Carboxylic Function Research Articles

PEGylation of NIR Cd0.3Pb0.7S aqueous quantum dots for stabilization and reduction of nonspecific binding to cells

Cd0.3Pb0.7S (CdPbS) aqueous quantum dots (AQDs) made with 3-mercaptoproprionic acid (MPA) as a ligand have the advantages of emitting near-infrared light, well above 800 nm, that completely circumvents interference from tissue autofluorescence and have significant amounts of ligands for bioconjugation. However, retaining the right amount of MPA became a challenge when using CdPbS AQDs for bioimaging because retaining too much MPA could lead to significant nonspecific staining in cell imaging while insufficient MPA could cause AQDs instability in biological systems. Here we examined PEGylation (i.e. chemically linking amine-functionalized polyethylene glycol (PEG)) to modify MPA on the AQDs surface to improve AQDs stability and reduce nonspecific staining. In addition, for conjugation with antibodies, a bifunctional PEG with a carboxyl functionality was used to permit chemical linkage of a PEG to an antibody on the other end. It was found that performing PEGylation at the thiol concentration where the zeta potential becomes saturated stabilized the CdPbS AQDs suspension and reduced nonspecific binding to cells. Furthermore, with the bifunctional PEG, the CdPbS AQDs were conjugated with antibodies and the AQD-Ab conjugates were shown to stain cancer cells specifically against normal cells with a signal-to-noise ratio of 8.

Selective detection of nanomaterials: Gold nanorod imprinted matrices

Anisotropic nanostructures such as nanorods can be found in an increasing number of applications such as catalysis and imaging. Although their synthesis is well developed, their selective detection and separation are still in their infancy. Here, we demonstrate for the first time the selective recognition of gold nanorods (GNRs) by the nanoparticle-imprinted matrix (NAIM) approach. Specifically, GNRs stabilized by citrate (GNRs-cit) were adsorbed on an electrode surface modified with a positively charged polymer. The adsorption was followed by the electrochemical deposition of an aryldiazonium-based matrix around the GNRs-cit. Nanocavities having the shape of the imprinted GNRs were formed upon the removal of the nanoobject by electrochemical dissolution. We find that these nanocavities showed the ability to reuptake selectively GNRs similar to those initially imprinted. Furthermore, our findings clearly show that the recognition of the GNRs, namely, their reuptake by the nanocavities, depends on both the physical, i.e., structural fitness, and the chemical interactions between the imprinted GNRs and the matrix. For example, whereas a matrix bearing carboxylic acid functionalities repelled the GNRs stabilized by citric acid, a matrix formed by the electropolymerization of 4-acetylbenzenediazonium (ABD) exhibited good reuptake. A reuptake percentage, which is the ratio between the number of GNRs uptaken by the nanocavities divided by the number of the originally imprinted GNRs, of ca. 50% was obtained.

Surface Charge-Switchable Antifouling Block Copolymer with Bacteriostatic Properties.

Zwitterionic polymers are an emerging family of effective, low-fouling materials that can withstand unintended interactions with biological systems while exhibiting enhanced activity in bacterial matrix deterioration and biofilm eradication. Herein, we modularly synthesized an amphiphilic block copolymer, ZABCP, featuring potential bacteriostatic properties composed of a charge-switchable polyzwitterionic segment and a redox-sensitive pendant disulfide-labeled polymethacrylate block. The leucine-appended polyzwitterionic segment with alternatively positioned cationic amine and anionic carboxylate functionalities undergoes charge alterations (+ve → 0 → -ve) on pH variation. By introducing appropriate amphiphilicity, ZABCP forms distinct vesicles with redox-sensitive bilayer membranes and zwitterionic shielding coronas, enabling switching of surface charge. ZABCP vesicles exhibit 180 ± 20 nm hydrodynamic diameter, and its charge switching behavior in response to pH was confirmed by the change of zeta potential value from -23 to +36 mV. The binding interaction between ZABCP vesicles with lysozyme and pepsin proteins strengthens when the surface charge shifts from neutral (pH 7.4) to either anionic or cationic. This surface-charge-switchable phenomenon paves the way for implementing cationic ZABCP vesicles for bacterial cell growth inhibition, which is shown by the pronounced transition of cellular morphology, including clustering, aggregation, or elongation as well as membrane disruption for both Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative). Such enhanced bacteriostatic activity could be ascribed to a strong electrostatic interaction between cationic vesicles and negatively charged bacterial membranes, leading to cell membrane disruption. Overall, this study provides a tailor-made approach to adopt low-fouling properties and potential bacteriostatic activity using zwitterionic polymers through precise control of pH.

