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This Perspective covers discovery and mechanistic aspects as well as initial applications of novel ionization processes for use in mass spectrometry that guided us in a series of subsequent discoveries, instrument developments, and commercialization. Vacuum matrix-assisted ionization on an intermediate pressure matrix-assisted laser desorption/ionization source without the use of a laser, high voltages, or any other added energy was simply unbelievable, at first. Individually and as a whole, the various discoveries and inventions started to paint, inter alia , an exciting new picture and outlook in mass spectrometry from which key developments grew that were at the time unimaginable, and continue to surprise us in its simplistic preeminence. We, and others, have demonstrated exceptional analytical utility. Our current research is focused on how best to understand, improve, and use these novel ionization processes through dedicated platforms and source developments. These ionization processes convert volatile and nonvolatile compounds from solid or liquid matrixes into gas-phase ions for analysis by mass spectrometry using, e.g. , mass-selected fragmentation and ion mobility spectrometry to provide accurate, and sometimes improved, mass and drift time resolution. The combination of research and discoveries demonstrated multiple advantages of the new ionization processes and established the basis of the successes that lead to the Biemann Medal and this Perspective. How the new ionization processes relate to traditional ionization is also presented, as well as how these technologies can be utilized in tandem through instrument modification and implementation to increase coverage of complex materials through complementary strengths.

Polymers have a wide range of applications depending on their composition, size, and architecture. Varying any of these three characteristics can greatly impact the resulting chemical, physical, and mechanical properties. While many techniques are available to determine polymer composition and size, determining the exact polymer architecture is more challenging. Herein, tandem mass spectrometry (MS/MS) and ion mobility mass spectrometry (IM-MS) methods are utilized to derive crucial architectural information about dithiol-yne comb polymers. Based on their unique fragmentation products and IM drift times, dithiol-yne oligomers with distinct architectures were successfully differentiated and characterized. Additionally, experimental collision cross-sections (Ω) derived via IM-MS were compared to theoretically extracted Ω values from molecular dynamics simulated structures to deduce the architectural motif of these comb oligomers. Overall, this work demonstrates the benefits of combining various mass spectrometry techniques in order to gain a complete understanding of a complex polymer mixture.

Organometallic-mediated chain growth polymerization of readily accessible chemical building blocks is responsible for important commercial and technological advances in polymer science, but the incorporation of heteroatoms into the polymer backbone through these mechanisms remains a challenge. Transition metal π-allyl complexes are well-developed organometallic intermediates for carbon-heteroatom bond formation in small-molecule catalysis yet remain underexplored in polymer science. Here, we developed a regioselective palladium-phosphoramidite-catalyzed chain-growth allylic amination polymerization of vinyl aziridines for the synthesis of novel nitrogen-rich polymers via ambiphilic π-allyl complexes. The polymerization accessed a linear microstructure with four carbons between each nitrogen, which is challenging to achieve through other chain-growth polymerization approaches. The highly regioselective allylic amination polymerization demonstrated the characteristics of a controlled polymerization and was able to achieve molar masses exceeding 20 kg mol -1 with low dispersities ( D̵ < 1.3). The identification of the polymer structure and well-defined chain ends were supported by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and chain extension experiments demonstrate opportunities for building more complex materials from this method. A Hammett study was performed to understand the role of the catalyst and monomer structure on regioselectivity, and the data supported a mechanism wherein regioselectivity was primarily controlled by the ligand-metal complex. Postpolymerization desulfonylation provided access to a novel polyamine that demonstrated broad anticancer activity in vitro, which highlights the benefits of unlocking novel polyamine microstructures through regioselective chain-growth allylic amination polymerization.

The chain architecture and topology of macromolecules impact their physical properties and final performance, including their crystallization process. In this work, comb polymers constituted by poly(ethylene glycol), PEG, side chains, and a dithiol-yne-based ring polymer backbone have been studied, focusing on the micro- and nanostructures of the system, thermal behavior, and crystallization kinetics. The designed comb system allows us to investigate the role of a ring backbone, the impact of varying the distance between two neighboring side chains, and the effect of the molecular weight of the side chain. The results reflect that the governing factor in the crystalline properties is the molar mass of the side chains and that the tethering of PEG chains to the ring backbone brings important constraints to the crystallization process, reducing the crystallinity degree and slowing down the crystallization kinetics in comparison to analogue PEG homopolymers. We demonstrate that the effect of spatial hindrance in the comb-like PEG polymers drives the morphology toward highly ordered, self-assembled, semicrystalline superstructures with either extended interdigitated chain crystals or novel (for comb polymers) interdigitated folded chain lamellar crystals. These structures depend on PEG molecular weight, the distance between neighboring tethered PEG chains, and the crystallization conditions (nonisothermal versus isothermal). This work sheds light on the role of chain architecture and topology in the structure of comb-like semicrystalline polymers., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Zwitterionic ring-expansion polymerization (ZREP) is a polymerization method in which a cyclic monomer is converted into a cyclic polymer through a zwitterionic intermediate. In this review, we explored the ZREP of various cyclic polymers and how mass spectrometry assists in identifying the product architectures and understanding their intricate reaction mechanism. For the majority of polymers (from a few thousand to a few million Da) matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is the most effective mass spectrometry technique to determine the true molecular weight (MW) of the resultant product, but only when the dispersity is low (approximately below 1.2). The key topics covered in this study were the ZREP of cyclic polyesters, cyclic polyamides, and cyclic ethers. In addition, this study also addresses a number of other preliminary topics, including the ZREP of cyclic polycarbonates, cyclic polysiloxanes, and cyclic poly(alkylene phosphates). The purity and efficiency of those syntheses largely depend on the catalyst. Among several catalysts, N-heterocyclic carbenes have exhibited high efficiency in the synthesis of cyclic polyesters and polyamides, whereas tris(pentafluorophenyl)borane [B(C 6 F 5 ) 3 ] is the most optimal catalyst for cyclic polyether synthesis., (© 2024 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd.)

