Tertiary Amine Functional Groups Research Articles

Identifying the Influences on Network Formation in Structural Isomers of Multifunctional Epoxies Using Near-Infrared Spectroscopy.

The network formation of four epoxy-rich formulations of the structural isomers of triglycidyl aminophenol and diaminodiphenyl sulfone has been monitored by using two complementary techniques, near-infrared spectroscopy and resin temperature monitoring. The differences between these networks have been described using the concentration of epoxide, primary amine, secondary amine, and tertiary amine functional groups and the actual temperature of the resin compared to the oven temperature during the cure schedule. It was found that initially, the 3,3'-diaminodiphenyl sulfone (33'DDS) formulations were more reactive and primary amines were completely consumed before the 4,4'-diaminodiphenyl sulfone (44'DDS) formulations. Secondary amines were formed more quickly in 33'DDS formulations compared to 44'DDS. The triglycidyl-meta-aminophenol (TGmAP) formulations consumed secondary amines and produced tertiary amines faster than the triglycidyl-para-aminophenol (TGpAP) formulations, indicating higher levels of cross-linking occurred earlier in the curing reaction. Etherification occurred much earlier in the TGpAP formulations than in the TGmAP formulations. Results suggest that internal cyclization occurs in the three meta isomer-containing formulations, and a corresponding lack of this effect in TGpAP/44'DDS results in a more homogeneous cross-linked network.

Application of a new chitosan derivative for adsorption of copper (II) and oxyanions of chromium (VI)

This study describes the synthesis of a new bioadsorbent from chitosan using ethylenediaminetetraacetic dianhydride (EDTAD) as a modifying agent and its successful application for removal of a cationic ion (copper (II) (Cu2+)) and oxyanions of chromium (VI) (Cr6+) from single-component aqueous systems. The new multifunctionalised chitosan derivative (C1) was produced through chemical modification of the primary hydroxyl function of chitosan with EDTAD to introduce carboxylic and tertiary amine functional groups, maintaining the secondary amines on the chitosan surface. Such a transformation was important not only to increase the adsorptive potential of chitosan but also to allow C1 to be used in acidic media, thus solving the problem of solubility of most chitosan derivatives. C1 was characterised by spectroscopic methods. The effects of solution pH, contact time and initial solute concentration on the removal of copper (II) and chromium (VI) by C1 were investigated in aqueous solutions. C1 showed an experimental maximum adsorption capacity of 106 mg/g for copper (II) and 194 mg/g for chromium (VI).

Adsorptive recovery of volatile fatty acids from wastewater fermentation broth

This work developed an adsorptive separation and recovery process for anaerobically generated volatile fatty acids (VFAs) from swine wastewater fermentation. Batch adsorption studies were conducted using several weak anion exchange resins and synthetic adsorbent resins to identify a suitable candidate. Relite RAM2 with a tertiary amine functional group showed the highest adsorption (over 98%) of hexanoic acid. Under the different pH values (1.8–7.5) and extraction temperatures (30–50 °C), the highest adsorption was observed at a pH of 3.2, which is below the pKa of hexanoic acid, at all the evaluated temperatures. A full factorial design was used to optimize the resin and VFA concentrations, wherein over 99% adsorption could be achieved when the ratio of VFA to resin was below 0.23 (g/g) for model solution (VFAs in water). The adsorption equilibrium could be achieved within 30 min of contact time and 0.5% w/v NaOH was identified as a suitable desorption agent. Under the optimal conditions, 65–72% of VFAs present in fermentation broth was adsorbed, which was increased to 72–76% by using fresh resins. The VFAs adsorption and recovery efficiency were maintained for 9 successive cycles without requiring extensive resin washing and regeneration for both model solution and fermentation broth. Overall, the work presents a comprehensive study for resin adsorption to recover VFAs and provides a potential industrial-relevant process to recover VFAs from fermentation broth.

