Effect of solutes structure and pH on the n-octanol/water partition coefficient of ionizable organic compounds.

Liquid-liquid partition coefficient is a useful tool to predict biological and environmental fate of organic compounds, for example bioaccumulation or toxicity of lipophilic contaminants. Conversely, the partitioning of ionizable compounds is poorly studied in contrast to that of neutral compounds. Yet, such topic deserves attention, since numerous organic contaminants are ionizable as well as their degradation products. Hence, the contribution of charged species has to be considered in order to model accurately the mass balance or partition of ionizable compounds. In this context, we investigated the liquid-liquid partition of 13 ionizable compounds (oxalic acid, histidine, benzimidazole, etc.), covering various classes of compounds (carboxylic acids, amino-acids, etc.). The n-octanol/water partition coefficient was measured from pH 1 up to 13, in order to fully gather the distribution of both neutral and charged species. Empirical models describing these results are reviewed and partition parameters adjusted for charged species. The study of benzoic acid derivatives (benzoic, salicylic, ortho- and iso-phthalic acids) provides insights on the influence of chemical groups on the partitioning. In the case of tryptophan, the use of acid/base microconstants allowed to estimate the partition of both the zwitterion and its neutral tautomer. Despite a major zwitterionic form (log PZ(tryptophan) = -1.58 ± 0.30), the minor but neutral tautomer (log PN(tryptophan) = +0.03 ± 0.30) drives the partition equilibrium. Overall, the provided data may be useful to assess the retention of contaminants, its dependency on pH and salinity variations, and thus understanding their environmental fate. Such data may also be useful as well for molecular simulation involving solvation of organic ions in aqueous and non-aqueous solvents.

[1]  T. Hofmann,et al.  Sorption and Mobility of Charged Organic Compounds: How to Confront and Overcome Limitations in Their Assessment , 2022, Environmental science & technology.

[2]  S. Tanabe,et al.  Occurrence of Pharmaceutically Active Compounds and Potential Ecological Risks in Wastewater from Hospitals and Receiving Waters in Sri Lanka , 2021, Environmental toxicology and chemistry.

[3]  J. Robinet,et al.  Mobility of organic compounds in a soft clay-rich rock (Tégulines clay, France). , 2021, Chemosphere.

[4]  G. Lefèvre,et al.  Diffusion of organic anions in clay-rich media: Retardation and effect of anion exclusion. , 2018, Chemosphere.

[5]  N. Jarvis Meta‐analysis of pesticide sorption in subsoil , 2018, Environmental toxicology and chemistry.

[6]  G. Lefèvre,et al.  Adsorption of polar organic molecules on sediments: Case-study on Callovian-Oxfordian claystone. , 2017, Chemosphere.

[7]  Carla A. Ng,et al.  Assessing the bioaccumulation potential of ionizable organic compounds: Current knowledge and research priorities , 2017, Environmental toxicology and chemistry.

[8]  M. R. Housaindokht,et al.  Surfactant Effects on Tautomeric and Microscopic Equilibria of Tryptophan: Experimental and Theoretical Studies , 2017 .

[9]  R. Erickson,et al.  Observed and modeled effects of pH on bioconcentration of diphenhydramine, a weakly basic pharmaceutical, in fathead minnows , 2015, Environmental toxicology and chemistry.

[10]  J. Douwes,et al.  Partitioning of persistent organic pollutants (POPs) between human serum and breast milk: a literature review. , 2012, Chemosphere.

[11]  B. Noszál,et al.  Lipophilicity of zwitterions and related species: a new insight. , 2011, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[12]  B. Noszál,et al.  The complete microspeciation of arginine and citrulline. , 2011, Journal of pharmaceutical and biomedical analysis.

[13]  D. Rothstein Effects of amino-acid chemistry and soil properties on the behavior of free amino acids in acidic forest soils , 2010 .

[14]  B. Kuhn,et al.  Intramolecular hydrogen bonding in medicinal chemistry. , 2010, Journal of medicinal chemistry.

[15]  A. Weigelt,et al.  Uptake of intact amino acids by plants depends on soil amino acid concentrations , 2009 .

[16]  Wenjing Fu,et al.  Influence of soil pH on the sorption of ionizable chemicals: Modeling advances , 2009, Environmental toxicology and chemistry.

[17]  F. Gobas,et al.  Biodegradation of mono-alkyl phthalate esters in natural sediments. , 2008, Chemosphere.

[18]  T. Fujita,et al.  The Analysis of the Ortho Effect , 2007 .

[19]  J. Tolls,et al.  The effect of pH and ionic strength on the sorption of sulfachloropyridazine, tylosin, and oxytetracycline to soil , 2006, Environmental toxicology and chemistry.

[20]  S. Cuttle,et al.  Rapid intrinsic rates of amino acid biodegradation in soils are unaffected by agricultural management strategy , 2005 .

