pKa Values Research Articles

AttenGpKa: A Universal Predictor of Solvation Acidity Using Graph Neural Network and Molecular Topology.

Rapid and accurate calculation of acid dissociation constant (pKa) is crucial for designing chemical synthesis routes, optimizing catalysts, and predicting chemical behavior. Despite recent progress in machine learning, predicting solvation acidity, especially in nonaqueous solvents, remains challenging due to limited experimental data. This challenge arises from treating experimental values in different solvents as distinct data domains and modeling them separately. In this work, we treat both the solutes and solvents equally from a perspective of molecular topology and propose a highly universal framework called AttenGpKa for predicting solvation acidity. AttenGpKa is trained using 26,522 experimental pKa values from 60 pure and mixed solvents in the iBonD database. As a result, our model can simultaneously predict the pKa values of a compound in various solvents, including pure water, pure nonaqueous, and mixed solvents. AttenGpKa achieves universality by using graph neural networks and attention mechanisms to learn complex effects within solute and solvent molecules. Furthermore, encodings of both solute and solvent molecules are adaptively fused to simulate the influence of the solvent on acid dissociation. AttenGpKa demonstrates robust generalization in extensive validations. The interpretability studies further indicate that our model has effectively learnt electronic and solvent effects. A free-to-use software is provided to facilitate the use of AttenGpKa for pKa prediction.

Bioinspired Diiron Complex with Proton Shuttling and Redox-Active Ligand for Electrocatalytic Hydrogen Evolution.

A μ-oxo diiron complex, featuring the pyridine-2,6-dicarboxamide-based thiazoline-derived redox-active ligand, H2L (H2L = N2,N6-bis(4,5-dihydrothiazol-2-yl)pyridine-2,6-dicarboxamide), was synthesized and thoroughly characterized. [FeIII-(μ-O)-FeIII] showed electrocatalytic hydrogen evolution reaction activity in the presence of different organic acids of varying pKa values in dimethylformamide. Through electrochemical analysis, we found that [FeIII-(μ-O)-FeIII] is a precatalyst that undergoes concerted two-electron reduction to generate an active catalyst. Fourier transform infrared spectrum of reduced species and density functional theory (DFT) investigation indicate that the active catalyst contains a bridged hydroxo unit which serves as a local proton source for the Fe(III) hydride intermediate to release H2. We propose that in this active catalyst, the thiazolinium moiety acts as a proton-transferring group. Additionally, under sufficiently strong acidic conditions, bridged oxygen gets protonated before two-electron reduction. In the presence of exogenous acids of varying strengths, it displays electro-assisted catalytic response at a distinct applied potential. Stepwise electron-transfer and protonation reactions on the metal center and the ligand were studied through DFT to understand the thermodynamically favorable pathways. An ECEC or EECC mechanism is proposed depending on the acid strength and applied potential.

Development of a novel ratiometric fluorescent probe for real-time monitoring of acidic pH and its applications in food samples and biosystem

In this research, a high-efficiency ratiometric fluorescent probe TZTF for sensitive detecting the fluctuations of acidic pH was synthesized. The fluorescent color changed from bright blue to orange in the pH values range from 8.0 to 1.0 with the pKa value of 5.41. Meanwhile, the probe demonstrated excellent selectivity, good anti-interference ability, prominent reversibility, outstanding photostability, and low cytotoxicity. The detection mechanism of TZTF towards acidic pH was verified through 1H NMR analysis and DFT calculation. Additionally, probe TZTF was also applied to evaluate the freshness of meat samples, as the pH value of meat samples may decrease if they are not stored properly, and the subsequent acid-catalyzed denaturation of proteins may pose a threat to human health through the food chain. More importantly, fluorescence imaging experiments confirmed that TZTF is appropriate for real-time tracking of pH variations in living cells and living zebrafish.

