SMD Implicit Solvation Research Articles

Insights into rare earth element speciation: unraveling sulfate and hydrolysis complexes through DFT calculations.

Rare earth elements (REE) are indispensable in numerous green technologies owing to their exceptional physical and chemical attributes. Separating REE is a pivotal process to meet the increasing demands of the high-tech industry. Understanding the hydrolysis of REE in aqueous environments marks the initial stride in comprehending their separation mechanisms. Sulfate commonly coexists in high-concentration solutions alongside REE, stemming from mineral processing. We analyzed the hydrolysis of REE and their complexes with sulfate using DFT methods. We present and discuss on the structural characteristics of hydrolysis species and sulfate complexes in alignment with existing experimental data. Estimates of Gibbs free energies for hydrolysis and sulfate complex formation were compared against literature values. REE pose challenges owing to the labile nature of aqua complexes and the pivotal role of system dynamics. We showed that hydrolysis reactions could be suitably modeled, yielding an error margin of approximately 5kcalmol-1 concerning experimental values, employing the M06 exchange-correlation functional with the SMD implicit solvation model. However, sulfate chemical species proved to be more challenging, exhibiting larger error margins with substantial variations across the REE series. The Raman spectrum analysis of lanthanum sulfate complexes demonstrated excellent agreement with experimental values. We applied the M06, PBE, and PBE0 exchange-correlation functionals combined with def2-TZVP basis sets and SMD to obtain the Gibbs free energies of hydrolysis and sulfate complexation with lanthanides in aqueous solution. The calculations were performed using the ORCA program.

QM-CSA: A Novel Quantum Mechanics-Based Protocol for Evaluation of the Carcinogen-Scavenging Activity of Polyphenolic Compounds.

In this study, a novel quantum mechanics-based protocol for the evaluation of carcinogen-scavenging activity (QM-CSA) is developed. The QM-CSA protocol represents a universal and quantitative approach to evaluate and compare the activation-free energies for alkylation reactions between individual polyphenolic compounds and chemical carcinogens of the epoxy type at physiological conditions by applying two scales: the absolute scale allowing for the comparison with guanine and the relative scale allowing the comparison with glutathione as a reference compound. The devised quantum mechanical methodology was validated by comparing the activation-free energies calculated with 14 DFT functionals in conjunction with two implicit solvation models (SMD and CPCM) and the experimental activation-free energies for reactions between nine investigated chemical carcinogens and guanine. According to the obtained results, the best agreement with experimental data was achieved by applying DFT functionals M11-L and MN12-L in conjunction with the flexible 6-311++G(d,p) basis set and implicit solvation model SMD, and the obtained uncertainties were proven to be similar to the experimental ones. To demonstrate the applicability of the QM-CSA protocol, functionals M11-L, and MN12-L in conjunction with the SMD implicit solvation model were applied to calculate activation-free energies for the reactions of nine investigated chemical carcinogens of the epoxy type with three catechins, namely EGCG, EGC, and (+)-catechin. The order of CSA in this series of catechins in comparison to guanine and glutathione was determined as (+)-catechin > EGC > EGCG. The obtained results, for the first time, demonstrated the evaluation and comparison of CSA in a series of selected catechins with respect to glutathione and guanine. Moreover, the presented results provide valuable insights into the reaction mechanisms and configurations of the corresponding transition states. The novel QM-CSA protocol is also expected to expand the kinetic data for alkylation reactions between various polyphenolic compounds and chemical carcinogens of the epoxy type, which is currently lacking in the scientific literature.

Rationalizing the Mechanism of Peroxyformate Decomposition: Computational Insights To Understand Solvent Influence.

The heterolytic decomposition of tert‐butyl peroxyformate to tert‐butanol and carbon dioxide, catalyzed by pyridine, is a long‐known example of a reaction whose kinetics are strongly affected by solvent polarity. From DFT and ab initio methods together with the SMD implicit solvation model, an extension on the formerly accepted mechanism is proposed. This novel proposal involves the formation of a carbonic acid ester intermediate and its further decomposition, through an unreported pyridine‐mediated stepwise route. Computed barriers for this mechanism at DLPNO/CCSD(T)‐def2‐TZVP are in excellent agreement with experimental kinetic data across different solvents. Furthermore, the strong relationships between activation energies, geometric parameters in the transition state and the characteristics of the different solvents are also analyzed in depth.

