydrophobic guest molecules and surface functionalization with a wide range of functional groups. In addition, we have also demonstrated a new and simple approach to tune the size of the nanoparticles.
Co-reporter:Nicholas M. Matsumoto, Daniella C. González-Toro, Reuben T. Chacko, Heather D. Maynard and S. Thayumanavan
Polymer Chemistry 2013 vol. 4(Issue 8) pp:2464-2469
Publication Date(Web):27 Feb 2013
DOI:10.1039/C3PY00085K
The covalent conjugation of bovine serum albumin (BSA) to disulfide cross-linked polymeric nanogels is reported. Polymeric nanogel precursors were synthesized via a reversible addition-fragmentation chain transfer (RAFT) random copolymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA) and pyridyl disulfide methacrylate (PDSMA). Reaction of the p(PEGMA-co-PDSMA) with dithiothreitol resulted in the formation of nanogels. PDSMA serves as both a crosslinking agent and a reactive handle for the surface modification of the nanogels. Lipophilic dye, DiI, was sequestered within the nanogels by performing the crosslinking reaction in the presence of the hydrophobic molecule. Thiol-enriched BSA was conjugated to nanogels loaded with DiI via a thiol-disulfide exchange reaction between the BSA and the surface exposed nanogel pyridyl disulfides. Conjugation was confirmed by fast protein liquid chromatography, dynamic light scattering, and agarose and polyacrylamide gel electrophoresis. We expect that this methodology is generally applicable to the preparation of nanogel–protein therapeutics.
Co-reporter:Daniella C. González-Toro, S. Thayumanavan
European Polymer Journal 2013 Volume 49(Issue 10) pp:2906-2918
Publication Date(Web):October 2013
DOI:10.1016/j.eurpolymj.2013.05.002
•The review highlights recent advances in protein–polymer conjugation.•The review presents different models for covalent conjugation of proteins with linear polymers.•The review examines advances in the development of protein conjugates using nanostructures.•The review also examines the potential future work in the polymer–protein bioconjugation field.Linear polymers have been considered the best molecular structures for the formation of efficient protein conjugates due to their biological advantages, synthetic convenience and ease of functionalization. In recent years, much attention has been dedicated to develop synthetic strategies that produce the most control over protein conjugation utilizing linear polymers as scaffolds. As a result, different conjugate models, such as semitelechelic, homotelechelic, heterotelechelic and branched or star polymer conjugates, have been obtained that take advantage of these well-controlled synthetic strategies. Development of protein conjugates using nanostructures and the formation of said nanostructures from protein–polymer bioconjugates are other areas in the protein bioconjugation field. Although several polymer–protein technologies have been developed from these discoveries, few review articles have focused on the design and function of these polymers and nanostructures. This review will highlight some recent advances in protein-linear polymer technologies that employ protein covalent conjugation and successful protein-nanostructure bioconjugates (covalent conjugation as well) that have shown great potential for biological applications.Graphical abstract
Co-reporter:Longyu Li, Ja-Hyoung Ryu, and S. Thayumanavan
Langmuir 2013 Volume 29(Issue 1) pp:50-55
Publication Date(Web):December 3, 2012
DOI:10.1021/la3033463
Influence of Hofmeister ions has been investigated on the size and guest encapsulation stability of a polymeric nanogel. While variations in macroscopic phase transitions have been observed in response to the presence of salts, changes in the size and host–guest behavior of polymeric aggregates in the presence of salts have not been explored in any detail. We find that the size and core density of nanogel, which was prepared by self-crosslinking from a random copolymer that contains oligo(ethylene glycol) (OEG) and pyridyl disulfide (PDS) units as side-chain functionalities, can be fine-tuned through the addition of both chaotropes and kosmotropes during nanogel formation. We also demonstrate that the change in core density affects the guest encapsulation stability and stimuli-responsive character of the nanogel.
Co-reporter:Rajasekhar R. Ramireddy;Dr. Ayyagari V. Subrahmanyam; S. Thayumanavan
Chemistry - A European Journal 2013 Volume 19( Issue 48) pp:16374-16381
Publication Date(Web):
DOI:10.1002/chem.201302442
Abstract
Supramolecular nano-assemblies that reduce nonspecific interactions with biological macromolecules, such as proteins, are of great importance for various biological applications. Recently, zwitterionic materials have been shown to reduce nonspecific interactions with biomolecules, owing both to their charge neutrality and their ability to form a strong hydration layer around zwitterions via electrostatic interactions. Here, new triazole-based zwitterionic moieties are presented that are incorporated as the hydrophilic functionalities in facially amphiphilic dendrons. The amphiphilic zwitterionic dendrons spontaneously self-assemble in aqueous solutions forming micelle-type aggregates, which were confirmed by DLS, TEM, and fluorescence techniques. The structural and functional characteristics of the zwitterionic dendrons are also compared with the corresponding charge-neutral PEG-based dendrons and anionic carboxylate-based dendrons. Surface-charge measurements, temperature sensitivity and evaluation of interactions of these assemblies with proteins form the bases for these comparisons.
Co-reporter:Daniella C. González-Toro ; Ja-Hyoung Ryu ; Reuben T. Chacko ; Jiaming Zhuang
Journal of the American Chemical Society 2012 Volume 134(Issue 16) pp:6964-6967
Publication Date(Web):April 5, 2012
DOI:10.1021/ja3019143
Supramolecular nanoassemblies, which are capable of binding and delivering either lipophilic small molecules or hydrophilic molecules, are of great interest. Concurrently binding and delivering this combination of molecules is cumbersome, because of the opposing supramolecular host requirements. We describe the development of a versatile nanoassembly system that is capable of binding and delivering both, a protein and a lipophilic small molecule, simultaneously inside the cells.
Co-reporter:Diego Amado Torres ; Malar A. Azagarsamy
Journal of the American Chemical Society 2012 Volume 134(Issue 17) pp:7235-7237
Publication Date(Web):April 13, 2012
DOI:10.1021/ja301204z
We report a new approach for the rapid screening of analyte binding affinities for a target protein. We demonstrate that a molecular probe, with a pro-fluorophore substrate and ligand moieties, can be hindered from enzymatic access when bound to the target protein. When analytes displace the probe from the protein’s binding pocket, a fluorescence profile is generated. This profile is used to discriminate analytes based on their relative binding affinities.
Co-reporter:Bhooshan C. Popere, Andrea M. Della Pelle, Ambata Poe, Ganapathy Balaji and S. Thayumanavan
Chemical Science 2012 vol. 3(Issue 10) pp:3093-3102
Publication Date(Web):13 Jul 2012
DOI:10.1039/C2SC20731A
Here we report the synthesis, electrochemical properties, and optical properties of five novel π-conjugated alternating copolymers based on the BODIPY core. These polymers were synthesized via the Sonogashira polymerization reaction and contain BODIPY units alternating with comonomers such as 9,9-bis(2-ethylhexyl)-9H-fluorene (FL), 9-(2-ethylhexyl)-9H-carbazole (CBz), 2,2′-bithiophene (BT), 4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b:3,4-b']dithiophene (CPDT) and 4-(2-ethylhexyl)-4H-dithieno[3,2-b:2',3'-d]pyrrole (DTP). These comonomers were rationally chosen based on their gas phase ionization potential (IP) values estimated by density functional theory (DFT) calculations. Cyclic voltammetry on drop-cast thin films, as well as solutions of these polymers, revealed that the highest occupied molecular orbitals (HOMOs) of the resulting polymers correlated well with the ionization potentials (donor strength) of the comonomers. On the contrary, the lowest unoccupied molecular orbital (LUMO) energy levels of all copolymers were fairly invariant, independent of the comonomer used. This suggests that the BODIPY moiety provides the primary influence on the LUMO levels of the polymer. In addition to the experimentally determined HOMO/LUMO energy levels bearing good correlation with theoretical estimates, all polymers were found to possess broad absorption spectra covering the entire visible range, thus making them truly panchromatic. These polymers provide us with a toolset to tune the frontier molecular orbital energy levels, while retaining the low band gap and broad absorption of these polymers.
Co-reporter:Jiaming Zhuang, Siriporn Jiwpanich, V. D. Deepak, and S. Thayumanavan
ACS Macro Letters 2012 Volume 1(Issue 1) pp:175
Publication Date(Web):December 13, 2011
DOI:10.1021/mz200123f
A facile methodology to prepare water-dispersible nanogels based on pentafluorophenyl acrylate and polyethylene glycol methacrylate random copolymer and diamine cross-linkers has been developed. The cross-linking reaction was characterized by FTIR and 19F NMR. We show that those nanogels are (i) water-dispersible; (ii) can conveniently encapsulate lipophilic guest molecules; (iii) can be prepared with different nanosizes; and (iv) are engineered to allow for surface decoration with additional functional groups.