Preparation of polymeric vesicles with tertiary amine and epoxy functional groups via polymerization-induced self-assembly

Polymeric vesicles with tertiary amine and epoxy functional groups were fabricated via the reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of 2-(diisopropylamino) ethyl methacrylate (DIPEMA) and glycidyl methacrylate (GlyMA) in an ethanol-water mixture by using poly (ethylene oxide)-4-(4-Cyanopentanoic acid) dithiobenzoate (mPEG45-CPADB) as the macro-chain-transfer agent (macro-CTA). Biocompatible polymer mPEG45 with molecular weight of 2000 and 4-(4-Cyanopentanoic acid) dithiobenzoate (CPADB) were used for the macro-CTA synthesizing via the esterification reaction. Investigation of the degree of polymerization (DP) of the hydrophobic block P(DIPEMA-co-GlyMA) and the solid content indicated that both have significant effect on the particle morphology and particle diameter. 1H NMR and FTIR analysis indicated the existing of tertiary amine and epoxy functional groups on the produced vesicles.

Removal of PFAS from groundwater using weak‐base anion exchange resins

AbstractThis research provides new insights on the application of weak‐base (WB) anion exchange resins (AERs) for groundwater treatment of six perfluoroalkyl acids (PFAAs) with different properties. Continuous‐flow column adsorption and regeneration experiments involving WB, polyacrylic, and WB, polystyrene resins were conducted considering salt‐only regeneration solutions and two representative strong‐base (SB)‐AERs of analogous polymer composition and a third solution of methanol/salt used as baseline for comparison. The WB, polyacrylic resin was regenerated using salt‐only solutions of NaOH due to deprotonation of the tertiary amine functional group at alkaline pH. However, organic cosolvent was required to weaken the hydrophobic interactions between PFAAs and the nonpolar WB, polystyrene resin. Removal was predominantly influenced by polymer composition with free‐base WB‐AERs exhibiting similar selectivity and higher capacity as SB resin counterparts. This work highlights WB‐AER selection based on PFAA‐selective removal and more sustainable regeneration strategies.

Removal of perfluoroalkyl acids and common drinking water contaminants by weak-base anion exchange resins: Impacts of solution pH and resin properties

The underlying chemistry of weak-base (WB) anion exchange resins (AERs) for contaminant removal from water is not well documented in the literature. To address this, batch adsorption experiments were conducted at pH 4, 7, and 10 using two representative WB-AERs (polyacrylic IRA67 and polystyrene IRA96) and two representative strong-base (SB) AERs (polyacrylic IRA458 and polystyrene A520E), of differing polymer composition, for the removal of nitrate, sulfate, 3-phenylpropionic acid (3-PPA) as surrogate for natural organic matter, and six perfluoroalkyl acids (PFAAs). Under acidic (pH 4) and neutral (pH 7) conditions, the selectivity of AERs for each contaminant was predominantly influenced by polymer composition followed by the size of the resin functional group. This result reflected the WB-AERs being fully protonated and functioning identical to SB-AERs. Isotherm model parameters revealed WB-AER had higher capacity than SB-AER with analogous polymer composition and porosity regardless of resin selectivity for each contaminant. Under basic conditions (≥ pH 10), contaminant removal by WB-AERs declined due to deprotonation of the tertiary amine functional groups. Removal of PFAAs by the more hydrophobic polystyrene WB-AER (IRA96) remained approximately constant with changing pH, which was possibly due to electrostatic interactions with remaining protonated amine functional groups on the resin.

Structural Regulation at Poly(ethylene glycol) Termini Facilitates the Formation of Injectable Hydrogels with Modulated Degradation and Release of Biomacromolecules

Hydrogels possessing modulated degradation and release behaviors are beneficial for the biological field. However, modulating the degradability and release behavior of a particular class of hydrogels requires a major structural alteration of a cross-linker as well as an adjustment in concentration, both of which affect the initial modulus and gelation kinetics. Herein, we address this shortcoming by a single step installation of a leaving nucleophile at the termini of PEG via the ether (O–CH2–Ph–, Cl′-PEG-Cl′) and ester (−Ph–COO–, Cl-PEG-Cl) spacers separately. These two PEG derivatives separately or in combination lead to the rapid formation of hydrogels when combined with a variety of macromolecules with tertiary amine functional group. The hydrogels exhibit a wide variation in degradation properties and time-dependent water swelling depending on the type and proportion of the PEG derivatives. The gelation kinetics is faster when the termini of the PEG derivative contain benzyl chloride groups connected through the ether spacer and is explained by density functional theory. Importantly, the ultimate moduli of the as prepared hydrogels are almost similar irrespective of the termini structure of the PEG derivatives and their proportion. The hydrogels exhibit modulated release profiles of model dextran and bovine serum albumin at pH 7.4. Prolonged delivery of biomacromolecules is achieved with the hydrogel prepared with Cl′-PEG-Cl′ or the combination Cl′-PEG-Cl′+Cl-PEG-Cl. More importantly, hydrogels prepared with Cl′-PEG-Cl′ or the Cl′-PEG-Cl′+Cl-PEG-Cl combination exhibit triggered release (60–100%) of a model protein (isoelectric point ≤ 7.4) and high molecular weight dextran (neutral) at a constant pH of 5 when compared to that at pH 7.4. The key advantages of our design are the access to a library of biological relevant hydrogels from easily available/synthesized amine-functional macromolecules and PEG derivatives with slight variations in the termini structures.

