Ester Function Research Articles

γ-Ester-Functionalized 1,1-Dicyanomethylene-3-indanone End-Capped Nonfullerene Acceptors for High-Performance, Annealing-Free Organic Solar Cells.

Modifying the end-capping groups in nonfullerene acceptors (NFAs) is an effective strategy for modulating their properties and that of the entire NFAs. This study reports the synthesis of a novel γ-ester-functionalized IC end-capping group (IC-γe) and its incorporation into the benzothiadiazole-fused central core, yielding isomer-free IC-γe end-capped NFAs, such as Y-IC-γe, Y-FIC-γe, and Y-ClIC-γe. The resultant NFAs exhibited similar absorption profiles but upshifted the lowest unoccupied molecular orbital energy level compared with those of the ester-free analogues, such as Y6 and Y7. Without thermal annealing, an excellent power conversion efficiency (PCE) of 16.4% is realized in the annealing-free OSC based on Y-FIC-γe with the PM6 donor polymer, which outperforms the OSCs based on Y-IC-γe and Y-ClIC-γe. In addition, the OSCs based on asymmetric Y-FIC-γe and Y-ClIC-γe have higher thermal stability with more than 83% PCE retention at an elevated temperature after 456 h than the symmetric Y-IC-γe case. In this study, we not only establish the structure-property relationship regarding the ester functionality and symmetricity tuning on the NFAs but also diagnose the reasons for the best-performing Y-FIC-γe-based OSCs, providing useful information for a novel high-performing NFA design strategy.

Highly Active and Thermally Robust Nickel Enolate Catalysts for the Synthesis of Ethylene-Acrylate Copolymers.

The insertion copolymerization of polar olefins and ethylene remains a significant challenge in part due to catalysts' low activity and poor thermal stability. Herein we demonstrate a strategy toward addressing these obstacles through ligand design. Neutral nickel phosphine enolate catalysts with large phosphine substituents reaching the axial positions of Ni achieve activity of up to 7.7×103 kg mol-1 h-1 (efficiency >35×103 g copolymer/g Ni) at 110 °C, notable for ethylene/acrylate copolymerization. NMR analysis of resulting copolymers reveals highly linear microstructures with main-chain ester functionality. Structure-performance studies indicate a strong correlation between axial steric hindrance and catalyst performance.

Dual Function of β-Hydroxy Dithiocinnamic Esters: RAFT Agent and Ligand for Metal Complexation.

The reversible addition-fragmentation chain-transfer (RAFT) process has become a versatile tool for the preparation of defined polymers tolerating a large variety of functional groups. Several dithioesters, trithiocarbonates, xanthates, or dithiocarbamates have been developed as effective chain transfer agents (CTAs), but only a few examples have been reported, where the resulting end groups are directly considered for a secondary use besides controlling the polymerization. Herein, it is demonstrated that β-hydroxy dithiocinnamic esters represent a hitherto overlooked class of materials, which are originally designed for the complexation of transition metals but may as well act as reversible CTAs. Modified with a suitable leaving group (R-group), these vinyl conjugated dithioesters indeed provide reasonable control over the polymerization of acrylates, acrylamides, or styrene via the RAFT process. Kinetic studies reveal linear evolutions of molar mass with conversion, while different substituents on the aromatic unit has only a minor influence. Block extensions prove the livingness of the polymer chains, although extended polymerization times may lead to side reactions. The resulting dithiocinnamic ester end groups are still able to form complexes with platinum, which verifies that the structural integrity of the end group is maintained. These findings open a versatile new route to tailor-made polymer-bound metal complexes.

Understanding the Reshaping of Fluorinated Polyester Vitrimers by Kinetic and DFT Studies of the Transesterification Reaction.

Vitrimers are a third class of polymers gathering the mechanical properties and solvent resistance of 3D thermosets and the reprocessability of thermoplastics. This unique behaviour is due to the triggering of certain covalent exchange reactions that allow the network to rearrange upon application of a stimulus. The constitutive feature of vitrimers is the adoption of a glass-like viscosity during the rearrangement of the network, often due to an associative mechanism for the exchange reaction. Transesterification networks are one of the most studied type of vitrimers that usually require the incorporation of a catalyst, implying the associated drawbacks. Following up on a recent report on catalyst-free transesterification vitrimers in which the ester functions are particularly reactive thanks to the presence of fluorine atoms in α- or β-position, parallel DFT calculations and an experimental kinetic study on model molecules are presented in order to quantitatively assess the effect of neighbouring fluorinated groups on the transesterification reaction rate.

