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Linear polyethylenimine (L-PEI) has been the gold standard for gene delivery and is typically prepared by hydrolysis from poly(2-oxazoline)s. Recently, also the anionic polymerization of activated aziridines was reported as a potential pathway toward linear and well-defined polyamines. However, only sulfonamide-activated aziridines so far undergo the living anionic polymerization and their desulfonylation was only reported scarcely. This is mainly due to the relatively high stability of the sulfonamides and the drastic change in solubility during the desulfonylation. Herein, we investigated the desulfonylation of such poly(aziridine)s prepared from tosylated or mesylated propyleneimine to afford linear polypropylenimine (L-PPI) as an alternative to L-PEI. Different desulfonylation strategies for tosylated (Ts) and mesylated (Ms) PPI were studied. The reductive cleavage of the sulfonamide with sodium bis(2-methoxy ethoxy) aluminum hydride yielded 80% of deprotected amine groups. Quantitative conversion to L-PPI was obtained, when the tosylated PPI was hydrolyzed under acidic conditions with

Despite the difficulties associated with controlling the polymerization of ring-strained nitrogen containing monomers, the resulting polymers have many important applications, such as antibacterial and antimicrobial coatings, CO2 adsorption, chelation and materials templating, and non-viral gene transfection. This review highlights the recent advances on the polymerizations of aziridine and azetidine. It provides an overview of the different routes to produce polyamines, from aziridine and azetidine, with various structures (i.e. branched vs. linear) and degrees of control. We summarize monomer preparation for cationic, anionic and other polymerization mechanisms. This comprehensive review on the polymerization of aziridine and azetidine monomers will provide a basis for the development of future macromolecular architectures using these relatively exotic monomers.

Living anionic polymerization gives access to well-defined polymers, but it demands strict purification of reagents and solvents. This work presents the azaanionic polymerization (AAROP) of aziridines as a robust living polymerization technique, with the ease of controlled radical polymerizations. AAROP does not require inert atmosphere and remains living in the presence of large amounts of water or alcohols. Mesyl-, tosyl-, or brosyl-activated aziridines were polymerized with up to 100-fold excess of a protic impurity with respect to the initiator and still being active for chain extension. This allowed the preparation of polyols by anionic polymerization without protective groups, as only minor initiation occurred from the alcohols. The tolerance toward protic additives lies in the electron-withdrawing effect of the activating groups, decreasing the basicity of the propagating species, while maintaining a strong nucleophilic character. In this way, competing alcohols and water are only slightly involved...

The development of a convenient and rapid method to synthesize radiolabeled, enantiomerically pure amino acids (AAs) as potential positron emission tomography (PET) imaging agents for mapping various biochemical transformations in living organisms remains a challenge. This is especially true for the synthesis of carbon-11-labeled AAs given the short half-life of carbon-11 (11 C, t1/2 =20.4 min). A facile synthetic pathway to prepare enantiomerically pure 11 C-labeled l-asparagine was developed using a partially protected serine as a starting material with a four-step transformation providing a chiral five-membered cyclic sulfamidate as the radiolabeling precursor. Its structure and absolute configuration were confirmed by X-ray crystallography. Utilizing a [11 C]cyanide nucleophilic ring opening reaction followed by selective acidic hydrolysis and deprotection, enantiomerically pure l-[4-11 C]asparagine was synthesized. Further optimization of reaction parameters, including base, metal ion source, solvent, acid component, reaction temperature and reaction time, a reliable two-step method for synthesizing l-[4-11 C]asparagine was presented: within a 45±3 min (n=5, from end-of-bombardment), the desired enantiomerically pure product was synthesized with the initial nucleophilic cyanation yield of 69±4 % (n=5) and overall two-step radiochemical yield of 53±2 % (n=5) based on starting [11 C]HCN, and with radiochemical purity of 96±2 % (n=5).

Ruthenocenyl glycidyl ether (rcGE) is a novel monomer for the anionic polymerization and copolymerization with ethylene oxide to water-soluble, thermo-, and redox-responsive organometallic poly(ethylene glycol)s (PEGs). The polymers exhibit adjustable molecular weights, comonomer ratios, and narrow molecular weight distributions (typically Mw/Mn < 1.2). Real-time 1H NMR copolymerization kinetics prove random incorporation of rcGE into the polyether backbone in analogy to its ferrocene analog. The rcGE-co-EO copolymers are water-soluble with a lower critical solution temperature, depending on the rcGE content. Terpolymerization of ferrocenyl glycidyl ether, ethylene oxide, and rcGE produces the first random PEG derivatives with multiple redox response. Ruthenocenyl glycidyl ether broadens the field of organometallics, especially ruthenium-containing polymers, and these copolymers might find applications in catalysis, as redox-active surfactants, or as staining reagents in electron microscopy.

