Current Organic Chemistry - Volume 21, Issue 26, 2017

Developing immunoassays for detecting natural and synthetic contaminants in foods and environments have raised great attention. Thus, tailoring the structure of the conjugates via hapten design has been regarded as an original and efficient way to obtain a high-quality antibody. To promote the development of this kind of antibodies and immunoassays, we first introduced three historic stages of hapten development: singlehapten (investigation) stage, multiple-hapten (screening) stage and rational hapten (design) stage. And then, we reviewed the current hapten fundamentals relative to its precise design including basic concepts, hapten compositions (target residue, linker/arm and active group for conjugation), and general rules of hapten design which may have effect on inducing antibody features. We especially highlighted the current new knowledge about the effect of hapten “foot” moiety and immune-active position because they contribute to antibody's specificity or/and affinity. Finally, the main applications, challenges and prospects of antibodies developed based on hapten-protein conjugates were discussed. It is rational that, with the maturation of the haptenantibody interaction theory, more and more novel antibodies against organic contaminants in foods and environments can be developed and widely applied in the future.

Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous contaminants produced by natural or anthropogenic processes and found in various environment and food samples. A number of PAHs are carcinogenic and listed as priority pollutants in a variety of regulations. For a long time, much public attention has been drawn on PAHs due to the sensitive issue of environmental risks and food safety. In recent years, immunoassay methods have been applied in environmental and food analysis of PAHs and employed as highly sensitive, selective and cost-effective alternative to complement traditional chromatographic analysis. In this article, the rapid progress in the immunoassays for analysis of PAHs in food and environmental samples, such as selecting haptens, producing antibodies and developing immunoanalytical methods, has been reviewed. Since there was a comprehensive review published in 2002, this article is mainly focusing on the achievements since 2002 in this field. Some significant works before 2002 are also included. Although there have been quite a few antibodies and immunoassays for PAHs available, more novel antibodies and immunoanalytical methods are still welcome. Moreover, class-selective determinations and quantitative structure-activity relationship (QSAR) techniques are likely to play an important role in PAHs immunoassays in the future.

Food-borne mycotoxins are now recognized as a major cause of food safety issue. Currently, a number of immunochemical methods have been applied to mycotoxin analysis because of their high specificity, facilitate sample preparation, and ease of use. These methods include widely applicable ELISAs, biosensors, and noninstrumental immunoassays. As a rule, immunoassay is based on specific interaction between antigen and antibodies. Aiming at improving the sensitivity and reliability of immunoassays for mycotoxins, researchers have focused their efforts on developing natural (e.g. poly and monoclonal antibodies, antibody fragments, and nanobodies) and artificial antibodies (e.g. aptamers, peptides, and molecular imprinted polymers). Furthermore, researchers also found that the quality of mycotoxin-carrier conjugates is equally essential to the sensitivity and reliability of immunoassays. Recently, various research has been conducted to develop substitutes for mycotoxin conjugates include anti-idiotype antibodies, phage displayed peptides, and anti-idiotype nanobodies. This review will focus on the general aspects of the development of antibody against mycotoxin and the main principles and stages of the development of immunochemical methods for mycotoxins analysis.

Carbamate chemicals are N-substituted esters of the organic compound carbamic acid, which are widely used in the agrochemical industry as pesticides. Most carbamate pesticides are potentially hazardous for human health and thus their levels in food and the environment should be carefully monitored. Detection and quantification of carbamates are conventionally performed by high-performance liquid chromatography or gas chromatography, combined with mass spectrometry; even though these techniques are specific and sensitive, they often use laborious sample pre-treatment and time-consuming protocols while they require expensive instrumentation and highly trained personnel. Thus, during the last decades several research papers have reported on the development of immunoassays and/or immunosensor devices that aim at the simple, rapid, high-throughput and, if possible, on-site analysis of various carbamate pesticides in environmental, crop and food samples. This review summarizes the current status of the immunoanalytical techniques reported so far for carbamate pesticides, namely carbaryl, carbofuran, methiocarb, metolcarb, propoxur (N-methyl carbamates), chlorpropham (N-phenyl carbamate), and carbendazim (benzimidazole-type carbamate); since the above pesticides are substances of low molecular weight, special emphasis has been put on the synthetic hapten derivatives (bearing mostly a carboxyl-group) of the parental pesticide, the hapten-conjugates used for animal immunization and the anti-hapten antibodies raised, on which the carbamate immunoassays/ immunosensors are based.

Organophosphorus (OP) chemicals are mainly used as pesticides to control pests in both agricultural and domestic settings. The widespread and frequent use of OP pesticides has resulted in their presence as residues in environment and food. Due to their high toxicity and powerful inhibitors of cholinesterases, it is essential to monitor the residual OP chemicals in the environment and organism. Immunoassays for OP chemicals are now well-established techniques, and they meet the demand for rapid, simple, cost-effective onsite analysis. Haptens, antibodies, and labels are the key components of immunoassays for OP chemicals. This review gives an overview of the design and synthesis of immunizing and coating haptens, coupling of haptens to a carrier, reported antibodies against OP chemicals (e.g., polyclonal, monoclonal and recombinant antibody), and traditional and novel labeling materials for immunoassay signal detection (e.g., radioactive isotope, enzyme, fluorescent compound, and colloidal gold). In addition, we discussed future considerations and opportunities for advancing the development of immunoassays for OP chemicals.