Biodiesel Production from Sapindus Trifoliatus oil using Mg doped CaO Heterogeneous Nanocatalyst

ABSTRACT Biodiesel has gained increasing attention worldwide as an alternate source of energy that directly replaces fuels from fossil fuels. In this study, the transesterification process is reported using the heterogeneous nanocatalyst Mg-doped CaO for biodiesel production from Sapindus trifoliatus oil. The characterization methods such as FT-IR, XRD, and SEM were used to characterize the synthesized Mg-doped CaO catalyst. Both experimental and conventional methods were adopted to optimize the process parameters in biodiesel production. A maximum biodiesel conversion of 91.75% was obtained under the optimized conditions of temperature 58°C for a time of 73 min with 4% (w/w) catalyst concentration and 15:1 methanol:oil molar ratio. The low reaction temperature and time helped to develop the economically feasible process. For three cycles, the synthesized nanocatalyst was reused efficiently. The biodiesel methyl ester function groups were determined by GC-FID. The biodiesel physicochemical properties were also analyzed and compared with the ASTM standards.

Abstract 5449: Novel seleno-biotin compound inhibits viability of and induces reactive oxygen species (ROS)-mediated apoptosis in ovarian cancer cells

Abstract Ovarian cancer is one of the most common cancers in women and even with the currently available treatment options, including surgery, radiation, and chemotherapy, it caused 13,940 deaths in US alone in 2020. Thus, there is a continuous need for developing novel approaches for the treatment of ovarian cancer, particularly drug resistant ovarian cancer, as ovarian cancer most adversely affects the lives patients. Here in, we have designed seleno-biotin derivatives as potential therapeutics for ovarian cancer. The rational for designing these hybrid small molecules is two fold: (i) The biotin receptors are up-regulated in various carcinomas including ovarian cancer cells while being expressed at low levels in normal cells. Due to the high affinity of biotin towards BR, biotin has been used as a conjugate for several targeted imaging, sensing, and delivery in vitro and in vivo. (ii) Organoselenium compounds with appropriate selenium moieties have shown therapeutic efficacy in several pre-clinical cancer models. Therefore, we designed several analogs of biotin by conjugating selenium moieties connected through ester, selenoester, or amide functionalities and their cytotoxicities were assessed using four different ovarian cancer cell lines. Ester-linked biotin-selenocyanate compound 2, out of the other analogs, in direct comparison to biotin alone, more effectively reduced the cell viability (IC50 9.8-18.5 µM against all the tested cell lines) and induced apoptosis in ovarian cancer cells in dose dependent manner as demonstrated by the cell viability assay. It showed three times more potency (IC50 14.08 µM) than standard drugs 5-FU (IC50 48.4 µM) and cisplatin (IC50 41.0 µM) against drug-resistant Hey A8 cancer cells and three times more activity with an IC50 value of 9.8 µM as compared to 5-FU (IC50 25.92 µM) against ES-2 cells. The above findings were supported by trypan blue dye exclusion assay, Annexin V/7-AAD, Caspase 3/7 apoptosis assays and Western blotting of apoptotic proteins. Compound 2 effectively caused cell cycle arrest of the treated OVCAR-3 cells in S-phase of the cell cycle, thus causing regulatory changes in the cell cycle proteins, as evident by Western blotting. In addition, compound 2 redox cycles was demonstrated by DCFDA based reactive oxygen species estimation. These experiments demonstrate that selenium modified biotin which contains a covalently attached redox cycling selenide group has the potential for human therapeutic applications against ovarian and other cancers over-expressing biotin receptors. Citation Format: Asif Raza, Amandeep Singh, Amin Shantu, L. Mallory Boylan, Julian E. Spallholz, Arun Sharma. Novel seleno-biotin compound inhibits viability of and induces reactive oxygen species (ROS)-mediated apoptosis in ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5449.