Synthesis of tertiary amine functionalized Multi-Stimuli-Responsive latex nanoparticles by semicontinuous emulsion Polymerization: Investigation of responsivities and antimicrobial activity

Stimuli-responsive core–shell nanoparticles (CSNPs) are an important class of smart polymers, which their physical and chemical properties could be changed in response to induced external stimuli. In this study, the amphiphilic CSNPs were synthesized via semi-continuous seeded emulsion polymerization using dimethylamino ethyl methacrylate (DMAEMA) as a hydrophilic monomer, and styrene as a hydrophobic monomer. Developed CSNPs were obtained in two series, poly(N, N-dimethylamino ethyl methacrylate) (PDMAEMA)-polystyrene (PS) core–shell particles and PS-PDMAEMA core–shell particles. The PDMAEMA chains exhibited different responsivities towards temperature rising, pH change, and CO2-gas, which their smart behaviors were investigated by dynamic light scattering (DLS) analysis. The temperature-responsivity of CSNPs was confirmed by observed particle size variation in the case of PDMAEMA-PS (increase) and PS-PDMAEMA (decrease) core–shell latex particles, when temperature increased to 70 °C, above the lower critical solution temperature (LCST) of PDMAEMA. Protonation of tertiary amine functional groups in the presence of CO2 bubbling led to an increase in the size of CSNPs as a result of water swelling of PDMAEMA chains. On the other hand, the size of CSNPs was changed in acidic (pH = 4) and basic (pH = 10) media by swelling and deswelling of PDMAEMA located in the core or shell. Obtained results indicated that maximum antimicrobial activity was observed for PS-PDMAEMA CSNPs compared to PDMAEMA-PS, which is probably due to presence of the PDMAEMA on the surface and increase of positive charge related to amine groups in this sample. The developed antimicrobial latexes have potential applications for using as antibacterial additives in water-based coatings and adhesives.

Chemoselective, Scalable Nickel-Electrocatalytic O-Arylation of Alcohols.

The formation of aryl-alkyl ether bonds through cross coupling of alcohols with aryl halides represents a useful strategic departure from classical SN 2 methods. Numerous tactics relying on Pd-, Cu-, and Ni-based catalytic systems have emerged over the past several years. Herein we disclose a Ni-catalyzed electrochemically driven protocol to achieve this useful transformation with a broad substrate scope in an operationally simple way. This electrochemical method does not require strong base, exogenous expensive transition metal catalysts (e.g., Ir, Ru), and can easily be scaled up in either a batch or flow setting. Interestingly, e-etherification exhibits an enhanced substrate scope over the mechanistically related photochemical variant as it tolerates tertiary amine functional groups in the alcohol nucleophile.

Chemoselective, Scalable Nickel‐Electrocatalytic O‐Arylation of Alcohols

AbstractThe formation of aryl‐alkyl ether bonds through cross coupling of alcohols with aryl halides represents a useful strategic departure from classical SN2 methods. Numerous tactics relying on Pd‐, Cu‐, and Ni‐based catalytic systems have emerged over the past several years. Herein we disclose a Ni‐catalyzed electrochemically driven protocol to achieve this useful transformation with a broad substrate scope in an operationally simple way. This electrochemical method does not require strong base, exogenous expensive transition metal catalysts (e.g., Ir, Ru), and can easily be scaled up in either a batch or flow setting. Interestingly, e‐etherification exhibits an enhanced substrate scope over the mechanistically related photochemical variant as it tolerates tertiary amine functional groups in the alcohol nucleophile.