Theoretical estimates of equilibrium carbon and hydrogen isotope effects in microbial methane production and anaerobic oxidation of methane

Microbial production and consumption of methane are widespread in natural and artificial environments, with important economic and climatic implications. Attempts to use the isotopic composition of methane to identify its sources are complicated by incomplete understanding of the mechanisms of variation in methane’s isotopic composition. Knowledge of the equilibrium isotope fractionations among the large organic intracellular intermediates in the microbial pathways of methane production and consumption must form the basis of any exploration of the mechanisms of isotopic variation, but estimates of these equilibrium isotope fractionations are currently unavailable. To address this gap, we calculated the equilibrium isotopic fractionation of carbon (13C/12C) and hydrogen (D/H) isotopes among compounds in the anaerobic methane metabolisms, as well as the abundance of double isotope substitutions (“clumping,” i.e., a single 13C–D bond or two 12C–D bonds) in these compounds. The isotope fractionation factors were calculated using density functional theory at the M06-L/def2-TZVP level of theory with the SMD implicit solvation model, which we recently tested against measured equilibrium isotope fractionations. The computed 13β and 2β values decrease with decreasing oxidation state of the carbon atom in the molecules, resulting in a preference for enrichment in 13C and D in the molecules with more oxidized carbon. Using the computed β values, we calculated the equilibrium isotope fractionation factors in the prominent methanogenesis pathways (hydrogenotrophic, methylotrophic and acetoclastic) and in the pathway for anaerobic oxidation of methane (AOM) over a temperature range of 0–700 °C. Our calculated equilibrium fractionation factors compare favorably with experimental constraints, where available, and were then used to investigate the relation between the apparent isotope fractionation during methanogenesis or AOM and the thermodynamic drive for these reactions. We show that a detailed map of the equilibrium fractionation factors along these metabolic pathways allows for an evaluation of the contribution of equilibrium and kinetic isotope effects to apparent isotope fractionations observed in laboratory, natural and artificial settings. The comprehensive set of equilibrium isotope fractionation factors calculated in this study provides a firm basis for future explorations of isotope effects in methane metabolism.

DFT study on dibenzofuran conversion to cyclohexane and benzene in gas, water and methanol solvents

Hydrodeoxygenation (HDO) of dibenzofuran is studied using density functional theory (DFT) with SMD implicit solvation model to give products like benzene and cyclohexane. Water and methanol are used as solvents, and gas-phase calculations are also performed for comparison. HDO is proposed via two major route- 1) saturation of phenyl rings followed by deoxygenation, 2) cleavage of C–O bond for oxy –removal followed by ring saturation. First, thermochemical parameters like Gibbs free energy change and enthalpy change are calculated at varying temperature in gas, water and methanol. Then, the solvation free energy is calculated for methanol and water to determine the ease of separation of products from the solvents. Finally, a Single Point Energy calculation is performed in the gas phase. It is found that water is the best solvent among three mediums and offers a significant advantage in some reactions such as the conversion of dibenzofuran to 1,2,3,4,4a,9b-hexahydrodibenzo[b,d]furan, 2-cyclohexyl phenol to bicyclo-hexan-2-ol and biphenyl to cyclohexyl benzene. Water is also found to be a better medium for separation of all the intermediates and products from the solvent over methanol. The effect of temperature was also studied, and it was found that the increase in temperature is unfavourable in all mediums for almost all reactions.

LogP prediction performance with the SMD solvation model and the M06 density functional family for SAMPL6 blind prediction challenge molecules.

This work presents a quantum mechanical model for predicting octanol-water partition coefficients of small protein-kinase inhibitor fragments as part of the SAMPL6 LogP Prediction Challenge. The model calculates solvation free energy differences using the M06-2X functional with SMD implicit solvation and the def2-SVP basis set. This model was identified as dqxk4 in the SAMPL6 Challenge and was the third highest performing model in the physical methods category with 0.49 log Root Mean Squared Error (RMSE) for predicting the 11 compounds in SAMPL6 blind prediction set. We also collaboratively investigated the use of empirical models to address model deficiencies for halogenated compounds at minimal additional computational cost. A mixed model consisting of the dqxk4 physical and hdpuj empirical models found improved performance at 0.34 log RMSE on the SAMPL6 dataset. This collaborative mixed model approach shows how empirical models can be leveraged to expediently improve performance in chemical spaces that are difficult for ab initio methods to simulate.