Co-reporter:Sean Bickerton, Siriporn Jiwpanich, and S. Thayumanavan
Molecular Pharmaceutics 2012 Volume 9(Issue 12) pp:3569-3578
Publication Date(Web):October 22, 2012
DOI:10.1021/mp3004226
Polymer-based nanoassemblies have emerged as viable platforms for the encapsulation and delivery of lipophilic molecules. Among the criteria that such carriers must meet, if they are to be effective, are the abilities to efficiently solubilize lipophilic guests within an assembled scaffold and to stably encapsulate the molecular cargo until desired release is achieved through the actions of appropriately chosen stimuli. The former feature, dictated by the inherent loading capacity of a nanocarrier, is well studied, and it has been established that slight variations in assembly structure, such as introducing hydrophobic content, can improve miscibility with the lipophilic guests and increase the driving force for encapsulation. However, such clear correlations between assembly properties and the latter feature, nanocarrier encapsulation stability, are not yet established. For this purpose, we have investigated the effects of varying hydrophobic content on the loading parameters and encapsulation stabilities of self-cross-linked polymer nanogels. Through investigating this nanogel series, we have observed a fundamental relationship between nanoassembly structure, loading capacity, and encapsulation stability. Furthermore, a combined analysis of data from different loading amounts suggests a model of loading-dependent encapsulation stability that underscores an important correlation between the principal features of noncovalent encapsulation in supramolecular hosts.Keywords: encapsulation stability; fluorescence resonance energy transfer; hydrophobicity; loading capacity; polymeric nanogel;
Co-reporter:Bhooshan C. Popere, Andrea M. Della Pelle, Ambata Poe and S. Thayumanavan
Physical Chemistry Chemical Physics 2012 vol. 14(Issue 12) pp:4043-4057
Publication Date(Web):11 Jan 2012
DOI:10.1039/C2CP23422J
Research in the field of organic photovoltaics has gained considerable momentum in the last two decades owing to the need for developing low-cost and efficient energy harvesting systems. Elegant molecular architectures have been designed, synthesized and employed as active materials for photovoltaic devices thereby leading to a better molecular structure–device property relationship understanding. In this perspective, we outline new macromolecular scaffolds that have been designed within the purview of each of the three fundamental processes involving light harvesting, charge separation and charge transport.
Co-reporter:Ganapathy Balaji, Andrea M. Della Pelle, Bhooshan C. Popere, A. Chandrasekaran and S. Thayumanavan
Organic & Biomolecular Chemistry 2012 vol. 10(Issue 17) pp:3455-3462
Publication Date(Web):24 Feb 2012
DOI:10.1039/C2OB25087J
We report the syntheses and properties of thienopyrrole based unsymmetrical and extended heteroacenes, which are isoelectronic with heptacene (30π) and nonacene (38π), respectively. Optical and electrochemical properties of these seven and nine rings fused systems are studied. The optoelectronic properties of the syn and anti-isomers of the unsymmetrical heteroacenes are also compared. The influence of the position of the heteroatoms in the fused corona, upon the optical and electrochemical properties, is rationalized based on the contributions from the benzenoid vs. quinonoid-type structures of these molecules.
Co-reporter:Rajasekhar R. Ramireddy, Krishna R. Raghupathi, Diego Amado Torres and S. Thayumanavan
New Journal of Chemistry 2012 vol. 36(Issue 2) pp:340-349
Publication Date(Web):16 Jan 2012
DOI:10.1039/C2NJ20879B
In the past decade, there has been an increasing interest in supramolecular systems that can undergo physical or chemical transformations upon encountering a specific stimulus. Micelle-forming amphiphilic systems based on polymers and dendrimers are particularly preferred over small molecule amphiphiles, due to their ability to sequester and release a vast library of hydrophobic guest molecules at micromolar polymer or dendrimer concentrations. Here we review a relatively underexplored, yet rapidly advancing, field of amphiphilic systems based on a dendritic architecture that exhibit stimuli sensitive behaviour. In particular, we will be focusing on stimuli such as temperature, pH, enzymatic and non-enzymatic proteins. These stimuli-responsive systems offer a unique opportunity in the field of drug delivery and sensing.
Co-reporter:Volkan Yesilyurt;Rajasekharreddy Ramireddy;Malar A. Azagarsamy ; S. Thayumanavan
Chemistry - A European Journal 2012 Volume 18( Issue 1) pp:223-229
Publication Date(Web):
DOI:10.1002/chem.201102727
Abstract
Supramolecular nanoassemblies that respond to the presence of proteins are of great interest, as aberrations in protein concentrations represent the primary imbalances found in a diseased state. We present here a molecular design, syntheses, and study of facially amphiphilic dendrimers that respond to the presence of the protein, immunoglobulin G. It is of particular interest that the ligand functionality, utilized for causing the binding-induced disassembly, be lipophilic. Demonstration of binding with lipophilic ligands greatly expands the repertoire of binding-induced disassembly, since this covers a rather large class of ligand moieties designed for proteins and these provide specific insights into the mechanistic pathways that are available for the binding-induced disassembly process. Here, we describe the details of the binding induced disassembly, including the change in size of the assembly in response to proteins, concurrent release of noncovalently encapsulated guest molecules, and the specificity of the disassembly process.
Co-reporter:Ja-Hyoung Ryu, Sean Bickerton, Jiaming Zhuang, and S. Thayumanavan
Biomacromolecules 2012 Volume 13(Issue 5) pp:
Publication Date(Web):March 29, 2012
DOI:10.1021/bm300201x
Nanoscale vehicles for delivery have been of interest and extensively studied for two decades. However, the encapsulation stability of hydrophobic drug molecules in delivery vehicles and selective targeting these vehicles into disease cells are potential hurdles for efficient delivery systems. Here we demonstrate a simple and fast synthetic protocol of nanogels that shows high encapsulation stabilities. These nanogels can also be modified with various targeting ligands for active targeting. We show that the targeting nanogels (T-NGs), which are prepared within 2 h by a one-pot synthesis, exhibit very narrow size distributions and have the versatility of surface modification with cysteine-modified ligands including folic acid, cyclic arginine-glycine-aspartic acid (cRGD) peptide, and cell-penetrating peptide. T-NGs hold their payloads, undergo facilitated cell internalization by receptor-mediated uptake, and release their drug content inside cells due to the reducing intracellular environment. Selective cytotoxicity to cells, which have complementary receptors, is also demonstrated.
Co-reporter:Chikkannagari Nagamani;Jing Guo
Journal of Polymer Science Part A: Polymer Chemistry 2012 Volume 50( Issue 6) pp:1187-1196
Publication Date(Web):
DOI:10.1002/pola.25880
Abstract
Biaryl hydroxy polymers with orthogonal disposition of proton transporting OH moieties have been synthesized via conventional free radical polymerization. The polymers are characterized for their thermal stability and proton conductivity, and the results are compared with the corresponding styrenic hydroxy polymers. The orthogonal disposition of OH moieties in biaryl polymers does result in lower Ea for proton transport. However, the lower Ea values in biaryl polymers did not translate into a net increase in proton conductivity. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Co-reporter:Feng Wang ; Akamol Klaikherd
Journal of the American Chemical Society 2011 Volume 133(Issue 34) pp:13496-13503
Publication Date(Web):July 8, 2011
DOI:10.1021/ja204121a
A series of oligomers, containing oligo(ethylene glycol) (OEG) moieties, with the same composition of amphiphilic functionalities has been designed, synthesized, and characterized on the basis of their temperature-sensitive behavior. The non-covalent amphiphilic aggregates, formed from these molecules, influence their temperature sensitivity. Covalent tethering of the amphiphilic units also has a significant influence on their temperature sensitivity. The lower critical solution temperatures of these oligomers show increasingly sharp transitions with increasing numbers of OEG functional groups, indicating enhanced cooperativity in dehydration of the OEG moieties when they are covalently tethered. These molecules were also engineered to be concurrently sensitive to enzymatic reaction and pH. This possibility was investigated using porcine liver esterase as the enzyme; we show that enzymatic action on the pentamer lowers its temperature sensitivity. The product moiety from the enzymatic reaction also gives the amphiphilic oligomer a pH-dependent temperature sensitivity.
Co-reporter:Chikkannagari Nagamani, Usha Viswanathan, Craig Versek, Mark T. Tuominen, Scott M. Auerbach and S. Thayumanavan
Chemical Communications 2011 vol. 47(Issue 23) pp:6638-6640
Publication Date(Web):06 May 2011
DOI:10.1039/C1CC11207D
The dynamic nature of hydrogen bonds in phenolic polymers, where the hydrogen bond donor/acceptor reorientation can occur in a single site, presents lower barriers for proton transport.
Co-reporter:Ganapathy Balaji, Tejaswini S. Kale, Ashok Keerthi, Andrea M. Della Pelle, S. Thayumanavan, and Suresh Valiyaveettil
Organic Letters 2011 Volume 13(Issue 1) pp:18-21
Publication Date(Web):November 30, 2010
DOI:10.1021/ol1023486
Perylenediimide−pentathiophene systems with varied architecture of thiophene units were synthesized. The photophysical, electrochemical, and charge transport behavior of the synthesized compounds were studied. Both molecules showed a low band gap of ∼1.4 eV. Surprisingly, the molecule with pentathiophene attached via β-position to the PDI unit upon annealing showed a predominant hole mobility of 1 × 10−4 cm2 V−1 s−1 whereas the compound with branched pentathiophene attached via β-position showed an electron mobility of 9.8 × 10−7 cm2 V−1 s−1. This suggests that charge transport properties can be tuned by simply varying the architecture of pentathiophene units.
