Esterification Chemistry Research Articles

Esterification as a Demonstration of Electrochemically Powered Catalytic Dehydration

AbstractThe reliance on wasteful stoichiometric reagents to accomplish dehydration reactions such as esterification, amidation, and alcohol substitution is a longstanding challenge in synthetic chemistry. To address this problem, an electrochemical approach has been developed as a new conceptual platform for dehydration reactions. As a proof-of-concept demonstration, an electrochemical esterification protocol has been described that proceeds at room temperature, without acid or base additives, and without consuming stoichiometric reagents. This approach therefore overcomes key complications of esterification chemistry, and we envision that it will similarly enable improvements to a range of important, related transformations.1 Introduction2 An Electrochemical Design for Catalytic Dehydration3 Electrochemical Esterification4 Conclusions

Charge inversion under plasma-nanodroplet reaction conditions excludes Fischer esterification for unsaturated fatty acids: a chemical approach for type II isobaric overlap.

Direct infusion ionization methods provide the highest throughput strategy for mass spectrometry (MS) analysis of low-volume samples. But the trade-off includes matrix effects, which can significantly reduce analytical performance. Herein, we present a novel chemical approach to tackle a special type of matrix effect, namely type II isobaric overlap. We focus on detailed investigation of a nanodroplet-based esterification chemistry for differentiating isotopologue [M + 2] signal due to unsaturated fatty acid (FA) from the monoisotopic signal from a saturated FA. The method developed involves the online fusion of nonthermal plasma with charged nanodroplets, enabling selective esterification of saturated FAs. We discovered that unsaturated FAs undergo spontaneous intramolecular reaction via a novel mechanism based on a carbocation intermediate to afford a protonated lactone moiety (resonance stabilized cyclic carbonium ion), whose mass is the same as the original protonated unsaturated FA. Therefore, the monoisotopic signal from any saturated FA can be selectively shifted away from the mass-to-charge position where the isobaric interference occurs to enable effective characterization by MS. The mechanism governing the spontaneous intramolecular reactions for unsaturated FAs was validated with DFT calculations, experimentation with standards, and isotope labeling. This novel insight achieved via the ultrafast plasma-nanodroplet reaction environment provides a potentially useful synthetic pathway to achieve catalyst-free lactone preparation. Analytically, we believe the performance of direct infusion MS can be greatly enhanced by combining our approach with prior sample enrichment steps for applications in biomedicine and food safety. Also, combination with portable mass spectrometers can improve the efficiency of field studies since front-end separation is not possible under such conditions.

Synthesis and Characterization of Amino-Functional Polyester Dendrimers Based On Bis-MPA with Enhanced Hydrolytic Stability and Inherent Antibacterial Properties.

Polyester dendrimers based on 2,2 bis(hydroxymethyl)propionic acid have been reported to be degradable, non-toxic, and exhibit good antimicrobial activity when decorated with cationic charges. However, these systems exhibit rapid depolymerization, from the outer layer inwards in physiological neutral pHs, which potentially restricts their use in biomedical applications. In this study, we present a new generation of amine functional bis-MPA polyester dendrimers with increased hydrolytic stability as well as antibacterial activity for Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) planktonic bacteria strains. These new derivatives show generally good cytocompatibility for the concentrations they are active toward bacteria, in monocyte/macrophage-like cells (Raw 264.7), and human dermal fibroblasts. Fluoride - promoted esterification chemistry, anhydride chemistry, and click reactions were utilized to produce a library from generations 1-3 and with cationic peripheral groups ranging from 6 to 24 groups, respectively. The dendrimers were successfully purified using conventional purification techniques as well as characterized by matrix-assisted laser desorption ionization time-of-flight mass spectroscopy, nuclear magnetic resonance, and size exclusion chromatography. As proof of synthetic versatility, dendritic-linear-dendritic block copolymer were successfully synthesized to display cysteamine peripheral functionalities as well as the scaffolding ability with biomedically relevant lipoic acid and methoxy polyethylene glycol.