Mass spectrometry (MS) has become an essential technique to characterize dendrimers as it proved efficient at tackling analytical challenges raised by their peculiar onion-like structure. Owing to their chemical diversity, this review covers benefits of MS methods as a function of dendrimer classes, discussing advantages and limitations of ionization techniques, tandem mass spectrometry (MS/MS) strategies to determine the structure of defective species, as well as most recently demonstrated capabilities of ion mobility spectrometry (IMS) in the field. Complementarily, the well-defined structure of these macromolecules offers major advantages in the development of MS-based method, as reported in a second section reviewing uses of dendrimers as MS and IMS calibration standards and as multifunctional charge inversion reagents in gas phase ion/ion reactions., (© 2024 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd.)

Polysulfamides are the -SO 2 - analogues of polyureas and form an intriguing family of polymers containing hydrogen-bond donor and acceptor groups. However, unlike polyureas, their physical properties are mostly unknown because of the scarcity of synthetic methods to access such polymers. Herein, we report an expedient synthesis of AB monomers for the synthesis of polysulfamides via Sulfur(VI) Fluoride Exchange (SuFEx) click polymerization. Upon optimization of the step-growth process, a variety of polysulfamides were isolated and characterized. The versatility of the SuFEx polymerization allowed structural modulation of the main chain through the incorporation of aliphatic or aromatic amines. While all synthesized polymers presented high thermal stability via thermogravimetric analysis, the glass-transition temperature and crystallinity were shown to be highly tied to the structure of the backbone between repeating sulfamide units through differential scanning calorimetry and powder X-ray diffraction. Careful analysis via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and X-ray crystallography also revealed the formation of macrocyclic oligomers during the polymerization of one AB monomer. Finally, two protocols were developed to efficiently degrade all synthesized polysulfamides through either chemical recycling for polymers derived from aromatic amines or oxidative upcycling for those based on aliphatic amines., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Herein, we report the toxicity evaluation of a new prototype dispersant system, silicon dioxide nanoparticles (NPs) functionalized with (3-glycidoxypropyl)triethoxysilane (GPS) and grafted poly(ε-caprolactone)- block -poly[oligo(ethylene glycol)methyl methacrylate mono-methyl ether] (NP-PCL-POEGMA). This serves as a follow up of our previous study where grafted silicon dioxide NPs functionalized with GPS and grafted hyperbranched poly(glycidol) (NP-HPG) were evaluated for reducing the toxicity in embryo, juvenile, and adult fish populations. In this study, the NP-HPG sample is used as a baseline to compare against the new NP-PCL-POEGMA samples. The relative size was established for three NP-PCL-POEGMA samples via cryogenic transmission electron microscopy. A quantitative mortality study determined that these NPs are non-toxic to embryo populations. An ethoxyresorufin-O-deethylase assay was performed on these NP-PCL-POEGMA samples to test for reduced cytochrome P450 1A after the embryos were exposed to the water-accommodated fraction of crude oil. Overall, these NP-PCL-POEGMA NPs better protected the embryo populations than the previous NP-HPG sample (using a protein activity end point), showing a trend in the right direction for prototype dispersants to replace the commercially utilized Corexit.

Macrocyclic poly(glycidyl phenyl ether) (pGPE) synthesized via zwitterionic ring opening polymerization is typically contaminated by chains with linear and tadpole architecture. Although mass spectrometry (MS) analysis can readily confirm the presence of the linear byproduct, due to its unique mass, it is unable to differentiate between the cyclic and tadpole structures, which are constitutional isomers produced by backbiting reactions in monomeric or dimeric chains, respectively. To overcome this problem, ultraperformance reversed-phase liquid chromatography interfaced with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) was employed. The separation achieved by UPLC revealed that the tadpole isomer elutes before the cyclic structure because of the increased polarity afforded by its distinctive substituents. The ratio of tadpole to cyclic species increased with the degree of polymerization, in agreement with the synthetic method used, as the potential for forming tadpole structures by backbiting is entropically favored in longer polymer chains. Once separated, the two isomers could be independently characterized by tandem mass spectrometry. The macrocyclic and tadpole species exhibit unique fragmentation patterns, including structurally diagnostic fragments for each structure.