Co-reporter:Krishna R. Raghupathi;Dr. Malar A. Azagarsamy ; S. Thayumanavan
Chemistry - A European Journal 2011 Volume 17( Issue 42) pp:11752-11760
Publication Date(Web):
DOI:10.1002/chem.201101066
Abstract
Stimuli sensitive, facially amphiphilic dendrimers have been synthesized and their enzyme-responsive nature has been determined with dual fluorescence responses of both covalently conjugated and non-covalently bound reporter units. These dual responses are correlated to ascertain the effect of enzymatic action on micellar aggregates and the consequential guest release. The release of the guest molecule is conveniently tuned by stabilizing the micellar aggregates through photochemical crosslinking of hydrophobic coumarin units. This photo-crosslinking is also utilized as a tool to investigate the mode of enzyme–substrate interaction in the context of aggregate–monomer equilibrium.
Co-reporter:Volkan Yesilyurt;Rajasekharreddy Ramireddy ; S. Thayumanavan
Angewandte Chemie International Edition 2011 Volume 50( Issue 13) pp:3038-3042
Publication Date(Web):
DOI:10.1002/anie.201006193
Co-reporter:Bhooshan C. Popere, Andrea M. Della Pelle, and S. Thayumanavan
Macromolecules 2011 Volume 44(Issue 12) pp:4767-4776
Publication Date(Web):May 19, 2011
DOI:10.1021/ma200839q
Four novel π-conjugated copolymers incorporating 4,4-difluoro-4-borata-3a-azonia-4a-aza-s-indacene (BODIPY) core as the “donor” and quinoxaline (Qx), 2,1,3-benzothiadiazole (BzT), N,N′-di(2′-ethyl)hexyl-3,4,7,8-naphthalenetetracarboxylic diimide (NDI), and N,N′-di(2′-ethyl)hexyl-3,4,9,10-perylene tetracarboxylic diimide (PDI) as acceptors were designed and synthesized via Sonogashira polymerization. The polymers were characterized by 1H NMR spectroscopy, gel permeation chromatography (GPC), UV–vis absorption spectroscopy, and cyclic voltammetry. Density functional theory (DFT) calculations were performed on polymer repeat units, and the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels were estimated from the optimized geometry using B3LYP functional and 6-311g(d,p) basis set. Copolymers with Qx and BzT possessed HOMO and LUMO energy levels comparable to those of BODIPY homopolymer, while PDI stabilized both HOMO and LUMO levels. Semiconductor behavior of these polymers was estimated in organic thin-film transistors (OTFT). While the homopolymer, Qx, and BzT-based copolymers showed only p-type semiconductor behavior, copolymers with PDI and NDI showed only n-type behavior.
Co-reporter:J. Sreedhar Reddy, Tejaswini Kale, Ganapathy Balaji, A. Chandrasekaran, and S. Thayumanavan
The Journal of Physical Chemistry Letters 2011 Volume 2(Issue 6) pp:648-654
Publication Date(Web):March 3, 2011
DOI:10.1021/jz200126s
Thiophene-based semiconductors are often hole conductors that have been converted to electron-transporting materials by incorporation of electron-withdrawing groups at terminal positions, such as fluorinated substituents. This conversion of an otherwise p-type material to n-type material is often attributed to the lowering of the lowest unoccupied molecular orbital (LUMO) energy level due to the increased electron affinity in the molecule. Yet, it is not clear if lowering of LUMO energy level is a sufficient condition for yielding n-type material. Herein, we report small-molecule semiconductors based on cyclopentadithiophene (CPD), which can be orthogonally functionalized at two different positions, which allows us to tune the frontier orbital energy levels. We find that simply lowering the LUMO energy level, without inclusion of fluoro groups, does not result in conversion of the otherwise p-type material to n-type material, whereas incorporation of fluorinated substituents does. This indicates that charge transport behavior is not an exclusive function of the frontier orbital energy levels.Keywords: charge mobility; charge transport; cyclopentadithiophene; field effect transistor; frontier orbital energy levels;
Co-reporter:Volkan Yesilyurt;Rajasekharreddy Ramireddy ; S. Thayumanavan
Angewandte Chemie 2011 Volume 123( Issue 13) pp:3094-3098
Publication Date(Web):
DOI:10.1002/ange.201006193
Co-reporter:Siriporn Jiwpanich ; Ja-Hyoung Ryu ; Sean Bickerton
Journal of the American Chemical Society 2010 Volume 132(Issue 31) pp:10683-10685
Publication Date(Web):July 20, 2010
DOI:10.1021/ja105059g
Exchange dynamics of lipophilic guest molecules, encapsulated in supramolecular nanoassemblies in aqueous solutions, have implications in evaluating the stability of drug delivery vehicles. This is because exchange dynamics is related to the propensity of a nanocarrier to be leaky. We describe a fluorescence resonance energy transfer (FRET) based method to evaluate guest exchange dynamics in the aqueous phase. We have utilized this method to analyze the stability of encapsulation in polymeric nanogels and other related amphiphilic nanoassemblies.
Co-reporter:Ja-Hyoung Ryu ; Reuben T. Chacko ; Siriporn Jiwpanich ; Sean Bickerton ; R. Prakash Babu
Journal of the American Chemical Society 2010 Volume 132(Issue 48) pp:17227-17235
Publication Date(Web):November 15, 2010
DOI:10.1021/ja1069932
Nanoscopic vehicles that stably encapsulate drug molecules and release them in response to a specific trigger are of great interest due to implications in therapeutic applications, especially for cancer therapy. For this purpose, we have synthesized highly stable polymeric nanogels, in which the kinetics of guest molecule release can be fine-tuned by control over cross-linking density. The polymer nanogel precursor is based on a random copolymer that contains oligoethyleneglycol (OEG) and pyridyldisulfide (PDS) units as side-chain functionalities. By introducing variations into the precursor polymer, such as molecular weight and the relative percentages of hydrophilic OEG units and hydrophobic PDS functionalities, we have achieved significant control over nanogel size. We show that the noncovalently encapsulated guest molecules can be released in response to a redox trigger, glutathione (GSH). Stability of dye encapsulation inside the nanogels and tunability in the release of guest molecules have been demonstrated through in vitro fluorescence resonance energy transfer (FRET) experiments. We show in vitro doxorubicin delivery into breast cancer cells (MCF-7) with nanogels of different cross-linking density to demonstrate that it plays a key role in the stable encapsulation of hydrophobic drug molecules and the cell-uptake efficiencies.
Co-reporter:Malar A. Azagarsamy ; Volkan Yesilyurt
Journal of the American Chemical Society 2010 Volume 132(Issue 13) pp:4550-4551
Publication Date(Web):March 16, 2010
DOI:10.1021/ja100746d
Disassembling a supramolecular assembly and releasing the contents of the assembly in response to a stimulus are important goals of supramolecular chemistry. When proteins are used as the stimulus, the biological relevance of the supramolecular event dramatically increases. Although there have been efforts in which such disassembly has been achieved using enzymatic action, such events based on ligand−receptor interactions have been very limited. Here we demonstrate protein-binding-induced disassembly of dendrimer-based amphiphilic nanocontainers. We show that this disassembly is selective to the targeted protein and that the disassembly event causes a release of the sequestered guest molecules. We propose that the disassembly is caused by alteration of the hydrophilic−lipophilic balance caused by the protein binding.
Co-reporter:Sunita S. Satav, Shreedhar Bhat and S. Thayumanavan
Biomacromolecules 2010 Volume 11(Issue 7) pp:
Publication Date(Web):June 24, 2010
DOI:10.1021/bm1005454
A possible approach to handling the harmful side effects of an analgesic overdose, without losing its therapeutic potential, involves feedback regulated delivery of an antidote. For example, overdose of morphine causes hypoventilation, an inadequate ventilation to perform gas exchanges in lungs leading to increased CO2 concentration in the blood. Taking advantage of CO2 as a toxicity marker, a hydrogel-based delivery vehicle containing dimethylamino groups [poly(N,N-dimethylaminoethyl methacrylate) cross-linked by trimethylolpropane trimethacrylate] was designed. Stimulus controlled swelling of these hydrogels in naloxone delivery is discussed. A remarkable control over naloxone release was achieved against the concentration of the biomarker. The overall stimuli response of the gel could be enhanced further by encapsulating carbonic anhydrase, a metalloenzyme known to catalyze the reversible hydration of CO2. Thus, a feedback regulated drug delivery vehicle based on toxicity biomarker strategy was modeled successfully, which has the potential to mitigate risks associated with drug overdose.
Co-reporter:Arpornrat Nantalaksakul, Kothandam Krishnamoorthy and S. Thayumanavan
Macromolecules 2010 Volume 43(Issue 1) pp:37-43
Publication Date(Web):December 7, 2009
DOI:10.1021/ma901850z
Novel nonconjugated copolymer precursors containing polymerizable triEDOT and nonpolymerizable diphenyl triEDOT at side chains were synthesized by the ring-opening metathesis polymerization (ROMP). Subjecting these polymers to oxidative conditions selectively cross-links the triEDOT units, while leaving the diphenyl triEDOT groups intact. The resulting cross-linked polymers exhibit broad absorption signals with tunable contributions from the diphenyl triEDOT oligomers and conjugated EDOT polymers.