Acidity of saturated (hetero)cyclic α-fluoro carboxylic acids and lipophilicity of their amide derivatives

Analysis of the physicochemical parameters of saturated (hetero)cyclic carboxylic acids and their α-fluorinated analogues is described. Measured pKa values revealed a significant influence of the single fluorine substituent on the compound's acidity (pKa decreased by 1.3–2.4 units). This effect did not demonstrate additivity with electronic effects of other heteroatom (i.e., cyclic ether moiety). On the contrary, lipophilicity (LogP) of the corresponding anilides was almost unaffected upon α-substitution with a fluorine atom and mainly governed by the nature of the (hetera)cycloalkyl substituent. The obtained results suggest that polarization of the C–F bonds themselves does not define the fluorine effect on the compound's lipophilicity.

A novel approach for nanobubble generation toward biomedical applications

The stability of free-standing nanobubbles is a long-standing controversial problem due to the Laplace pressure catastrophe at the nanoscale. In most industrial circumstances, a large quantity of surfactants is required as stabilisers or emulsifiers to generate stable bubbles or foams. However, when surfactants exceed a certain level, they can adversely affect living organisms and pose environmental risks. Towards biomedical use, we investigated nanobubble generation through a mini-extruder in amino acid solutions. Herein, we considered glycine (having two acid dissociation constants, i.e. pKa values) and lysine (having three pKa values) as two model amino acids, conducting experiments with various concentrations (0.1 M, 0.5 M and 1 M), along with different pH values (above, equal to, and below the isoelectric points of each amino acids; 5.97 for glycine and 9.74 for lysine). Our results showcased the proof of concept that amino acids can stabilise nanobubbles in bulk for a few days. We achieved remarkable products of nanobubbles via nanopores by extrusion, with reproducible size distribution and stability. We also compared the extrusion protocol with the commonly used ultrasound method. It turned out that extrusion generated samples with smaller sizes and higher concentrations than sonication. This study provides a reliable protocol for generating small-scale nanobubbles for biomedical use, showing great potential in drug delivery for medical treatment.

Determination of ionization/protonation constant values of some guanine derivative drugs by traditional/ green RPLC and UV–Vis spectrophotometric methods

In this study, the greenreverse-phase liquid chromatography (RPLC) method was used in addition to the traditional RPLC method to determine the ionization/protonation constants (pKa) of the guanine derivatives ganciclovir, valacyclovir, and valganciclovir. The determination of these values was carried out in binary acetonitrile–water mixtures (for the traditional RPLC method), ethanol–water binary mixtures (for the green RPLC method), and in aqueous solution of a micelle-forming surfactant (for pure micellar chromatography). The pKa values sspKa of the compounds were calculated using the linear solvation energy relationship (LSER) method in the studied hydro-organic and micellar solvent-free mixtures. Moreover, the UV–Vis spectrophotometric method was used to compare the sspKa values of ganciclovir, valaciclovir, and valganciclovir obtained in a acetonitrile–water medium using another method. The pKa values ​​of the examined compounds in water were calculated using the linear relationship between the sspKa values ​​determined in hydroorganic mixtures and some macroscopic values ​​of acetonitrile and ethanol. Additionally, wwpKa values ​​were determined in the micellar solvent-free mobile phase. Subsequently, the wwpKa values calculated by these direct and indirect methods were compared and the agreement between them was excellent. By using the wwpKa value calculated for each compound, the ionization percentages were calculated at different pH (1–12) values with the Henderson-Hasselbalch equation. The environmental impact of the RPLC methods used in this study was assessed using the green metrics tools GAPI and AGREE. The result of the investigation was that the environmental suitability of the green methods is satisfactory.

Assessing pH-Dependent Conformational Changes in the Fusion Peptide Proximal Region of the SARS-CoV-2 Spike Glycoprotein.