Rationale: A calibration solution for mass spectrometry needs to cover the range of interest with intense and sufficiently narrowly spaced peaks. Limited options fulfilling this may lead to compromises between performance and ease of use. SpheriCal ® -ESI was designed to combine high calibration performance for electrospray ionization (ESI) mass spectrometric analysis of peptides in positive mode with quick and easy use., Methods: The developed calibration solution was tested using three mass spectrometers: two ion traps and one tandem quadrupole. The m/z errors of SpheriCal ® -ESI itself and of a tryptic digest of cytochrome C were measured after calibration. The results were compared with those achieved with ESI Tuning Mix. The memory effects of the dendrimers, and contamination from Na + in the calibration solution, were evaluated., Results: SpheriCal ® -ESI showed good shelf life as powder and was quickly reconstituted for use. Achieving intense and stable signals was straightforward. The accuracies and precisions were as expected for the instruments. SpheriCal ® -ESI was more precise and at least as accurate as ESI Tuning Mix. The memory effects and Na + contamination were found to be negligible in typical peptide solvents. In addition, the dendrimers showed predictable dissociations with product ions common to collision-induced dissociation in both ion trap and tandem quadrupole mass spectrometers., Conclusions: SpheriCal ® -ESI provided easily accessible calibration by showing intense signals at low infusion rates and at source settings equal or similar to those used in peptide analysis. Nine calibration points in the range of interest gave precise and accurate results. Memory effects and contamination were negligible even without rinsing., (© 2020 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Aqueous ring-opening metathesis polymerization (ROMP) is a powerful tool for polymer synthesis under environmentally friendly conditions, functionalization of biomacromolecules, and preparation of polymeric nanoparticles via ROMP-induced self-assembly (ROMPISA). Although new water-soluble Ru-based metathesis catalysts have been developed and evaluated for their efficiency in mediating cross metathesis (CM) and ring-closing metathesis (RCM) reactions, little is known with regards to their catalytic activity and stability during aqueous ROMP. Here, we investigate the influence of solution pH, the presence of salt additives, and catalyst loading on ROMP monomer conversion and catalyst lifetime. We find that ROMP in aqueous media is particularly sensitive to chloride ion concentration and propose that this sensitivity originates from chloride ligand displacement by hydroxide or H 2 O at the Ru center, which reversibly generates an unstable and metathesis inactive complex. The formation of this Ru-(OH) n complex not only reduces monomer conversion and catalyst lifetime but also influences polymer microstructure. However, we find that the addition of chloride salts dramatically improves ROMP conversion and control. By carrying out aqueous ROMP in the presence of various chloride sources such as NaCl, KCl, or tetrabutylammonium chloride, we show that diblock copolymers can be readily synthesized via ROMPISA in solutions with high concentrations of neutral H 2 O (i.e., 90 v/v%) and relatively low concentrations of catalyst (i.e., 1 mol %). The capability to conduct aqueous ROMP at neutral pH is anticipated to enable new research avenues, particularly for applications in biological media, where the unique characteristics of ROMP provide distinct advantages over other polymerization strategies.

Since their discovery, cyclic polymers have attracted great interest because of their unique properties. Today, the preparation of these macrocyclic structures still remains a challenge for polymer chemists, and most of the preparation pathways lead to an inescapable contamination by linear by-products. As the properties of the polymers are closely related to their structure, it is of prime importance to be able to assess the architectural purity of a sample., Methods: In this work, the suitability of ion mobility spectrometry-mass spectrometry (IMS-MS) for the quantification of two isomers was investigated. A cyclic poly(L-lactide) was prepared through photodimerization of its linear homologue. Since IMS-MS can be used to differentiate cyclic polymer ions from their linear analogues because of their more compact three-dimensional conformation, the present work envisaged the use of IMS-MS for the quantification of residual linear polymers within the cyclic polymer sample., Results: Using the standard addition method to plot calibration curves, the fraction of linear contaminants in the sample was determined. By doing so, unrealistically high values of contamination were measured., Conclusions: These results were explained by an ionization efficiency issue. This work underlines some intrinsic limitations when using IMS-MS in the context of the relative quantification of isomers having different ionization efficiencies. Nevertheless, the linear-to-cyclic ratio can be roughly estimated by this method., (© 2019 John Wiley & Sons, Ltd.)

