A new structure-activity model for Ah receptor binding. Polychlorinated dibenzo-p-dioxins and dibenzofurans

Journal Article · · Chemical Research in Toxicology; (United States)

DOI:https://doi.org/10.1021/tx00030a020· OSTI ID:6221111

Kafafi, S A; Afeefy, H Y; Said, H K; Hakimi, J M ^[1]

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1. The Johns Hopkins Univ., Baltimore, MD (United States)

A new structure-affinity model for the aromatic hydrocarbon (Ah) receptor is reported. The proposed mathematical model completely eliminates multiple regression analysis in its formulation and overcomes the cross-class comparison inherent to classical quantitative structure-activity relationships. Taking the polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) as model xenobiotics, the binding affinity of a PCDD relative to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is shown to be analytically related to the electron affinities, entropies, and lipophilicities of PCDD and TCDD. From the calculated dissociation constants of PCDD-Ah receptor complexes, the corresponding equilibrium constants of PCDF-Ah complexes could be computed, in agreement with the experimental observation that the trend in the binding affinities of PCDDs and PCDFs to the Ah receptor are similar. The reported model is capable of qualitatively explaining the quantitatively estimating the in vitro binding affinities of PCDDs, PCDFs, and relates xenobiotics to the Ah receptor. Therefore, a halogenated aromatic compound is expected to have a higher affinity for the cytosolic protein that TCDD if it is less lipophilic and has a higher electron affinity and lower entropy. Furthermore, the affinities of structurally related polychlorinated aromatic xenobiotics for the Ah receptor could be computed from their entropies and electron affinities. 31 refs., 1 fig., 1 tab.

• OSTI ID: 6221111
• Journal Information: Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 5:6; ISSN CRTOEC; ISSN 0893-228X
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
990200 -- Mathematics & Computers
AROMATICS
ENTROPY
HYDROCARBONS
IN VITRO
MATHEMATICAL MODELS
MATHEMATICS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
PHYSICAL PROPERTIES
POLYCYCLIC AROMATIC HYDROCARBONS
PROTEINS
RECEPTORS
REGRESSION ANALYSIS
STATISTICS
STRUCTURE-ACTIVITY RELATIONSHIPS
THERMODYNAMIC PROPERTIES
XENOBIOTICS