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A 500 nm charge-stabilized latex is converted into 40 nm sterically-stabilized nanoparticles via reverse sequence polymerization-induced self-assembly (PISA).

We report the rational design of aldehyde-functional sterically stabilized diblock copolymer nano-objects in aqueous solution via polymerization-induced self-assembly. More specifically, reversible addition-fragmentation chain transfer aqueous dispersion polymerization of 2-hydroxypropyl methacrylate is conducted using a water-soluble precursor block in which every methacrylic repeat unit contains a pendent oligo(ethylene glycol) side chain capped with a cis-diol unit. Systematic variation of the reaction conditions enables the construction of a pseudo-phase diagram, which ensures the reproducible targeting of pure spheres, worms, or vesicles. Selective oxidation of the pendent cis-diol groups using aqueous sodium periodate under mild conditions introduces geminal diols (i.e., the hydrated form of an aldehyde obtained in the presence of water) into the steric stabilizer chains without loss of colloidal stability. In the case of diblock copolymer vesicles, such derivatization leads to the formation of a worm population, indicating partial loss of the original morphology. However, this problem can be circumvented by cross-linking the membrane-forming block prior to periodate oxidation. Moreover, such covalently stabilized aldehyde-functionalized vesicles can be subsequently reacted with either glycine or histidine in aqueous solution, followed by reductive amination to prevent hydrolysis of the labile imine bond. ζ potential measurements confirm that this derivatization significantly affects the electrophoretic behavior of these vesicles. Similarly, the membrane-crosslinked aldehyde-functionalized vesicles can be reacted with a model globular protein, bovine serum albumin, to produce "stealthy" protein-decorated vesicles.

A series of thermoresponsive diblock copolymer worm gels is prepared via reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate using a water-soluble methacrylic precursor bearing pendent cis-diol groups. Selective oxidation using an aqueous solution of sodium periodate affords the corresponding aldehyde-functional worm gels. The aldehyde groups are located within the steric stabilizer chains and the aldehyde content can be adjusted by varying the periodate/cis-diol molar ratio. These aldehyde-functional worm gels are evaluated in terms of their mucoadhesion performance with the aid of a fluorescence microscopy-based assay. Using porcine urinary bladder mucosa as a model substrate, we demonstrate that these worm gels offer a comparable degree of mucoadhesion to that afforded by chitosan, which is widely regarded to be a ‘gold standard’ positive control in this context. The optimum degree of aldehyde functionality is approximately 30%: lower degrees of functionalization lead to weaker mucoadhesion, whereas higher values compromise the desirable thermoresponsive behavior of these worm gels.

RAFT aqueous emulsion polymerization of isopropylideneglycerol monomethacrylate (IPGMA) is used to prepare a series of PGEO5MA

We report the rational design of aldehyde-functional sterically stabilized diblock copolymer nano-objects in aqueous solution

Aldehyde groups enable facile conjugation to proteins, enzymes, oligonucleotides or fluorescent dyes, yet there are no literature examples of water‐soluble aldehyde‐functional vinyl monomers. We report the synthesis of a new hydrophilic cis‐diol‐based methacrylic monomer (GEO5MA) by transesterification of isopropylideneglycerol penta(ethylene glycol) using methyl methacrylate followed by acetone deprotection via acid hydrolysis. The corresponding water‐soluble aldehyde monomer, AGEO5MA, is prepared by aqueous periodate oxidation of GEO5MA at 22 °C. RAFT polymerization of GEO5MA yields the water‐soluble homopolymer, PGEO5MA. Aqueous periodate oxidation of the terminal cis‐diol units on PGEO5MA at 22 °C affords a water‐soluble aldehyde‐functional homopolymer (PAGEO5MA). Moreover, a library of hydrophilic statistical copolymers bearing cis‐diol and aldehyde groups was prepared using sub‐stoichiometric periodate/cis‐diol molar ratios. The aldehyde groups on PAGEO5MA homopolymer were reacted in turn with three amino acids to demonstrate synthetic utility., A water‐soluble aldehyde monomer (AGEO5MA) was prepared by oxidation of GEO5MA at 22 °C. RAFT aqueous polymerization yielded PAGEO5MA homopolymer, which was oxidized using sub‐stoichiometric periodate/cis‐diol molar ratios to yield hydrophilic statistical copolymers with cis‐diol and aldehyde groups. Three PGEO5MA‐based diblock copolymers were converted into aldehyde‐functional copolymers, which were derivatized with amino acids.