Reaction Kinetics, Product Branching, and Potential Energy Surfaces of 1O2-Induced 9-Methylguanine-Lysine Cross-Linking: A Combined Mass Spectrometry, Spectroscopy, and Computational Study.

We report a kinetics and mechanistic study on the 1O2 oxidation of 9-methylguanine (9MG) and the cross-linking of the oxidized intermediate 2-amino-9-methyl-9H-purine-6,8-dione (9MOGOX) with Nα-acetyl-lysine-methyl ester (abbreviated as LysNH2) in aqueous solutions of different pH. Experimental measurements include the determination of product branching ratios and reaction kinetics using mass spectrometry and absorption spectroscopy, and the characterization of product structures by employing collision-induced dissociation. Strong pH dependence was revealed for both 9MG oxidation and the addition of nucleophiles (water and LysNH2) at the C5 position of 9MOGOX. The 1O2 oxidation rate constant of 9MG was determined to be 3.6 × 107 M-1·s-1 at pH 10.0 and 0.3 × 107 M-1·s-1 at pH 7.0, both of which were measured in the presence of 15 mM LysNH2. The ωB97XD density functional theory coupled with various basis sets and the SMD implicit solvation model was used to explore the reaction potential energy surfaces for the 1O2 oxidation of 9MG and the formation of C5-water and C5-LysNH2 adducts of 9MOGOX. Computational results have shed light on reaction pathways and product structures for the different ionization states of the reactants. The present work has confirmed that the initial 1O2 addition represents the rate-limiting step for the oxidative transformations of 9MG. All of the downstream steps are exothermic with respect to the starting reactants. The C5-cross-linking of 9MOGOX with LysNH2 significantly suppressed the formation of spiroiminodihydantoin (9MSp) resulting from the C5-water addition. The latter became dominant only at the low concentration (∼1 mM) of LysNH2.

Chemoselectivity in the Oxidation of Cycloalkenes with a Non-Heme Iron(IV)-Oxo-Chloride Complex: Epoxidation vs. Hydroxylation Selectivity

We report and analyze chemoselectivity in the gas phase reactions of cycloalkenes (cyclohexene, cycloheptene, cis-cyclooctene, 1,4-cyclohexadiene) with a non-heme iron(IV)-oxo complex [(PyTACN)Fe(O)(Cl)]+, which models the active species in iron-dependent halogenases. Unlike in the halogenases, we did not observe any chlorination of the substrate. However, we observed two other reaction pathways: allylic hydrogen atom transfer (HAT) and alkene epoxidation. The HAT is clearly preferred in the case of 1,4-cyclohexadiene, both pathways have comparable reaction rates in reaction with cyclohexene, and epoxidation is strongly favored in reactions with cycloheptene and cis-cyclooctene. This preference for epoxidation differs from the reactivity of iron(IV)-oxo complexes in the condensed phase, where HAT usually prevails. To understand the observed selectivity, we analyze effects of the substrate, spin state, and solvation. Our DFT and CASPT2 calculations suggest that all the reactions occur on the quintet potential energy surface. The DFT-calculated energies of the transition states for the epoxidation and hydroxylation pathways explain the observed chemoselectivity. The SMD implicit solvation model predicts the relative increase of the epoxidation barriers with solvent polarity, which explains the clear preference of HAT in the condensed phase.

Computational Study of the pH-Dependent Competition between Carbonate and Thymine Addition to the Guanine Radical.

When oligonucleotides are oxidized by carbonate radical, thymine and carbonate can add to guanine radical, yielding either a guanine-thymine cross-link product (G∧T) or 8-oxo-7,8-dehydroguanine (8oxoG) and its further oxidation products such as spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh). The ratio of thymine addition to carbonate addition depends strongly on the pH. Details of the mechanism have been explored by density functional calculations using the ωB97XD/6-31+G(d,p) level of theory with the SMD implicit solvation method, augmented with a few explicit waters. Free energies of intermediates and transition states in aqueous solution have been calculated along the pathways for addition of thymine, CO32-/HCO3- and carbonate radical to guanine radical. The pH dependence was examined by using appropriate explicit proton donors/acceptors as computational models for buffers at pH 2.5, 7, and 10. Deprotonation of thymine is required for nucleophilic addition at C8 of guanine radical, and thus is favored at higher pH. The barrier for carbonate radical addition is lower than for bicarbonate or carbonate dianion addition; however, for low concentrations of carbonate radical, the reaction may proceed by addition of bicarbonate/carbonate dianion to guanine radical. Thymine and bicarbonate/carbonate dianion addition are followed by oxidation by O2, loss of a proton from C8 and decarboxylation of the carbonate adduct. At pH 2.5, guanine radical cation can be formed by oxidization with sulfate radical. Water addition to guanine radical cation is the preferred path for forming 8oxoG at pH 2.5.