Preparation of Functionalized Amides Using Dicarbamoylzincs.

We report a new convenient preparation of dicarbamoylzincs of type (R1R2NCO)2Zn by the treatment of ZnCl2 and formamides R1R2NCHO with LiTMP in THF (15 °C, 15 min) or by the reaction of formamides R1R2NCHO with TMP2Zn (25 °C, 16 h). This second method tolerates sensitive groups such as an ester, ketone or nitro function. Reaction of these dicarbamoylzincs with allylic, benzylic, aryl, alkenyl bromides, acid chlorides, aldehydes or enones provided various polyfunctional amides in 47–97 % yields. 13C NMR characterization of these new carbamoylzinc derivatives is reported.

Isopropenyl Esters (iPEs) in Green Organic Synthesis.

The need for greener compounds able to replace conventional ones with similar reactivity is crucial for the development of sustainable chemistry. Isopropenyl esters (iPEs) represent one eco-friendly alternative to acyl halides and anhydrides. This review provides a comprehensive overview of the preparation methodologies and reported synthetic applications of iPEs and, in particular, of isopropenyl acetate (iPAc). Intriguingly, the presence of a C=C double bond adjacent to the ester functionality makes iPEs appealing in different chemoselective organic synthesis transformations. For instance, the acyl moiety is suitable for transesterification reactions in presence of different heteroatom-based nucleophiles (C-, O-, N-, S-, Se-); these reactions are irreversible thanks to the formation of acetone, obtained upon keto-enol tautomerization of the prop-1-en-2-ol (isopropenyl) leaving group. Similarly, the unsaturation contained in the isopropenyl synthon could be selectively exploited in organic synthesis for electrophilic and/or radical additions as well as in metal-catalyzed cross-coupling reactions. To conclude, iPEs recently found major interest in the direct modification of biomass (i.e. lignin or cellulose) and in the implementation of tandem reactions of esterification-acetalization by exploiting the co-formation of acetone during the reaction.

Mimetics of ADP-Ribosylated Histidine through Copper(I)-Catalyzed Click Chemistry.

A convergent synthesis provided nearly perfect τ-ADP-ribosylated histidine isosteres (His*-τ-ADPr) via a copper(I)-catalyzed cycloaddition between an azido-ADP-ribosyl analogue and an oligopeptide carrying a propargyl glycine. Both α- and β-configured azido-ADP-ribosyl analogues have been synthesized. The former required participation of the C-2 ester functionality during glycosylation, while the latter was obtained in high stereoselectivity from an imidate donor with a nonparticipating para-methoxy benzyl ether. Four His*-τ-ADPr peptides were screened against a library of human ADP-ribosyl hydrolases.

Influence of Different Substitution Patterns on the 2D Crystalline Aggregation of Small Molecules on HOPG Surfaces.

A series of benzoic and terephthalic acid derivatives and their corresponding ethyl esters have been synthesized. These are decorated with dendritic units carrying alkoxy chains that differ in the number of alkoxy groups and/or their substitution pattern. These molecules were deposited from solution on highly oriented pyrolytic graphite, and the resulting supramolecular surface patterns have been studied by scanning tunneling microscopy at the solid/liquid interface. Thus, we were able to perform a systematic study on the influence of orthogonal functional groups governing the supramolecular assembly, that is, the alkoxy chains of dendritic units and the carboxylic acid (ester) functions, on the intermolecular interactions, that is, van der Waals interactions and hydrogen bonding between the adsorbed species that drive the pattern formation.

Impact of the Hydrolysis and Methanolysis of Bidesmosidic Chenopodium quinoa Saponins on Their Hemolytic Activity.