Covalent Surface Modification of Ti3C2Tx MXene with Chemically Active Polymeric Ligands Producing Highly Conductive and Ordered Microstructure Films.

As interest continues to grow in Ti3C2Tx and other related MXenes, advancement in methods of manipulation of their surface functional groups beyond synthesis-based surface terminations (Tx: -F, -OH, and ═O) can provide mechanisms to enhance solution processability as well as produce improved solid-state device architectures and coatings. Here, we report a chemically important surface modification approach in which "solvent-like" polymers, polyethylene glycol carboxylic acid (PEG6-COOH), are covalently attached onto MXenes via esterification chemistry. Surface modification of Ti3C2Tx with PEG6-COOH with large ligand loading (up to 14% by mass) greatly enhances dispersibility in a wide range of nonpolar organic solvents (e.g., 2.88 mg/mL in chloroform) without oxidation of Ti3C2Tx two-dimensional flakes or changes in the structure ordering. Furthermore, cooperative interactions between polymer chains improve the nanoscale assembly of uniform microstructures of stacked MXene-PEG6 flakes into ordered thin films with excellent electrical conductivity (∼16,200 S·cm-1). Most importantly, our covalent surface modification approach with ω-functionalized PEG6 ligands (ω-PEG6-COOH, where ω: -NH2, -N3, -CH═CH2) allows for control over the degree of functionalization (incorporation of valency) of MXene. We believe that installing valency onto MXenes through short, ion conducting PEG ligands without compromising MXenes' features such as solution processability, structural stability, and electrical conductivity further enhance MXenes surface chemistry tunability and performance and widens their applications.

Synthesis and Characterization of Cationic Dendrimer‐PDMS Hybrids

A modular strategy for the synthesis of dendron-linear polymer hybrids comprised of a flexible polydimethylsiloxane (PDMS) midblock with cationic 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) dendron end groups is developed. The invention of a scalable methodology to access quaternary ammonium carboxylate building blocks and their direct use in esterification chemistry enables rapid access to cationic bis-MPA dendrons. The convergent click coupling of highly charged dendrons to hydrophobic PDMS chain-ends gives a 12-membered family of hybrids that are comprised of different dendron generations (G1-3) and quaternary ammonium alkyl chain lengths (C4 , C8 , C12 , C16 ). This provides a library of materials with variable hydrophobicity, charge density, and chain-end valency. The physical behavior of the dendron-linear PDMS hybrid copolymers significantly changes after introduction of the cationic dendron end-groups and leads to soft-solid materials as a result of inhibited chain mobility. These PDMS-dendron hybrids are expected to behave as surface-active antimicrobial additives in bulk cross-linked silicone systems.

Self-Assembled Polyester Dendrimer/Cellulose Nanofibril Hydrogels with Extraordinary Antibacterial Activity.

Cationic dendrimers are intriguing materials that can be used as antibacterial materials; however, they display significant cytotoxicity towards diverse cell lines at high generations or high doses, which limits their applications in biomedical fields. In order to decrease the cytotoxicity, a series of biocompatible hybrid hydrogels based on cationic dendrimers and carboxylated cellulose nanofibrils were easily synthesized by non-covalent self-assembly under physiological conditions without external stimuli. The cationic dendrimers from generation 2 (G2) to generation 4 (G4) based on trimethylolpronane (TMP) and 2,2-bis (methylol)propionic acid (bis-MPA) were synthesized through fluoride promoted esterification chemistry (FPE chemistry). FTIR was used to show the presence of the cationic dendrimers within the hybrid hydrogels, and the distribution of the cationic dendrimers was even verified using elemental analysis of nitrogen content. The hybrid hydrogels formed from G3 and G4 showed 100% killing efficiency towards Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) with bacterial concentrations ranging from 105 CFU/mL to 107 CFU/mL. Remarkably, the hybrid hydrogels also showed good biocompatibility most probably due to the incorporation of the biocompatible CNFs that slowed down the release of the cationic dendrimers from the hybrid hydrogels, hence showing great promise as an antibacterial material for biomedical applications.