Photo-redox mediated ring-opening metathesis polymerization (photo-ROMP) is an emerging ROMP technique that uses an organic redox mediator and a vinyl ether initiator, in contrast to metal-based initiators traditionally used in ROMP. The reversibility of the redox-mediated initiation and propagation steps enable spatiotemporal control over the polymerization. Herein, we explore a simple, inexpensive means of controlling molecular weight, using alpha olefins as chain transfer agents. This method enables access to low molecular weight oligomers, and molecular weights between 1 and 30 kDa can be targeted simply by altering the stoichiometry of the reaction. This method of molecular weight control was then used to synthesize a functionalized norbornene copolymer in a range of molecular weights for specific materials applications., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Unlike their more common linear counterparts, cyclic polymers have a ring-like structure and a lack of chain ends. Because of their topology, cyclic polymers exhibit a unique set of properties when compared with linear or branched macromolecules. For example, cyclic homopolymers exhibit a reduced hydrodynamic volume and a slower degradation profile compared with their linear analogues. Cyclic block copolymers self-assemble into compact nanostructures, as illustrated by their reduced domain spacing when cast into thin films and their reduced micellar size in solution. Although methods for preparing well-defined cyclic polymers have only been available since 1980, the extensive utilization of the cyclic topology in nature highlights the vital role that a cyclic architecture can play in imparting valuable physical properties, such as increased chemical stability or propensity towards self-assembly. This Review describes the major developments in the synthesis of cyclic polymers and provides an overview of their fundamental physical properties. In this context, preliminary studies exploring potential applications will be critically assessed and the remaining challenges for the field delineated.

In 2,2,5-trimethyl-1,3-dioxane-5-carb-oxy-lic acid, C 8 H 14 O 4 , the carboxyl group occupies an equatorial position on the 1,3-dioxane ring. In the crystal, O-H⋯O hydrogen bonds form chains of mol-ecules, which are linked into a three-dimensional network by C-H⋯O hydrogen bonds. The asymmetric unit of 2,2,5-trimethyl-1,3-dioxane-5-carb-oxy-lic anhydride, C 16 H 26 O 7 , consists of two independent mol-ecules, which are linked by C-H⋯O hydrogen bonds. In the crystal, these units are connected into corrugated layers two mol-ecules thick and parallel to the ab plane by additional C-H⋯O hydrogen bonds., (© Giesen et al. 2020.)

Tandem mass spectrometry (MS 2 ) has been employed to elucidate the topology and branching architecture of star-branched polyethers. The polymers were ionized by matrix-assisted laser desorption/ionization (MALDI) to positive ions and dissociated after leaving the ion source via laser-induced fragmentation. The bond scissions caused under MALDI-MS 2 conditions occur preferentially near the core-branch joining points due to energetically favorable homolytic and heterolytic bond cleavages near the core and release of steric strain and/or reduction of crowding. This unique fragmentation mode detaches complete arms from the core generating fragment ion series at the expected molecular weight of each branch. The number of fragment ion distributions observed combined with their mass-to-charge ratios permit conclusive determination of the degree of branching and the corresponding branch lengths, as demonstrated for differently branched homo- and mikto-arm polyether stars synthesized via azide-alkyne click chemistry. The results of this study underscore the utility of MS 2 for the characterization of branching architecture and branch lengths of (co) polymers with two or more linear chains attached to a functionalized central core.

Herein, the design, synthesis, and characterization of an unprecedented copolymer consisting of alternating linear and dendritic segments is described. First, a 4th-generation Hawker-type dendron with two azide groups was synthesized, followed by a step-growth azide-alkyne "click" reaction between the 4th-generation diazido dendron and poly(ethylene glycol) diacetylene to create the target polymers. Unequal reactivity of the functional groups was observed in the step-growth polymerization. The resulting copolymers, with alternating hydrophilic linear and hydrophobic dendritic segments, can spontaneously associate into a unique type of microphase-segregated nanorods in water., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of branched polymers, consisting of a poly(ethylene glycol) (PEG) core and lipophilic peripheral dendrons, were synthesized and their self-assembly into reverse micelles studied toward the ultimate goal of carrier-mediated transdermal drug delivery. More specifically, this investigation systematically explores the structure-property contributions arising from location and extent of branching by varying the number of branch points at the core and the generation of dendrons at the polar/nonpolar interface. For branching at the core, PEGs were selected with one, two or four arms, with one terminal functionality per arm. For peripheral branching, end groups were modified with polyester dendrons (of dendritic generations 0, 1, and 2) for each of the three cores. Finally, lauric acid (LA) was used to esterify the periphery, yielding a library of branched, amphiphilic polymers. Characterization of these materials via MALDI-TOF MS, GPC and NMR confirmed their exceptionally well-defined structure. Furthermore, atomic force microscopy (AFM) and dynamic light scattering (DLS) confirmed these polymers' abilities to make discrete aggregates. As expected, increased multiplicity of branching resulted in more compact aggregates; however, the location of branching (core vs periphery) did not seem as important in defining aggregate size as the extent of branching. Finally, computational modeling of the branched amphiphile series was explored to elucidate the macromolecular interactions governing self-assembly in these systems.

