Estrogen-active nonylphenols from an isomer-specific viewpoint: a systematic numbering system and future trends

Abstract

4-Nonylphenols (NPs) are very important environmentally relevant substances. They are persistent, toxic, endocrine-disrupting chemicals that are priority hazardous substances of the EU Water Framework Directive. NPs are degradation products of 4-nonylphenol ethoxylates (NPEs), a widely used group of nonionic surfactants. The technical synthesis of NP leads to a complex mixture of NPs consisting of isomeric compounds that have different branched nonyl side chains. It has recently become clear that an isomer-specific view is absolutely necessary when it comes to correctly evaluating the biological effects of NPs and their behavior in the environment, including degradation processes. To rationalize the identification of individual NP isomers in scientific studies, we have developed a numbering system for all possible NP isomers that follows the IUPAC rules of substituent characterization in alkylphenols. The 211 possible constitutional isomers of NP are numbered according to a hierarchical and logical system. In the future, multidimensional coupling systems--for example GCxGC-TOF-MS--will be needed to study these highly complex class of substances.

Elucidation of theipso-Substitution Mechanism for Side-Chain Cleavage of α-Quaternary 4-Nonylphenols and 4-t-Butoxyphenol inSphingobium xenophagumBayram

“…The acronyms for the various 4-nonylphenol isomers used in this study are based on the systematic numbering systems proposed by Guenther and coworkers (17). The sources and purities of the nonylphenol isomers 4-NP 1 , 4-NP 2 , 4-(1,1,2,4-tetramethyl-pentyl)-phenol (4-NP 93 ), and 4-(1-ethyl-1,4-dimethyl-pentyl)-phenol (4-NP 112 ) (Fig.…”

“…Nonylphenols are highly toxic to aquatic organisms (25,32,35) and are able to mimic estrogens in fishes, mammals, and other animals (33,35,41). The estrogenic activity of the individual isomers varies widely (16,23), and therefore the isomeric composition of nonylphenol mixtures needs to be taken into account for investigations about the environmental fate and the toxic effects of nonylphenol compounds (17).…”

Protecting aquatic organisms from chemicals: the harsh realities

“…But 4-NP is not one chemical at all; in fact it could consist of 211 isomers, because the nonyl group can be, and is, branched in many different ways (Guenther et al 2006). In fact, many of these isomers can exist as two or four enantiomers (mirror images of one another), leading to the remarkable fact that 4-NP can exist in 550 different structures (Guenther et al 2006). Thus, perhaps 4-NP should not be considered as one chemical, but as 550!…”

Optical Resolution and Absolute Configuration of Branched 4-Nonylphenol Isomers and Their Estrogenic Activities

“…10,11) Consequently, in the field of NP research, it is absolutely necessary to consider NPs from an isomer-specific viewpoint. 12) Although a few groups have reported the synthesis of NP isomers, [13][14][15][16][17] all of these NP isomers were optically inactive (racemic) compounds. In our previous studies, we described preparative fractionation of a commercial NP mixture using HPLC to afford fourteen NP isomers (Fig.…”