Shubham Vyas

Conformational sampling with implicit solvation models can incorrectly favor intramolecular bonding. Explicit solvation during sampling can act as a conformational chaperone disrupting these bonds and improving COSMO-RS solvation energy predictions.

The extreme persistence of per- and polyfluoroalkyl substances (PFAS) in the environment is rooted in their three-dimensional molecular conformation. The helical twist adopted by perfluoroalkyl chains due to hyperconjugation involving their recalcitrant C–F bonds governs their resistance to degradation, yet a quantitative, continuous metric for helicity has remained absent. Here we introduce a data-driven framework that quantifies backbone helicity using three statistical descriptors: void-state (binary occupancy) spatial autocorrelations, local backbone principal component analysis, and persistent homology. We further validate each statistical descriptor against geometric dihedral benchmarks and DFT-calculated Vibrational Circular Dichroism (VCD) spectra. The framework is initially established on a homologous series of perfluorocarboxylic acids (FC2 through FC16) and their hydrogenated analogues, then extended across perfluorosulfonic acids, fluorotelomer alcohols, polyfluoroalkyl hexanoic acid analogues, and longer-chain PFOA and PFOS analogues. Agreement between statistical, geometric, and spectroscopic definitions of helicity is established for PFCAs and extended to structurally distinct subfamilies, including PFOA analogues of varying fluorine content and perfluorosulfonic acids, demonstrating that the descriptors are robust to changes in headgroup chemistry and fluorine substitution pattern. The framework provides a chemistry-agnostic toolset for incorporating backbone conformation into predictive models of PFAS environmental fate and degradation reactivity.

Perfluoroalkyl sulfonamides (FASAs) are a class of per- and polyfluoroalkyl substances (PFAS) found throughout the environment in water, soil, and biota. Sorption behavior, bioaccumulation, and environmental longevity of ionogenic molecules like FASAs is governed by the acid dissociation constant (pKa). However, limited experimental pKa values are available for FASAs, with most values computationally modeled with unknown accuracy. In this research 19F Nuclear Magnetic Resonance (NMR) spectroscopy was used to experimentally determine the pKa of perfluorobutane sulfonamide (FBSA) (6.22 ± 0.06), N-methyl (Me) FBSA (7.46 ± 0.03), perfluorohexane sulfonamide (FHxSA) (6.22 ± 0.04), perfluorooctane sulfonamide (FOSA) (6.4 ± 0.3), Me-FOSA (7.7 ± 0.3), and N-ethyl FOSA (8.0 ± 0.3). The pKa of low aqueous solubility FASAs (FOSA, MeFOSA, and EtFOSA) were determined using acetonitrile (ACN):aqueous buffer mixtures and an aggregated mathematical approach developed to simultaneously fit the data for 40, 50, and 60% ACN. Fluorinated carbon number did not significantly impact pKa. Methyl substitution of nitrogen (MeFBSA) increased the pKa by 1.24 log units for C4 and 1.3 log units for C8 FASAs. Ethyl substitution increased the pKa by 1.6 log units (FOSA vs EtFOSA). Experimentally measured values were compared to four different prediction models. Our internally corrected DFT model gave the best agreement with experimental values while Chemicalize gave pKa values up to 4 log units lower than experimental values.

Hydrothermal alkaline treatment (HALT) is an innovative approach that was developed for the destruction of per- and polyfluoroalkyl substances (PFAS). While HALT has been shown to effectively destroy a wide range of PFAS detected in various sample matrices, a comprehensive understanding of the controlling reaction mechanisms and transformation pathways remains limited. Herein, we selected trifluoromethanesulfonate (TFMS), the shortest-chain and likely one of the most recalcitrant PFAS reported to date, to probe degradation mechanisms and identify transformation products. The results indicate that HALT of TFMS proceeds via general nucleophilic substitution and base-promoted pathways, leading to 65.7% mineralization of the parent compound after a 180 min reaction of 0.1 M TFMS at 350 °C in 1 M NaOH. For the degraded TFMS, approximately 100% of fluorine and sulfur were converted to fluoride and sulfate, respectively, while carbon was distributed mainly as carbonate (95%) and formate (5%), along with the production of hydrogen. These findings are supported by both experimental and computational evidence. Hydroxide plays dual roles by initiating the reaction as the nucleophile and promoting subsequent steps by maintaining strongly basic conditions. The initial degradation step is rate-determining, with an estimated energy barrier of 27.8 kcal/mol. Similar mechanisms are proposed for reactions of longer-chain perfluoroalkyl sulfonic acids (PFSAs). Finally, the key factors governing PFSA reactivity across chain lengths from C1 to C8 were identified as reaction temperature, nucleophile type and concentration, and reaction time. This study addresses a critical knowledge gap in PFAS hydrothermal reactions and further establishes HALT as an effective technology for PFAS destruction and defluorination.