Saponins are specific metabolites abundantly present in plants and several marine animals. Their high cytotoxicity is associated with their membranolytic properties, i.e., their propensity to disrupt cell membranes upon incorporation. As such, saponins are highly attractive for numerous applications, provided the relation between their molecular structures and their biological activities is understood at the molecular level. In the present investigation, we focused on the bidesmosidic saponins extracted from the quinoa husk, whose saccharidic chains are appended on the aglycone via two different linkages, a glycosidic bond, and an ester function. The later position is sensitive to chemical modifications, such as hydrolysis and methanolysis. We prepared and characterized three sets of saponins using mass spectrometry: (i) bidesmosidic saponins directly extracted from the ground husk, (ii) monodesmosidic saponins with a carboxylic acid group, and (iii) monodesmosidic saponins with a methyl ester function. The impact of the structural modifications on the membranolytic activity of the saponins was assayed based on the determination of their hemolytic activity. The natural bidesmosidic saponins do not present any hemolytic activity even at the highest tested concentration (500 µg·mL−1). Hydrolyzed saponins already degrade erythrocytes at 20 µg·mL−1, whereas 100 µg·mL−1 of transesterified saponins is needed to induce detectable activity. The observation that monodesmosidic saponins, hydrolyzed or transesterified, are much more active against erythrocytes than the bidesmosidic ones confirms that bidesmosidic saponins are likely to be the dormant form of saponins in plants. Additionally, the observation that negatively charged saponins, i.e., the hydrolyzed ones, are more hemolytic than the neutral ones could be related to the red blood cell membrane structure.

Synthesis of d‐glucitolbased Gemini amphiphilic nanotransporters

AbstractA newer class of Gemini amphiphiles was prepared using d‐glucitol as a template. C18 alkyl chains are incorporated on the template to confer hydrophobicity while monomethoxy polyethylene glycol (mPEG) moiety of varied size imparts hydrophilicity. An acetonide group mounted on glucitol moiety is used to maintain rigidity in the amphiphilic architecture and to study its impact on aggregation and transport ability. The aggregation behavior of the synthesized amphiphiles was studied through fluorescence spectroscopy, dynamic light scattering (DLS), and cryo‐transmission electron microscopy (cryo‐TEM). Their nanotransport potential was demonstrated using hydrophobic model guests like the fluorescent dye Nile red and the pharmacologically active agent curcumin. Cytotoxicity and cellular uptake studies were carried out over HeLa cancer cells to evaluate their biological applicability. The ester functionalities in the amphiphiles enable them to exhibit sensitivity towards hydrolases. Candida antarctica lipase (Novozym‐435) has been successfully utilized to facilitate the enzyme‐assisted release of the encapsulated dye.

Thermal rearrangement in thermal cascade reaction polymers via ortho-carbonate ester functionalization of polyimides and their gas separation performance

Thermal Rearrangement Polymers have a strong potential regarding to gas separation membrane materials, especially for the purification of methane containing gas streams, due to their inter-connected bottleneck-type pores. However, most TR polymers reveal high permeabilities and high conversions only at high temperatures of 450 °C. Our study demonstrates a method to enhance the permeability at lower annealing temperatures by tailoring the thermally triggered decomposition and reaction cascade via modification and temperature protocol. In this study a set of seven carbonate ester modifications was prepared and thermo-analytically studied by means of DSC and TGA-FTIR on-line analysis combined with structure determination methods and quantum mechanical simulations. Two decarboxylative alkyl-transfer reaction mechanisms were formulated for the decomposition reaction of the carbonate ester group. A correlation of the size and branching of the carbonate ester connected alkyl group and its effect on the film properties and gas separation performance was studied. High polyimide to polybenzoxazole conversions were determined for the modified polymers and a 2008 upper bound performance was obtained for all materials, after annealing at 400 °C. Furthermore, the ethyl carbonate ester (ECO3PI-1) polymer entered the target zone above an ideal selectivity of CO2/CH4 of 30 after aging, making it an attractive membrane material.