Production of NiO, NiO/Ag, NiO/Au, and NiO/Pt hollow spheres by using block copolymer stabilized microspheres as a template

AbstractHollow spheres of nickel oxide (NiO) and silver, gold, and platinum nanoparticle loaded NiO composites were successfully produced by using polystyrene (PS) latexes as hard template. Due to the presence of tertiary amine based diblock copolymer stabilizer on the surface of PS, the tertiary amine functional groups provided homogene deposition of nickel hydroxide, and then the precursor NiO salt production on the surface of PS latexes with a controlled precipitation technique. Then, NiO and NiO/metal NP hollow spheres were produced by calcination at 600 °C. Thermogravimetric analysis indicated that the amounts of NiO and NiO‐composite after calcination were in the range of 21.1–29.7 wt%. The diameters of metal oxide spheres were in the range of 2.0–2.7 μm and the shell thickness were in the range of 250–350 nm. These structures had very low densities due to their porous and hollow structures and had outer layers with highly rough surfaces due to formation of nanosheets, which may offer important advantages for catalysis studies.

One-Shot Preparation of Polybasic Ternary Hybrid Cryogels Consisting of Halloysite Nanotubes and Tertiary Amine Functional Groups: An Efficient and Convenient Way by Freezing-Induced Gelation.

A convenient method for the preparation of polybasic ternary hybrid cryogels consisting of Halloysite nanotubes (HNTs) and tertiary amine functional groups by freezing-induced gelation is proposed. Ternary hybrid gels were produced via one-shot radical terpolymerization of 2-hydroxyethyl methacrylate (HEMA), 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS), and DEAEMA in the presence of HNTs. The equilibrium swelling in various swelling media and the mechanical properties of the produced ternary hybrid gels were analyzed to investigate their network structure and determine their final performance. The swelling ratio of HNT-free gels was significantly higher than the ternary hybrid gels composed of high amount of HNTs. The addition of HNTs to terpolymer network did not suppress pH- and temperature-sensitive behavior. While DEAEMA groups were effective for pH-sensitive swelling, it was determined that both HEMA and DEAEMA groups were effective in temperature-sensitive swelling. Ternary hybrid gels simultaneously demonstrated both negative and positive temperature-responsive swelling behavior. The swelling ratio changed considerably according to swelling temperature. Both DEAEMA and HEMA monomers in terpolymer structure were dominant in temperature-sensitive swelling. Mechanical tests in compression of both as-prepared and swollen-state demonstrated that strength and modulus of hybrid cryogels significantly increased with addition of HNTs without significant loss of mechanical strength. Ultimately, the results of the current system can benefit characterization with analysis tools for the application of innovative materials.

Production of NiMn2O4 hollow spheres and CoFe2O4 bowl-like structures by using block copolymer stabilized polystyrene spheres as a hard template.

The aim of this study is to highlight the use of polystyrene (PS) latexes stabilized with block copolymers as a hard template in the production of metal oxide hollow spheres. PS latexes produced by dispersion polymerization by stabilizing with tertiary amine methacrylate-based diblock copolymer were used as a hard template in the preparation of nickel manganese oxide (NiMn2O4) hollow spheres and cobalt iron oxide (CoFe2O4) bowl-like structures. Thanks to the diblock copolymer stabilizer with tertiary amine functional groups on the PS surface, precursor salts of CoFe2O4 and NiMn2O4 were first homogeneously deposited on the surface of PS latexes with a controlled precipitation technique. Then, metal oxide hollow spheres and bowl-like structures were produced by calcination. XRD results showed that CoFe2O4 and NiMn2O4 structures were successfully obtained after calcination. The thermogravimetric analysis results showed that the CoFe2O4 and NiMn2O4 contents of the hybrid PS spheres were in the range of 26.0-28.6 wt%. SEM images showed that the inorganic-polymer spheres fused with each other after calcination to form larger magnetic CoFe2O4 bowl-like structures. SEM images also indicated successful production of highly rough NiMn2O4 hollow spheres with nanosheets on the surface.

Fabrication and characterization of structurally stable pH-responsive polymeric vesicles by polymerization-induced self-assembly.