Copper Soaps Formation in Verdigris-Linseed Oil Painting Mixtures: A Multispectroscopic Characterization.

Copper acetate (also known as verdigris) is a bimetallic Cu(II) greenish pigment widely used in oil paintings. Since ancient times, this pigment has been known as a degradation-prone compound, especially when combined with lipidic binders. However, the degradation mechanism and the involved species have not yet been disclosed. In this article, we study verdigris interactions with linseed oil in painting mock-ups, stressing out the formation of copper-based complexes and proposing reaction routes. Such complex systems are studied by applying a complementary multispectroscopic approach: a combination of continuous-wave (CW) electron paramagnetic resonance (EPR), electron spin echo envelope modulation (ESEEM), and Raman and attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopies. Based on the experimental evidence, we propose the following mechanism: the neutral copper acetate shifts to a basic verdigris-promoting triglyceride hydrolysis, aided by the coordination of Cu(II) cations toward the carboxylic functions. The increased amount of free fatty acids in the mixtures triggers the formation of monomeric Cu(II) complexes. Afterward, the oil polymerization reaction occurs, and secondary oxidation species, containing OH groups in the alkyl chain, act as further ligands for copper nuclei. This is the first time, to the best of our knowledge, that a comprehensive view is proposed.

Unraveling the influence of biomaterial’s functional groups in Cd biosorption: a density functional theory calculation

Abstract Several biomass wastes, including forest wastes, bagasse, algae, and others, have been studied to determine their biosorption capability for adsorbing different ranges of heavy metals in the literature. Most experimental studies have not clearly shown the impact of functional groups in biomaterials discovered by FTIR analysis on the investigated biosorption processes. Because of this, the findings of this study indicate that it is necessary to theoretically investigate the influence of identified functional groups (as determined by FTIR analysis) on the biosorption activities of the sorbent or biomaterial prepared for the removal of cadmium metal from an effluent. Using the most geometrical structure for cadmium (Cd) metal, a series of identified functional groups for the sorbent were analyzed using FTIR to determine their mode and intensity of interaction to computationally understand better how they each influence the biosorption of cadmium. This was done to determine how each functional group contributes to the intensity of the cadmium biosorption, using a ground-state B3LYP density functional theory calculation performed in a Spartan 20 simulation package utilizing the 6-31G* and LANL2DZ > Kr basis sets. According to the study’s findings, carboxylate (–COO*) had the most significant effect on cadmium biosorption activity of all the functional groups studied due to the stronger binding strength obtained for it. Therefore, this research suggests exploring biomaterials with greater intensity for carboxylate function, which would aid cadmium sorption efficiency in an effluent treatment process.

Titanium Tetrachloride-Assisted Direct Esterification of Carboxylic Acids.

Ester compounds, widely found in pharmaceutical and natural products, play a crucial role in organic synthesis, prompting the development of numerous methods for their synthesis. An important chemical approach in synthesizing esters from carboxylic acids involves the activation of the carboxyl function, requiring the conversion of the hydroxyl group into a suitable leaving group. This paper presents the findings of our investigations into an efficient method for producing esters from carboxylic acids and alcohols, using the Lewis acid titanium tetrachloride. Titanium tetrachloride has proven highly effective as a coupling reagent for the one-pot formation of esters from carboxylic acids and alcohols operating under mild and neutral conditions. Notably, the reaction eliminates the need for bases, yielding carboxylic esters in high purity and yields. The method is efficient, even with long-chain carboxylic acids, and operates well with primary alcohols in dichloromethane. Steric hindrance, potentially present in carboxylic acids, has a moderate effect on the reaction. Alcohol substrates that easily form stable carbocations require, instead, the use of non-polar solvents like hexane for the reaction.

A Convenient Oligonucleotide Conjugation via Tandem Staudinger Reaction and Amide Bond Formation at the Internucleotidic Phosphate Position.