One of the entry mechanisms of the SARS-CoV-2 coronavirus into host cells involves endosomal acidification. It has been proposed that under acidic conditions, the fusion peptide proximal region (FPPR) of the SARS-CoV-2 spike glycoprotein acts as a pH-dependent switch, modulating immune response accessibility by influencing the positioning of the receptor binding domain (RBD). This would provide indirect coupling of RBD opening to the environmental pH. Here, we explored this possible pH-dependent conformational equilibrium of the FPPR within the SARS-CoV-2 spike glycoprotein. We analyzed hundreds of experimentally determined spike structures from the Protein Data Bank and carried out pH-replica exchange molecular dynamics to explore the extent to which the FPPR conformation depends on pH and the positioning of the RBD. A meta-analysis of experimental structures identified alternate conformations of the FPPR among structures in which this flexible regions was resolved. However, the results did not support a correlation between the FPPR conformation and either RBD position or the reported pH of the cryo-EM experiment. We calculated pKa values for titratable side chains in the FPPR region using PDB structures, but these pKa values showed large differences between alternate PDB structures that otherwise adopt the same FPPR conformation type. This hampers the comparison of pKa values in different FPPR conformations to rationalize a pH-dependent conformational change. We supplemented these PDB-based analyses with all-atom simulations and used constant-pH replica exchange molecular dynamics to estimate pKa values in the context of flexibility and explicit water. The resulting titration curves show good reproducibility between simulations, but they also suggest that the titration curves of the different FPPR conformations are the same within the error bars. In summary, we were unable to find evidence supporting the previously published hypothesis of an FPPR pH-dependent equilibrium: neither from existing experimental data nor from constant-pH MD simulations. The study underscores the complexity of the spike system and opens avenues for further exploration into the interplay between pH and SARS-CoV-2 viral entry mechanisms.

Influence of Fe(II), Fe(III), and Al(III) isomorphic substitutions on acid-base properties of edge surfaces of cis-vacant montmorillonite: Insights from first-principles molecular dynamics simulations and surface complexation modeling

Abstract Knowing the influence of isomorphic substitutions on the acid-base properties of smectite edge surfaces is an important aspect of the detailed understanding of clay minerals’ interfacial properties with implications in the modeling of adsorption processes. We investigated the intrinsic acidity constants of Fe(II)/Fe(III) and Al(III) substituted edge surface sites of montmorillonite with a cis-vacant structure, which includes four crystallographic orientations perpendicular to [010], [010], [110], and [110], using the first-principles molecular dynamics (FPMD) based vertical energy gap method. Fe(II) and Fe(III) substitutions resulted, respectively, in a significant increase and decrease in pKa values of amphoteric groups directly associated with Fe octahedra. In addition, Fe(II) substitution increased the pKa values of the neighboring silanol sites, while Fe(III) substitution had a weak influence on these sites. The Al-substituted tetrahedra had amphoteric sites with higher pKa values than the non-substituted Si tetrahedra, and they increased significantly the pKa values of the sites bridging the tetrahedral and octahedral sheets on surfaces perpendicular to [010] and [110]. The acid-base properties of substituted and non-substituted surface sites of cis-vacant montmorillonite were used to build a state-of-the-art surface complexation model, which successfully reproduced the best available experimental acid-base titration data. This model was further used to predict acid-base properties of dioctahedral smectites (montmorillonite, beidellite, and nontronite) according to their cis- or trans-vacant structures and their layer chemistry. According to these predictions, these smectites exhibit very similar overall pH buffering properties despite significant differences in structure and chemistry. A detailed analysis of the acid-base properties as a function of crystallographic directions demonstrated, however, that these differences should have a large influence on the adsorption of ionic species.

