127090-71-5

Usage

Uses

Used in Biochemistry and Molecular Biology:
2-[1-(2-aminoethoxy)-1-methylethoxy]ethylamine is used as a crosslinking agent for cell lysate, specifically for linking polypeptides whose lysine side chains are nearest to each other. This application is crucial in the study of protein-protein interactions and the structural analysis of proteins within a cellular context.
Used in Polymer Synthesis:
In the field of polymer chemistry, 2-[1-(2-aminoethoxy)-1-methylethoxy]ethylamine is used as a pH-sensitive cross-linker in the synthesis of polyurea and polyurethane. Its acid degradability allows for the creation of responsive materials that can change properties or degrade under specific conditions, which is valuable in various applications such as drug delivery and smart materials.
Used in Chemical Conjugation:
This diamine is also used for chemical conjugation through various reactions, including acylation, alkylation, and reactions with isothiocyanates, isocyanates, acyl azides, NHS esters, sulfonyl chlorides, aldehydes, carbonates, aryl halides, imidoesters, carbodiimides, anhydrides, and fluorophenyl esters. This versatility makes it a valuable tool in the development of new chemical compounds and materials.
Used in Epoxy Crosslinking:
2-[1-(2-aminoethoxy)-1-methylethoxy]ethylamine can also crosslink epoxies, which is an important application in the manufacturing of adhesives, coatings, and composite materials. Its ability to crosslink epoxies provides a means to create strong, durable, and versatile materials for a wide range of industrial applications.

Upstream product

• 28464-41-7 2,2-bis-(2-chloro-ethoxy)-propane 
• 116-11-0 2-Methoxypropene 
• 2002-24-6 2-amino-ethanol hydrochloride 
• 77-76-9 2,2-dimethoxy-propane 
• 1009829-93-9 C₁₁H₁₆F₆N₂O₄ 
• 127090-70-4 2,2-di-(2-phthalimidoethoxy)propane 

Relevant academic research and scientific papers

Acid degradable and biocompatible polymeric nanoparticles for the potential codelivery of therapeutic agents

The synthesis of well-defined functional nanoparticles for the encapsulation of hydrophobic and hydrophilic drugs is described. Nanoparticles were built from amphiphilic copolymers consisting of P(OEG-A) homopolymers chain extended with vinyl benzyl chloride (VBC) and pentafluorophenyl acrylate (PFP-A) comonomers. Subsequently, the pendant chlorine atoms, introduced into the chains by VBC units, were substituted using sodium methanethiosulfonate, yielding copolymer chains with methanethiosulfonate (MTS) pendant functionality. The thiol/MTS exchange chemistry afforded by the MTS groups was then used to introduce different functional groups by reacting with a range of thiols. These copolymers were self-assembled in water yielding nanoparticles with sizes of ～20 nm. The activated esters in the copolymer were used to cross-link the nanoparticles with difunctional amino compounds (cross-linkers). A cross-linker bearing an acid cleavable bond (ketal) was used to generate pH-sensitive core-shell nanoparticles. Drug encapsulation and release was modeled using hydrophobic (Nile Red) and hydrophilic (thiol-modified fluorescein isothiocyanate, FITC) dye molecules. The release of each dye was monitored using UV-vis spectroscopy, demonstrating the possibility of selective release of single dye or the simultaneous release of both dyes depending on the experimental stimuli. An in vitro study confirmed that the nanoparticles were nontoxic to the NIH-3T3 cell line. Cell uptake analysis by flow cytometry and fluorescence microscopy indicated a higher uptake for cross-linked nanoparticles than for non-cross-linked nanoparticles.

Reversibly Cross-Linked Polyplexes Enable Cancer-Targeted Gene Delivery via Self-Promoted DNA Release and Self-Diminished Toxicity