Theoretical study on complexes and reactions of boron isotopic exchange separation with fluorinated anisoles as novel donors

Semi-empirical and ab initio density-functional theory (DFT) methods were evaluated for the description of isotope exchange reactions to produce enriched 10B species. We found that DFT calculations using M06-2X/6-311+G(3d,2p) functional and basis sets in combination with the SMD implicit solvation model were able to correctly predict the performance of various anisole-derived donor molecules. We confirmed that fluorination results in greatly increased separation factors, and successfully identified the o- and 2,4-difluorinated anisole as superior donors for chemical exchange distillation. These findings provide the basis for an efficient approach to rapidly screen and design new donor species.

Improved pKa Prediction of Substituted Alcohols, Phenols, and Hydroperoxides in Aqueous Medium Using Density Functional Theory and a Cluster-Continuum Solvation Model.

Acid dissociation constants (pKa's) are key physicochemical properties that are needed to understand the structure and reactivity of molecules in solution. Theoretical pKa's have been calculated for a set of 72 organic compounds with -OH and -OOH groups (48 with known experimental pKa's). This test set includes 17 aliphatic alcohols, 25 substituted phenols, and 30 hydroperoxides. Calculations in aqueous medium have been carried out with SMD implicit solvation and three hybrid DFT functionals (B3LYP, ωB97XD, and M06-2X) with two basis sets (6-31+G(d,p) and 6-311++G(d,p)). The effect of explicit water molecules on calculated pKa's was assessed by including up to three water molecules. pKa's calculated with only SMD implicit solvation are found to have average errors greater than 6 pKa units. Including one explicit water reduces the error by about 3 pKa units, but the error is still far from chemical accuracy. With B3LYP/6-311++G(d,p) and three explicit water molecules in SMD solvation, the mean signed error and standard deviation are only -0.02 ± 0.55; a linear fit with zero intercept has a slope of 1.005 and R2 = 0.97. Thus, this level of theory can be used to calculate pKa's directly without the need for linear correlations or thermodynamic cycles. Estimated pKa values are reported for 24 hydroperoxides that have not yet been determined experimentally.

Computational Study of Oxidation of Guanine by Singlet Oxygen (1 Δg ) and Formation of Guanine:Lysine Cross-Links.

Oxidation of guanine in the presence of lysine can lead to guanine-lysine cross-links. The ratio of the C4, C5 and C8 crosslinks depends on the manner of oxidation. Type II photosensitizers such as Rose Bengal and methylene blue can generate singlet oxygen, which leads to a different ratio of products than oxidation by type I photosensitizers or by one electron oxidants. Modeling reactions of singlet oxygen can be quite challenging. Reactions have been explored using CASSCF, NEVPT2, DFT, CCSD(T), and BD(T) calculations with SMD implicit solvation. The spin contamination in open-shell calculations were corrected by Yamaguchi's approximate spin projection method. The addition of singlet oxygen to guanine to form guanine endo- peroxide proceeds step-wise via a zwitterionic peroxyl intermediate. The subsequent barrier for ring closure is smaller than the initial barrier for singlet oxygen addition. Ring opening of the endoperoxide by protonation at C4-O is followed by loss of a proton from C8 and dehydration to produce 8-oxoGox . The addition of lysine (modelled by methylamine) or water across the C5=N7 double bond of 8-oxoGox is followed by acyl migration to form the final spiro products. The barrier for methylamine addition is significantly lower than for water addition and should be the dominant reaction channel. These results are in good agreement with the experimental results for the formation of guanine-lysine cross-links by oxidation by type II photosensitizers.

Computational studies on the interactions of glycine amino acid with graphene, h-BN and h-SiC monolayers.