The reverse micelle self-assembly of lipophile-functionalized poly(ethylene glycol) (PEG) dendrimer hybrids is probed for applications in carrier-mediated transdermal drug delivery. Under investigation are topologically diverse amphiphiles featuring controlled branching motifs at either the polymer core (one-, two-, and four-arm PEG) and the polar/nonpolar interface (peripheral dendritic generations 0-2). Thus, a systematic investigation of the effect of branching location (core vs peripheral) on carrier properties is described. Dye-encapsulation experiments verify these materials are capable of forming well-defined aggregates and solubilizing polar compounds. Further quantification of reverse micelle critical micelle concentration and dye loading capacity for the branched amphiphile library was obtained through spectroscopy characterization. Both core and peripheral branching are shown to significantly influence dynamic encapsulation behavior, with evidence of location-based contributions extending beyond multiplicity of branching alone. Finally, the in vitro transdermal diffusion of the reverse micelle carriers was investigated through Franz diffusion cell experiments using physiologically relevant juvenile porcine dermis. The permeation results, combined with previously reported aggregate size trends, show the complex relationship between polymer branching and transdermal transport, with the lowest core- and highest peripherally-branched amphiphilic analogs exhibiting optimal transdermal permeation characteristics for this set of branched carriers.

There are many techniques that can be employed in the characterization of synthetic homopolymers, but few provide as useful of information for end group analysis as matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). This tutorial demonstrates methods for optimization of the sample preparation, spectral acquisition, and data analysis of synthetic polymers using MALDI-TOF MS. Critical parameters during sample preparation include the selection of the matrix, identification of an appropriate cationization salt, and tuning the relative proportions of the matrix, cation, and analyte. The acquisition parameters, such as mode (linear or reflector), polarization (positive or negative), acceleration voltage, and delay time, are also important. Given some knowledge of the chemistry involved to synthesize the polymer and optimizing both the data acquisition parameters and the sample preparation conditions, spectra should be obtained with sufficient resolution and mass accuracy to enable the unambiguous determination of the end groups of most homopolymers (masses below 10,000) in addition to the repeat unit mass and the overall molecular weight distribution. Though demonstrated on a limited set of polymers, these general techniques are applicable to a much wider range of synthetic polymers for determining mass distributions, though end group determination is only possible for homopolymers with narrow dispersity.

Calibrants based on synthetic dendrimers have been recently proposed as a versatile alternative to peptides and proteins for both MALDI and ESI mass spectrometry calibration. Because of their modular synthetic platform, dendrimer calibrants are particularly amenable to tailoring for specific applications. Utilizing this versatility, a set of dendrimers has been designed as an internal calibrant with a tailored mass defect to differentiate them from the majority of natural peptide analytes. This was achieved by incorporating a tris-iodinated aromatic core as an initiator for the dendrimer synthesis, thereby affording multiple calibration points (m/z range 600-2300) with an optimized mass-defect offset relative to all peptides composed of the 20 most common proteinogenic amino acids. Graphical abstract ᅟ.

Pickering emulsions offer an established method of stabilizing oil-in-water emulsions as either an alternative to surfactants or as an additive together with surfactants, providing greater colloidal stability even at low particle concentrations. This work presents a novel experimental approach to study the influence of several system parameters on the effectiveness of Pickering emulsion systems. Specifically, a dodecane oil drop stabilized by hard carbon microspheres in an aqueous saline solution is used as a model system to obtain both quantitative and qualitative information on the effectiveness of the microspheres as a function of their surface wetting properties. The test setup, in which a macroscopic oil drop is brought into contact with a test surface in a controlled motion and environment, allows for several aspects of the test (for e.g., oil drop size, approach velocity, normal force, solution ionic strength, temperature, pH, and presence of surfactants) to be potentially controlled and studied precisely. To demonstrate the capabilities of the experimental set-up, hard carbon microspheres are modified with a poly(styrenesulfonate) shell through ATRP in order to tune the wettability of the particles through choice of polymer, which are then used to stabilize a dodecane oil drop in an aqueous saline solution. The particles effectively form a steric barrier preventing the spreading of an oil drop on hydrophobic surfaces and also preventing the coalescence of stabilized oil drops., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Extensive all-atom molecular dynamics simulations were carried out on three novel amphiphilic homopolymers in explicit polar and nonpolar solvent environments. These nonlinear polymers have potential applications in drug delivery and consisted of 32 repeating bifurcated amphiphilic side chains bound to an alkynyl functionalized cyclic framework. All of the polymer systems investigated have the same backbone and hydrophobic dodecyl side chains and differ only in the nature of the hydrophilic side chains. This report focuses on the solvent polarity induced conformational changes exhibited as a result of the different hydrophilic modifications. Our simulations of polymer microenvironment provides useful information about the amphiphilic phase segregation that drives the formation of normal micelle-like and reverse micelle-like nanostructures that are expected to occur in response to solvents of varying polarities.