Pyrethroids exist in numerous commercial insecticide formulations and have been used extensively all over the globe for pest control indoors and outdoors in many fields such as agriculture, public health, home use, and veterinary applications. The use of pyrethroids has increased continuously in recent years. This review aims to provide the latest research progress on newly developed haptens and antibodies, as well as their main applications in monitoring pyrethroid residues in the medical, environmental and agricultural fields. Two types of haptens were designed for pyrethroid insecticides. One recognized only a specific pyrethroid insecticide, whereas the other detected a series of pyrethroid insecticides with common molecular structures. Haptens and their conjugates were prepared to produce either monoclonal or polyclonal antibodies. The literature reviews have shown that a major trend for using enzyme immunoassay (EIA) methods to detect pyrethroid pesticide residues is to design universal immune haptens and prepare selective broad-spectrum antibodies. Besides, to develop immune detection methods for pyrethroid residues is an important research and development topic for monitoring the quality and safety of agricultural products worldwide.

Sulfonamide (SA) drugs are among the antimicrobial agents utilized for preventing and treating animal infections. Unfounded use of SA drugs may contribute to such problems as chemical residues in food and the environment. As a sensitive, selective and rapid method, the immunoassay has been investigated with varying parameters by numerous research groups for monitoring and determining sulfonamide residues. To understand the development of the immunoassay for sulfonamides, a thorough summary of the methods for detecting sulfonamide residues present in food, feed, and environmental or biological samples is presented. Since the approach to the immunoassay development has involved the design and synthesis of haptens for sulfonamides, the discussion focuses on the design of haptens and their effects on the antibody features, as well as on immunoassay specificity and sensitivity.

Nitrofurans are a broad group of drugs once widely used for the treatment of microbial and protozoal infections in many livestock species. However, as concerns grew globally with regard to the potentially carcinogenic and mutagenic effects of their residues in foods, they have been banned from use in many parts of the world. In order to monitor compliance to these bans, it is essential to have fit-for-purpose testing methods. Immunoassays are the screening tool of choice for many testing laboratories due to their relative low cost, ease of use and high sensitivity. As is the case with all immunoassays, the most important reagents required are high quality, high affinity antibodies that exhibit the required sensitivity and specificity. Generating such antibodies for the nitrofuran family of compounds has required a great deal of effort in the design of immunogens, as the compounds, due to size, are not capable of eliciting an immune response in hosts and are not easily conjugated to carrier proteins. This article reviews the range of strategies used to successfully generate suitable antibodies to a wide range of these drugs and their metabolites. In addition, the platform technologies for nitrofuran detection have moved from simple enzyme-linked immunosorbent assay (ELISA)-based procedures to more sophisticated multiplexing systems which can undertake faster and broader spectrum testing for the parent drugs and their metabolites. Reviews of the technologies used for immunochemical detection of the nitrofurans and of commercially available test kits are also presented.

Background: Calix[4]phyrins are fascinating hybrid molecules that contain a mixture of sp2- and sp3- hybridized meso-carbon bridges and bear analogy to both porphyrins and calix[4]pyrroles and hence find use in various applications. Various methods have been reported in the literature for the synthesis of calix [4] phyrins but with disadvantages of using corrosive acids and getting mixture of products, the separation of which is tedious. Hence, mild synthetic route for synthesis of calix[4]phyrins is highly desirable. Objective: Mild and efficient synthesis of calix[4]phyrins and their binding studies with neutral molecules are presented in this manuscript. Methods: Various functional calix[4]phyrins were synthesized by the condensation reaction of acetone with various functional dipyrromethanes catalyzed by reusable heterogeneous Amberlyst™-15 at ambient temperature followed by oxidation with DDQ. Different solvents were used as reaction medium to optimize the yield of calix[4]phyrins. Non-covalent interactions of 5,15-di-(p-methoxyphenyl)-10,10,20,20-tetramethylcalix[4] phyrin with p-nitrophenol and p-nitrotoluene were studied using UV-Vis spectrophotometer. Results: Amberlyst™-15 acts as an efficient catalyst for the synthesis of calix[4]phyrins in moderate to good yields. Dichloromethane was found to be best suitable solvent for the synthesis of calix[4]phyrins. In the UVVis studies of 5,15-di-(p-methoxyphenyl)-10,10,20,20-tetramethylcalix[4]phyrin with p-nitrophenol as well as with p-nitrotoluene, two clear isobestic points were observed in each spectra showing that two molecules are interacting with each other. Conclusion: An efficient method is developed to synthesize a parallel library of calix[4]phyrins. Non-covalent interactions between 5,15-di-(p-methoxyphenyl)-10,10,20,20-tetramethylcalix[4]phyrin as neutral donor and aromatic nitro compounds as neutral acceptors are established by UV-Vis studies.