Polycations often suffer from the irreconcilable inconsistency between transfection efficiency and toxicity. Polymers with high molecular weight (MW) and cationic charge feature potent gene delivery capabilities, while in the meantime suffer from strong chemotoxicity, restricted intracellular DNA release, and low stability in vivo. To address these critical challenges, we herein developed pH-responsive, reversibly cross-linked, polyetheleneimine (PEI)-based polyplexes coated with hyaluronic acid (HA) for the effective and targeted gene delivery to cancer cells. Low-MW PEI was cross-linked with the ketal-containing linker, and the obtained high-MW analogue afforded potent gene delivery capabilities during transfection, while rapidly degraded into low-MW segments upon acid treatment in the endosomes, which promoted intracellular DNA release and reduced material toxicity. HA coating of the polyplexes shielded the surface positive charges to enhance their stability under physiological condition and simultaneously reduced the toxicity. Additionally, HA coating allowed active targeting to cancer cells to potentiate the transfection efficiencies in cancer cells in vitro and in vivo. This study therefore provides an effective approach to overcome the efficiency-toxicity inconsistence of nonviral vectors, which contributes insights into the design strategy of effective and safe vectors for cancer gene therapy. (Chemical Presented).

Formulation of Acid-Sensitive Micelles for Delivery of Cabazitaxel into Prostate Cancer Cells

We report the synthesis of an amphiphilic triblock copolymer composed of a hydrophilic poly(ethylene glycol) (PEG) block, a central poly(acrylic acid) (PAA) block, and a hydrophobic poly(methyl methacrylate) (PMMA) block using atom transfer radical polymerization technique. We examined the self-assembly of PEG-b-PAA-b-PMMA copolymers in aqueous solutions forming nanosized micelles and their ability to encapsulate hydrophobic guest molecules such as Nile Red (NR) dye and cabazitaxel (CTX, an anticancer drug). We used 2,2β′-(propane-2,2-diylbis(oxy))-diethanamine to react with the carboxylic acid groups of the central PAA block forming acid-labile, shell cross-linked micelles (SCLM). We investigated the loading efficiency and release of different guest molecules from non-cross-linked micelles (NSCLM) and shell cross-linked micelles (SCLM) prepared by reacting 50% (SCLM-50) and 100% (SCLM-100) of the carboxylic acid groups in the PAA in physiologic (pH 7.4) and acidic (pH 5.0) buffer solutions as a function of time. We examined the uptake of NR-loaded NSCLM, SCLM-50, and SCLM-100 micelles into PC-3 and C4-2B prostate cancer cells and the effect of different micelle compositions on membrane fluidity of both cell lines. We also investigated the effect of CTX-loaded NSCLM, SCLM-50, and SCLM-100 micelles on the viability of PC-3 and C4-2B cancer cells compared to free CTX as a function of drug concentration. Results show that PEG-b-PAA-b-PMMA polymers form micelles at concentrations ≥11 μg/mL with an average size of 40-50 nm. CTX was encapsulated in PEG-b-PAA-b-PMMA micelles with 55% loading efficiency in NSCLM. In vitro release studies showed that 30% and 85% of the loaded CTX was released from SCLM-50 micelles in physiologic (pH 7.4) and acidic (pH 5.0) buffer solutions over 30 h, confirming micelles' sensitivity to solution pH. Results show uptake of NSCLM and SCLM into prostate cancer cells delivering their chemotherapeutic cargo, which triggered efficient cancer cell death. PEG-b-PAA-b-PMMA micelles were not hemolytic and did not cause platelet aggregation, which indicate their biocompatibility.

Ketal cross-linked poly(ethylene glycol)-poly(amino acid)s copolymer micelles for efficient intracellular delivery of doxorubicin

A biocompatible, robust polymer micelle bearing pH-hydrolyzable shell cross-links was developed for efficient intracellular delivery of doxorubicin (DOX). The rationally designed triblock copolymer of poly(ethylene glycol)-poly(l-aspartic acid)-poly(l-phenylalanine) (PEG-PAsp-PPhe) self-assembled to form polymer micelles with three distinct domains of the PEG outer corona, the PAsp middle shell, and the PPhe inner core. Shell cross-linking was performed by the reaction of ketal-containing cross-linkers with Asp moieties in the middle shells. The shell cross-linking did not change the micelle size and the spherical morphology. Fluorescence quenching experiments confirmed the formation of shell cross-linked diffusion barrier, as judged by the reduced SternVolmer quenching constant (KSV). Dynamic light scattering and fluorescence spectroscopy experiments showed that shell cross-linking improved the micellar physical stability even in the presence of micelle disrupting surfactants, sodium dodecyl sulfate (SDS). The hydrolysis kinetics study showed that the hydrolysis half-life (t1/2) of ketal cross-links was estimated to be 52 h at pH 7.4, whereas 0.7 h at pH 5.0, indicating the 74-fold faster hydrolysis at endosomal pH. Ketal cross-linked micelles showed the rapid DOX release at endosomal pH, compared to physiological pH. Confocal laser scanning microscopy (CLSM) showed that ketal cross-linked micelles were taken up by the MCF-7 breast cancer cells via endocytosis and transferred into endosomes to hydrolyze the cross-links by lowered pH and finally facilitate the DOX release to inhibit proliferation of cancer cells. This ketal cross-linked polymer micelle is promising for enhanced intracellular delivery efficiency of many hydrophobic anticancer drugs.

