The Determination of Abraham Descriptors and Their Application to Crop Protection Research

Acree

et al. 2014

J. Org. Chem.

ABSTRACT:1 H NMR chemical shifts have been obtained in the solvents deuterochloroform and dimethyl sulfoxide. The difference in the chemical shifts of an OH or NH group in these two solvents, Δδ = δ(DMSO) − δ(CDCl 3 ), can be converted into the hydrogen bond acidity, A, of the group using the equation A = 0.0065 + 0.133Δδ. The NMR A value, A NMR , can be used as a quantitative assessment of intramolecular hydrogen bonding. We list values of Δδ and A NMR for 55 compounds containing an OH group and 60 compounds with an NH group. For the hydroxy compounds, if A > 0.5 then the OH group is not part of an intramolecular hydrogen bond, but if A < 0.1 then the OH group forms part of an intramolecular hydrogen bond. For NH compounds, if A > 0.16 the NH group is not part of an intramolecular hydrogen bond, and if A < 0.05 the NH group is part of an intramolecular hydrogen bond. No comparison compounds are needed, and the method is extremely simple. We further show how it is possible to relate intramolecular hydrogen bonding to the actual effect on values of a number of physicochemical, environmental, and biochemical properties. ■ INTRODUCTION Shalaeva et al.1 have recently shown that the presence of an intramolecular hydrogen bond (intraHB) in a molecule can considerably alter the properties of a molecule. These include properties relevant to drug design such as solubility, permeability, and partition. It is therefore important to be able to identify molecules that possess intraHBs and, if possible, to assess the effect of an intraHB on the molecular properties. Testa and co-workers 2−5 were the first to show that the effect of intraHBs could be observed in water−solvent partition coefficients (as log P) and particularly in differences between partition coefficients in water−octanol and water−aprotic solvent systems. They set out differences in log P for water− octanol and water−heptane partitions (eq 1) and showed that intraHBs greatly reduce the value of Δ(log P) oct−hept . They also observed similar effects due to intraHBs in other water−octanol and water−solvent systems.4,5 Leo 6 used octanol and chloroform as the two solvent systems in order to calculate the hydrogen bond acidity of a solute, and Feng et al. 7 used dibutyl ether and cyclohexane as the solvent systems to calculate solute hydrogen bond acidity.

Section: ■ Introductionmentioning

confidence: 99%

“…We shall not deal with the determination of the solute descriptors from experimental data, as this has been described several times in some detail (see refs 9 and 10 and especially the review by Clarke and Mallon 11 ). The coefficients in eq 2 for log P values in a number of water− solvent systems 12 are given in Table 1.…”

Section: ■ Introductionmentioning

confidence: 99%

An NMR Method for the Quantitative Assessment of Intramolecular Hydrogen Bonding; Application to Physicochemical, Environmental, and Biochemical Properties

Acree

et al. 2014

J. Org. Chem.

“…The values of log Kp of the 247 compounds or species in our data set covers both 'highly permeable' and 'poorly permeable' values, varying from -10.01 to -3.00, and meets a normal distribution very well, with a mean of -6.027 and a standard deviation of 1.165, as seen in Figure 1. Stephens et al (2012) and Zhang et al (2012) or obtained as described before (Abraham et al, 2015a;Abraham et al, 2015b;Clarke and Mallon, 2012); ionic descriptors obtained as described before (Abraham and Acree, 2016). b Cited studies where log Kp (obs) was obtained.…”

Section: Resultsmentioning

confidence: 99%

“…We use the term "ions" for permanent ions such as Na + and Cl − , and the term "ionic species" for ions derived from protonation of basic compounds and deprotonation of acidic compounds. The compound descriptors for neutral molecules are obtained from a variety of experimental processes, as explained in a number of reviews Clarke and Mallon, 2012;Poole et al, 2013), and Abraham and Acree have reviewed the methods used to obtain descriptors for ions and ionic species (Abraham and Acree, 2016). The coefficients (c, e, s, a, b, v, j + and j -) in Eq.…”

Section: Methods Lfer Modelmentioning

confidence: 99%

An equation for the prediction of human skin permeability of neutral molecules, ions and ionic species

Zhang

International Journal of Pharmaceutics

Liu

2017

Accepted ManuscriptThis is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

“…(1) given solute. The method has been described in considerable detail [8][9][10][11], especially by Clarke and Mallon [11] who give a number of specific examples.…”

Section: Methodsmentioning

confidence: 99%

On the solubility of quercetin

Journal of Molecular Liquids

Acree

2014

There is considerable disagreement over the solubility of quercetin in water. Experimental values of log Cw with Cw in mol/L range from -2.52 to -5.89, a difference of over three log units. We have applied a methodology based on linear free energy equations for water-solvent and gassolvent partitions to study solubilities. These are related to partition coefficients through Ps = Cs/Cw where Cs and Cw are solubilities of a given solute in a solvent and in water. We find that known solubilities of quercetin in methanol and ethanol at 298 K and a known water-solvent partition coefficient can be accommodated in the same model if the water solubility at 298 K, as log Cw, is taken as -3.90, that is near to the middle of the range of experimental values. Our model successfully predicts solubilities of quercetin in water-ethanol mixtures near to the ethanol rich mixtures.