Co-reporter:Ja-Hyoung Ryu, Raghunath Roy, Judy Ventura and S. Thayumanavan
Langmuir 2010 Volume 26(Issue 10) pp:7086-7092
Publication Date(Web):January 14, 2010
DOI:10.1021/la904437u
Amphiphilic polymers of different hydrophilic−lipophilic ratios were prepared by free radical polymerization using two monomers consisting of triethylene glycol as the hydrophilic part and an alkyl chain connected by disulfide bond as the hydrophobic part. These polymers form micelle-like nanoassemblies in aqueous media and can encapsulate hydrophobic drug molecules up to 14% of their mass. In a reducing environment, these polymeric micelles disassemble and dissolve in water, since the amphiphilic polymers are converted into hydrophilic polymers upon cleavage of the disulfide bond. This disassembly event results in the release of hydrophobic molecules that had been encapsulated inside the micelle, the rate of which was found to be dependent on the concentration of the reducing agent, glutathione (GSH). In vitro experiments also show that the GSH-dependent release of the doxorubicin can be used to effect cytotoxicity in MCF-7 cells.
Co-reporter:Tejaswini S. Kale, K. Krishnamoorthy, Mukundan Thelakkat and S. Thayumanavan
The Journal of Physical Chemistry Letters 2010 Volume 1(Issue 7) pp:1116-1121
Publication Date(Web):March 16, 2010
DOI:10.1021/jz1002204
Hole-transporting triarylamine units have been incorporated along the periphery of different generations of a benzyl ether dendrimer, and their field effect mobilities were measured. The charge mobility was found to decrease with generation. We observed that increasing the density of charge transport units in the dendrimer by incorporating triarylamines in every layer of the dendrimer improves the hole mobility in all generations. The mobility increases 4-fold from generation zero to one; the mobility drops and levels off at higher generations. We find that lower generation dendrimers with high density of charge transporting functionalities may prove to be good candidates for applications such as organic photovoltaics. Considering the versatility of dendrons as components of solid state nanoassemblies, the studies here provide useful guidelines for incorporating charge transport functionalities in these branched architectures.Keywords (keywords): charge mobility; dendrimers; field effect transistor; hole transport; triarylamine;
Co-reporter:Dr. Ayyagari V. Subrahmanyam; Sankaran Thayumanavan; George W. Huber
ChemSusChem 2010 Volume 3( Issue 10) pp:1158-1161
Publication Date(Web):
DOI:10.1002/cssc.201000136
Co-reporter:Chikkannagari Nagamani;Craig Versek;Michael Thorn;Mark T. Tuominen
Journal of Polymer Science Part A: Polymer Chemistry 2010 Volume 48( Issue 9) pp:1851-1858
Publication Date(Web):
DOI:10.1002/pola.23932
Abstract
Proton transport (PT) plays an important role in many biological processes as well as in materials for renewable energy devices. Gaining insights into functional group requirements for PT would aid the design of new materials that provide enhanced proton conduction. In this report, we outline our efforts to understand the most probable proton conduction pathway in 1H-1,2,3-triazole systems. In triazole-based systems, both imidazole- and pyrazole-like pathways are possible. By systematically comparing structurally analogous polymers based on N-heterocycles and benz-N-heterocycles, we find that the imidazole-like pathway makes a significant contribution to the proton transfer in 1H-1,2,3-triazole systems, while the contribution from pyrazole-like pathway is negligible. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1851–1858, 2010
Co-reporter:Malar A. Azagarsamy ; Punidha Sokkalingam
Journal of the American Chemical Society 2009 Volume 131(Issue 40) pp:14184-14185
Publication Date(Web):September 16, 2009
DOI:10.1021/ja906162u
We demonstrate a new enzyme-induced disassembly of amphiphilic nanocontainers based on dendrimers. Disassembly and the ensuing release of noncovalently bound guest molecules are of great interest because of their implications in areas such as drug delivery and sensing. Achieving these with a protein as the stimulus is of even greater importance, because proteins are the primary indicators of biological imbalances. We achieved disassembly of the nanocontainers by disturbing the hydrophilic−lipophilic balance in the amphiphilic dendrimer building blocks.
Co-reporter:Ja-Hyoung Ryu ; Soojin Park ; Bokyung Kim ; Akamol Klaikherd ; Thomas P. Russell
Journal of the American Chemical Society 2009 Volume 131(Issue 29) pp:9870-9871
Publication Date(Web):July 1, 2009
DOI:10.1021/ja902567p
We have prepared functionalized nanoporous thin films from a polystyrene-block-polyethylene oxide block copolymer, which was made cleavable due to the intervening disulfide bond. The cleavage reaction of the disulfide bond leaves behind free thiol groups inside the nanopores of polystyrene thin film. This nanoporous thin film can be used as a template for generating gold nanoring structures. This strategy can provide a facile method to form a highly ordered array of biopolymer or metal−polymer composite structures.
Co-reporter:Akamol Klaikherd ; Chikkannagari Nagamani
Journal of the American Chemical Society 2009 Volume 131(Issue 13) pp:4830-4838
Publication Date(Web):March 16, 2009
DOI:10.1021/ja809475a
Stimuli-responsive polymers are arguably the most widely considered systems for a variety of applications in biomedical arena. We report here a novel triple stimuli sensitive block copolymer assembly that responds to changes in temperature, pH and redox potential. Our block copolymer design constitutes an acid-sensitive THP-protected HEMA as the hydrophobic part and a temperature-sensitive PNIPAM as the hydrophilic part with an intervening disulfide bond. The micellar properties and the release kinetics of the encapsulated guest molecule in response to one stimulus as well as combinations of stimuli have been evaluated. Responsiveness to combination of stimuli not only allows for fine-tuning the guest molecule release kinetics, but also provides the possibility of achieving location-specific delivery.
Co-reporter:Siriporn Jiwpanich, Britto S. Sandanaraj and S. Thayumanavan
Chemical Communications 2009 (Issue 7) pp:806-808
Publication Date(Web):05 Jan 2009
DOI:10.1039/B815263B
In fluorophore-cored dendrimers with peripheral binding functionalities, the effect of generation upon protein binding-induced fluorescence quenching can be unpredictable; this is because the increase in fluorophore-binding functionality distance with generation is also accompanied by an increase in the number of binding moieties and the interplay between the two features is utilized to create patterns for metalloprotein sensing.
Co-reporter:Nadnudda Rodthongkum, Jacqueline D. Washington, Elamprakash N. Savariar, S. Thayumanavan and Richard W. Vachet
Analytical Chemistry 2009 Volume 81(Issue 12) pp:5046
Publication Date(Web):May 21, 2009
DOI:10.1021/ac900661e
Amphiphilic homopolymers that self-assemble into reverse micelles in nonpolar solvents have been used by us in the context of a two-phase liquid−liquid extraction protocol to selectively extract peptides from aqueous solution for MALDI-MS detection. In this manuscript, we investigate the scope of these materials in terms of its extraction capabilities, using compounds with varying isoelectric points (pI) and pKa values over a range of aqueous solution pHs. We find that the aqueous solution pH and analyte pKa values are the major factors controlling extraction selectivity. We also find that the experimental extraction efficiencies correspond very well with the fractional compositions of species calculated using analyte pKa values, indicating that these extraction materials can be used to simultaneously generate titration-type curves for each individual peptide in a mixture. We predict that such titration curves, along with accurate mass measurements, could represent a new way of improving protein identification procedures.
Co-reporter:Elamprakash N. Savariar;Jonathan Koppelman ;Sankaran Thayumanavan
Israel Journal of Chemistry 2009 Volume 49( Issue 1) pp:41-47
Publication Date(Web):
DOI:10.1560/IJC.49.1.41
Abstract
Biaryl dendritic micelles have been used for generating fluorescence response patterns that are used for sensing metalloproteins. By varying the generation of the dendrimer and the encapsulated dye molecules, the differential receptors for four different metalloproteins have been created. The pattern obtained from these dendritic micelles indeed confirms that the combination of dendrimer generation and electronic energy levels of the fluorescent transducers can be used for generating analyte-specific patterns.
Co-reporter:Yangbin Chen and S. Thayumanavan
Langmuir 2009 Volume 25(Issue 24) pp:13795-13799
Publication Date(Web):July 7, 2009
DOI:10.1021/la901692a
Amphiphilic homopolymer films have been immobilized onto substrates to study the interactions of these polymers with proteins. X-ray photoelectron spectroscopy (XPS) was utilized to measure the amount of protein adsorption. Amphiphilic homopolymers have been shown to reduce protein adsorption, despite the high affinity of the hydrophobic or hydrophilic functional groups by themselves toward proteins. This protein-resistant property seems to arise from the unique molecular-scale alternation of incompatible functionalities. The combination of incompatible functionalities with a predefined alternating pattern within a monomer could provide a potential design for nonfouling materials.
