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1. Building chemical intuition about physicochemical properties of C8-per-/poly-fluoroalkyl carboxylic acids through computational means

   Simpson, S. ; Antle, J. ; Larock, M. ; Aga, D. ; Falls, Z. ; Atilla-Gokcumen, G. ; Ng, C. ( March 2024 , ACS Spring 2024)

   We have predicted acid dissociation constants (pKa), octanol-water partition coefficients (KOW), and DPMC lipid membrane-water partition coefficients (Klipid-w) of 150 different 8-carbon containing poly-/per-fluoroalkyl carboxylic acids (C8-PFCAs) utilizing COMSO-RS theory. Different trends associated with functionalization, degree of fluorination, degree of saturation, degree of chlorination, and branching are discussed based upon the predicted values for the partition coefficients. In general, functionalization closest to the carboxylic head group had the greatest impact on the value of the predicted physicochemical properties. 

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2. Comparison of Chemotherapeutic Activities of Rhodamine-Based GUMBOS and NanoGUMBOS

   https://doi.org/10.3390/molecules25143272  

   Bhattarai, Nimisha ; Chen, Mi ; Perez, Rocio L. ; Ravula, Sudhir ; Strongin, Robert M. ; McDonough, Karen ; Warner, Isiah M. ( July 2020 , Molecules)

   Rhodamine derivatives have been widely investigated for their mitochondrial targeting and chemotherapeutic properties that result from their lipophilic cationic structures. In previous research, we have found that conversion of Rhodamine 6G into nanoGUMBOS, i.e., nanomaterials derived from a group of uniform materials based on organic salts (GUMBOS), led to selective chemotherapeutic toxicity for cancer cells over normal cells. Herein, we investigate the chemotherapeutic activity of GUMBOS derived from four different rhodamine derivatives, two bearing an ester group, i.e., Rhodamine 123 (R123) and SNAFR-5, and two bearing a carboxylic acid group, i.e., rhodamine 110 (R110) and rhodamine B (RB). In this study, we evaluate 1) relative hydrophobicity via octanol–water partition coefficients, 2) cytotoxicity, and 3) cellular uptake in order to evaluate possible structure–activity relationships between these different compounds. Intriguingly, we found that while GUMBOS derived from R123 and SNAFR-5 formed nanoGUMBOS in aqueous medium, no distinct nanoparticles are observed for RB and R110 GUMBOS. Further investigation revealed that the relatively high water solubility of R110 and RB GUMBOS hinders nanoparticle formation. Subsequently, while R123 and SNAFR-5 displayed selective chemotherapeutic toxicity similar to that of previously investigated R6G nanoGUMBOS, the R110 and RB GUMBOS were lacking in this property. Additionally, the chemotherapeutic toxicities of R123 and SNAFR-5 nanoGUMBOS were also significantly greater than R110 and RB GUMBOS. Observed results were consistent with decreased cellular uptake of R110 and RB as compared to R123 and SNAFR-5 compounds. Moreover, these results are also consistent with previous observations that suggest that nanoparticle formation is critical to the observed selective chemotherapeutic properties as well as the chemotherapeutic efficacy of rhodamine nanoGUMBOS. 

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3. Influence of microbial weathering on the partitioning of per- and polyfluoroalkyl substances (PFAS) in biosolids

   https://doi.org/10.1039/D2EM00350C  

   Lewis, Asa J. ; Ebrahimi, Farshad ; McKenzie, Erica R. ; Suri, Rominder ; Sales, Christopher M. ( December 2022 , Environmental Science: Processes & Impacts)

   Per- and polyfluoroalkyl substances (PFAS) are a large group of man-made fluorinated organic chemicals that can accumulate in the environment. In water resource recovery facilities (WRRFs), some commonly detected PFAS tend to partition to and concentrate in biosolids where they can act as a source to ecological receptors and may leach to groundwater when land-applied. Although biosolids undergo some stabilization to reduce pathogens before land application, they still contain many microorganisms, contributing to the eventual decomposition of different components of the biosolids. This work demonstrates ways in which microbial weathering can influence biosolids decomposition, degrade PFAS, and impact PFAS partitioning in small-scale, controlled laboratory experiments. In the microbial weathering experiments, compound-specific PFAS biosolids–water partitioning coefficients ( K d ) were demonstrated to decrease, on average, 0.4 logs over the course of the 91 day study, with the most rapid changes occurring during the first 10 days. Additionally, the highest rates of lipid, protein, and organic matter removal occurred during the same time. Among the evaluated independent variables, statistical analyses demonstrated that the most significant solids characteristics that impacted PFAS partitioning were organic matter, proteins, lipids, and molecular weight of organics. A multiple linear regression model was built to predict PFAS partitioning behavior in biosolids based on solid characteristics of the biosolids and PFAS characteristics with a R 2 value of 0.7391 when plotting predicted and measured log  K d . The findings from this work reveal that microbial weathering can play a significant role in the eventual fate and transport of PFAS and their precursors from biosolids. 

