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Professional development in safety lies at the crossroads of various logics, each with their own objectives, limits and power games. The arbitration and choices that are made at different levels (individual, collective and organizational) are therefore subject to constraints. It is of major importance to be aware of these constraints, to take them into consideration and recognize them in order to identify the levers for improvement in safety performance. This chapter synthesises the main findings from the book, highlighting what is currently considered to be at stake in terms of safety training, in the industrial world (industry and other stakeholders such as regulatory authorities), and offers avenues for further research.

The standard substrate complexation mechanism engages natural binding sites. In contrast, supramolecular structures may form complexes with proteins by penetrating in regions which are either naturally unstable or become temporarily accessible due to structural rearrangements related to the protein’s function. This may result in enhancement of irreversible processes (e.g. immune complexation or complement activation) or inhibition of reversible processes (e.g. enzymatic catalysis). Only ribbon-like supramolecular structures may form complexes with proteins. Having anchored itself inside the protein, the supramolecular ligand is protected against environmental factors such as changes in pH. This type of interaction represents a unique, nonstandard phenomenon in the context of proteomics.

Supramolecular Congo red has been used to validate long-lasting theories regarding intramolecular signaling in antibodies and its relation to activation of the complement system. Strong enhancement of antigen-antibody complexation resulting from the binding of supramolecular ligands enables also polyclonal antibodies having intermediate affinity to trigger complement cascade apart of high affinity antibody fraction. This would not have been possible in the absence of Congo red. The property of antibodies provides specifically their ability to trigger the complement system allowed when sufficient structural strain is produced by antigen complexation provides an evidence of intramolecular signaling.

The selective complexation of supramolecular ligands with antibodies engaged in immune complexes enables their using as carriers of drugs in immunotargeting system.

Self-assembled organic compounds which form ribbon-like micellar clusters may attach themselves to proteins, penetrating in areas of low stability. Such complexation involves regions other than the protein’s natural binding site. The supramolecular ligand adheres to beta folds or random coils which become susceptible to complexation as a result of function-related structural changes – e.g. antibodies engaged in immune complexes or acute phase proteins. However, even seemingly unsusceptible helical proteins may bind Congo red if they include chameleon sequences (short peptide fragments capable of adopting different secondary conformations depending on environmental conditions). Examples of such proteins include hemoglobin and albumin. Complexation of supramolecular Congo red is often associated with increased fluorescence, indicating breakdown of ligand micelles in the complex. This phenomenon may be used in diagnostic tests.

Congo red and other supramolecular structures may intercalate various foreign compounds, particularly planar ones. Such hybrid ligands, acting as a unit, may attach themselves to proteins and penetrate into their interior, together with any intercalated substances. If the intercalant is a metal complexone, a stable metalloprotein may be formed. This chapter discusses intercalation of metal complexones with metal ions bound by supramolecular Congo red as a means of introducing contrast to amyloid-like aggregates in order to trace the initial stages of amyloidogenesis. We investigate the applicability of Titan yellow carrying silver ions, and the alizarin complexone carrying tungsten and lead ions.

This chapter discusses complexation of Congo red by amyloid structures comprising immunoglobulin light chains, particularly the so-called Bence-Jones (BJ) proteins. According to the presented study, in BJ proteins the V domain is substantially less stable than the C domain. This conclusion is based on quantitative analysis of the protein’s hydrophobic core, made possible by the fuzzy oil drop model. Results indicate that the V domain exhibits structural ordering characteristic of amyloid aggregates, i.e. linear propagation of local hydrophobicity peaks and troughs rather than a monocentric hydrophobic core (typically present in globular proteins). On this basis, the authors propose a hypothetical arrangement of V domains which leads to formation of an amyloid. Structural similarities between V domains in BJ proteins and other types of amyloid aggregates enable the authors to study the specific mechanism of Congo red complexation by amyloids.

The proposed Congo red complexation mechanism builds upon the authors’ previous experience with bioinformatics tools. The subject should be of interest to researchers specializing in protein folding studies and misfolding diseases.

The antimicrobial activity of metal ions, especially silver ions, has been known since ancient times. Consequently, finding an accessible, cheap and efficient carrier of metal ions remains an important challenge in molecular biology. The supramolecular system presented in this chapter consists of a mixture of Congo red and Titan yellow molecules forming a supramolecular ligand which is a potent complexing agent of silver ions. Delivery of ions in complex with supramolecular dye is advantageous due to the reduced toxicity. In addition, the use of Congo red provides selective action and – thanks to increased solubility – facilitates efficient dispersion of the carrier dye and excretion from the organism.

A new method of dispersion of single-wall carbon nanotubes (SWNT) in aqueous solution using supramolecular compounds is proposed in this chapter. The described system consists of SWNT overlaid by Congo red. SWNT are formed from a rolled layer of graphene, providing a large surface area for binding compounds with planar, aromatic structures (including drugs). Congo red is able to associate with proteins in the form of supramolecular, ribbon-like structures, and may bind various drugs by intercalation.

The study reveals strong interactions between Congo red and the surface of SWNT. The authors’ aim was to explain the mechanism driving this interaction. Spectral analysis of the SWNT-CR complex, effects of sonication on CR binding, microscopic imaging and molecular modelling analyses are all discussed. Results indicate that binding of supramolecular Congo red to the surface of nanotubes is based on face-to-face stacking. Having attached itself to the surface of a nanotube, a dye molecule may attract other similarly oriented molecules, giving rise to a protruding supramolecular appendage. This explains the high affinity of CR for nanotubes and the resulting system’s capability to bind drugs.

Analysis of complexes formed by SWNT-CR with the model drug (DOX) and with other planar compounds (EB, TY) indicates that it may be possible to construct complexes capable of binding multiple compounds simultaneously.