Lysine-containing polymers have seen broad application due to their amines' inherent ability to bind to a range of biologically relevant molecules. The synthesis of multiple generations of polyester dendrimers bearing lysine groups on their periphery is described in this report. Their hydrolytic stabilities with respect to pH and time, their toxicity to a range of cell lines, and their possible application as nano-detoxification agents of organophosphate compounds are all investigated. These zeroth-, first-, and second-generation water-soluble dendrimers have been designed to bear exactly 4, 8, and 16 lysine groups, respectively, on their dendritic periphery. Such monodisperse bioactive polymers show potential for a range of applications including drug delivery, gene delivery, heavy metal binding, and the sequestration of organic toxins. These monodisperse bioactive dendrimers were synthesized using an aliphatic ester dendritic core (prepared from pentaerythritol) and protected amino acid moieties. This library of lysine-conjugated dendrimers showed the ability to efficiently capture the pesticide dichlorvos, confirming the potential of dendrimer-based antidotes to maintain acetylcholinesterase activity in response to poisoning events.

Polymer-ceramic nanocomposites have been thoroughly investigated previously for high energy storage devices. However, the increase in performance of these nanocomposites has proven to be significantly lower than predicted values. Through surface functionalization of high dielectric constant nanoparticles (NP), the flaws that reduce composite performance can be eliminated to form high energy density composite materials. Functionalization methods utilize high throughput printing and curing techniques (i.e., inkjet printing and xenon flash lamp curing) that are crucial for rapid adoption into industrial production. (Ba,Ca) (Zr,Ti)O3 NPs (50 nm) are synthesized through the solvothermal method and functionalized with alkene terminated methoxysilanes. A thiol-ene monomer ink system, PTD3 [pentaerythritol tetrakis (3-mercaptopropionate) (PEMP, P), 1,3-Diisopropenylbenzene (DPB, D), 2,4,6-Triallyloxy-1,3,5-triazine (TOTZ, T)], is used as a high breakdown polymer matrix. Neat polymer, alkene terminated NP-polymer composites, and hydrophilic, TBAOH functionalized NP-polymer composites were spin coated onto both copper laminated glass slides and printed onto copper substrates in 1 cm(2) patterns for testing. Alkene functionalized NPs increased the breakdown strength by ∼38% compared to the nonfunctionalized NPs. Functionalized NPs increased both the breakdown strength and dielectric constant compared to the neat polymer, increasing the energy density nearly 3-fold from 13.3 to 36.1 J·cm(-3).

The power of ion mobility spectrometry-mass spectrometry (IMS-MS) as an analytical technology for differentiating macromolecular architecture is demonstrated. The presence of architectural dispersity within a sample is probed by sequentially measuring both the drift time and the mass-to-charge ratio for every component within a polymer sample. The utility of this technology is demonstrated by investigating three poly(ethylene glycol) (PEG) architectures with closely related average molecular weights of about 9000 Da: a linear PEG, an unevenly branched miktoarm star PEG, and evenly branched homoarm star PEGs. The three architectures were readily distinguished when analyzed separately as "pure" architectures or when analyzed as mixtures. IMS-MS results are contrasted with matrix-assisted laser desorption/ionization-MS and viscometry measurements.

The delivery of genetic material to cells offers the potential to treat many genetic diseases. Cationic polymers, specifically poly(ethylene imine) (PEI), are promising gene delivery vectors due to their inherent ability to condense genetic material and successfully affect its transfection. However, PEI and many other cationic polymers also exhibit high cytotoxicity. To systematically study the effect of polymer architecture on gene delivery efficiency and cell cytotoxicity, a set of cyclic PEIs were prepared for the first time and compared to a set of linear PEIs of the exact same molecular weight. Subsequent in vitro transfection studies determined a higher transfection efficiency for each cyclic PEI sample when compared to its linear PEI analogue in addition to reduced toxicity relative to the branched PEI "gold standard" control. These results highlight the critical role that the architecture of PEI can play in both optimizing transfection and reducing cell toxicity.

The protective performance of zeolite coating on AZ91D magnesium alloy was evaluated using potentiodynamic polarisation and electrochemical impedance spectroscopy (EIS) in 0.1 M sodium chloride solution (NaCl). Electrical equivalent circuit (EEC) was developed based upon hypothetical corrosion mechanisms and simulated to correspond to the experimental data. The morphology and the chemical nature of the coating were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. Post corrosion morphologies of the zeolite coated and the uncoated AZ91D alloy were investigated using SEM. The corrosion resistance of the zeolite coated specimen was at least one order of magnitude higher than the uncoated specimen.

We have studied the conformational changes of two novel amphiphilic homopolymers in water and toluene relevant to delivery applications using molecular dynamics simulations supplemented with enhanced sampling techniques. The individual homopolymer repeating units are amphiphilic with a hydrophobic dodecyl chain and a hydrophilic tetra(ethylene glycol) chain attached via ether linkages to each repeating unit of the polymer backbone. Two polymer topologies were examined: one cyclic and one an exact linear analog. Here we show that these polymers exhibit highly dynamic conformations with the side arm orientations driven by the solvent polarity. In water these polymers exhibit a compact conformation with the hydrophobic arms retracted toward the backbone core, whereas in toluene the hydrophobic arms extended into the solvent. Different from the hydrophobic arms, the hydrophilic ethylene glycol chain orientations and backbone conformations are largely unperturbed by the solvent polarity. Probing the polymer microenvironment in different solvents to examine solute uptake supports the hypothesis that these polymers can selectively encapsulate/release guest molecules depending on the solvent polarity, highlighting the potential of these polymers as drug delivery vehicles.