Co-reporter:Suhrit Ghosh;Volkan Yesilyurt;Elamprakash N. Savariar;Katharine Irvin
Journal of Polymer Science Part A: Polymer Chemistry 2009 Volume 47( Issue 4) pp:1052-1060
Publication Date(Web):
DOI:10.1002/pola.23204
Abstract
Formation of micelle-type assembly from supramolecular complexation of a surfactant and an oppositely charged homopolymer is demonstrated. The lower CAC observed for these assemblies suggest that the electrostatic interaction provides an amphiphilic homopolymer-like structure. The stimulus-induced disassembly of these supramolecular structures has been accomplished with variations in redox characteristics, ionic strength, and pH of the medium. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1052–1060, 2009
Co-reporter:Malar A. Azagarsamy, Kothandam Krishnamoorthy, Kulandaivelu Sivanandan and S. Thayumanavan
The Journal of Organic Chemistry 2009 Volume 74(Issue 24) pp:9475-9485
Publication Date(Web):November 12, 2009
DOI:10.1021/jo902109u
Whereas encapsulation of functional groups at the core of dendrimers is well-understood, very little is known about their intermediate layers or even the periphery. Here we report on a systematic investigation of every layer of dendrimers by incorporating a single ferrocene unit in well-defined locations in dendrons. Site-specific incorporation of the ferrocene unit was achieved by utilizing the dendrimer sequencing methodology. We show here that the redox potential values of ferrocene at intermediate layers were remarkably different from those at the core and the periphery. Although redox potential values were location-dependent, no significant change in the rate of heterogeneous electron transfer (k0) was observed with respect to locations. This was attributed to the possibility that free rotation of dendrimer nullifies the distance between the electrode and ferrocene unit. Finally, we also show that no Faradaic current was observed for the amphiphilic assemblies of these dendrons, whereas the same dendron did exhibit significant Faradaic current in nonassembling solvent environments.
Co-reporter:Tejaswini S. Kale, Akamol Klaikherd, Bhooshan Popere and S. Thayumanavan
Langmuir 2009 Volume 25(Issue 17) pp:9660-9670
Publication Date(Web):May 19, 2009
DOI:10.1021/la900734d
Amphiphilic molecules self-assemble in solvents because of the differential solvation of the hydrophilic and lipophilic functionalities. Small-molecule surfactants have long been known to form micelles in water that can solubilize lipophilic guest molecules in their water-excluded interior. Polymeric surfactants based on block copolymers are also known to form several types of aggregates in water owing either to the mutual incompatibility of the blocks or better solvation of one of the blocks by the solvent. Incorporating amphiphilicity at smaller length scales in polymers would provide an avenue to capture the interesting properties of macromolecules and fine tune their supramolecular assemblies. To address this issue, we designed and synthesized amphiphilic homopolymers containing hydrophilic and lipophilic functionalities in the monomer. Such a polymer can be imagined to be a string of small-molecule surfactants tethered together such that the hydrophilic and lipophilic functionalities are located on opposite faces, rendering the assemblies facially amphiphilic. This feature article describes the self-assembly of our amphiphilic homopolymers in polar and apolar solvents. These homopolymers not only form micelles in water but also form inverse micelles in organic solvents. Subtle changes to the molecular structure have been demonstrated to yield vesicles in water and inverted micelles in organic solvents. The characterization of these assemblies and their applications in separations, catalysis, and sensing are described here.
Co-reporter:Raghunath Roy, D. Joseph Jerry and S. Thayumanavan
Biomacromolecules 2009 Volume 10(Issue 8) pp:
Publication Date(Web):July 8, 2009
DOI:10.1021/bm900370p
The basic TAT peptide, responsible for translocation of the HIV-TAT protein, has been conjugated to a variety of artificial nanoscopic materials to transport them across the cellular membrane. However, attempts to translocate genes using the TAT-peptide had met with limited success. We hypothesized that the cationic nature of the peptide does not allow for displaying these peptides on the surface of the polyplex. To circumvent this potential issue, we have developed a new molecular design strategy where the TAT-peptide can be effectively displayed on the surface of the polyplex, thus enhancing gene expression.
Co-reporter:ElamprakashN. Savariar;MatthewM. Sochat;Akamol Klaikherd Dr.
Angewandte Chemie 2008 Volume 121( Issue 1) pp:116-120
Publication Date(Web):
DOI:10.1002/ange.200804136
Co-reporter:ElamprakashN. Savariar;MatthewM. Sochat;Akamol Klaikherd Dr.
Angewandte Chemie International Edition 2008 Volume 48( Issue 1) pp:110-114
Publication Date(Web):
DOI:10.1002/anie.200804136
Co-reporter:K. Krishnamoorthy, Raghunath Reddy Dasari, Arpornrat Nantalaksakul and S. Thayumanavan
Chemical Communications 2007 (Issue 7) pp:739-741
Publication Date(Web):18 Jan 2007
DOI:10.1039/B614236B
The accessibility of the electroactive periphery was studied and compared for dendrimers and linear analogs by heterogeneous electron transfer using microelectrodes.
Co-reporter:Ashootosh Vasant Ambade;Britto Selvaraj Sanaraj;Akamol Klaikherd;S Thayumanavan
Polymer International 2007 Volume 56(Issue 4) pp:
Publication Date(Web):12 DEC 2006
DOI:10.1002/pi.2185
This review discusses recent advances in protein sensing using fluorescent polyelectrolytes that are mainly water-soluble conjugated polymers. A quencher-labeled substrate or fluorophore-labeled substrate is generally used as a probe. In the presence of an enzyme, the linker between substrate and quencher/fluorophore is cleaved and fluorescence of the polymer is either ‘turned on’ or ‘turned off’. Fluorescence behavior of these conjugated polymers is highly sensitive to conformation of the polymeric chains. Since upon binding with proteins the conformation is perturbed and fluorescence is affected, these polyelectrolytes have been used to study conformational changes in proteins. The conformation-dependent fluorescence is also a limitation for these sensors in some cases and non-conjugated polyelectrolytes have been shown to provide an alternative. Copyright © 2006 Society of Chemical Industry
Co-reporter:Selvanathan Arumugam, Dharma Rao Vutukuri, S. Thayumanavan, V. Ramamurthy
Journal of Photochemistry and Photobiology A: Chemistry 2007 Volume 185(2–3) pp:168-171
Publication Date(Web):25 January 2007
DOI:10.1016/j.jphotochem.2006.05.032
A styrene based water soluble polymer (polymer-A) has been explored as a host for solubilizing otherwise insoluble aromatic hydrocarbons in water. The increased local concentration of encapsulated aromatic hydrocarbons within the hydrophobic pockets of polymer-A was utilized for performing efficient photodimerization of acenaphthylene (1) and six 9-substituted anthracenes [AnCOOH, AnCHO, AnCH2OH, AnCH3, AnBr and AnCN] in water. Photodimerization of these aromatic hydrocarbons were more efficient than in water and yielded dimers even at low concentrations (∼10−4 M). At the same concentration of anthracenes in organic solvents such as benzene and methanol, no dimers were formed even after 48 h of irradiation. Although the polymer-A was able to increase the local concentration of the reactant aromatics it was unable to orient them towards a single dimer.
Co-reporter:Elamprakash N. Savariar
Journal of Polymer Science Part A: Polymer Chemistry 2004 Volume 42(Issue 24) pp:6340-6345
Publication Date(Web):3 NOV 2004
DOI:10.1002/pola.20467
A copolymer of N-isopropylacrylamide with the N-hydroxysuccinimide ester of methacrylic acid has found use in a variety of applications. Here we report our efforts to gain control over the molecular weight distribution of this copolymer with controlled radical polymerization methods, such as atom transfer radical polymerization, reversible addition–fragmentation transfer (RAFT), and nitroxide-mediated polymerization. We have found that RAFT is capable of affording these copolymers with a polydispersity index of 1.1–1.2. Our results for all three polymerizations are reported. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 6340–6345, 2004
Co-reporter:Reuben T. Chacko, Judy Ventura, Jiaming Zhuang, S. Thayumanavan
Advanced Drug Delivery Reviews (15 June 2012) Volume 64(Issue 9) pp:836-851
Publication Date(Web):15 June 2012
DOI:10.1016/j.addr.2012.02.002
In this review we put the spotlight on crosslinked polymer nanogels, a promising platform that has the characteristics of an “ideal” drug delivery vehicle. Some of the key aspects of drug delivery vehicle design like stability, response to biologically relevant stimuli, passive targeting, active targeting, toxicity and ease of synthesis are discussed. We discuss several delivery systems in this light and highlight some examples of systems, which satisfy some or all of these design requirements. In particular, we point to the advantages that crosslinked polymeric systems bring to drug delivery. We review some of the synthetic methods of nanogel synthesis and conclude with the diverse applications in drug delivery where nanogels have been fruitfully employed.Download high-res image (339KB)Download full-size image
Co-reporter:Ja-Hyoung Ryu ; Siriporn Jiwpanich ; Reuben Chacko ; Sean Bickerton
Journal of the American Chemical Society () pp:
Publication Date(Web):May 26, 2010
DOI:10.1021/ja102316a
The stability of encapsulation in self-assembly systems is limited during blood circulation because of a requisite concentration for assembly formation. For deliberate molecular design for stable encapsulation, targeting, and triggered release, we have developed a facile synthetic method for highly stable, polymeric nanogels using a simple intra/interchain cross-linking reaction. We show a simple, emulsion-free method for the preparation of biocompatible nanogels that provides the ability to encapsulate hydrophobic guest molecules and surface functionalization which has potential for targeted delivery. We show that the noncovalently encapsulated guest molecules can be released in response to a biologically relevant stimulus.