Smart polymeric vesicles with both tertiary amine and epoxy functional groups were fabricated for the first time via a reversible addition–fragmentation chain transfer dispersion polymerization approach, using (2-(diisopropylamino)ethyl methacrylate (DIPEMA) and glycidyl methacrylate (GlyMA) in an ethanol–water mixture. Monitoring of the in situ polymerization revealed the low molecular weight distributions and the intermediate structures of spheres and worms, indicating an evolution in particle morphology. A phase diagram was constructed for reproducible fabrication of the vesicles, and copolymer composition was found to be more related to particle morphology. The vesicles exhibited superior structural stability for the cross-linking of the core through epoxydiamine chemistry, and intelligent pH responsibility due to the presence of the tertiary amine groups. The cross-linked vesicles showed good stability and reversibility during the swelling and shrinking cycles by switching the pH values, which endowed them with potential cell-like transmission functions. This research thus provides a method for producing structurally stable pH-responsive polymeric vesicles, and the reported vesicles are based on commercially available starting materials for possible industrial scale-up.

Design, evaluation and optimization of taste masked clarithromycin powder.

Clarithromycin (CLA) is an extremely bitter macrolide antibiotic used to treat paediatric and adult infections. The bitter taste affects patient adherence and may compromise therapy. This research developed a taste masked CLA resinate using Indion® 234, a weak acidic cation exchange resin. The factors affecting formation of the CLA-resin complex were assessed. Design of experiments was used to optimize response while evaluating input variables such as temperature, CLA-resin ratio,stirring time and pH. CLA loading efficiency was determined spectrophotometrically and CLA release using USP Apparatus II. Differential Scanning Calorimetry (DSC), Scanning Electron Microscop (SEM), Fourier Transform Infrared (FT-IR) Spectroscopy and X-ray Diffraction (XRD) were used to confirm complex formation. A spectrophotometric method was used to assess taste evaluation. The optimum CLA-resin ratio, temperature, and stirring time were 1:4, 80 °C, 3 hours, respectively, at pH 8. Characterization techniques revealed that CLA was crystalline and the complex amorphous in nature. FT-IR spectra of resinate revealed the absence of resonance due to the tertiary amine functional group that is responsible for the bitter taste of CLA. CLA was stable in simulated salivary fluid and was released within 3 hours in gastric fluid. All CLAresin batches revealed complete taste masking. Taste analysis highlighted the improvement of taste masking properties of the resinate as the CLA to resin ratio, increased.

The Capacitive Behavior of Polyluminol on Carbon Nanotubes Electrodes

AbstractA polymerized luminol carbon nanotube (CNT) composite electrode was developed via an in situ chemical polymerization (CpLum) process. Density functional theory (DFT) simulation suggested the luminol molecules were preferentially aligned flat on the CNTs. This was further demonstrated through a morphological study, which showed the CpLum wrapped around each CNT homogeneously with an average thickness of 4.5±1.5 nm. The surface chemical analysis by X‐ray photoelectron spectroscopy (XPS) revealed a progressive increase in the nitrogen content and stabilized at 9 %. Deconvolution of the high‐resolution N 1s spectra suggested the presence of secondary and tertiary amine functional groups, which are the signatures of polymerized luminol. The composite electrodes exhibited a pseudocapacitive‐like behavior with 3.5 times increase in charge storage. The contributions from the CpLum coating and CNT substrate were differentiated and were further deconvoluted to quantify the capacitive charge storage of each component. The thin CpLum coating contributed 70 % of the total charge storage through pseudocapacitance. CpLum‐CNT electrodes also showed a high rate capability and good cycling stability, very promising for electrochemical capacitors.

AmberliteTM IRA67: A novel and efficient ion exchange resin catalyst for the synthesis of 1, 8-dioxoxanthene derivatives

The catalytic performance of AmberliteTM IRA67, the heterogeneous weak Base Exchange resin which bears tertiary amine functional group, for the synthesis of 1, 8-dioxoxanthene derivatives were inve...

A Si-rhodamine-based near-infrared fluorescent probe for visualizing endogenous peroxynitrite in living cells, tissues, and animals.