Staudinger reaction on the solid phase between an electronodeficit organic azide, such as sulfonyl azide, and the phosphite triester formed upon phosphoramidite coupling is a convenient method for the chemical modification of oligonucleotides at the internucleotidic phosphate position. In this work, 4-carboxybenzenesulfonyl azide, either with a free carboxy group or in the form of an activated ester such as pentafluorophenyl, 4-nitrophenyl, or pentafluorobenzyl, was used to introduce a carboxylic acid function to the terminal or internal internucleotidic phosphate of an oligonucleotide via the Staudinger reaction. A subsequent treatment with excess primary alkyl amine followed by the usual work-up, after prior activation with a suitable peptide coupling agent such as a uronium salt/1-hydroxybenzotriazole in the case of a free carboxyl, afforded amide-linked oligonucleotide conjugates in good yields including multiple conjugations of up to the exhaustive modification at each phosphate position for a weakly activated pentafluorobenzyl ester, whereas more strongly activated and, thus, more reactive aryl esters provided only single conjugations at the 5'-end. The conjugates synthesized include those with di- and polyamines that introduce a positively charged side chain to potentially assist the intracellular delivery of the oligonucleotide.

Reductive Radical-Polar Crossover Enabled Carboxylative Alkylation of Aryl Thianthrenium Salts with CO2 and Styrenes.

Carboxylic functionalities are among the pivotal groups in bioactive molecules and in the synthesis of new lead compounds because of their unique character in the formation of hydrogen bonds and the possibility of constructing molecular complexes via amide couplings. We adopt the reductive radical-polar crossover strategy to introduce carboxyalkyl groups into arenes with styrenes and CO2 via thianthrenium salts. This protocol exhibits excellent potential as a straightforward and modular platform for site-selective carboxylative derivation of bioactive molecules.

Dual-facet engineering of surface carboxyl functionalization and interlayer potassium ions regulation in carbon nitride for enhanced CO2 photoreduction

Dual-facet engineering of surface carboxyl functionalization and interlayer potassium ions regulation in carbon nitride for enhanced CO2 photoreduction

Detection of basic amino acids under highly alkaline conditions using a perylene amine-derived probe

pH plays a crucial part in numerous chemical and physiological processes. In this work, a new perylene diimide derivative that acts as a pH-sensitive dye with Bay Area Carboxylic Acid functionality. The derivative utilizes the outstanding thermal, chemical and photochemical stability found in PDI materials and has remarkable UV–visible absorption and fluorescence emission qualities. Based on these properties, a fluorescent probe (PCA) was synthesised using a perylene tetracarbodiimide (PDI) backbone for the recognition of alkaline pH. In alkaline environments where the pH values are between 10 and 14, the fluorescence intensity significantly decreases, and a blue shift occurs, which is a standard feature of alkaline pH probes. The probe demonstrates exceptional sensing ability within the pH range of 10.00–14.00, with notable stability and reversibility. Encapsulation of the probe in a thin polymer film material enhances the pH sensing capability of the system. New sensor has been developed to detect basic amino acids by utilizing the probes' pH response characteristics. this sensor has also been applied to detect the concentration of arginine.

Allostreptopyrroles A-E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384.

Five new β-alkylpyrrole derivatives, allostreptopyrroles A-E (1-5), were isolated from the culture broth of Allostreptomyces RD068384. Their structures were elucidated by 1D and 2D NMR spectroscopic analyses, HRESIMS, and chemical derivatization. The absolute configurations of compounds 2 and 3 were predicted by comparison of experimental and calculated specific rotation data. Compounds 1-5 are the first examples of natural pyrroles substituted by formyl and carboxyl functionalities. Compounds 1, 4, and 5 showed cytotoxicity against Kasumi-1 human acute myeloblastic leukemia cells with IC50 values of 103, 105, and 105 μM, respectively, which are less active than the anticancer agent cisplatin, with an IC50 value of 70 μM.

Levofloxacin reposition-based design: synthesis, biological evaluation of new levofloxacin derivatives targeting topoisomerase II beta polymerase as promising anticancer agents, molecular docking, and physicochemical characterization.

