Hydrogen Bonding. Part 10. A Scale of Solute Hydrogen-Bond Basicity Using log K Values for Complexation in Tetrachloromethane.
TL;DR: In this paper, a scale of solute hydrogen-bond acidity using equilibrium constants (as log K values) for complexation of series of acids (i) against a given base in dilute solution in tetrachloromethane, equation (A).
Abstract: A scale of solute hydrogen-bond acidity has been constructed using equilibrium constants (as log K values) for complexation of series of acids (i) against a given base in dilute solution in tetrachloromethane, equation (A). Forty-five such equations have been solved to yield LB and DB, log Ki=LB log KAHI+DB(A) values characterising the base, and log KAH values that characterise the acid. In this analysis, use has been made of the novel observation that all the lines in equation (A) intersect at a given point where log K= log KAH=–1.1 with K on the molar scale. Some 190 log KAH values that constitute a reasonably general scale of solute hydrogen-bond acidity have been obtained. It is shown that there is no general connection between log KAH; and any proton-transfer quantities, although certain family dependences are obtained. A number of acid-base combinations are excluded from equation (A), and alternative log KAHE values have been determined for such cases. The general log KAH values may be transformed into α2H values suitable for use in multiple linear-regression analysis through the equation α2H=(log KAH+ 1.1)/4.636.
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TL;DR: The most commonly methods used in vitro determination of antioxidant capacity of food constituents are reviewed and presented, and the general chemistry underlying the assays in the present paper was clarified.
Abstract: Recently, there has been growing interest in research into the role of plant-derived antioxidants in food and human health. The beneficial influence of many foodstuffs and beverages including fruits, vegetables, tea, coffee, and cacao on human health has been recently recognized to originate from their antioxidant activity. For this purpose, the most commonly methods used in vitro determination of antioxidant capacity of food constituents are reviewed and presented. Also, the general chemistry underlying the assays in the present paper was clarified. Hence, this overview provides a basis and rationale for developing standardized antioxidant capacity methods for the food, nutraceutical, and dietary supplement industries. In addition, the most important advantages and shortcomings of each method were detected and highlighted. The chemical principles of these methods are outlined and critically discussed. The chemical principles of methods of 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS·+) scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH·) radical scavenging, Fe3+–Fe2+ transformation assay, ferric reducing antioxidant power (FRAP) assay, cupric ions (Cu2+) reducing power assay (Cuprac), Folin-Ciocalteu reducing capacity (FCR assay), peroxyl radical scavenging, superoxide anion radical (O
2
·−
) scavenging, hydrogen peroxide (H2O2) scavenging, hydroxyl radical (OH·) scavenging, singlet oxygen (1O2) quenching assay and nitric oxide radical (NO·) scavenging assay are outlined and critically discussed. Also, the general antioxidant aspects of main food components were discussed by a number of methods which are currently used for detection of antioxidant properties food components. This review consists of two main sections. The first section is devoted to main components in the foodstuffs and beverages. The second general section is some definitions of the main antioxidant methods commonly used for determination of antioxidant activity of components in the foodstuffs and beverages. In addition, there are given some chemical and kinetic basis and technical details of the used methods.
1,278 citations
Cites background from "Hydrogen Bonding. Part 10. A Scale ..."
...6) and the very much larger rate constant for reaction of the radical with the phenoxide anion (Abraham et al. 1990; Foti et al. 2004a, 2004b), the SPLET process (Fig....
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TL;DR: The results suggest that 2D descriptors and hierarchical clustering methods are best at separating biologically active molecules from inactives, a prerequisite for a good compound selection method.
Abstract: An evaluation of a variety of structure-based clustering methods for use in compound selection is presented. The use of MACCS, Unity and Daylight 2D descriptors; Unity 3D rigid and flexible descriptors and two in-house 3D descriptors based on potential pharmacophore points, are considered. The use of Ward's and group-average hierarchical agglomerative, Guenoche hierarchical divisive, and Jarvis−Patrick nonhierarchical clustering methods are compared. The results suggest that 2D descriptors and hierarchical clustering methods are best at separating biologically active molecules from inactives, a prerequisite for a good compound selection method. In particular, the combination of MACCS descriptors and Ward's clustering was optimal.
631 citations
TL;DR: The development of a conceptual framework for HAT with a Marcus theory approach is described, which shows that the Marcus approach based on free energies and intrinsic barriers captures much of the essential chemistry of HAT reactions.
Abstract: Hydrogen atom transfer (HAT), a key step in many chemical, environmental, and biological processes, is one of the fundamental chemical reactions: A−H + B → A + H−B. Traditional HAT involves p-block radicals such as tert-BuO• abstracting H• from organic molecules. More recently, the recognition that transition metal species undergo HAT has led to a broader perspective, with HAT viewed as a type of proton-coupled electron transfer (PCET). When transition metal complexes oxidize substrates by removing H• (e− + H+), typically the electron transfers to the metal and the proton to a ligand. Examples with iron-imidazolinate, vanadium-oxo, and many other complexes are discussed. Although these complexes may not “look like” main group radicals, they have the same pattern of reactivity. For instance, their HAT rate constants parallel the A−H bond strengths within a series of similar reactions. Like main group radicals, they abstract H• much faster from O−H bonds than from C−H bonds of the same strength, showing tha...