We describe a method to construct water-soluble porphyrinic nanospheres with enhanced photo-physical properties as a result of precluding (via intra-molecular host-guest interactions) the individual porphyrins units from aromatic-aromatic stacking.

End groups play a critical role in macromolecular coupling reactions for building complex polymer architectures, yet their identity and purity can be difficult to ascertain using traditional analytical technique. Recent advances in mass spectrometry techniques have made matrix-assisted laser desorption/ionization time-of-fight (MALDI-TOF) mass spectrometry a rapid and powerful tool for providing detailed information about the identity and purity of homopolymer end groups. In this work, MALDI-TOF mass spectrometry was used to study end groups of linear polyethylene glycols. In particular, the identifications of alcohol, amine and thiol end groups are investigated because these nucleophilic moieties are among the most common within biological and synthetic macromolecules. Through comparative characterization of alcohol, amine, and thiol end groups, the exact identification of these end groups could be confirmed by selective and quantitative modification. The precision of this technique enables the unambiguous differentiation of primary amino groups relative to hydroxyl groups, which differ by only 1 mass unit. In addition, the quantitative conversion of various polyethylene glycol end groups using highly efficient coupling reactions such as the thiol-ene and azide-alkyne click reactions can be confirmed using MALDI-TOF mass spectrometry., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The utilization of dendrimer calibrants as an alternative to peptides and proteins for high mass calibration is explored. These synthetic macromolecules exhibited a number of attractive advantages, including exceptional shelf-lives, broad compatibility with a wide range of matrices and solvents, and evenly spaced calibration masses across the mass range examined, 700-30,000 u. The exceptional purity of these dendrimers and the technical simplicity of this calibration platform validate their broad relevance for high molecular weight mass spectrometry.

The synthesis of branched poly(ethylene glycol) (PEG) derivatives, namely star PEG and dendronized PEG, can be challenging and their purity can be difficult to ascertain using traditional techniques, such as NMR and GPC. Herein, the detailed characterization of these branched PEGs using MALDI-ToF MS was investigated in order to confirm their structural purity. In this light, mass spectrometry offers a number of advantages for polymer characterization, including the ability to get detailed structural data, such as end group masses, from microgram-scale samples. In addition, the ability to rapidly acquire data from crude reaction aliquots makes MALDI-ToF MS ideal for monitoring end group transformations., (Copyright © 2013 Elsevier B.V. All rights reserved.)

High purity homo-arm and mikto-arm poly(ethylene glycol) (PEG) stars are successfully prepared by the combination of epoxide ring-openings and azide-alkyne click reactions. First, monohydroxy-PEG was modified via epoxide chemistry to bear one hydroxyl and one azide functionality at the same end. An alkyne-functionalized PEG chain was then coupled to the azide. Subsequently, the remaining hydroxyl could be reactivated to an azide again and again to enable stepwise addition of alkyne-functionalized polymer arms. The use of efficient reactions for this iterative route provides star polymers with an exact number of arms, and a tailorable degree of polymerization for each arm. Detailed characterization confirms the high purity of multi-arm polyethylene glycol products., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

While amphiphilic block copolymers have demonstrated their utility for a range of practical applications, the behavior of cyclic block copolymers remains largely unexplored due to limited synthetic access. To investigate their micelle formation, biocompatible cyclic amphiphilic poly(ethylene glycol)-polycaprolactone, c-(PEG-PCL), was synthesized by a combination of ring-opening polymerization (ROP) and click chemistry. In addition, exactly analogous linear block copolymers have been prepared as a control sample to elucidate the role of polymer architecture in their self-assembly and acid-catalyzed degradation.

[M + Ag](+) ions from cyclic and linear polystyrenes and polybutadienes, formed by matrix-assisted laser desorption ionization (MALDI), give rise to significantly different fragmentation patterns in tandem mass spectrometry (MS(2)) experiments. In both cases, fragmentation starts with homolytic cleavage at the weakest bond, usually a C-C bond, to generate two radicals. From linear structures, the separated radicals depolymerize extensively by monomer losses and backbiting rearrangements, leading to low-mass radical ions and much less abundant medium- and high-mass closed-shell fragments that contain one of the original end groups, along with internal fragments. With cyclic structures, depolymerization is less efficient, as it can readily be terminated by intramolecular H-atom transfer between the still interconnected radical sites (disproportionation). These differences in fragmentation reactivity result in substantially different fragment ion distributions in the MS(2) spectra. Simple inspection of the relative intensities of low- versus high-mass fragments permits conclusive determination of the macromolecular architecture, while full spectral interpretation reveals the individual end groups of linear polymers or the identity of the linker used to form the cyclic polymer.