In the present work, the adsorption of glycine amino acid and its zwitterionic form onto three different hexagonal sheets, namely graphene, boron-nitride (h-BN) and silicon carbide (h-SiC), has been investigated within the framework of Density Functional Theory (DFT) calculations. The energetics and geometrical parameters of the considered systems have been explored at the GGA-PBE level in combination with Grimme's empirical dispersion corrections with Becke-Johnson damping, the DFT-D3(BJ) method. Based on the obtained results, we found that both the glycine molecule and its zwitterionic conformation tend to be chemisorbed onto the surface of h-SiC (Eads ranges from -1.01 to -1.319 eV) while the types of interactions are recognized to be of non-covalent nature for the case of graphene (Eads ranges from -0.121 to -0.345 eV) and h-BN (Eads ranges from -0.103 eV to -0.325 eV) systems. Moreover, the empirical dispersion corrections applied in these calculations significantly improved the results and confirmed the crucial role of dispersion corrections in obtaining reliable geometries and adsorption energies. Our findings revealed that the electronic properties of the considered systems did not change during the adsorption process and these monolayers preserve their inherent electronic properties as they interact with the glycine molecule. Using the SMD implicit solvation model, the effect of solvation has also been evaluated by re-optimizing the structures within a medium with a dielectric constant of 78.39 (liquid water) and it has been shown that the strength of the interaction between the glycine conformers and hexagonal sheets has decreased. The accuracy of the obtained values has been evaluated by some benchmark calculations at the hybrid PW6B95 level of theory and reasonable consistency is found between the results of the PBE-D3 method and our benchmark system. In summary, h-SiC exhibited the highest affinity toward glycine conformers and gained an important edge over other monolayers. Our findings would actively encourage experimentalists to explore the potential applications of these materials in drug delivery, biofunctionalization of nanostructured monolayers as well as electronic and nanosensor devices.

Ab Initio Modeling Of Friction Reducing Agents Shows Quantum Mechanical Interactions Can Have Macroscopic Manifestation.

Two of the most commonly encountered friction-reducing agents used in plastic sheet production are the amides known as erucamide and behenamide, which despite being almost identical chemically, lead to markedly different values of the friction coefficient. To understand the origin of this contrasting behavior, in this work we model brushes made of these two types of linear-chain molecules using quantum mechanical numerical simulations under the density functional theory at the B97D/6-31G(d,p) level of theory. Four chains of erucamide and behenamide were linked to a 2 × 10 zigzag graphene sheet and optimized both in vacuum and in continuous solvent using the SMD implicit solvation model. We find that erucamide chains tend to remain closer together through π-π stacking interactions arising from the double bonds located at C13-C14, a feature behenamide lacks, and thus a more spread configuration is obtained with the latter. It is argued that this arrangement of the erucamide chains is responsible for the lower friction coefficient of erucamide brushes, compared with behenamide brushes, which is a macroscopic consequence of cooperative quantum mechanical interactions. While only quantum level interactions are modeled here, we show that behenamide chains are more spread out in the brush than erucamide chains as a consequence of those interactions. The spread-out configuration allows more solvent particles to penetrate the brush, leading in turn to more friction, in agreement with macroscopic measurements and mesoscale simulations of the friction coefficient reported in the literature.

Density Functional Theory Calculation of pKa's of Thiols in Aqueous Solution Using Explicit Water Molecules and the Polarizable Continuum Model.

The pKa's of substituted thiols are important for understanding their properties and reactivities in applications in chemistry, biochemistry, and material chemistry. For a collection of 175 different density functionals and the SMD implicit solvation model, the average errors in the calculated pKa's of methanethiol and ethanethiol are almost 10 pKa units higher than for imidazole. A test set of 45 substituted thiols with pKa's ranging from 4 to 12 has been used to assess the performance of 8 functionals with 3 different basis sets. As expected, the basis set needs to include polarization functions on the hydrogens and diffuse functions on the heavy atoms. Solvent cavity scaling was ineffective in correcting the errors in the calculated pKa's. Inclusion of an explicit water molecule that is hydrogen bonded with the H of the thiol group (in neutral) or S(-) (in thiolates) lowers error by an average of 3.5 pKa units. With one explicit water and the SMD solvation model, pKa's calculated with the M06-2X, PBEPBE, BP86, and LC-BLYP functionals are found to deviate from the experimental values by about 1.5-2.0 pKa units whereas pKa's with the B3LYP, ωB97XD and PBEVWN5 functionals are still in error by more than 3 pKa units. The inclusion of three explicit water molecules lowers the calculated pKa further by about 4.5 pKa units. With the B3LYP and ωB97XD functionals, the calculated pKa's are within one unit of the experimental values whereas most other functionals used in this study underestimate the pKa's. This study shows that the ωB97XD functional with the 6-31+G(d,p) and 6-311++G(d,p) basis sets, and the SMD solvation model with three explicit water molecules hydrogen bonded to the sulfur produces the best result for the test set (average error -0.11 ± 0.50 and +0.15 ± 0.58, respectively). The B3LYP functional also performs well (average error -1.11 ± 0.82 and -0.78 ± 0.79, respectively).