NHC[sbnd]Catalyzed β-Carbon functionalization of carboxylic esters towards formation of δ-Lactams: A mechanistic study

In the realm of NHeterocyclic carbene (NHC) catalysis, γ-carbon functionalization of carboxylic esters has rapidly developed in recent years, however, the mechanisms and stereoselectivity of β-carbon functionalization of carboxylic esters remain poorly understood. Herein, we investigated the mechanism and key factors controlling the regio- and stereoselectivity of the [3 + 3] cycloaddition between an ester and a benzofuran mediated by chiral NHC catalyst using density functional theory (DFT) computations. Our proposed mechanism includes binding of the NHC to ester, C − O bond dissociation, carbon-carbon bond formation, HOAr-assisted protonation, HCO3−-mediated deprotonation, intramolecular cycloaddition and elimination of the NHC. The carbon-carbon bond formation determines the stereoselectivity and preferably generates the S-configurational δ-lactam, in consistent with experimental observations. Non-covalent interaction (NCI) results indicate that weak C–H···O, C–H···N and π···π interactions play key roles to control the stereoselectivity. The global reactivity indexes (GRIs) and electron localization function (ELF) analyses show that the role of the NHC is to promote the dissociation of C–O bond of the ester, thus making it more electrophilic to react with the nucleophilic benzofuran.

Valorisation of the diterpene podocarpic acid – Antibiotic and antibiotic enhancing activities of polyamine conjugates

As part of our search for new antimicrobials and antibiotic adjuvants, a series of podocarpic acid-polyamine conjugates have been synthesized. The library of compounds made use of the phenolic and carboxylic acid moieties of the diterpene allowing attachment of polyamines (PA) of different lengths to afford a structurally-diverse set of analogues. Evaluation of the conjugates for intrinsic antimicrobial properties identified two derivatives of interest: a PA3-4–3 (spermine) amide-bonded variant 7a that was a non-cytotoxic, non-hemolytic potent growth inhibitor of Gram-positive Staphylococcus aureus (MRSA) and 9d, a PA3-8-3 carbamate derivative that was a non-toxic selective antifungal towards Cryptococcus neoformans. Of the compound set, only one example exhibited activity towards Gram-negative bacteria. However, in the presence of sub-therapeutic amounts of either doxycycline (4.5 µM) or erythromycin (2.7 μM) several analogues were observed to exhibit weak to modest antibiotic adjuvant properties against Pseudomonas aeruginosa and/or Escherichia coli. The observation of strong cytotoxicity and/or hemolytic properties for subsets of the library, in particular those analogues bearing methyl ester or n-pentylamide functionality, highlighted the fine balance of structural requirements and lipophilicity for antimicrobial activity as opposed to mammalian cell toxicity.

Limited Secondary Organic Aerosol Production from Acyclic Oxygenated Volatile Chemical Products.

Volatile chemical products (VCPs) have recently been identified as potentially important unconventional sources of secondary organic aerosol (SOA), in part due to the mitigation of conventional emissions such as vehicle exhaust. Here, we report measurements of SOA production in an oxidation flow reactor from a series of common VCPs containing oxygenated functional groups and at least one oxygen within the molecular backbone. These include two oxygenated aromatic species (phenoxyethanol and 1-phenoxy-2-propanol), two esters (butyl butyrate and butyl acetate), and four glycol ethers (carbitol, methyl carbitol, butyl carbitol, and hexyl carbitol). We measured gas- and particle-phase products with a suite of mass spectrometers and particle-sizing instruments. Only the aromatic VCPs produce SOA with substantial yields. For the acyclic VCPs, ether and ester functionality promotes fragmentation and hinders autoxidation, whereas aromatic rings drive SOA formation in spite of the presence of ether groups. Therefore, our results suggest that a potential strategy to reduce urban SOA from VCPs would be to reformulate consumer products to include less oxygenated aromatic compounds.

Substituted Malonic Acid Half Oxyesters (SMAHOs): Green Nucleophiles for Organic Synthesis

AbstractSubstituted malonic acid half‐oxyesters (SMAHOs) constitute an original family of malonic acid derivatives. They could be mostly used as pro‐nucleophiles through decarboxylative processes, making them enolate equivalents for the elaboration of greener methodologies. In addition to the native ester function, the presence of a substituent on the malonic position affords additional opportunities for structural diversification. These reagents are particularly well‐suited for the development of organocatalyzed processes, which has recently led to olefination and addition reactions as relevant synthetic routes to elaborated structures under mild conditions.