Dual Location, Dual Acidic pH/Reduction-Responsive Degradable Block Copolymer: Synthesis and Investigation of Ketal Linkage Instability under ATRP Conditions

Stimuli-responsive degradation (SRD) undergoing chemical transition through the cleavage of labile linkages has been proved to dramatically increase the versatility of stimuli-responsive block copolymers. In particular, dual or multiple stimuli-responsive degradable block copolymers that can be triggered by two endogenous stimuli of acidic pH and reduction are in high demand. Here, a new strategy utilizing atom transfer radical polymerization (ATRP) is reported to synthesize a dual acidic pH/reduction-responsive degradable block copolymer (DLDSRD) labeled with an acidic pH-labile ketal linkage at the block junction and pendant reductively cleavable disulfide groups in hydrophobic block at dual locations. A robust route with multiple steps utilizing carbamate chemistry to endow stability during protection/deprotection steps enables the synthesis of a novel poly(ethylene glycol)-based ATRP macroinitiator labeled with a ketal linkage (PEG-ketal-Br macroinitiator). Conducting ATRP allows for the synthesis of a series of DLDSRD diblock copolymers consisting of a hydrophilic poly(ethylene glycol) block covalently conjugated through a ketal linkage with a hydrophobic polymethacrylate block having multiple disulfide pendants. Analysis shows an unexpectedly high degree of polymerization of the hydrophobic polymethacrylate block that could be attributed to the instability of ketal linkages under ATRP conditions. The preliminary results from aqueous micellization and dual acidic pH/reduction-responsive cleavage of ketal and disulfide linkages suggest the feasibility of DLDSRD-based nanoassemblies toward effective drug delivery exhibiting precisely controlled release in response to dual stimuli at dual locations (core and interfaces).

Acid degradable cross-linked micelles for the delivery of cisplatin: A comparison with nondegradable cross-linker

Well-defined and nontoxic cross-linked polymeric micelles, containing either permanent or acid degradable cross-linkers, were employed for efficient intracellular delivery of cisplatin. The self-assembled structures were generated from triblock copolymers of poly(oligo(ethylene glycol) methylether methacrylate)-block-poly(N-hydroxysuccinic methacrylate)-block-poly(1,1-di-tert-butyl 3-(2-(methacryloyloxy)ethyl) butane-1,1,3-tricarboxylate) (POEGMEMA-b-PNHSMA-b-PMAETC) loaded with cisplatinum. The polymeric micelles were subsequently cross-linked via a reaction between pendant activated esters at the nexus core of the triblock copolymer using acid degrdabale ketal diamino cross-linkers. An in vitro study confirmed that both uncross-linked and cross-linked micelles prior to the loading of the platinum drug were nontoxic against OVCAR-3 cells even at high polymer concentration (around 300 ?g mL?1). The drug loaded cross-linked platinum polymeric micelles were superior to the uncross-linked platinum polymeric micelles in terms of cytotoxicity against OVCAR-3, due to a higher cellular uptake. Although there was no significant difference in cytotoxicity of cross-linked platinum polymeric micelles using different cross-linkers (permanent and acid cleavable) after 72 h of exposure, the difference was noticeable after 24 h of incubation, highlighting a much higher activity for acid degradable crosslinked micelles with conjugated platinum drugs. Moreover, the clonogenic assay suggested that cross-linked micelle loaded platinum drugs, in contrast to uncross-linked micelles, can effectively inhibit the OVCAR-3 cell regrowth for an extended period of time (10 days), even at very low micellar concentrations. In summary, acid degradable linkers ensure high cellular uptake compared to uncross-linked micelles but also lead to a faster drug action in comparison to a permanently cross-linked micelle.