Co-reporter:Hui Wang, Jiaming Zhuang, Krishna R. Raghupathi and S. Thayumanavan
Chemical Communications 2015 - vol. 51(Issue 97) pp:NaN17268-17268
Publication Date(Web):2015/09/28
DOI:10.1039/C5CC07408H
We report a simple, robust, and general strategy for protein detection based on supramolecular dissociation. The simplicity of the design is exemplified by the fact that the host assemblies can be widely varied and that these assemblies can be achieved from commercially available surfactants. An operating mechanism that is consistent with all the data has been proposed.
Co-reporter:Longyu Li, Kishore Raghupathi, Cunfeng Song, Priyaa Prasad and S. Thayumanavan
Chemical Communications 2014 - vol. 50(Issue 88) pp:NaN13432-13432
Publication Date(Web):2014/07/04
DOI:10.1039/C4CC03688C
Self-assembly of random copolymers has attracted considerable attention recently. In this feature article, we highlight the use of random copolymers to prepare nanostructures with different morphologies and to prepare nanomaterials that are responsive to single or multiple stimuli. The synthesis of single-chain nanoparticles from random copolymers and their potential applications are also discussed in some detail. We aim to draw more attention to these easily accessible copolymers, which are likely to play an important role in translational polymer research.
Co-reporter:Longyu Li, Cunfeng Song, Matthew Jennings and S. Thayumanavan
Chemical Communications 2015 - vol. 51(Issue 8) pp:NaN1428-1428
Publication Date(Web):2014/11/12
DOI:10.1039/C4CC08000A
Reagent-free synthetic methods are of great interest because of their simplicity and implications in green chemistry. We have taken advantage of photoinduced heterodisulfide metathesis to generate crosslinked polymer nanoparticles. The method of development and the mechanistic basis for the synthetic approach are outlined in this communication.
Co-reporter:Ambata M. Poe, Andrea M. Della Pelle, Ayyagari V. Subrahmanyam, William White, Guillaume Wantz and S. Thayumanavan
Chemical Communications 2014 - vol. 50(Issue 22) pp:NaN2915-2915
Publication Date(Web):2014/01/22
DOI:10.1039/C3CC49648A
A series of acceptor–donor–acceptor molecules containing terminal BODIPY moieties conjugated through the meso position were synthesized. Deep LUMO energy levels and good visible absorption led to their use as acceptors in bulk heterojunction solar cells. Inverted devices were fabricated, reaching efficiencies as high as 1.51%.
Co-reporter:Siriporn Jiwpanich, Britto S. Sandanaraj and S. Thayumanavan
Chemical Communications 2009(Issue 7) pp:NaN808-808
Publication Date(Web):2009/01/05
DOI:10.1039/B815263B
In fluorophore-cored dendrimers with peripheral binding functionalities, the effect of generation upon protein binding-induced fluorescence quenching can be unpredictable; this is because the increase in fluorophore-binding functionality distance with generation is also accompanied by an increase in the number of binding moieties and the interplay between the two features is utilized to create patterns for metalloprotein sensing.
Co-reporter:Chikkannagari Nagamani, Usha Viswanathan, Craig Versek, Mark T. Tuominen, Scott M. Auerbach and S. Thayumanavan
Chemical Communications 2011 - vol. 47(Issue 23) pp:NaN6640-6640
Publication Date(Web):2011/05/06
DOI:10.1039/C1CC11207D
The dynamic nature of hydrogen bonds in phenolic polymers, where the hydrogen bond donor/acceptor reorientation can occur in a single site, presents lower barriers for proton transport.
Co-reporter:Bhooshan C. Popere, Andrea M. Della Pelle, Ambata Poe, Ganapathy Balaji and S. Thayumanavan
Chemical Science (2010-Present) 2012 - vol. 3(Issue 10) pp:NaN3102-3102
Publication Date(Web):2012/07/13
DOI:10.1039/C2SC20731A
Here we report the synthesis, electrochemical properties, and optical properties of five novel π-conjugated alternating copolymers based on the BODIPY core. These polymers were synthesized via the Sonogashira polymerization reaction and contain BODIPY units alternating with comonomers such as 9,9-bis(2-ethylhexyl)-9H-fluorene (FL), 9-(2-ethylhexyl)-9H-carbazole (CBz), 2,2′-bithiophene (BT), 4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b:3,4-b']dithiophene (CPDT) and 4-(2-ethylhexyl)-4H-dithieno[3,2-b:2',3'-d]pyrrole (DTP). These comonomers were rationally chosen based on their gas phase ionization potential (IP) values estimated by density functional theory (DFT) calculations. Cyclic voltammetry on drop-cast thin films, as well as solutions of these polymers, revealed that the highest occupied molecular orbitals (HOMOs) of the resulting polymers correlated well with the ionization potentials (donor strength) of the comonomers. On the contrary, the lowest unoccupied molecular orbital (LUMO) energy levels of all copolymers were fairly invariant, independent of the comonomer used. This suggests that the BODIPY moiety provides the primary influence on the LUMO levels of the polymer. In addition to the experimentally determined HOMO/LUMO energy levels bearing good correlation with theoretical estimates, all polymers were found to possess broad absorption spectra covering the entire visible range, thus making them truly panchromatic. These polymers provide us with a toolset to tune the frontier molecular orbital energy levels, while retaining the low band gap and broad absorption of these polymers.
Co-reporter:Jiaming Zhuang, Mallory R. Gordon, Judy Ventura, Longyu Li and S. Thayumanavan
Chemical Society Reviews 2013 - vol. 42(Issue 17) pp:NaN7435-7435
Publication Date(Web):2013/06/13
DOI:10.1039/C3CS60094G
In this review, we outline examples that illustrate the design criteria for achieving macromolecular assemblies that incorporate a combination of two or more chemical, physical or biological stimuli-responsive components. Progress in both fundamental investigation into the phase transformations of these polymers in response to multiple stimuli and their utilization in a variety of practical applications are highlighted. Using these examples, we aim to explain the origin of employed mechanisms of stimuli responsiveness which may serve as a guideline to inspire future design of multi-stimuli responsive materials.
Co-reporter:Bhooshan C. Popere, Andrea M. Della Pelle, Ambata Poe and S. Thayumanavan
Physical Chemistry Chemical Physics 2012 - vol. 14(Issue 12) pp:NaN4057-4057
Publication Date(Web):2012/01/11
DOI:10.1039/C2CP23422J
Research in the field of organic photovoltaics has gained considerable momentum in the last two decades owing to the need for developing low-cost and efficient energy harvesting systems. Elegant molecular architectures have been designed, synthesized and employed as active materials for photovoltaic devices thereby leading to a better molecular structure–device property relationship understanding. In this perspective, we outline new macromolecular scaffolds that have been designed within the purview of each of the three fundamental processes involving light harvesting, charge separation and charge transport.
Co-reporter:Ganapathy Balaji, Andrea M. Della Pelle, Bhooshan C. Popere, A. Chandrasekaran and S. Thayumanavan
Organic & Biomolecular Chemistry 2012 - vol. 10(Issue 17) pp:NaN3462-3462
Publication Date(Web):2012/02/24
DOI:10.1039/C2OB25087J
We report the syntheses and properties of thienopyrrole based unsymmetrical and extended heteroacenes, which are isoelectronic with heptacene (30π) and nonacene (38π), respectively. Optical and electrochemical properties of these seven and nine rings fused systems are studied. The optoelectronic properties of the syn and anti-isomers of the unsymmetrical heteroacenes are also compared. The influence of the position of the heteroatoms in the fused corona, upon the optical and electrochemical properties, is rationalized based on the contributions from the benzenoid vs. quinonoid-type structures of these molecules.
Co-reporter:Sompit Wanwong, Ambata Poe, Ganapathy Balaji and S. Thayumanavan
Organic & Biomolecular Chemistry 2014 - vol. 12(Issue 15) pp:NaN2478-2478
Publication Date(Web):2014/02/13
DOI:10.1039/C3OB41648H
Cyclopentadithiophene (CPDT) derivatives with different heteroatom conformations have been synthesized. The optical, electrochemical and charge transport properties of these molecules are reported. The CPDT-anti-ketone not only exhibits the lowest optical and electronic bandgaps, but also exhibits reasonable hole mobility, 3 × 10−3 cm2 (V s)−1. Changing the carbonyl conformation to the syn position or incorporating the imine functionality results in a blue-shift in the lower energy band of the absorption spectrum indicative of the increased bandgaps.
Co-reporter:Conghui Yuan, Ying Chang, Jie Mao, Shirong Yu, Weiang Luo, Yiting Xu, S. Thayumanavan and Lizong Dai
Journal of Materials Chemistry A 2015 - vol. 3(Issue 14) pp:NaN2866-2866
Publication Date(Web):2015/02/18
DOI:10.1039/C4TB01880J
Intermolecular B–N coordination has been recognized as a promising driving force for molecular self-organization. However, direct utilization of this intermolecular interaction as a building bridge for the supramolecular self-assembly of chemical functionalities to form nano-sized architectures remains a daunting challenge. Here, we outline a multiple intermolecular B–N coordination based supramolecular system, where small boronate molecules can be brought together in solution to form nanoparticles with controllable sizes and morphologies. We not only demonstrate the intrinsic switchable fluorescence and the stimuli-responsive capabilities of designed boronate molecules, but also show that the stabilized or surface functionalized nanoparticles are degradable in response to pH and D-glucose and able to retain the fluorescence features of the boronate molecules. Additionally, the degraded nanoparticles can repair themselves through the reformation of B–N coordination.