Repositioning of already approved medications through repurposing or re-profiling for new medical uses after certain structural modifications is a novel approach in drug discovery. Fluoroquinolone antibiotics are one of the cardinal agents investigated for potential anticancer activities. In this work, levofloxacin was repositioned for anticancer activities. A series of levofloxacin-based compounds were designed and synthesized through the derivatization of levofloxacin's carboxylic acid functionality. The newly synthesized compounds were screened for cytotoxic activities against breast, liver, and leukemia cancer cell lines. Their effect on normal cells was also investigated. The target compounds were evaluated for their proliferative inhibitory activity toward topoisomerase II beta polymerization. Compound 5 showed higher inhibitory activity against a breast cancer cell line (MCF-7) with IC50 = 1.4 μM and lesser side effects on a normal breast cell line (MCF-10a) with IC50 = 30.40 μM than reference drugs. The best activity against a liver cancer cell line (Hep3B) was exhibited by compounds 3c, 4b, 5, 7, 8, 13a and 13c with IC50 values ranging from 0.43 to 8.79 μM. Regarding the effect of compounds 5 and 13a on a leukemia cancer cell line (L-SR), their IC50 values were 0.96 and 3.12 μM, respectively. Compounds 3c and 5 showed Topo2β inhibitory effects on Hep3B cells (81.33% and 83.73%, respectively), which was better than levofloxacin and etoposide as reference drugs. Cytometry cell cycle analysis revealed that compounds 3c and 5 arrested the cell cycle at the S phase (37.56% and 39.09%, respectively). Compounds 3c and 5 exhibited an elevation in active caspase-3 levels by 4.9 and 4.5 folds, respectively. Molecular modeling simulation of compounds 3c and 5 demonstrated energy scores (-29.77 and -20.46 kcal mol-1, respectively) more than those of the reference drugs as they interact with the most essential amino acids required for good affinity towards human topoisomerase II beta enzyme (PDB ID: 3QX3). Physicochemical characteristics of the most promising cytotoxic compounds 3c and 5 were investigated and compared to etoposide and levofloxacin as reference drugs. However, they showed high gastrointestinal absorption and could not penetrate the blood-brain barrier.

Selective separation of methylene blue from aqueous solution using Mn/Pd decorated chemically modified MoS2 nanocomposites

The presence of dyes in wastewater is posing as serious threat to human health. There are a huge number of physical, chemical, biological and hybrid methods available for the removal of colorants (dyes) from aqueous environment. In this work, we demonstrate the fabrication of new nanocomposites, MoS2-COOH/gly@M (M= Mn, Pd), with high adsorption property fabricated by chemically immobilizing manganese and palladium metallic centers onto the glycine- modified molybdenum disulfide (MoS2) material. The chemical and physical properties of adsorbents were analyzed using Fourier transform infrared spectrometer (FT-IR), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) companied by energy dispersive X-ray and mapping (EDAX & MAP) analyses. Zeta potential (ξ) technique was also used to measure the surface charge of adsorbents. Performances of nanocomposites were investigated on the sewage as adsorbent for dye removal. Synthesized nanocomposites revealed selective adsorption of methylene blue (MB) dye from aqueous mixture of MB and methyl orange (MO). Results displayed the equivalent high adsorption capacity for MB and MO up to 553 and 619 mg/g, respectively (green reaction condition= 120 min contact time, ,25 °C, pH 2.0 and pH 7.0, in the presence of 2 mg adsorbent and 50 mg/L (30 mL) initial concentration of MO and MB). The remarkable adsorption capacity of dye by MoS2-COOH/gly@M (M= Mn, Pd) nanocomposites can be attributed to the intermolecular interactions due to the presence of the amine, hydroxyl, and carboxyl functionalities. To describe the adsorption mechanism of MO and MB dye by synthesized nanomaterials, the pseudo-first-order and pseudo-second-order kinetics were further studied. Isotherm models displayed that the adsorption of MB and MO onto the MoS2-COOH/gly@M (M= Mn, Pd) nanocomposites is more correspondent with the Freundlich model with high-correlation coefficients. The results showed that the electrostatic attraction and H-bonding interaction were the basic cause of the adsorption of these anionic and cationic dyes on the surface of the nanocomposites. One of the distinguished properties of adsorbents is their capability to selectively adsorb MB from an admixture of MO and MB. The adsorption selectively has expanded in the following order: MoS2 < MoS2-COOH/gly@Mn < MoS2-COOH/gly@Pd. Based on the results, this new type of nanocomposites has potential to act as an effective and affordable adsorbent material for dye removal from an industrial sewage.

Cu3(BTC)2 metal organic framework as a promising adsorbent for operative exclusion of toxic dyes and herbicide