Near-infrared fluorescent probe based on the regulatory dye pKa for imaging of H2S in rice roots and living cells

Hydrogen sulfide (H2S) is a key factor in various biological processes such as plant grow and its response to environmental stress. Here, we develop a novel near-infrared (NIR) fluorescent probe for detecting hydrogen sulfide based on the regulatory NIR dye pKa values. After triggering the H2S substitution response, probe A with introducing the cyano moiety not only exhibits a significant near-infrared emission (Emax: 724 nm) response in physiological environments, but also shows a fast response, high selectivity, and sensitivity (LOD as 0.52 µM). In addition, probe A with low biological cytotoxicity is successfully used for imaging detection of cellular exogenous and endogenous hydrogen sulfide. More importantly, in situ imaging of probe A tracks the H2S fluctuations in the rice root system and its response to environmental stress. Hence, this work offers a new NIR fluorescence imaging monitoring tool for hydrogen sulfide in biological systems.

Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands

Ir(III) and Ru(II) polypyridyl complexes are promising photosensitizers (PSs) for photodynamic therapy (PDT) due to their outstanding photophysical properties. Herein, one series of cyclometallated Ir(III) complexes and two series of Ru(II) polypyridyl derivatives bearing three different thiazolyl-β-carboline N^N′ ligands have been synthesized, aiming to evaluate the impact of the different metal fragments ([Ir(C^N)2]+ or [Ru(N^N)2]2+) and N^N’ ligands on the photophysical and biological properties. All the compounds exhibit remarkable photostability under blue-light irradiation and are emissive (605 < λem < 720 nm), with the Ru(II) derivatives displaying higher photoluminescence quantum yields and longer excited state lifetimes. The Ir PSs display pKa values between 5.9 and 7.9, whereas their Ru counterparts are less acidic (pKa > 9.3). The presence of the deprotonated form in the Ir-PSs favours the generation of reactive oxygen species (ROS) since, according to theoretical calculations, it features a low-lying ligand-centered triplet excited state (T1 = 3LC) with a long lifetime. All compounds have demonstrated anticancer activity. Ir(III) complexes 1–3 exhibit the highest cytotoxicity in dark conditions, comparable to cisplatin. Their activity is notably enhanced by blue-light irradiation, resulting in nanomolar IC50 values and phototoxicity indexes (PIs) between 70 and 201 in different cancer cell lines. The Ir(III) PSs are also activated by green (with PI between 16 and 19.2) and red light in the case of complex 3 (PI = 8.5). Their antitumor efficacy is confirmed by clonogenic assays and using spheroid models. The Ir(III) complexes rapidly enter cells, accumulating in mitochondria and lysosomes. Upon photoactivation, they generate ROS, leading to mitochondrial dysfunction and lysosomal damage and ultimately cell apoptosis. Additionally, they inhibit cancer cell migration, a crucial step in metastasis. In contrast, Ru(II) complex 6 exhibits moderate mitochondrial activity. Overall, Ir(III) complexes 1–3 show potential for selective light-controlled cancer treatment, providing an alternative mechanism to chemotherapy and the ability to inhibit lethal cancer cell dissemination.

Proton Solvation Free Energy in Liquid Ammonia at Room Temperature

AbstractThe investigation of experimental pKa values in liquid ammonia at room temperature for a series of 30 organic compounds containing eight distinct chemical groups enabled an accurate assessment of the proton ammoniation free energy. The deprotonation free energies, as well as the solvation free energies of acids and conjugate bases, were computed using a combination of quantum chemical and electrostatic approaches. Two thermodynamic schemes were employed to reproduce experimental pKa values while scanning a large interval of probable values of proton ammoniation free energy. The desired quantity corresponded to the lowest mean absolute deviation of the overall reproduced pKa values of the series. As a result, the proton ammoniation free energy was evaluated to be −275.0 Kcal/mol. Test results show that this proposed value is well suited for pKa calculation in liquid ammonia at room temperature.