Co-reporter:Longyu Li, Kishore Raghupathi, Conghui Yuan and S. Thayumanavan
Chemical Science (2010-Present) 2013 - vol. 4(Issue 9) pp:NaN3660-3660
Publication Date(Web):2013/07/10
DOI:10.1039/C3SC50899D
Nanocarriers that can be effectively transported across cellular membranes have potential in a variety of biomedical applications. Among these, materials that are capable of changing their surface properties and thus gain entry into a cell, in response to a specific tissue environment, are of particular interest. In this manuscript we report a facile route to prepare nanogels, which generate surface charge with pH as stimulus. This is achieved by designing a polymeric nanogel containing 2-diisopropylamino (DPA) moieties. The choice of DPA nanogel is based on its pKb, which causes this functional group to be rapidly protonated upon change in pH. It is noteworthy that the pH change at which the surface charge is generated in the nanogel corresponds to the slightly acidic conditions observed in the extracellular environment of solid tumor. We show that the pH at which the charge is generated, i.e. the isoelectric point (pI) of the nanogel, can be adjusted by varying the percentage of DPA units in the nanogel, its preparation process and crosslinking density. Intracellular delivery of these nanogels was greatly enhanced in an acidic pH environment due to the surface charge generation. This study demonstrates the versatile nature of the nanogels to introduce specific functionalities with relative ease to achieve desired functional behavior.
Co-reporter:Conghui Yuan, Kishore Raghupathi, Bhooshan C. Popere, Judy Ventura, Lizong Dai and S. Thayumanavan
Chemical Science (2010-Present) 2014 - vol. 5(Issue 1) pp:NaN234-234
Publication Date(Web):2013/09/26
DOI:10.1039/C3SC52347K
Nanoscale assemblies with stimuli-sensitive features have attracted significant attention due to implications in a variety of areas ranging from materials to biology. Recently, there have been excellent developments in obtaining nanoscale structures that are concurrently sensitive to multiple stimuli. Such nanostructures are primarily focused on a single nanostructure containing an appropriate combination of functional groups within the nanostructure. In this work, we outline a simple approach to bring together two disparate supramolecular assemblies that exhibit very different stimuli-sensitive characteristics. These composite nanostructures comprise a block copolymer micelle core and nanogel shell, both of which can preserve their respective morphology and stimulus sensitivities. The block copolymer is based on poly(2-(diisopropylamino)ethylmethacrylate-b-2-aminoethylmethacrylate hydrochloride), which contains a pH-sensitive hydrophobic block. Similarly, the redox-sensitive nanogel is derived from a poly(oligoethyleneglycolmonomethylethermethacrylate-co-glycidylmethacrylate-co-pyridyldisulfide ethylmethacrylate) based random copolymer. In addition to the independent pH-response of the micellar core and redox-sensitivity of the nanogel shell in the composite nanostructures, the synergy between the micelles and the nanogels have been demonstrated through a robust charge generation in the nanogels during the disassembly of the micelles. The supramolecular assembly and disassembly have been characterized using transmission electron microscopy, dynamic light scattering, zeta potential measurements, fluorescence spectroscopy and cellular uptake.
Co-reporter:K. Krishnamoorthy, Raghunath Reddy Dasari, Arpornrat Nantalaksakul and S. Thayumanavan
Chemical Communications 2007(Issue 7) pp:NaN741-741
Publication Date(Web):2007/01/18
DOI:10.1039/B614236B
The accessibility of the electroactive periphery was studied and compared for dendrimers and linear analogs by heterogeneous electron transfer using microelectrodes.
Co-reporter:Piyachai Khomein and S. Thayumanavan
Chemical Communications 2017 - vol. 53(Issue 37) pp:NaN5192-5192
Publication Date(Web):2017/04/11
DOI:10.1039/C7CC00963A
Flat aromatic structures are ubiquitous in organic semiconducting molecules. The possibility of endowing these inherently anisotropic molecules with isotropic structures is explored using a polymeric nanoparticle attachment strategy. Preliminary findings, outlined in this manuscript, suggest that this might be a simple and effective strategy for organic semiconductors with consistent mobilities.
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![Acetic acid, [3-butoxy-5-(hydroxymethyl)phenoxy]-, 1,1-dimethylethylester](http://img.cochemist.com/ccimg/872600/872576-19-7_b.png)
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![Ethanol, 2-[2-(2-methoxyethoxy)ethoxy]-, 1-(4-methylbenzenesulfonate)](/data/chemimg/636900/62921-74-8.png)
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![11-oxo-2,3,5,6,7,11-Hexahydro-1H-pyrano[2,3-f]pyrido[3,2,1-ij]quinoline-10-carboxylic acid](/data/chemimg/86700/55804-65-4_b.png)
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![3-[2-(2-carboxyethylsulfanyl)ethylsulfanyl]propanoic Acid](http://img.cochemist.com/ccimg/40300/40252-80-0_b.png)
![2-{5-[(3-NITROBENZYL)SULFANYL]-1,3,4-OXADIAZOL-2-YL}PYRAZINE](http://img.cochemist.com/ccimg/34900/34897-67-1.png)
![2-{5-[(3-NITROBENZYL)SULFANYL]-1,3,4-OXADIAZOL-2-YL}PYRAZINE](http://img.cochemist.com/ccimg/34900/34897-67-1_b.png)
![Poly[imino(1,3-propanediyl)]](http://img.cochemist.com/ccimg/32900/32841-79-5.png)
![Poly[imino(1,3-propanediyl)]](http://img.cochemist.com/ccimg/32900/32841-79-5_b.png)
![Benzene, [(methoxymethoxy)methyl]-](http://img.cochemist.com/ccimg/31700/31600-55-2.png)
![Benzene, [(methoxymethoxy)methyl]-](http://img.cochemist.com/ccimg/31700/31600-55-2_b.png)
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![Hexanoic acid, 6-[(2-aminobenzoyl)amino]-](http://img.cochemist.com/ccimg/27500/27493-00-1_b.png)
![Cyclopenta[2,1-b:3,4-b']dithiophen-4-one](http://img.cochemist.com/ccimg/25800/25796-77-4.png)
![Cyclopenta[2,1-b:3,4-b']dithiophen-4-one](http://img.cochemist.com/ccimg/25800/25796-77-4_b.png)
![7H-Cyclopenta[1,2-b:4,3-b']dithiophen-7-one](http://img.cochemist.com/ccimg/25800/25796-72-9.png)
![7H-Cyclopenta[1,2-b:4,3-b']dithiophen-7-one](http://img.cochemist.com/ccimg/25800/25796-72-9_b.png)
![2,5-Pyrrolidinedione, 1-[(1-oxodecyl)oxy]-](http://img.cochemist.com/ccimg/22200/22102-66-5.png)
![2,5-Pyrrolidinedione, 1-[(1-oxodecyl)oxy]-](http://img.cochemist.com/ccimg/22200/22102-66-5_b.png)
![2-Propenoic acid,2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethyl ester](http://img.cochemist.com/ccimg/19900/19812-60-3.png)
![2-Propenoic acid,2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethyl ester](http://img.cochemist.com/ccimg/19900/19812-60-3_b.png)
![2H-Pyran, 2-[(3-bromophenyl)methoxy]tetrahydro-](http://img.cochemist.com/ccimg/17200/17100-67-3.png)
![2H-Pyran, 2-[(3-bromophenyl)methoxy]tetrahydro-](http://img.cochemist.com/ccimg/17200/17100-67-3_b.png)
![Ferrate(2-), [7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(4-)-κN21,κN22,κN23,κN24]-, hydrogen (1:2), (SP-4-2)-](/data/chemimg/522800/14875-96-8.png)