In Vitro Analysis of Organic Ester Functional Groups in Carious Dentine

Background: With the implementation of minimally invasive selective caries removal protocols to treat cavitated, deep carious dentine lesions, there is a need to investigate specific biochemical moiety distributions to help characterise and distinguish between infected (contaminated) and affected (demineralised) zones within the dentine lesion. The present in vitro investigation aimed to compare the distribution of ester functional groups (1740 cm−1) within carious dentine tissue (infected and affected dentine). The null hypothesis stipulated that there are no differences in ester function intensity/distribution within carious dentine lesions. Materials and Methods: From a total of five extracted human molar teeth with carious dentine lesions, 246 points from 10 sections of carious dentine were examined using high-resolution Raman spectroscopy and characterised into infected, affected and sound dentine. The peak intensity of the characteristic vibration mode of the ester function was calculated from sample scans. Results: Analyses indicated a statistically significant difference in the spectroscopic vibration bands of esters between the infected and affected dentine zones. Conclusion: The ester functional group is higher in intensity in the caries-infected dentine zone compared to the affected tissue. This finding could be used to develop an objective indicator for the selective operative management of carious dentine.

Using Triethylborane to Manipulate Reactivity Ratios in Epoxide-Anhydride Copolymerization: Application to the Synthesis of Polyethers with Degradable Ester Functions.

The anionic ring-opening copolymerization (ROCOP) of epoxides, namely of ethylene oxide (EO), with anhydrides (AH) generally produces strictly alternating copolymers. With triethylborane (TEB)-assisted ROCOP of EO with AH, statistical copolymers of high molar mass including ether and ester units could be obtained. In the presence of TEB, the reactivity ratio of EO (rEO), which is normally equal to 0 in its absence, could be progressively raised to values lower than 1 or higher than 1. Conditions were even found to obtain rEO equal or close to 1. Samples of P(EO-co-ester) with minimal compositional drift could be synthesized; upon basic degradation of their ester linkages, these samples afforded poly(ethylene oxide) (PEO) diol samples of narrow molar mass distribution. In other cases where rEO were lower or higher than 1, the PEO diol samples eventually isolated after degradation exhibited a broader distribution of molar masses because of the compositional drift of initial P(EO-co-ester) samples.

Structure-Activity Relationship Studies of New Sinapic Acid Phenethyl Ester Analogues Targeting the Biosynthesis of 5-Lipoxygenase Products: The Role of Phenolic Moiety, Ester Function, and Bioisosterism.

Sinapic acid is found in many edible plants and fruits, such as rapeseed, where it is the predominant phenolic compound. New sinapic acid phenethyl ester (SAPE) analogues were synthesized and screened as inhibitors of the biosynthesis of 5-lipoxygenase (5-LO) in stimulated HEK293 cells and polymorphonuclear leukocytes (PMNL). Inhibition of leukotriene biosynthesis catalyzed by 5-LO is a validated therapeutic strategy against certain inflammatory diseases and allergies. Unfortunately, the only inhibitor approved to date has limited clinical use because of its poor pharmacokinetic profile and liver toxicity. With the new analogues synthesized in this study, the role of the phenolic moiety, ester function, and bioisosterism was investigated. Several of the 34 compounds inhibited the biosynthesis of 5-LO products, and 20 compounds were 2-11 times more potent than zileuton in PMNL, which are important producers of 5-LO products. Compounds 5i (IC50: 0.20 μM), 5l (IC50: 0.20 μM), and 5o (IC50: 0.21 μM) bearing 4-trifluoromethyl, methyl, or methoxy substituent at meta-position of the phenethyl moiety were 1.5 and 11.5 times more potent than SAPE (IC50: 0.30 μM) and zileuton (IC50: 2.31 μM), respectively. Additionally, compound 9 (IC50: 0.27 μM), which was obtained after acetylation of the 4-hydroxyl of SAPE, was equivalent to SAPE and 8 times more active than zileuton. Furthermore, compound 20b (IC50: 0.27 μM) obtained after the bioisosteric replacement of the ester function of SAPE by the 1,2,4-oxadiazole heterocycle was equivalent to SAPE and 8 times more active than zileuton. Thus, this study provides a basis for the rational design of new molecules that could be developed further as anti 5-LO therapeutics.