Linear polyethylenimine (L-PEI), a standard for nonviral gene delivery, is usually prepared by hydrolysis from poly(2-oxazoline)s. Lately, anionic polymerization of sulfonamide-activated aziridines had been reported as an alternative pathway toward well-defined L-PEI and linear polyamines. However, desulfonylation of the poly(sulfonyl aziridine)s typically relied on harsh conditions (acid, microwave) or used a toxic solvent (e.g., hexamethylphosphoramide). In addition, the drastic change of polarity requires solvents, which keep poly(sulfonyl aziridine)s as well as L-PEI in solution, and only a limited number of strategies were reported. Herein, we prepared 1-(4-cyanobenzenesulfonyl) 2-methyl-aziridine (

Competitive copolymerization gives access to gradient copolymers with simple one-step and one-pot strategies. Due to the living nature of the sulfonyl-aziridine polymerization, gradient copolymers can be obtained with low dispersities and adjustable molar masses. The combination of different sulfonyl activating groups allowed to fine-tune the reactivity difference of the comonomers and thus an exact adjustment of the gradient strength. Sulfonyl-activated aziridines are to date the only monomer class providing access to gradient copolymers with reactivity ratios ranging from (1 ≤ r1 ≤ 2; 1 ≥ r2 ≥ 0.5) for statistical or soft gradient copolymers to block copolymers (r1 ≥ 20, r2 ≤ 0.02), only by adjusting the electron-withdrawing effect of the activation groups: the reactivity ratios were calculated by different models for a library of eight comonomers. This library was further used to classify between hard, medium, and soft gradients. From the data obtained from the monomer library, it was possible to predi...

“A living race” – polymerization kinetics of anionic polymerizations depends strongly on the solvent polarity and reactivity of the growing chain end. Both the carb- and oxyanionic polymerization is under control at the university lab and on the industrial level, however, no information for the aza-anionic polymerization of aziridines has been reported systematically. This work studies the polymerization of two activated aziridines (2-methyl-N-mesylaziridine (MsMAz) and 2-methyl-N-tosylaziridine (TsMAz)) by real-time 1H NMR spectroscopy. This technique allows monitoring the consumption of the monomer precisely during the polymerization under different conditions (temperature, solvent, initiator and counter-ion variation). From the experimental data, propagation rate constants (kp) were calculated and analyzed. The polymerization of MsMAz was monitored at different temperatures (20, 50, and 100 °C). The increase of temperature increases the speed of polymerization, but keeps the living behavior. Furthermore, the influence of different solvents on the polymerization speed was examined, proving solvating solvents such as DMSO and DMF as the fastest solvents. Two different initiators, the potassium salts of N,N′-(1,4-phenylenebis(methylene))dimethanesulfonamide (BnBis(NHMs)), the first bifunctional initiator for the AROP of aziridines, and of N-benzyl-sulfonamide (BnNHMs) were compared. The variation of the counter ions Li+, Na+, K+, and Cs+ (generated from the respective bis(trimethylsilyl)amide salts) proved successful polymerization of both monomers with all counter ions. Slight variations have been detected in the order: Cs+ > Li+ > Na+ > K+, which is in strong contrast for the AROP of epoxides, shows a strong gegenion-dependent kinetic profile. This allows the use of commercially available initiators, such as BuLi for the synthesis of PAz. With these results in hand, the azaanionic polymerization can be used as a valuable tool in the family of anionic polymerization for the preparation of structurally diverse polysulfonamides and polyamines under a broad variety of conditions, while maintaining the living behavior.

An ideal system for stimuli-responsive and amphiphilic (block) polymers would be the copolymerization of aziridines with epoxides. However, to date, no copolymerization of these two highly strained three-membered heterocycles had been achieved. Herein, we report the combination of the living oxy- and azaanionic ring-opening polymerization of ethylene oxide (EO) and sulfonamide-activated aziridines. In a single step, well-defined amphiphilic block copolymers are obtained by a one-pot copolymerization. Real-time 1H NMR spectroscopy revealed the highest difference in reactivity ratios ever reported for an anionic copolymerization (with r1 = 265 and r2 = 0.004 for 2-methyl- N-tosylaziridine/EO and r1 = 151 and r2 = 0.013 for 2-methyl- N-mesylaziridine/EO), leading to the formation of block copolymers with monomodal and moderate molecular weight distributions ( Mw/ Mn mostly ≤1.3). The amphiphilic diblock copolymers were used to stabilize emulsions and to prepare polymeric nanoparticles by miniemulsion polymerization, representing a novel class of nonionic and responsive surfactants. In addition, this unique comonomer reactivity of activated-Az/EO allows fast access to multiblock copolymers, and we prepared the first amphiphilic penta- or tetrablock copolymers containing aziridines in only one or two steps, respectively. These examples render the combination of epoxide and aziridine copolymerizations via a powerful strategy for producing sophisticated macromolecular architectures and nanostructures.