Stability and spatial arrangement of the 2,4-dichlorophenoxyacetic acid and β-cyclodextrin inclusion compound: A theoretical study

The present letter reports results from a comprehensive theoretical analysis of the inclusion process involving 2,4-dichlorophenoxyacetic acid (2,4-D) and β-cyclodextrin (β-CD) for which the experimental data of formation is available. Spatial arrangement and stabilization energies were evaluated in gas phase and aqueous solution through density functional theory (DFT) and through the use of SMD implicit solvation approach. The discussed methodology was applied to predict the stability and identify the most favorable form (deprotonated or neutral) as well as the most probable spatial arrangement of the studied inclusion compound.

Calculations of pKa's and redox potentials of nucleobases with explicit waters and polarizable continuum solvation.

The SMD implicit solvation model augmented with one and four explicit water molecules was used to calculate pKa's and redox potentials of N-methyl-substituted nucleic acid bases guanine, adenine, cytosine, thymine, and uracil. Calculations were carried out with the B3LYP/6-31+G(d,p) level of theory. The same numbers of water molecules were hydrogen bonded to the neutral, protonated, and deprotonated nucleobases in their unoxidized and oxidized forms. The improvement in pKa1 involving neutrals and cations was modest. By contrast, the improvement in pKa2 involving neutrals and anions was quite significant, reducing the mean absolute error from 4.6 pKa units with no waters, to 2.6 with one water and 1.7 with four waters. For the oxidation of nucleobases, adding explicit waters did little to improve E(X(•),H(+)/XH), possibly because both species in the redox couple are neutral molecules at pH 7.

Computational Prediction of One-Electron Reduction Potentials and Acid Dissociation Constants for Guanine Oxidation Intermediates and Products

Reduction potentials and pK(a) values were calculated for intermediates and products along three major pathways for guanine oxidation using the B3LYP and CBS-QB3 levels of theory with the SMD implicit solvation model. N-methylated nucleobases were used as models for nucleoside species. Ensemble averaged reduction potentials at pH 7 (E7) were obtained by combining calculated standard reduction potentials with calculated pKa values in addition to accounting for tautomerization energies. Calculated pK(a) values are reasonable based on experimental estimates and chemical intuition. Pathway A leads to guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp). The first step is the oxidation of 8-oxoguanine which proceeds by the loss of an electron followed by the loss of two protons and loss of another electron, yielding 8-oxopurine. The calculated E7 values for the remaining intermediates and products are at least 0.3 V higher than that of guanine, indicating that further oxidation of these species is unlikely. Pathway B leads to two formamidopyrimidine isomers (FAPyG and 2,5FAPyG). Species along this pathway have calculated reduction potentials that are much lower than the oxidation potential for guanine and would likely be very short-lived in an oxidatively stressed environment. Pathway C leads to reduced spiroiminodihydantoin and 5-carboxamido-5-formamido-2-iminohydantoin (2Ih). Similar to pathway A, the calculated reduction potentials for species along this pathway are at least 0.4 V higher than that of guanine.

Comparative theoretical investigation on the isomerization energies of long-chain perfluoroalkanes: A case study with perfluorooctanoic acid congeners

AbstractThe gas and solution phase relative thermodynamic stabilities of the 39 linear and branched perfluorooctanoic acid (PFOA) congeners in both their acid and anionic forms were calculated at various levels of density functional (B3LYP, wB97XD, and M062X functionals with the 6-311++G(d,p) basis set) and second order Moller-Plesset perturbation (MP2/6-311++G(d,p)//B3LYP/6-311++G(d,p)) theory using the SMD implicit solvation model. The B3LYP functional does not accurately model the expected trends in thermodynamic stability of PFOA isomers with linear versus branched perfluoroalkyl chains. Calculations obtained with the M062X and MP2 model chemistries suggest these theoretical methods may be more appropriate for relative thermodynamic stability studies on various perfluoroalkyl compounds.