A Chemically Driven Rotary Molecular Motor Based on Reversible Lactone Formation with Perfect Unidirectionality

Summary Among the amazing variety of ingenious molecular machines present in living organisms, enabling motility, responsiveness, and out-of-equilibrium behavior among others, rotary motors, such as the ATPase and bacterial flagellar motors, hold a special position. While these biological machines are mainly powered by chemical conversion and artificial light-driven rotary molecular motors have been well established, genuine chemically driven rotary motor systems are very limited. Here, we report a chemically powered rotary molecular motor based on biaryl structures that allows complete 360° unidirectional rotation i.e., >99% based on simple esterification chemistry. All the stereoisomers involved in the 4-stage rotary process have been characterized using X-ray crystallography confirming the relative stereochemistry of each isomer in accordance with the sequential and complete stereoselective operation of the rotary system. Having established the basic principles of this novel molecular rotary motor, it will facilitate the design of more sophisticated future artificial machine systems driven solely by chemical energy.

Telodendrimer-Based Macromolecular Drug Design using 1,3-Dipolar Cycloaddition for Applications in Biology.

An architectural polymer containing hydrophobic isoxazole-based dendron and hydrophilic polyethylene glycol linear tail is prepared by a combination of the robust ZnCl2 catalyzed alkyne-nitrile oxide 1,3-dipolar cycloaddition and esterification chemistry. This water soluble amphiphilic telodendrimer acts as a macromolecular biologically active agent and shows concentration dependent reduction of glioblastoma (U251) cell survival.

Designing Branched Deoxybenzoin Polyesters as Polymeric Flame Retardants

ABSTRACTAB2 monomers present opportunities to conduct one‐pot syntheses of highly branched or “hyperbranched” polymers, which are known for their distinct physical and chemical properties relative to linear polymers. This paper describes the synthesis of a deoxybenzoin‐containing AB2 monomer and its use in step‐growth polymerization to prepare branched aromatic polyesters. Highly soluble deoxybenzoin polymers were obtained with degrees of branching reaching 0.36 and estimated molecular weights approaching 20 kDa. The phenolic chain ends of the polymer allowed for post‐polymerization modification by silylation and esterification chemistry. TGA and microscale combustion calorimetry revealed these novel aromatic polyesters to possess the critically important characteristics of flame‐retardant polymers, such as high char yield and low heat release. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1765–1770

A highly tumor-targeted nanoparticle of podophyllotoxin penetrated tumor core and regressed multidrug resistant tumors

Podophyllotoxin (PPT) exhibited significant activity against P-glycoprotein mediated multidrug resistant (MDR) tumor cell lines; however, due to its poor solubility and high toxicity, PPT cannot be dosed systemically, preventing its clinical use for MDR cancer. We developed a nanoparticle dosage form of PPT by covalently conjugating PPT and polyethylene glycol (PEG) with acetylated carboxymethyl cellulose (CMC-Ac) using one-pot esterification chemistry. The polymer conjugates self-assembled into nanoparticles (NPs) of variable sizes (20–120 nm) depending on the PPT-to-PEG molar ratio (2–20). The conjugate with a low PPT/PEG molar ratio of 2 yielded NPs with a mean diameter of 20 nm and released PPT at ∼5%/day in serum, while conjugates with increased PPT/PEG ratios (5 and 20) produced bigger particles (30 nm and 120 nm respectively) that displayed slower drug release (∼2.5%/day and ∼1%/day respectively). The 20 nm particles exhibited 2- to 5-fold enhanced cell killing potency and 5- to 20-fold increased tumor delivery compared to the larger NPs. The biodistribution of the 20 nm PPT-NPs was highly selective to the tumor with 8-fold higher accumulation than all other examined tissues, while the larger PPT-NPs (30 and 120 nm) exhibited increased liver uptake. Within the tumor, >90% of the 20 nm PPT-NPs penetrated to the hypovascular core, while the larger particles were largely restricted in the hypervascular periphery. The 20 nm PPT-NPs displayed significantly improved efficacy against MDR tumors in mice compared to the larger PPT-NPs, native PPT and the standard taxane chemotherapies, with minimal toxicity.