Predictive modeling of pH on the transport of Co(II) Ions from aqueous solutions through supported ceramic polymer membrane

Optimal pH is essential for efficient cobalt extraction from polymeric membrane systems, with D2EHPA used as an extractant for Co(II) at pH < 7, achieving 47% efficiency. The pH of piperazine as a stripping agent increases to a concentration of 0.48 M, and the extraction efficiency of Co(II) > 80%. Depending on the functional group of (C4H10N2), the optimal pH for separation was 9.8. The study revealed that pKa value was calculated to predict the ideal pH, and its value was 9.73, which is nearly to the pH, since the pH of the strip concentration and the properties of the membrane affect the extraction of cobalt at 30 °C. The partition ratio indicates the high distribution of the extract in supported ceramic polymer membrane (SCPM). The ceramic component provides mechanical strength and rigidity to the overall membrane structure, allowing it to withstand high pressures and temperatures during operation Study various factors such as the effect of pH on the ionization of the extract; effect of pH on band ionization; effect of pH on the temperature in the extract, effect of pH on the solute, effect of the band at different pH ranges and a comparison was made between the predictive model and experimental data that was proven through mathematical modeling using the MATLAB program.

Predicting the amino group pKa of amino acids using machine learning-QSPR methods

Amino acids are one of the main building blocks of proteins, and because of this connection and their main role in biochemistry, they are of great interest in pharmaceutical industries today. In nature, there are approximately 300 amino acids, out of which 20 are present in the human body and are responsible for protein synthesis. As a result, amino acids are widely used in various fields such as biological sciences, chemistry, medicine, and various industries. This research focuses on estimating the acid dissociation constant (pKa) of the amino group related to 52 amino acids using the quantitative structure–property relationship (QSPR) method, employing four different regression models: Genetic Algorithm-Multivariable Linear Regression (GA-MLR), Particle Swarm Optimization-Support Vector Machine (PSO-SVM), Feed Forward Neural Network (FFNN), and Decision Tree (DT). Using the GA-MLR, the optimal number of descriptors for estimating pKa was determined to be 9. By comparing different machine learning models, it can be observed that the coefficient of determination (R2) follows the trend R2 PSO-SVM = 0.9681 > R2 FFNN = 0.9539 > R2 DT = 0.9329 > R2 GA-MLR = 0.9231. Therefore, the PSO-SVM model provided the best prediction, while the FFNN, DT, and GA-MLR models ranked next in terms of precision in predicting the pKa of amino acids. By dividing the data into test/train sets in a ratio of approximately 20/80, the model's validity was confirmed due to the nearness of the R2 values between the training and testing sets. Ultimately, the best model is capable of predicting the pKa value of the amino group in amino acids with a mean absolute percent error of 1.18 %.

Stimulus-Responsive Gas Marbles as an Amphibious Carrier for Gaseous Materials.

Gas marbles are a new family of particle-stabilized soft dispersed system with a soap bubble-like air-in-water-in-air structure. Herein, stimulus-responsive character is successfully introduced to a gas marble system for the first time using polymer particles carrying a poly(tertiary amine methacrylate) (pKa ≈7) steric stabilizer on their surfaces as a particulate stabilizer. The gas marbles exhibited long-term stability when transferred onto the planar surface of liquid water, provided that the solution pH of the subphase is basic and neutral. In contrast, the use of acidic solutions led to immediate disintegration of the gas marbles, resulting in release of the inner gas. The critical minimum solution pH required for long-term gas marble stability correlates closely with the known pKa value for the poly(tertiary amine methacrylate) stabilizer. It also demonstrates amphibious motions of the gas marbles.