Commercial aminoalcohols, namely, 2-(methyl amino)ethanol (1) and diethanolamine (2), are investigated as direct initiators, i.e., with no need of protection of the hydroxyl groups, for the N-heterocyclic carbene-organocatalyzed ring-opening polymerization (NHC-OROP) of 2-methyl-N-p-toluenesulfonyl aziridine. NHC-OROP’s are performed at 50 °C in tetrahydrofuran, in the presence of 1,3-bis(isopropyl)-4,5(dimethyl)imidazol-2-ylidene (Me5-IPr) as organocatalyst. Thus, nonprotected and nonactivated aminoalcohol initiators 1 and 2 provide a direct access to metal-free α-hydroxy-ω-amino- and α,α′-bis-hydroxy-ω-amino telechelics on the basis of polyaziridine (PAz), respectively. Excellent control over molar masses, narrow dispersities (Đ ≤ 1.20), and high chain-end fidelity are evidenced by combined analyses, including NMR spectroscopy, size exclusion chromatography, and MALDI ToF mass spectrometry. The amino-initiated NHC-OROP is therefore tolerant to the presence of nonprotected hydroxyl group(s). The as-obtai...

The development of a convenient and rapid method to synthesize radiolabeled, enantiomerically pure amino acids (AAs) as potential positron emission tomography (PET) imaging agents for mapping various biochemical transformations in living organisms remains a challenge. This is especially true for the synthesis of carbon-11-labeled AAs given the short half-life of carbon-11 (

The first orthogonal ferrocene monomer, vinyl ferrocenyl glycidyl ether (VfcGE), for both anionic and radical polymerization – without the need of a protection group – is presented. Anionic ring-opening copolymerization of VfcGE and ethylene oxide (EO) generates stimuli-responsive, multifunctional poly[(vinyl ferrocenyl glycidyl ether)-co-(ethylene oxide)] (P[VfcGE-co-EO]) copolymers (molecular weights of ca. 7500 g mol−1 and low molecular weight dispersities (Đ ≤ 1.14)). The amount of the equimolar ferrocenyl and vinyl groups are controlled by the comonomer ratio up to 15.4 mol% VfcGE. The pendant vinyl groups of P[VfcGE-co-EO] were post-modified with 3-mercaptopropionic acid via thiol–ene chemistry. The EO copolymers exhibit temperature-, redox-, and pH-responsive behavior in water depending on the polymers’ microstructure. Free radical polymerization of VfcGE leads to polyalkylene:(vinyl ferrocenyl glycidyl ether) with pendant epoxide side chains at each ferrocene unit. The resulting polymer was used to generate redox-responsive protein nanoparticles with bovine serum albumin (BSA) by nucleophilic ring-opening of the pendant epoxides.

Carbon-11 (β+ emitter, t 1/2 = 20.4 min) radiolabeled l-glutamine is a potentially useful molecular imaging agent that can be utilized with positron emission tomography for both human oncological diagnosis and plant imaging research. Based upon a previously reported [11C]cyanide end-capping labeling method, a systematic investigation of nucleophilic cyanation reactions and acidic hydrolysis reaction parameters, including base, metal ion source, phase transfer catalyst, solvent, reaction temperature and reaction time, was conducted. The result was a milder, more reliable, two-step method which provides l-[5-11C]-glutamine with a radiochemical yield of 63.8 ± 8.7 % (range from 51 to 74 %, n = 10) with >90 % radiochemical purity and >90 % enantiomeric purity. The total synthesis time was 40–50 min from the end of bombardment. In addition, an Fmoc derivatization method was developed to measure the specific activity of this radiotracer.

4-Styrenesulfonyl-(2-methyl)aziridine (StMAz), the first orthogonal aziridine monomer, for both anionic ring-opening and radical polymerization is presented. Both polymerization pathways are accessible without using protective groups. Aza-anionic ring-opening polymerization (A-AROP) of StMAz and other methyl-aziridine derivatives provide multifunctional polyaziridines. Molecular weights between 3000 and 13 000 g mol−1 are obtained with low molecular weight dispersities (Ð = 1.1). The amount of vinyl groups in linear polyaziridines from A-AROP depends on the monomer/comonomer ratio. The vinyl groups of P(StMAz)- homo- or copolymers are entirely convertible by thiol-ene addition. This allows modification with multiple functional groups. Free radical polymerization of StMAz leads to polyalkylenes with aziridine side groups, which are known to be efficiently addressable via nucleophiles. Polysulfonamides still belong to a rather new class of polymers accessible by anionic polymerization. Enlarging the scope of postpolymerization modifications on polyaziridines/-sulfonamides is important for further macromolecular architectures. The aziridine and the vinyl group are combined to develop the first orthogonal monomer for aza-anionic polymerization and radical polymerization.