Synthetic organic dyes and herbicide pollutants pose a significant threat to water quality due to their high solubility in water and widespread industrial discharge. In water conservation developments, the Metal-Organic Frameworks (MOFs) are considered confident and substantial for the exclusion of toxic organic dyes, due to their multi-potential assets of cost-effective, high pore volume, high thermal stability, easy adaptation to toxic dye molecules, and most of them are stable in water, etc. Hence, the green synthetic methodology was employed for the combination of Cu3(BTC)2 MOF, which is draped with carboxylate functionality ligands, as an adsorbent to remove the hazardous dyes of Methyl Orange (MO), Acid Yellow (AY), and toxic herbicide of Atrazine (ATZ) from contaminated wastewater. As-reported Cu3(BTC)2 was evidently characterized by XRD, FTIR, TGA, XPS, SEM, and EDAX analysis. The equilibrium adsorption capacity (Qe) value of as-reported Cu3(BTC)2 for AY, MO, and ATZ was better in comparison with the formerly reported adsorbent. The high adsorption capacity of Cu3(BTC)2 for AY (777 mg/g), MO (903 mg/g), and ATZ (484 mg/g) is principally explained by π-π and electrostatic interaction. As a result, Cu3(BTC)2 is reported and proposed as a suitable adsorbent for the abolition of toxic dyes and herbicides from contaminated water.

Fabricating the multibranch carboxyl-modified cellulose for hemorrhage control

Excessive bleeding is associated with a high mortality risk. In this study, citric acid and ascorbic acid were sequentially modified on the surface of microcrystalline cellulose (MCAA) to increase its carboxyl content, and their potential as hemostatic materials was investigated. The MCAA exhibited a carboxylic group content of 9.52 %, higher than that of citric acid grafted microcrystalline cellulose (MCA) at 4.6 %. Carboxyl functionalization of microcrystalline cellulose surfaces not only plays a fundamental role in the structure of composite materials but also aids in the absorption of plasma and stimulation of platelets. Fourier -transform infrared (FT-IR), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS) spectra confirmed that carboxyl groups were successfully introduced onto the cellulose surface. Physical properties tests indicated that the MCAA possessed higher thermal stability (Tmax = 472.2 °C) compared to microcrystalline cellulose (MCC). Additionally, in vitro hemocompatibility, cytotoxicity and hemostatic property results demonstrated that MCAA displayed good biocompatibility (hemolysis ratio <1 %), optimal cell compatibility (cell viability exceeded 100 % after 72 h incubation), and impressive hemostatic effect (BCIMCAA = 31.3 %). Based on these findings, the hemostatic effect of covering a wound with MCAA was assessed, revealing enhanced hemostatic properties using MCAA in tail-amputation and liver-injury hemorrhage models. Furthermore, exploration into hemostatic mechanisms revealed that MCAA can significantly accelerate coagulation through rapid platelet aggregation and activation of the clotting cascade. Notably, MCAA showed remarkable biocompatibility and induced minimal skin irritation. In conclusion, the results affirmed that MCAA is a safe and potentially effective hemostatic agent for hemorrhage control.

Microwave-Assisted Chemical Purification and Ultrasonication for Extraction of Nano-Fibrillated Cellulose from Potato Peel Waste

Nanofibrillated cellulose was extracted from potato peel waste using a fast and green method with a simple process. To extract cellulose and eliminate non-cellulosic constituents, alkaline and hydrogen peroxide treatments were performed under microwave irradiation. The nanofibrillated cellulose was extracted from purified cellulose via TEMPO oxidation followed by ultrasonication. The TEM, FTIR, XRD, and TGA experiments were used to evaluate the structural, crystalline, and thermal properties of cellulose fiber and nanofiber. The chemical and FTIR analysis of bleached fibers indicates that almost all non-cellulosic components of biomass have been eliminated. The diameter of the extracted nanofibers is in the range of 4 to 22 nm. In terms of crystallinity, extracted nanocellulose had 70% crystallinity, compared to 17% for unprocessed lignocellulose fibers, which makes it an excellent choice for use as a reinforcement phase in biobased composites. Thermogravimetric analysis reveals that cellulose nanofibers are less thermally stable than potato peel pure cellulose, but it has a higher char content (28%) than pure cellulose (6%), which signifies that the carboxylate functionality acts as a flame retardant. The comparison between cellulose derived from microwave and conventional extraction methods confirmed that their impact on the removal of non-cellulosic materials is nearly identical.

Ring Transformation of Annulated Benzofuran Derivatives to Medium-Sized Lactones

AbstractBenzannulated eight- and nine-membered-ring lactones were prepared by ring transformation of annulated benzofuran derivatives. The reaction sequence starts with a Brønsted acid catalyzed hydration of the enol ether moiety of the starting materials furnishing hemiacetals as intermediate products which underwent retro-Claisen-type C–C bond cleavage under the reaction conditions. The use of 15 mol% TfOH and two equivalents of water in CHCl3 at 85 °C turned out to be optimal. Products with exocyclic carboxylate function could be further derivatized by amide formation. In total, eleven medium-sized lactones were prepared. Furthermore, three benzannulated spirolactones were obtained from starting materials with exocyclic carboxamide moiety.

