Design And Synthesis Of Haptens With A Terminal Carboxyl Group For Octachlorostyrene

Persistent organic pollutants (POPs), which is the most detrimental kind of toxic organic contaminants, pose a huge threat to ecosystem and human health, and have severely endangered the sustainable development of human society. POPs are also termed by Persistent Bioaccumulable Toxic chemicals (PBTs). To control and eliminate these POPs or PBTs has become an urgent global issue.Octachlorostyrene (OCS) is a polychlorinated aromatic compound which has a very special structure. Because of its potential hazards, OCS has been designated as one of of the12Level1priority PBT pollutants by US Environmental Protection Agency, which are the most concerning toxics among PBTs. So far, the detection of OCS still relies on conventional instrumental analysis, such as HPLC, GC and so on, while Immunoassays (IAs) based on specific recognition between the antigen and antibody offer a number of advantages over these conventional methods. IAs can provide a fast, simple and cost-effective method of detection, with sensitivity and specificity comparable to or even better than the conventional methods. More important, on-site analysis of numerous samples is possible with immunoassays. Thus, developing IAs for OCS will be of great significance.Antibodies with high specificity and high affinity are the core reagents for establishing IAs. However, OCS belongs to small molecular compounds which do not have immunogenicity unless coupling it to a macromolecular carrier, such as a protein, to from an immunogen. The immunogen can induce immune system to generate antibodies against OCS. Therefore, design and synthesis of haptens for OCS usually containing a spacer arm with a terminal functional group that will enable conjugation with carrier is a critical step before developing IAs for detection of OCS. Thus, this work was carried out as follows:Firstly, by analyzing the molecular structure and properties of OCS, re-synthesizing the hapten derivative starting from raw materials was determined, and an appropriate choice of modified position was made. Moreover, propargyl alcohol and pentachloronitrobenzene were chosen as readily available and inexpensive raw materials to prepare two hapten precursors via a suitable synthetic route after retrosynthetic analysis of OCS derivative, and the reaction conditions of every steps were optimized.Secondly, in order to increase possibilities of raising useful antibodies, thre e haptens for immunogens were designed and synthetized according to basic pri nciples,which were(E)-4,5-dichloro-5-(perchlorophenyl)pent-4-enoic acid,(E)-2-{[2,3-dichloro-3-(perchlorophenyl)allyl]thio}acetic acid and(E)-3-{[2,3-dichloro-3-(perchlorophenyl)allyl]thio}propanoic acid.The linking spacers in these hapterns were CH2CH2COOH,CH2SCH2COOH and CH2SCH2CH2COOOH respectively.Finally, in order to develop heterologous assay systems with a higher detec tion sensitivity than homologous assays,two haptens for competitors were desig ned and synthetized,which contained linking spacers of far different chemical st ructures from those haptens for immunogens.These two haptens are(E)-4-{4-{[2,3一dichloro一3一(perchlorophenyl)allyl]thio}butoxy}benzoic acid and(E)-4-{[(E)-2,3一dichloro一3一(perchlorophenyl)allyl]oxy}-4-oxobut-2-enoic acid.