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ELECTROSTATIC POTENTIAL ANALYSIS OF DIBENZO-P-DIOXINS AND STRUCTURALLY SIMILAR SYSTEMS IN RELATION TO THEIR BIOLOGICAL ACTIVITIES
Citation:
Politzer, P. AND J. Murray. ELECTROSTATIC POTENTIAL ANALYSIS OF DIBENZO-P-DIOXINS AND STRUCTURALLY SIMILAR SYSTEMS IN RELATION TO THEIR BIOLOGICAL ACTIVITIES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/D-89/148.
Description:
The electrostatic potential V(r) that is created in the space around a molecule by its nuclei and electrons is a rigorously defined property that is useful in (a) analyzing and predicting the reactive behavior of molecules, and (b) the study of biological recognition processes, such as drug receptor and enzyme-substrate interactions [1-5]. n this chapter, we will discuss methodology as related to both types of applications of the potential, and then focus on a study in the area of molecular recognition involving the analysis of the electrostatic potentials of dibenzo-p-dioxins and structurally similar molecules. ibenzo-p-dioxin (I) is the parent compound of a large family of derivatives, having halogens and other substituents at various positions. onsidering only chlorine as a substituent, there are seventy five possible derivatives of I. hen bromine, fluorine, and other types of substituent groups are taken into account, there are clearly hundreds of possibilities. These have varying degrees of toxicity, ranging from virtually none to very high: the latter is exemplified by the notorious 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, II) [6,7]. he toxic and other biological activities of the dibenzo-p-dioxins are believed to involve an initial binding to a cytosolic receptor [6]. uch an interaction of a molecule with a receptor is an example of a "recognition" process, in which the receptor recognizes that the molecule has certain key features that will promote their interaction, preceding the formation of any covalent bonds. uch key features have been successfully identified in a number of cases through the analysis of the electrostatic potentials of the molecules [8-13]. his has led to insights into the natures of the interactions and of the receptors themselves. n this chapter, we will present work that is part of a continuing study of the properties and behavior of dibenzo-n-dioxins and similar compounds, focusing upon the relationships between their electrostatic potentials and their biological activities.