Solubility of gases in liquids is governed by a complex interplay of electrostatic interactions, entropy, and molecular polarizability.

Physiologically relevant partition coefficients between an aqueous phase (plasma), lipids (cell membrane), and proteins are lacking for many per- and polyfluoroalkyl substances (PFAS). Biomimetic chromatography utilizes immobilized artificial membrane (IAM), human serum albumin (HSA), and alpha-1-glycoprotein (AGP) stationary phases to determine partition coefficients. A rapid-gradient biomimetic approach was used to determine partition coefficients for 81 target PFAS and 37 suspect PFAS in a 3M aqueous film forming foam. PFAS were categorized as acids, bases, or neutrals and used to interpret lipophilic contributions to binding on IAM, HSA, and AGP columns. Partition coefficients on the IAM membrane (log K_IAM: 1.4 to 7.9; median 3.4) and AGP protein (log k_AGP: -1.9 to 0.72; median 0.31) increased linearly with increasing fluorinated chain length, while those for HSA protein (log K_HSA: 0.45 to 5.1; median 4.3) reached a plateau at a specific chain length (∼C6-C8). Zwitterionic PFAS at pH 7.4 exhibited lower affinities for both the IAM membrane and HSA protein, which are likely due to the smaller fraction of the charged species at pH 7.4. The partition coefficients (CHI log D [chromatographic log D derived from the Chromatographic Hydrophobicity Index scaled to the octanol/water partition coefficient, log D]), log K_IAM, log K_HSA, and log k_AGP) expand our understanding of how PFAS behave in the body and provide a foundation for future toxicokinetic modeling.The rapid-gradient approach offers a novel method for measuring partition coefficients for PFAS in complex mixtures.

Removed because all co-authors did not approve of submission and posting.

Organic azides are valuable precursors in synthetic chemistry, particularly for nitrogen-based functionalization through photochemical activation. In this study, the photoreactivities of 4-azido-1-phenylbutan-1-one (1a) and 4-azido-(4-methoxy)phenylbutan-1-one (1b) were investigated using visible-light photocatalysts [Ir(dF(CF₃)ppy)₂(dtbpy)]PF₆ and [Ru(bpy)₃]Cl₂ to elucidate the mechanistic differences between triplet energy transfer and photoreductive electron transfer pathways. Direct irradiation of 1a in methanol favors the formation of a biradical species via intramolecular H atom abstraction to generate its lowest triplet ketone (T_1K) with an (n,π*) configuration, which selectively yields 2-phenyl-1-pyrroline derivative 2a. However, 1b reacts through its less reactive T_1K, which has a (π,π*) configuration, to form 2-phenyl-1H-pyrrole as the major product. When sensitized by [Ir(dF(CF₃)ppy)₂(dtbpy)]PF₆, selective excitation of the triplet azido moiety (T_A) of both 1a and 1b yields the corresponding pyrroline (2a and 2b) via triplet alkylnitrene (³1aN and³1bN) formation. In contrast, photoactivation of [Ru(bpy)₃]Cl₂ in the presence of diisopropylethylamine (DIPEA) results in photoreductive electron transfer, forming azido radical anion intermediates, which cyclize to also yield 2a and 2b. Product studies, cyclic voltammetry, laser flash photolysis, and DFT calculations supported these mechanistic assignments. This work demonstrates complementary approaches to control alkyl azide photoreactivity and unlock new strategies for visible-light-induced nitrogen incorporation.