621 citations
TL;DR: Results raise serious questions regarding application of the DPPH assay for ranking antioxidants and natural extracts and suggest possible redirection of this assay to distinguish active reaction mechanisms by comparing reactions rates and patterns in different solvents and in 50% water/methanol mixtures at different pH values.
Abstract: Kinetics and stoichiometry of reactions between the 2,2-diphenyl-1-picrylhydrazyl (DPPH) stable radical and 25 antioxidant compounds with different structure, molecular weight, number of −OH groups, and redox potential were investigated by recording the loss of DPPH• absorbance at 515 nm continuously for 10 min. A series of antioxidant concentrations was tested to determine linear response ranges and reaction saturation points. The primary feature distinguishing antioxidant activity—rate of initial reaction (<30 s)—was controlled by whether the dominant antioxidant mechanism was electron (very fast) or hydrogen atom (slow) transfer and by impairment of steric accessibility to the DPPH radical site by bulky ring adducts and multiple phenolic rings. Results raise serious questions regarding application of the DPPH assay for ranking antioxidants and natural extracts and suggest possible redirection of this assay to distinguish active reaction mechanisms by comparing reactions rates and patterns in different ...
298 citations
TL;DR: This paper reviews hydrogenbond basicity scales in general and introduces the pKBHX scale with a brief thermodynamic discussion on the treatment of polyfunctional compounds and discusses the effects of a medium more polar than the definition solvent CCl4 and changes in the reference HB donor on the p KBHX Scale.
Abstract: The hydrogen bond (HB) is one of the fundamental noncovalent interactions between a drug molecule and its local environment. For drug molecules, this local environment may be a biological target, a biological off-target, aqueous solution, a lipid membrane, or even a crystalline solid. Consequently, hydrogen bonding impacts a wide range of molecular properties critical to drug design including potency, selectivity, and permeability and solubility. Despite its importance, it is the authors’ experience that in general the medicinal chemistry community has a poor intuition for the relative basicity (i.e., strengths) of hydrogen-bond acceptors. In an attempt to assess the relative hydrogen-bond basicities of functional groups, it is common practice to resort to a simple correlation with pKBH, 8 which is generally incorrect and holds true only for closely related compounds in a series (i.e., a family dependent relationship). There is also a tendency to view hydrogen-bond acceptors as atomic sites and to consider them equivalent while disregarding the effects of organic functions and substituents that define the local molecular environment. This is evident in the lack of consideration for exploring hydrogen-bond basicity as an SAR parameter, as is commonly done to establish preferred steric, polar, basic, and acidic moieties. This poor intuition may partly stem from the lack of experimentally observable physical properties that are directly attributed to relative hydrogen-bondbasicities.Furthermore, despite thewell-known role of hydrogen bonds in protein-ligand interactions and the fact that hydrogen bonds are qualitatively well understood, it is generally admitted that quantitative data are needed. In the second section of this paper we review hydrogenbond basicity scales in general and introduce the pKBHX scale with a brief thermodynamic discussion on the treatment of polyfunctional compounds. In section 3 we discuss the effects of a medium more polar than the definition solvent CCl4 and changes in the reference HB donor on the pKBHX scale. In section 4, we present the pKBHX database and describe the fields of each entry,which correspond to threemain categories of data: HBA identification, thermodynamic, and spectroscopic. In section 5 we show that the pKBHX scale of HB basicity differs considerably from the pKBH scale of proton transfer basicity. This is important formedicinal chemistswho have a good knowledge of Broensted proton basicity scales and incorrectly consider HB basicity and proton basicity scales as equivalent. Section 6 reviews the hydrogen-bond basicities of functional groups relevant to medicinal chemistry while considering factors that modulate these values. Section 7 extends this medicinal chemistry discussion by providing examples of the role of hydrogen-bond basicity in properties of interest for drug design and briefly reviews computational approaches for addressing hydrogen bonding.
268 citations
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TL;DR: In this article, a scale of solute hydrogen-bond acidity using equilibrium constants (as log K values) for complexation of series of acids (i) against a given base in dilute solution in tetrachloromethane, equation (A).
Abstract: A scale of solute hydrogen-bond acidity has been constructed using equilibrium constants (as log K values) for complexation of series of acids (i) against a given base in dilute solution in tetrachloromethane, equation (A). Forty-five such equations have been solved to yield LB and DB, log Ki=LB log KAHI+DB(A) values characterising the base, and log KAH values that characterise the acid. In this analysis, use has been made of the novel observation that all the lines in equation (A) intersect at a given point where log K= log KAH=–1.1 with K on the molar scale. Some 190 log KAH values that constitute a reasonably general scale of solute hydrogen-bond acidity have been obtained. It is shown that there is no general connection between log KAH; and any proton-transfer quantities, although certain family dependences are obtained. A number of acid-base combinations are excluded from equation (A), and alternative log KAHE values have been determined for such cases. The general log KAH values may be transformed into α2H values suitable for use in multiple linear-regression analysis through the equation α2H=(log KAH+ 1.1)/4.636.
405 citations