Regular Arrays of Rod-Shaped Molecular Photoswitches: Synthesis, Preparation, Characterization, and Selective Photoswitching within Mono- and Bilayer Systems.

We assembled photoresponsive mono- and bilayer systems with well-defined properties from rod-shaped molecules equipped with different photoswitches. Using properly chosen chromophores (diarylethene-based switch and unidirectional light-driven molecular motor), we then selectively targeted layers made of the same types of photoswitches using appropriate monochromatic light. UV-vis analysis confirmed smooth and unrestricted photoisomerization. To achieve this, we synthesized a new class of triptycene-based molecular pedestals adept at forming sturdy Langmuir-Blodgett films on a water-air interface. The films were smoothly transferred to gold and quartz surfaces. Repeated deposition afforded bilayer systems: one layer containing diarylethene-based photoswitches and the other a unidirectional light-driven molecular motor. Structural analysis of both mono- and bilayer systems revealed the molecules to be tilted with carboxylic functions pointing to the surface. At least two different polymorphs differing in monolayer thickness and tilt angle (~40° and ~60°) were identified on the gold surface.

Dual functional behaviour of dicationic ionic liquid as extractant and hydrophobic biphasic solvent for extraction of Pb(II) in water

Herein, it was aimed to investigate the extraction ability of hydrophobic di-cationic imidazolium-based ionic liquid with inbuilt carboxylic acid functionalities for one of the heavy metals, Pb(II) from aqueous solution. Two dicationic ionic liquids, IL-1 named 1,1′(butane-1,4-diyl)bis(3-(4carboxyphenyl)-2-methyl-1H-imidazol-3-ium) chloride and IL-2 named 1,1′(dodecane-1,12-diyl)bis(3-(4carboxyphenyl)-2-methyl-1H-imidazol-3-ium)chloride tailored with (CH2)n bridging spacer chains, n = 4 and n = 12 respectively were synthesized. The Pb(II) displayed extraction percentages greater than 90% with both the aqueous biphasic system of IL-1 and IL-2. An efficient back-stripping of the Pb(II) metal ion was done using with aqueous solution of oxalic acid. Calcination of lead oxalate salt obtained showed highest purity of PbO confirmed by PXRD and EDX data. The established experimental condition with the synthesized ionic liquids is a distinguished one as no salting out agent, no extra extracting agents other than the synthesized ionic liquids were used. Moreover, the regeneration of the ionic liquid (IL-2), and back stripping of Pb(II) as oxalate salt makes this system an efficient one with negligible loss of the ionic liquid (IL-2) into the aqueous medium thus obliging the standards of environment-friendly sustainable development.

Carboxyl-Alkyl Functionalized Conjugated Polyelectrolytes for High Performance Organic Electrochemical Transistors.

Contemporary design principles for organic mixed ionic electronic conductors (OMIECs) are mostly based on the ethylene glycol moiety, which may not be representative of the OMIEC class as a whole. Furthermore, glycolated polymers can be difficult to synthesize and process effectively. As an emerging alternative, we present a series of polythiophenes functionalized with a hybrid carboxyl-alkyl side chain. By variation of the alkyl spacer length, a comprehensive evaluation of both the impact of carboxylic acid functionalization and alkyl spacer length was conducted. COOH-functionalization endows the polymer with preferential intrinsic low-swelling behavior and water processability to yield solvent-resistant conjugated polyelectrolytes while retaining substantial electroactivity in aqueous environments. Advanced in situ techniques, including time-resolved spectroelectrochemistry and Raman spectroscopy, are used to interrogate the materials' microstructure, ionic-electronic coupling, and operational stability in devices. To compare these materials' performance to state-of-the-art technology for the design of OMIECs, we benchmarked the materials and demonstrated significant application potential in both planar and interdigitated organic electrochemical transistors (OECTs). The polythiophene bearing carboxyl-butyl side chains exhibits greater electrochemical performance and faster doping kinetics within the polymer series, with a record-high OECT performance among conjugated polyelectrolytes ([μC*]pOECT = 107 ± 4 F cm-1 V-1 s-1). The results provide an enhanced understanding of structure-property relationships for conjugated polyelectrolytes operating in aqueous media and expand the materials options for future OMIEC development. Further, this work demonstrates the potential for conjugated polymers bearing alkyl-COOH side chains as a path toward robust OMIEC designs that may facilitate further facile (bio)chemical functionalization for a range of (bio)sensing applications.