Surface functionalization of nanodiamond particles via atom transfer radical polymerization

Ultradispersed diamond (UDD)/polymer brushes having excellent solution dispersibilities are prepared by atom transfer radical polymerization (ATRP) using the “grafting-from” synthesis strategy. ATRP initiators, covalently attached to oxidized surface carbon atoms of UDD aggregates using esterification chemistry, initiate polymerization of methacrylate monomers to form hydrophobic UDD/poly(iso-butyl methacrylate) and UDD/poly(tert-butyl methacrylate) polymer brushes. Acid hydrolysis of a UDD/poly(tert-butyl methacrylate) polymer brush affords a hydrophilic UDD/poly(methacrylic acid) polymer brush. Based on surface area measurements and GPC data, the calculated surface density of a representative UDD/polymer brush material is ca. five polymer chains/100 nm 2. A wide variety of UDD/polymer brush materials having controlled dispersibility and functional group reactivity are now potentially available using this synthesis strategy.

Interfacial chemistry on carboxylate‐functionalized monolayer assemblies

AbstractDeposition of trichlorosilanes with ester groups at their remote termini provides a convenient entry to carboxylic acid‐bearing siloxane‐anchored self‐assembled monolayers. The de‐esterification of these esters has been optimized to minimize monolayer damage, and their quantitative re‐esterification provides clear evidence for the stability of these systems. Both the structure of the ester‐terminated monolayer and its de‐esterification/esterification chemistry can be easily monitored by FTIR‐ATR measurements. This spectroscopic tool, together with a liquid cell that enables IR spectra to be measured in an aqueous environment, enables a detailed structural analysis of the carboxylic acid‐bearing siloxane‐anchored self‐assembled monolayers and an assessment of their acid/base behavior (by in situ titration). The use of D2O instead of H2O for the in situ titration experiments also improves the available IR window. Both monomeric and dimeric/oligomeric acid groups are seen, and the relative ease of deprotonation of these various species can be directly monitored. Monomers of alkyl carboxylic acids that are hydrogen bonded only to surrounding water molecules have a pKa = 4.9, while the pKa for the aggregated molecules is 9.3. Similar behavior is seen for surface‐bound benzoic acids, where the two pKa values are 4.7 and 9.0. The influence of temperature on these structures and their chemistry has been explored to a limited extent as well. When the alkylcarboxylic acid system is cooled to 10 °C, the pKa value for the acid monomers is reduced from 4.9 to 4.5 and increases from 9.3 to 10.3 for the aggregates.

Optimization techniques for carbodiimide activated synthesis of poly(( RS)-3,3,3-trifluorolactic acid); statistically designed experiments to optimize polymerization conditions

Poly(( RS)-3,3,3-trifluorolactic acid) was synthesized from the alphahydroxy acid, ( RS)-3,3,3-trifluorolactic acid, by esterification with 1,3-diisopropylcarbodiimide condensing agent and catalytic salts of 4-(dimethylamino)pyridine and protic acids. Literature data of related esterification chemistry indicated that temperature, solvent, and catalyst can affect the polymerization chemistry. Optimization of polymer product yield was desirable to understand better how to control the reaction as well as producing high molecular weight polymer in sufficient quantity for subsequent characterization. The goals of this study were to maximize the polymer yield and molecular weight through the use of statistically designed polymerization experiments. A D-optimal design was developed for the completion of this study. Two different solvents and catalysts were investigated. Also, the level of catalyst was varied. As a result of this experimental design study, optimum conditions for highest product yield and molecular weight (indicated by solution viscosity) were identified. Response surface plots show that polymerization in methylene chloride at 5–7°C with the catalytic salt 4-(dimethylamino)pyridinium 4-toluenesulfonate (DPTS) at fractional molar equivalent (with respect to monomer) quantities provided polymer consistent with the study objectives.