High molecular weight water-soluble polymers are widely used as flocculants or thickeners. However, synthesis of such polymers via solution polymerization invariably results in highly viscous fluids, which makes subsequent processing somewhat problematic. Alternatively, such polymers can be prepared as colloidal dispersions; in principle, this is advantageous because the particulate nature of the polymer chains ensures a much lower fluid viscosity. Herein we exemplify the latter approach by reporting the convenient one-pot synthesis of high molecular weight poly(glycerol monomethacrylate) (PGMA) via the reversible addition–fragmentation chain transfer (RAFT) aqueous emulsion polymerization of a water-immiscible protected monomer precursor, isopropylideneglycerol methacrylate (IPGMA) at 70 °C, using a water-soluble poly(glycerol monomethacrylate) (PGMA) chain transfer agent as a steric stabilizer. This formulation produces a low-viscosity aqueous dispersion of PGMA–PIPGMA diblock copolymer nanoparticles at 20% solids. Subsequent acid deprotection of the hydrophobic core-forming PIPGMA block leads to particle dissolution and affords a viscous aqueous solution comprising high molecular weight PGMA homopolymer chains with a relatively narrow molecular weight distribution. Moreover, it is shown that this latex precursor route offers an important advantage compared to the RAFT aqueous solution polymerization of glycerol monomethacrylate since it provides a significantly faster rate of polymerization (and hence higher monomer conversion) under comparable conditions.

A poly(glycerol monomethacrylate) (PGMA) chain transfer agent is chain-extended by reversible addition-fragmentation chain transfer (RAFT) statistical copolymerization of 2-hydroxypropyl methacrylate (HPMA) with glycidyl methacrylate (GlyMA) in concentrated aqueous solution via polymerization-induced self-assembly (PISA). A series of five free-standing worm gels is prepared by fixing the overall degree of polymerization of the core-forming block at 144 while varying its GlyMA content from 0 to 20 mol %. 1H NMR kinetics indicated that GlyMA is consumed much faster than HPMA, producing a GlyMA-rich sequence close to the PGMA stabilizer block. Temperature-dependent oscillatory rheological studies indicate that increasing the GlyMA content leads to progressively less thermoresponsive worm gels, with no degelation on cooling being observed for worms containing 20 mol % GlyMA. The epoxy groups in the GlyMA residues can be ring-opened using 3-aminopropyltriethoxysilane (APTES) in order to prepare core cross-linked worms via hydrolysis-condensation with the siloxane groups and/or hydroxyl groups on the HPMA residues. Perhaps surprisingly, 1H NMR analysis indicates that the epoxy-amine reaction and the intermolecular cross-linking occur on similar time scales. Cross-linking leads to stiffer worm gels that do not undergo degelation upon cooling. Dynamic light scattering studies and TEM analyses conducted on linear worms exposed to either methanol (a good solvent for both blocks) or anionic surfactant result in immediate worm dissociation. In contrast, cross-linked worms remain intact under such conditions, provided that the worm cores comprise at least 10 mol % GlyMA.

A series of non-ionic poly(glycerol monomethacrylate)–poly(2-hydroxypropyl methacrylate) (PGMA–PHPMA) diblock copolymer vesicles has been prepared by reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of HPMA at 70 °C at low pH using a carboxylic acid-based chain transfer agent. The degree of polymerization (DP) of the PGMA block was fixed at 43, and the DP of the PHPMA block was systematically varied from 175 to 250 in order to target vesicle phase space. Based on our recent work describing the analogous PGMA–PHPMA diblock copolymer worms [LovettJ. R.; Angew. Chem.2015, 54, 1279−128325418214], such diblock copolymer vesicles were expected to undergo an order–order morphological transition via ionization of the carboxylic acid end-group on switching the solution pH. Indeed, irreversible vesicle-to-sphere and vesicle-to-worm transitions were observed for PHPMA DPs of 175 and 200, respectively, as judged by turbidimetry, transmission electron microscopy (TEM), and dynamic light scattering (DLS) studies. However, such morphological transitions are surprisingly slow, with relatively long time scales (hours) being required at 20 °C. Moreover, no order–order morphological transitions were observed for vesicles comprising longer membrane-forming blocks (e.g., PGMA43–PHPMA225–250) on raising the pH from pH 3.5 to pH 6.0. However, in such cases the application of a dual stimulus comprising the same pH switch immediately followed by cooling from 20 to 5 °C, induces an irreversible vesicle-to-sphere transition. Finally, TEM and DLS studies conducted in the presence of 100 mM KCl demonstrated that the pH-responsive behavior arising from end-group ionization could be suppressed in the presence of added electrolyte. This is because charge screening suppresses the subtle change in the packing parameter required to drive the morphological transition.