Elucidating the Activation Mechanism of the Proton-sensing GPR68 Receptor

GPR68 is a proton-sensing G-protein Coupled Receptor (GPCR) involved in a variety of physiological processes and disorders including neoplastic pathologies. While GPR68 and few other GPCRs have been shown to be activated by a decrease in the extracellular pH, the molecular mechanism of their activation remains largely unknown. In this work, we used a combined computational and in vitro approach to provide new insight into the activation mechanism of the receptor. Molecular Dynamics simulations of GPR68 were used to model the changes in residue interactions and motions triggered by pH. Global and local rearrangements consistent with partial activation were observed upon protonation of the inactive state. Selected extracellular histidine and transmembrane acidic residues were found to have significantly upshifted pKa values during the simulations, consistently with their previously hypothesised role in activation through changes in protonation state. Moreover, a novel pairing between histidine and acidic residues in the extracellular region was highlighted by both sequence analyses and simulation data and tested through site-directed mutagenesis. At last, we identified a previously unknown hydrophobic lock in the extracellular region that might stabilise the inactive conformation and regulate the transition to the active state.

Critical roles of soil composition and pollutant properties on the degradation of PPCPs during ferrous/persulfate processes

Pharmaceuticals and personal care products (PPCPs) are widely used worldwide and cause potential soil pollution. Fe2+-activated persulfate (PS) processes (Fe-PAPs) are promising techniques for soil remediation. However, a knowledge gap exists in the mechanistic insights into the dominant factors affecting the degradation of different PPCPs in varied soil types. This study systematically investigated the roles of soil components and pollutant properties in the degradation of three PPCPs (triclosan (TCS), triclocarban (TCC), and naproxen (NPS)) in the nine soils in the Fe2+/PS system. The degradation efficiencies of TCS and NPS ranged from 10.92 % to 91.62 % and 46.59 % to 99.81 %, respectively, whereas nearly no degradation was observed for TCC. PPCPs with high water solubility, high energies of the highest occupied molecular orbital (EHOMO), low pKa values, low energy gap (ΔE), or low vertical ionization potential (VIP) were more favorable for degradation. XPS analysis suggested that aliphatic carbon (Ali–C–C(H)), ether or alcohol carbon (C–O), and aldehyde or ketonic carbon (CO) on SOM significantly inhibited TCS degradation. The results of ROS quenching experiments showed that SO4•− and 1O2 played major roles in TCS and NPS degradation in the six soils, with the relative contributions ranged from 24.82 % to 99.14 % and 0.15 % to 73.40 %, respectively. The interaction between soil components, active species, and pollutants resulted in the distinct intermediates of TCS and NPS in different soils. Our findings provide in-depth insights into the role of soil composition and pollutant properties on the remediation of PPCP-contaminated soils in Fe-PAPs.

Deprotonation of formic, acetic acids and bicarbonate ion in slit silica nanopores at infinite dilution and in the presence of electrolytes

Dielectric effects and the coupled electrostatics between the nanoconfined and the internal/external aqueous media contribute to the observed deviations of chemistry within the nanoconfined environment when compared with unconfined systems. A systematic understanding has remained elusive, especially with respect to background salt concentration and boundary condition effects like the nanopore surface chemistry and the reference state used to calculate free energies. We utilize molecular dynamics simulations along with thermodynamic integration to determine the free energy difference associated with acid-base chemistry in 2 nm and 4 nm slit pores open to a bulk-like reservoir. pKa increases are predicted when confining acetic acid, formic acid, and bicarbonate in the slits at infinite dilution conditions. We find that confinement weakens the acids, and the modulation of outer pore surface dipole magnitudes can tune the pKa shift values, suggesting that purely “intrinsic” electrostatic effect on confinement may not exist. At sufficiently high salt concentrations, the dielectric/electrostatic effects on pKa values diminish due to charge screening effects. These discoveries enable future modifications of nanopore chemistries to achieve desirable properties for industrial applications.