[21]  G. Foster,et al.  Tracking acidic pharmaceuticals, caffeine, and triclosan through the wastewater treatment process , 2005, Environmental toxicology and chemistry.

[22]  A. Berthod,et al.  Countercurrent Chromatography for the Measurement of the Hydrophobicity of Sulfonamide Amphoteric Compounds , 2004, Chromatographia.

[23]  F. Wania,et al.  Is vapor pressure or the octanol-air partition coefficient a better descriptor of the partitioning between gas phase and organic matter? , 2003 .

[24]  Bernard Testa,et al.  Lipophilicity and solvation of anionic drugs. , 2002, Chemistry.

[25]  J. Simons,et al.  Low-energy tautomers and conformers of neutral and protonated arginine. , 2001, Journal of the American Chemical Society.

[26]  C. Hall,et al.  α‐Helix formation: Discontinuous molecular dynamics on an intermediate‐resolution protein model , 2001, Proteins.

[27]  K. Takács-Novák,et al.  Ion-Pair Partition of Quaternary Ammonium Drugs: The Influence of Counter Ions of Different Lipophilicity, Size, and Flexibility , 1999, Pharmaceutical Research.

[28]  A. Berthod,et al.  Hydrophobicity of Ionizable Compounds. A Theoretical Study and Measurements of Diuretic Octanol−Water Partition Coefficients by Countercurrent Chromatography , 1999 .

[29]  H. Girault,et al.  Charge and Delocalisation Effects on the Lipophilicity of Protonable Drugs , 1999 .

[30]  J. Fein,et al.  Experimental study of octanol–water partition coefficients for2,4,6-trichlorophenol and pentachlorophenol: Derivation of an empirical model of chlorophenol partitioning behaviour , 1998 .

[31]  J. Dearden,et al.  QSAR study of the toxicity of benzoic acids to Vibrio fischeri, Daphnia magna and carp. , 1998, The Science of the total environment.

[32]  S. Yalkowsky,et al.  Correlation of Octanol/Water Solubility Ratios and Partition Coefficients , 1995 .

[33]  K. Takács-Novák,et al.  Lipophilicity of amphoteric molecules expressed by the true partition coefficient , 1995 .

[34]  J. Westall,et al.  Distribution of lithium chloride, sodium chloride, potassium chloride, hydrochloric acid, magnesium chloride, and calcium chloride between octanol and water , 1990 .

[35]  J. Sangster,et al.  Octanol‐Water Partition Coefficients of Simple Organic Compounds , 1989 .

[36]  Alan R. Fersht,et al.  Stabilization of protein structure by interaction of α-helix dipole with a charged side chain , 1988, Nature.

[37]  B. Testa,et al.  Thermodynamics and mechanism of partitioning of pyridylalkanamides in n-octanol/ water and di-n-butyl ether/water , 1987 .

[38]  Michele M. Miller,et al.  Relationships between octanol-water partition coefficient and aqueous solubility. , 1985, Environmental science & technology.

[39]  Tanii Hideji,et al.  Structure-toxicity relationship of acrylates and methacrylates , 1982 .

[40]  R. Cramer,et al.  Measurement of correlation of partition coefficients of polar amino acids. , 1981, Molecular pharmacology.

[41]  Manfred Schmidt,et al.  Partition coefficients of amino acids and hydrophobic parameters π of their side-chains as measured by thin-layer chromatography☆ , 1981 .

[42]  J. Colaizzi,et al.  pH-partition behavior of amino acid-like -lactam antibiotics. , 1973, Journal of pharmaceutical sciences.

[43]  A. Leo,et al.  Partition coefficients and their uses , 1971 .

[44]  J. Colaizzi,et al.  pH-Partition behavior of tetracyclines. , 1969, Journal of pharmaceutical sciences.

[45]  J. Biles,et al.  Physical chemical study of the distribution of some amine salts between immiscible solvents. , 1961, Journal of pharmaceutical sciences.

[46]  E. Bosch,et al.  Lipophilicity of amphoteric and zwitterionic compounds: A comparative study of determination methods. , 2017, Talanta.

[47]  Alex Avdeef,et al.  pH‐Metric log P. Part 1. Difference Plots for Determining Ion‐Pair Octanol‐Water Partition Coefficients of Multiprotic Substances , 1992 .

[48]  Han van de Waterbeemd,et al.  Structural effects in the lipophilicity of di- and polysubstituted benzenes as measured by reversed-phase high-performance liquid chromatography , 1987 .

[49]  M. Charton Nature of the ortho effect. VII. Nuclear magnetic resonance spectra , 1971 .

[50]  Mitsuo. Ito Ultraviolet absorption study of the molecular association of benzoic acid and its derivatives , 1960 .