1-Benzyl-2-(ethoxycarbonylmethylene)-2,3,4,5-tetrahydroimidazole undergoes annulation with a variety of 1,3-bis-electrophiles (α,β-unsaturated acid derivatives, β-ketoesters, α,β-unsaturated aldehydes) to form imidazo[1,2-a]pyridines.

Whereas 1-benzyl-2-lithiomethyl-4,5-dihydroimidazole undergoes reversible 1,2-addition to aldehydes and ketones, the derived phosphonate salt, 1-benzyl-2-lithio(diethylphosphono)methyl-4,5-dihydroimidazole, affords the condensation products, 2-(1-alkenyl)-4,5-dihydroimidazoles; these latter undergo conjugate addition with carbon nucleophiles.

Whereas 1-benzyl-2-lithiomethyl-4,5-dihydroimidazole undergoes reversible 1,2-addition to aldehydes and ketones, the derived phosphonate salt, 1-benzyl-2-lithio(diethylphosphono)methyl-4,5-dihydroimidazole, affords the condensation products, 2-(1-alkenyl)-4,5-dihydroimidazoles; these latter undergo conjugate addition with carbon nucleophiles.

The new dihydroimidazoles 3-methyl-1,5,6,10b-tetrahydroimidazo[5,1-a]isoquinoline and 1-methyl-3,3a,4,5-tetrahydroimidazo[1,5-a]quinoline are efficiently and conveniently prepared from isoquinoline and quinoline, via 1-aminomethyl-1,2,3,4-tetrahydroisoquinoline and 2-aminomethyl-1,2,3,4-tetrahydroquinoline and 2-aminomethyl-1,2,3,4-tetrahydroquinoline, respectively. Deprotonation of the fused dihydroimidazoles at the methyl substituent leads to homologation via C-alkylation, C-acylatioin, or C-phosphonylation–condensation. The properties of the tetrahydroimidazo[5,1-a]isoquinolines and tetrahydroimidazo[1,5-a]quinolines towards reducing agents mirror those of monocyclic dihydroimidazoles, affording aminomethyl-isoquinolines and -quinolines, respectively.

Whereas 1-benzyl-2-lithiomethyl-2-imidazoline undergoes reversible 1,2-addition to aldehydes and ketones, a derived phosphonate salt affords the condensation products, 2-(1-alkenyl)-2-imidazolines; the latter undergo conjugate addition with carbon nucleophiles.

The enaminoester 1-benzyl-2-(ethoxycarbonylmethylene)-imidazolidine undergoes N-acylation and conjugate C-addition with α,β-unsaturated acyl imidazolides to afford imidazo[1,2- a ]pyridones.

The enaminoester 1-benzyl-2-(ethoxycarbonylmethylene)-imidazolidine undergoes N-acylation and conjugate C-addition with α,β-unsaturated acyl imidazolides to afford imidazo[1,2- a ]pyridones.

2-Methyl-1-benzylimidazolidine (I) reacts with butyllitium and the carbonyl compounds (II) to form the carbinols (III) which are cleaved upon heating to recover (I) and its tautomer (IV).

This extension of previous studies on the quaternization of poly-4-vinyl pyridine) and related small molecules, e.g. 4-methyl pyridine, deals with several topics. Kinetic measurements on quaternization of polymer with methyl iodide show negligible neighbouring-group retardation when one reacted neighbour is present, but some retardation by two reacted neighbours. The production of charges does not affect the kinetics. This supports the notion that steric hindrance is responsible for retardation of this type of reaction. In some cases coloured quaternization products are formed, e.g. 4-methyl-N-n-propyl pyridinium bromide (MPPBr) prepared at 333 K is red, but that prepared at 298 K is colourless. Analysis of u.v.–visible spectra does not indicate that charge-transfer interactions in solution are a source of colour. There is no evidence from 13C and 1H n.m.r. spectra of impurities in the reaction products. It has been found that hydrogens undergo base-catalysed exchange with deuterium at rates depending on their position in the molecule. The crystal structure of MPPBr has been determined. There is no essential difference in structure between coloured and colourless samples, and no evidence for charge-transfer complex formation. The structure, with four molecules in each monoclinic unit cell of space group C2/c, reveals the presence of hydrogen-bonding between ring hydrogen atoms and Br– ions.