Theoretical study of the methylprolithospermate's pKa in aqueous solution

Protonation and deprotonation reactions play an important role in the biological processes. Such processes are fully thermodynamic and occur in complex media where functional groups are surrounded by other chemicals such as molecules, ions, water, etc. In this paper, the compound of interest is the methylprolithospermate (MPL) molecule, which was recently isolated from salvia yunnanensis CH Wright. The intended functional groups for deprotonation are -OH and -COOH. These are the potential groups depicted at four sites located in MPL. Three thermodynamic cycles were required for the estimation of MPL's pKa by the means of DFT at the levels of B3LYP and PW6B95 with the dual basis set 6–311++G(d,p)//6–31+G(d). Cycle 1 is the direct pKa calculation, Cycle 2 is also the direct pKa calculation with proton hydration, and Cycle 3, the proton exchange process with hydroxyl anion hydration. In these cycles, water molecules as, reagents as well as products, were held as monomers in one hand (monomer cycle approaches), and cluster on the other hand (cluster cycle approaches). The isodesmic scheme was used as benchmark method for pKa calculation and yielded: pKa1 = 3.6 ± 0.3, pKa2 = 6.6 ± 0.2, pKa3 = 9.3 ± 0.2, and pKa4 = 14.4. The inclusion of binding energies of MPL anions in the pKa calculation has improved the results. The best cycles depend on the level of waters and the level of acidity. The more the number of waters clustered to MPL anions, the more the deviation of pKa values.

Radical scavenging activity of bromophenol analogs: analysis of kinetics and mechanisms.

This theoretical study explores the antioxidant activity of five bromophenol analogs, with a particular focus on their interaction with different solvent environments of varying polarities. Key findings include the correlation between increased solvent polarity and enhanced antioxidant activity of these analogs, comparable in some instances to ascorbic acid. Notably, compound 5, developed by our research team, demonstrates superior antioxidant activity in both lipid and aqueous solutions, surpassing that of ascorbic acid and other tested analogs. This research contributes to the understanding of bromophenol analogs, presenting the first known kinetic and chemical stability data such as rate constants, pKa values, and branching ratios for reactions with the methylperoxyl radical (CH3OO•). The computational analyses were conducted using the Gaussian 09 software suite at the M05-2X/6-31 + G(d) computational level. These analyses employed conventional transition state theory to account for various potential mechanisms and effects of solvent polarity on the antioxidant activities of bromophenol analogs. The study meticulously calculated enthalpy under standard conditions (298.15K and 1atm) with necessary thermodynamic corrections. Additionally, the Quantum Mechanics-based Test for Overall Radical Scavenging Activity (QMORSA) protocol guided the evaluation of radical scavenging activity, ensuring a comprehensive assessment of the antioxidant potential of the compounds.

An Investigation of the Effect of pH on Micelle Formation by a Glutamic Acid-Based Biosurfactant

NMR spectroscopy, molecular modeling, and conductivity experiments were used to investigate micelle formation by the amino acid-based surfactant tridecanoic L-glutamic acid. Amino acid-based biosurfactants are green alternatives to surfactants derived from petroleum. NMR titrations were used to measure the monomeric surfactant’s primary and gamma (γ) carboxylic acid pKa values. Intramolecular hydrogen bonding within the surfactant’s headgroup caused the primary carboxylic acid to be less acidic than the corresponding functional group in free L-glutamic acid. Likewise, intermolecular hydrogen bonding caused the micellar surfactant’s γ carboxylic functional group to be less acidic than the corresponding monomer value. The binding of four positive counterions to the anionic micelles was also investigated. At pH levels below 7.0 when the surfactant headgroup charge was −1, the micelle hydrodynamic radii were larger (~30 Å) and the mole fraction of micelle-bound counterions was in the 0.4–0.7 range. In the pH range of 7.0–10.5, the micelle radii decreased with increasing pH and the mole fraction of micelle bound counterions increased. These observations were attributed to changes in the surfactant headgroup charge with pH. Above pH 10.5, the counterions deprotonated and the mole fraction of micelle-bound counterions decreased further. Finally, critical micelle concentration measurements showed that the micelles formed at lower concentrations at pH 6 when the headgroup charge was predominately −1 and at higher concentrations at pH 7 where headgroups had a mixture of −1 and −2 charges in solution.