Method for continuously preparing degradable curing agent based on tubular reaction device

The invention discloses a method for continuously preparing a degradable curing agent based on a tubular reaction device. Continuous synthesis, separation and solvent application are achieved throughthe solubility difference of raw material alkamine salt and product diamino acetal salt in a reaction solution; the reaction solution containing saturated diamino acetal salt after separation does notneed to be separated, and can be directly fed to a reaction system again to be subjected to a condensation substitution reaction after the raw material is supplemented. According to the method for continuously preparing the degradable curing agent by adopting the tubular reaction device, an existing intermittent production mode is changed, the product yield is greatly improved, the reaction period is shortened, the yield is increased, the productivity is improved, and the method has the characteristics of simple process, mild reaction conditions and environmental friendliness.

One-step preparation method of degradable curing agent

The invention discloses a one-step preparation method of a degradable curing agent, and relates to the technical field of preparation of degradable curing agents. The method comprises: adding alkaminesalt, a catalyst and a first solvent into a reactor, and starting stirring; metering a condensation reagent, adding the condensation reagent into the reactor in two times, and controlling the reaction temperature and the reaction pressure; adding a second solvent into the reaction solution, stirring and filtering; extracting a filter cake, carrying out alkaline hydrolysis to obtain a product, adding a NaOH aqueous solution for quenching, and filtering again to recover the catalyst; and extracting the aqueous solution of the product after alkaline hydrolysis by using an organic solvent, and desolventizing to obtain the product. According to the method, the reaction selectivity is improved by catalyzing the condensation reaction through the selective catalyst, the selected catalyst is a non-soluble catalyst, and the possibility that the water-soluble catalyst finally enters the wastewater is further reduced. According to the process, the yield of diaminoketal salt in the preparation process of the degradable curing agent is increased by adjusting the polarity of reaction liquid in the system.

SALTS OF DIAMINOACETALS AND DIAMINOKETALS AND THEIR SYNTHESIS, AND THEIR TRANSFORMATIONS TO DIAMINOACETALS AND DIAMINOKETALS

This application relates, in part, to novel salts represented by the following structure of Formula (1): wherein R1a is selected from the group consisting of hydrogen and optionally substituted alkyl (e.g., unsubstituted C1-6 alkyl, e.g., —CH3); R1b is optionally substituted alkyl (e.g., unsubstituted C1-6 alkyl, e.g., —CH3); each occurrence of R2 and R3 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, and optionally substituted aryl; R2 and R3 can combine with each other to form optionally substituted cycloalkyl; each m and n is independently an integer ranging from 1 to 20 (e.g., m and n is independently an integer ranging from 1 to 5); and each of Q1? and Q2? is independently a counterion (e.g., each of Q1? and Q2? is independently a counterion selected from the group consisting of chloride, bromide, fluoride, iodide, acetate, carboxylate, hydrogen sulfate, nitrate, and phenolate, and sulfonate, e.g., chloride), and methods of making the same.

Substituent Effects on the pH Sensitivity of Acetals and Ketals and Their Correlation with Encapsulation Stability in Polymeric Nanogels

The effect of structural variations in acetal- and ketal-based linkers upon their degradation kinetics is studied through the design, synthesis, and study of six series of molecules, comprising a total of 18 different molecules. Through this systematic study, we show that the structural fine-tuning of the linkers allows access to variations in kinetics of degradation of more than 6 orders of magnitude. Hammett correlations show that the ρ value for the hydrolysis of benzylidene acetals is about ?4.06, which is comparable to an SN1-like process. This shows that there is a strong, developing positive charge at the benzylic position in the transition state during the degradation of acetals. This positively charged transition state is consistent with the relative degradation rates of acetals vs ketals (correlated to stabilities of 1°, 2°, and 3° carboxonium ion type intermediates) and the observed effect of proximal electron-withdrawing groups upon the degradation rates. Following this, we studied whether the degradation kinetics study correlates with pH-sensitive variations in the host-guest characteristics of polymeric nanogels that contains these acetal or ketal moieties as cross-linking functionalities. Indeed, the trends observed in the small molecule degradation have clear correlations with the encapsulation stability of guest molecules within these polymeric nanogels. The implications of this fundamental study extend to a broad range of applications, well beyond the polymeric nanogel examples studied here.