Peroxynitrite (ONOO-) is an extremely powerful biological oxidant and it can react with a wide variety of molecular targets to result in a series of disease states, which has made ONOO- a central biological pathogenic factor. In order to disclose its various pathological events, a large number of fluorescent ONOO- probes have been developed in recent years. Nevertheless, some limitations still remain, such as short excitation and emission wavelengths, long fluorescence response times, and cross-interference caused by other reactive oxygen species (ROS). In this work, a new near-infrared (NIR) fluorescent probe, SiRTA, containing an aromatic tertiary amine functional group and a Si-rhodamine fluorophore, was developed for endogenous ONOO- detection and imaging. The probe exhibits not only a fast, sensitive, and specific fluorescence off-on response toward ONOO- in chemical systems but also excellent imaging ability for endogenous ONOO- in living cells. With the probe, the therapeutic effects of phenolic acid antioxidants in EA.hy926 endothelial cells suffering from ischemia-reperfusion injury and the pathogenesis of diabetes and diabetic nephropathy in pancreatic β-cells and diabetic rats have successfully been evaluated. These results indicate that SiRTA is a potentially outstanding imaging tool for studying the physiological and pathological events of ONOO- and relevant drug therapies.

Synthesis of N-vinylpyrrolidone/Acrylic acid nanoparticles for drug delivery: Method optimization

There are various approaches to deliver therapeutic agents to the preferred target. Polymeric nanoparticles were found to have pleasing suitability as a drug carrier. The goal of this research was to optimize the synthesis method to obtain the desirable %yield and particle properties of the new biocompatible polymer-based nanoparticles. The non-toxic polymer, N-vinyl pyrrolidone (NVP) and a widely used hydrophilic biocompatible acrylic acid (AA) monomer were used to form the drug nanocarriers. The synthesis method was optimized by changing the types of initiator (KPS or V50) and the monomers molar ratio (NVP:AA). It was found that by varying both the monomer molar ratio and the type of reaction initiator, did not have significant effect on the physicochemical characteristics of the nanocarriers. The FTIR spectra of all products exhibited the peaks of carboxylic acid, carbonyl, and tertiary amine functional group vibration. The particle size of the nanocarriers was in the range of 173.6 ± 18.4 to 201.4 ± 17.1 nm with negative surface charge. However, the yield obtained increased as the initiator was altered from KPS to V50, and when the acrylic acid molar ratio was increased from 1:1 to 1:3. In conclusion, changing the initiator and monomer molar ratio may affect the physicochemical properties of the nanocarriers and the %yield of the nanocarrier product. Further investigations are essential to obtain the favorable drug nanocarriers for drug delivery.

Abstract 2056: Development of quaternary amine linkers for ADCs: Application to auristatin E and tubulysin

Abstract The recent clinical success of antibody-drug conjugates (ADCs) has spawned an increased effort to identify new technologies, and the development of new drug-linker chemistry is vital to expand the scope of conjugatable payloads. The tertiary amine functional group is a common structural motif present in many bioactive compounds, including antimitotics of the auristatin and tubulysin classes. Traditionally, conjugation of tertiary amines required drug derivatization or modification to remove an N-alkyl group, thus creating a readily conjugatable secondary amine. However, identifying appropriate modifications that do not compromise the activity of the drug is frequently time consuming and often unsuccessful. To eliminate the need for such structural modifications, we sought a method for stable conjugation and facile release through the tertiary amine functional group by creating linkers with a quaternary amine point of attachment. To validate the linker strategy, quaternary amine-based cleavable linkers bearing auristatin E were synthesized and evaluated as ADCs. The conjugates were stable in rodent plasma, and were potent and immunologically specific both in vitro and in vivo in a Hodgkin lymphoma xenograft model. A second application of this technology has been demonstrated with tubulysins, another class of potent antimitotics containing a tertiary amine at the N-terminus. A cleavable quaternary amine linker containing a tubulysin analog was synthesized and ADCs were prepared and evaluated. The tubulysin conjugates were potent and immunologically specific across a panel of cancer cell lines, including multiple MDR-positive lines. Furthermore, the tubulysin conjugate displayed ‘bystander activity’ in an in vitro co-culture assay. The quaternary amine linkers represent an advance in linker technology and will enable the evaluation of drug classes previously inaccessible as ADCs. Citation Format: Patrick J. Burke, Joseph Z. Hamilton, Thomas A. Pires, Jocelyn R. Setter, Joshua H. Hunter, Julia H. Cochran, Brian E. Toki, Peter D. Senter, Robert P. Lyon, Scott C. Jeffrey. Development of quaternary amine linkers for ADCs: Application to auristatin E and tubulysin. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2056.