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4. Dimensionally reduced machine learning model for predicting single component octanol–water partition coefficients

   https://doi.org/10.1186/s13321-022-00660-1  

   Kenney, David H. ; Paffenroth, Randy C. ; Timko, Michael T. ; Teixeira, Andrew R. ( January 2023 , Journal of Cheminformatics)

   MF-LOGP, a new method for determining a single component octanol–water partition coefficients ($$LogP$$$\mathrm{LogP}$) is presented which uses molecular formula as the only input. Octanol–water partition coefficients are useful in many applications, ranging from environmental fate and drug delivery. Currently, partition coefficients are either experimentally measured or predicted as a function of structural fragments, topological descriptors, or thermodynamic properties known or calculated from precise molecular structures. The MF-LOGP method presented here differs from classical methods as it does not require any structural information and uses molecular formula as the sole model input. MF-LOGP is therefore useful for situations in which the structure is unknown or where the use of a low dimensional, easily automatable, and computationally inexpensive calculations is required. MF-LOGP is a random forest algorithm that is trained and tested on 15,377 data points, using 10 features derived from the molecular formula to make$$LogP$$$\mathrm{LogP}$predictions. Using an independent validation set of 2713 data points, MF-LOGP was found to have an average$$RMSE$$$\mathrm{RMSE}$= 0.77 ± 0.007,$$MAE$$$\mathrm{MAE}$= 0.52 ± 0.003, and$${R}^{2}$$$R^2$= 0.83 ± 0.003. This performance fell within the spectrum of performances reported in the published literature for conventional higher dimensional models ($$RMSE$$$\mathrm{RMSE}$= 0.42–1.54,$$MAE$$$\mathrm{MAE}$= 0.09–1.07, and$${R}^{2}$$$R^2$= 0.32–0.95). Compared with existing models, MF-LOGP requires a maximum of ten features and no structural information, thereby providing a practical and yet predictive tool. The development of MF-LOGP provides the groundwork for development of more physical prediction models leveraging big data analytical methods or complex multicomponent mixtures.

   Graphical Abstract

    

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5. Resolving identities of emerging per and polyfluoroalkyl substances isomers based on COSMO-RS derived retention factor and mass fragmentation patterns

   Simpson, Scott ; Guardian, M.G. ; Aga, D.S. ( December 2021 , Pacifichem)

   Chromatographic retention times and mass spectrometral fragmentation of per- and polyfluoroalkyl substances (PFASs) standards were determined using the optimized parameters obtained for liquid chromatography with tandem high-resolution mass spectrometry (LC-HRMS) analysis. Characteristic fragment ions obtained at various collision energies (MS2 fragmentation) were used for structural elucidation to predict the identities of newly discovered (emerging) PFASs detected in environmental samples. Moreover, the COnductor-like Screening MOdel for Realistic Solvents (COSMO-RS) was used to calculate the octanol-water partition coefficients (Kow) and mean isotropic polarizabilities of known PFASs, and the values were plotted against their chromatographic retention factors (k) to obtain a multivariable regression model that can be used to predict k values of unknown PFASs. Retention factor values of different structural isomers of the unknown PFASs were calculated and compared to the experimental k. For all the unknown PFASs, the predicted k value for the isomer that matches the corresponding MS2 fragmentation was found to be within 5% of the experimentally measured k value. This study demonstrates the applicability of a simple approach that combines the use of computationally-derived log Kow and polarizabilities, experimentally-determined k values, together with observed MS2 fragmentation patterns, in assigning the structures of emerging PFASs at environmentally relevant conditions when no reference standards are available. 

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