![Ferrate(2-), [7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(4-)-κN21,κN22,κN23,κN24]-, hydrogen (1:2), (SP-4-2)-](/data/chemimg/522800/14875-96-8_b.png)
![2-Naphthalenecarboxamide, 3-hydroxy-N-[2-(4-morpholinyl)ethyl]-](http://img.cochemist.com/ccimg/10200/10155-35-8.png)
![2-Naphthalenecarboxamide, 3-hydroxy-N-[2-(4-morpholinyl)ethyl]-](http://img.cochemist.com/ccimg/10200/10155-35-8_b.png)
![1H-Benzo[d][1,2,3]triazol-5-amine](http://img.cochemist.com/ccimg/3400/3325-11-9.png)
![1H-Benzo[d][1,2,3]triazol-5-amine](http://img.cochemist.com/ccimg/3400/3325-11-9_b.png)
![Benzene,[(10-bromodecyl)oxy]-](http://img.cochemist.com/ccimg/2100/2033-87-6.png)
![Benzene,[(10-bromodecyl)oxy]-](http://img.cochemist.com/ccimg/2100/2033-87-6_b.png)
![[1,1'-Biphenyl]-4-methanol, 3',5'-bis(methoxymethoxy)-2-(3,6,9,12,15-pentaoxahexadec-1-yloxy)-6-(2-propyn-1-yloxy)-](/data/chemimg/3723500/1190085-92-7.png)
![[1,1'-Biphenyl]-4-methanol, 3',5'-bis(methoxymethoxy)-2-(3,6,9,12,15-pentaoxahexadec-1-yloxy)-6-(2-propyn-1-yloxy)-](/data/chemimg/3723500/1190085-92-7_b.png)
![2,6-bis(trimethylsilyl)-4H-cyclopenta[2,1-b:3,4-b']dithiophen-4-one](http://img.cochemist.com/ccimg/1188000/1187970-48-4.png)
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![Benzenemethanol,3-[[3-[[3-(phenyl-1-pyrenylamino)phenyl]methoxy]phenyl]methoxy]-](http://img.cochemist.com/ccimg/903600/903562-01-6.png)
![Benzenemethanol,3-[[3-[[3-(phenyl-1-pyrenylamino)phenyl]methoxy]phenyl]methoxy]-](http://img.cochemist.com/ccimg/903600/903562-01-6_b.png)
![Benzaldehyde, 3-[(3-hydroxyphenyl)methoxy]-](http://img.cochemist.com/ccimg/903600/903562-00-5.png)
![Benzaldehyde, 3-[(3-hydroxyphenyl)methoxy]-](http://img.cochemist.com/ccimg/903600/903562-00-5_b.png)
![Benzenemethanol, 3-[[3-(phenyl-1-pyrenylamino)phenyl]methoxy]-](http://img.cochemist.com/ccimg/903600/903561-99-9.png)
![Benzenemethanol, 3-[[3-(phenyl-1-pyrenylamino)phenyl]methoxy]-](http://img.cochemist.com/ccimg/903600/903561-99-9_b.png)
![Benzenemethanol,3-[[3,5-bis[[3,5-bis(phenylmethoxy)phenyl]methoxy]phenyl]methoxy]-5-[[3-[[3,5-bis(phenylmethoxy)phenyl]methoxy]-5-[[3-(phenylmethoxy)-5-[[3-(phenyl-1-pyrenylamino)phenyl]methoxy]phenyl]methoxy]phenyl]methoxy]-](http://img.cochemist.com/ccimg/903600/903561-97-7.png)
![Benzenemethanol,3-[[3,5-bis[[3,5-bis(phenylmethoxy)phenyl]methoxy]phenyl]methoxy]-5-[[3-[[3,5-bis(phenylmethoxy)phenyl]methoxy]-5-[[3-(phenylmethoxy)-5-[[3-(phenyl-1-pyrenylamino)phenyl]methoxy]phenyl]methoxy]phenyl]methoxy]-](http://img.cochemist.com/ccimg/903600/903561-97-7_b.png)
![Benzenemethanol,3-[[3,5-bis(phenylmethoxy)phenyl]methoxy]-5-[[3-(phenylmethoxy)-5-[[3-(phenyl-1-pyrenylamino)phenyl]methoxy]phenyl]methoxy]-](http://img.cochemist.com/ccimg/903600/903561-95-5.png)
![Benzenemethanol,3-[[3,5-bis(phenylmethoxy)phenyl]methoxy]-5-[[3-(phenylmethoxy)-5-[[3-(phenyl-1-pyrenylamino)phenyl]methoxy]phenyl]methoxy]-](http://img.cochemist.com/ccimg/903600/903561-95-5_b.png)
![Benzenemethanol,3-(phenylmethoxy)-5-[[3-(phenyl-1-pyrenylamino)phenyl]methoxy]-](http://img.cochemist.com/ccimg/903600/903561-93-3.png)
![Benzenemethanol,3-(phenylmethoxy)-5-[[3-(phenyl-1-pyrenylamino)phenyl]methoxy]-](http://img.cochemist.com/ccimg/903600/903561-93-3_b.png)
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![BENZENE, 1,3-BIS[[3,5-BIS(HEXYLOXY)PHENYL]METHOXY]-5-(BROMOMETHYL)-](http://img.cochemist.com/ccimg/848500/848474-34-0_b.png)
![Benzenemethanol, 3,5-bis[[3,5-bis(hexyloxy)phenyl]methoxy]-](http://img.cochemist.com/ccimg/848500/848474-33-9.png)
![Benzenemethanol, 3,5-bis[[3,5-bis(hexyloxy)phenyl]methoxy]-](http://img.cochemist.com/ccimg/848500/848474-33-9_b.png)
![Benzenemethanol, 3,5-bis[[3-(phenyl-1-pyrenylamino)phenyl]methoxy]-](http://img.cochemist.com/ccimg/840600/840531-10-4.png)
![Benzenemethanol, 3,5-bis[[3-(phenyl-1-pyrenylamino)phenyl]methoxy]-](http://img.cochemist.com/ccimg/840600/840531-10-4_b.png)
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![Benzenesulfonamide, 4-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]-](http://img.cochemist.com/ccimg/154800/154715-61-4_b.png)
![Benzenemethanol,3-[[3,5-bis(phenylmethoxy)phenyl]methoxy]-5-hydroxy-](http://img.cochemist.com/ccimg/129900/129835-71-8.png)
![Benzenemethanol,3-[[3,5-bis(phenylmethoxy)phenyl]methoxy]-5-hydroxy-](http://img.cochemist.com/ccimg/129900/129835-71-8_b.png)
![Benzaldehyde, 4-[(2-ethylhexyl)oxy]-](http://img.cochemist.com/ccimg/119700/119630-71-6.png)
![Benzaldehyde, 4-[(2-ethylhexyl)oxy]-](http://img.cochemist.com/ccimg/119700/119630-71-6_b.png)
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![2-Propenoic acid, 2-methyl-, 2-[(tetrahydro-2H-pyran-2-yl)oxy]ethyl ester](/data/chemimg/1200100/34649-63-3.png)
![2-Propenoic acid, 2-methyl-, 2-[(tetrahydro-2H-pyran-2-yl)oxy]ethyl ester](/data/chemimg/1200100/34649-63-3_b.png)
![[1,1'-Biphenyl]-4-methanol, 2-hydroxy-3',5'-bis(methoxymethoxy)-6-(2-propyn-1-yloxy)-](/data/chemimg/3723500/1190085-95-0.png)
![[1,1'-Biphenyl]-4-methanol, 2-hydroxy-3',5'-bis(methoxymethoxy)-6-(2-propyn-1-yloxy)-](/data/chemimg/3723500/1190085-95-0_b.png)
![3-(2-{4-[3-(TRIFLUOROMETHYL)PHENYL]-1-PIPERAZINYL}ETHYL)[1,3]OXAZ<WBR />OLO[4,5-B]PYRIDIN-2(3H)-ONE](http://img.cochemist.com/ccimg/350100/350035-52-8.png)
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![Benzenemethanol, 3,5-bis[[3,5-bis(phenylmethoxy)phenyl]methoxy]-](http://img.cochemist.com/ccimg/129600/129536-40-9.png)
![Benzenemethanol, 3,5-bis[[3,5-bis(phenylmethoxy)phenyl]methoxy]-](http://img.cochemist.com/ccimg/129600/129536-40-9_b.png)
![5'-(2,4,6-Triphenylpyridin-1-ium-1-yl)-[1,1':3',1''-terphenyl]-2'-olate](http://img.cochemist.com/ccimg/10100/10081-39-7.png)
![5'-(2,4,6-Triphenylpyridin-1-ium-1-yl)-[1,1':3',1''-terphenyl]-2'-olate](http://img.cochemist.com/ccimg/10100/10081-39-7_b.png)
![1-Pyrenamine, N-[3-(bromomethyl)phenyl]-N-phenyl-](http://img.cochemist.com/ccimg/799600/799559-80-1.png)
![1-Pyrenamine, N-[3-(bromomethyl)phenyl]-N-phenyl-](http://img.cochemist.com/ccimg/799600/799559-80-1_b.png)
![Acetic acid, [3-formyl-5-(phenylmethoxy)phenoxy]-, 1,1-dimethylethylester](http://img.cochemist.com/ccimg/758800/758724-73-1.png)
![Acetic acid, [3-formyl-5-(phenylmethoxy)phenoxy]-, 1,1-dimethylethylester](http://img.cochemist.com/ccimg/758800/758724-73-1_b.png)
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![3H-Indolium,2-[3-(1,3-dihydro-3,3- dimethyl-1-octadecyl-2H-indol-2-ylidene)- 1-propenyl]-3,3-dimethyl-1-octadecyl-,perchlorate](http://img.cochemist.com/ccimg/41100/41085-99-8.png)
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![5H-Benzo[a]phenoxazin-5-one,9-(diethylamino)-](http://img.cochemist.com/ccimg/7400/7385-67-3.png)
![5H-Benzo[a]phenoxazin-5-one,9-(diethylamino)-](http://img.cochemist.com/ccimg/7400/7385-67-3_b.png)
![3,5,9-Trioxa-4-phosphaheptacos-18-en-1-aminium,4-hydroxy-N,N,N-trimethyl-10-oxo-7-[[(9Z)-1-oxo-9-octadecen-1-yl]oxy]-, innersalt, 4-oxide, (7R,18Z)-](http://img.cochemist.com/ccimg/4300/4235-95-4.png)
![3,5,9-Trioxa-4-phosphaheptacos-18-en-1-aminium,4-hydroxy-N,N,N-trimethyl-10-oxo-7-[[(9Z)-1-oxo-9-octadecen-1-yl]oxy]-, innersalt, 4-oxide, (7R,18Z)-](http://img.cochemist.com/ccimg/4300/4235-95-4_b.png)