Amphiphilic polymers are particularly useful for drug delivery because of their ability to self-assemble into discrete aggregates. While this behavior has been studied in depth for simple linear block copolymer amphiphiles, recent advances in synthetic methodologies have provided efficient routes to amphiphilic polymers with more complex architecture, including dendrimers, hyperbranched polymers, star polymers, and cyclic polymers. These architectures can impart unique advantages, such as increased stability, on their micellar aggregates. Herein the different strategies for preparing these complex amphiphiles are described, and the application of their assemblies towards drug delivery are summarized., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Cyclic dendronized polymers represent a new class of polymers which exhibit a donut-like "toroidal" shape. Two previous unreported methods for preparing this architecture, the divergent "graft-from" and the convergent click "graft-to" approaches, are explored and the resulting products fully characterized. This route is particularly attractive because it enables production of exact linear and cyclic dendronized analogues, enabling direct comparison of their physical properties. In this preliminary work, the divergent "graft from" approach appears to lead to materials with broad PDI at high DP, whereas the "graft to" approach yields more well-defined dendronized cyclic polymers at larger DP. On the basis of reports to date, a combination of click cyclization followed by click "grafting to" provides the most versatile route for the synthesis of cyclic dendronized polymers.

The surface modification of deep-cavity cavitands has been demonstrated by using the azide-alkyne "click" coupling to attach dendritic macromolecules or linear polymers onto their periphery. The resulting set of macromolecular cavitands exhibited tuneable solubility yet retained the ability to encapsulate guest molecules.

Amphiphilic star polymers offer substantial promise for a range of drug delivery applications owing to their ability to encapsulate guest molecules. One appealing but underexplored application is transdermal drug delivery using star block copolymer reverse micelles as an alternative to the more common oral and intravenous routes. We prepared 6- and 12-arm amphiphilic star copolymers via atom transfer radical polymerization (ATRP) of sequential blocks of polar oligo (ethylene glycol)methacrylate and nonpolar lauryl methacrylate from brominated dendritic macroinitiators based on 2,2-bis(hydroxymethyl) propionic acid. These star block copolymers demonstrate the ability to encapsulate polar dyes such as rhodamine B and FITC-BSA in nonpolar media via UV/vis spectroscopic studies and exhibit substantially improved encapsulation efficiencies, relative to self-assembled "1-arm" linear block copolymer analogs. Furthermore, their transdermal carrier capabilities were demonstrated in multiple dye diffusion studies using porcine skin, verifying penetration of the carriers into the stratum corneum.

Recent advances in the resolving power of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) enable the detailed characterization of linear homopolymers, and in particular provide invaluable data for the determination of their end-group functionalities. With the growing importance of macromolecular coupling reactions in building complex polymer architectures, the ability to accurately monitor end-group transformations is becoming increasingly important for synthetic polymer chemists. This tutorial demonstrates the application of MALDI-TOF MS in determining both end-group functionalities and their transformations for linear homopolymers. Examples of both polycaprolactone and polystyrene are examined, and the strengths and weaknesses of various approaches to data analysis are given., (Copyright 2010 John Wiley & Sons, Ltd.)

Despite decades of studies devoted to the unique physical properties and potential applications of cyclic polymer topologies, their exploration has remained limited because of synthetic inefficiencies and acyclic impurities. Many recently developed synthetic techniques offer efficient routes to well-defined cyclic macromolecules to answer this need. This tutorial review aims to provide a concise overview of the most significant synthetic contributions in this field, and highlight the relative advantages and disadvantages of each approach.

At neutral pH, dendronized deep-cavity cavitands were shown to form supramolecular nanocapsules via assembly around a range of guest molecules.

The use of polymeric carriers for drug delivery has become increasingly popular because of the ability to easily tune the physical and biological properties of macromolecules. With the growing commercial accessibility of branched and dendritic polymers, their incorporation into polymeric carriers is being explored with increased frequency. However, while a handful of systematic studies have explored the use of branched macromolecules for drug delivery, the role of polymer architecture in optimizing the polymeric carriers is not yet fully understood. Herein, the authors summarize the effect that architecture has on the basic physical properties of polymers, and review our preliminary understanding of the architectural effects on polymer-assisted drug delivery.

An efficient synthetic method for preparing bifurcated amphiphiles has been developed such that the functionality for attachment is located at the interface between the lipophilic and hydrophilic side chains. Attachment of the amphiphile to the repeat units of polymeric substrates enables the rapid preparation of amphiphilic homopolymers.

Polystyrene macrocycles have been prepared from ATRP precursors by modification of the terminal bromide to an azide, followed by "click" cyclization with a pendant alkyne from the initiator. This route offers exceptional control over the size and polydispersity of the macrocyclic polymers, as well as providing tolerance to a number of functional groups.