Novel 1,1-sulfonyl-sulfonamido alkenes for crosslinking and conjugation applications

Abstract

The current project consists of the study of new types of cross-linker molecules for VOC-free waterborne coatings. In fact, in the last decades, demand for environmentally-friendly coatings has driven the formulation market towards water-borne technologies. However, the requirement for higher performance in waterborne coatings has led to an increased level of research in this field.
Herein, is proposed a new crosslinking mechanism for water-borne coatings based on a latent reactive group, which is unveiled through during water evaporation. Particularly attractive molecules in this scenario are sulfone moieties since they have been widely studied in a broad range of pharmaceuticals and natural products due to their chemical and physical properties. Indeed, they are particularly good at acting as activating, electron-withdrawing, substituents, and they have an interesting ability to form α-carbanions with respect to the sulfone group which enables alkylation, acylation and aldol-like processes.
Within the frame of the use of sulfone compounds in organic synthesis, a literature review is presented as a first chapter. After a first brief introduction on general aspects of sulfones, the first section focuses on the most common methods for the synthesis of sulfones, followed by sulfones’ reactions which revolves around its ability to activate adjacent groups towards deprotonation, and hence, forming stabilised carbanions. Finally, focus is drawn to α,β-unsaturated sulfones and α,β-unsaturated gem-disulfones as good Michael acceptors and their ability to react with suitable nucleophilic heteroatoms, such as alcohols, thiols and amines.
Within the study of novel cross-linkers in the second chapter, an introduction to water-borne coatings and emulsion polymerisation is outlined. Further details on previous studies conducted in this group are also reported. Therefore, in this study efforts were focused on gaining and optimising the synthetic pathway which led to the target cross-linkers. In particular, a first section describes the optimisation of sulfonyl sulfonamide systems' synthesis, constructed by dimerisation of mesyl chloride to give a bis-sulfone halide which can be trapped by an amine. This amine encloses a desirable spacer and functional group. This method permitted the synthesis of various sulfonyl sulfonamide analogues in which the functional group was a polymerisable group such acrylate and styrene. Focus was then brought to the exploitation of the introduction of the unsaturated crosslinking moiety into the previously synthesised sulfonyl sulfonamide monomers. Therefore, novel vinyl sulfonyl sulfonamide monomers were obtained through Knoevenagel-type reaction and their ability to react with suitable nucleophilic heteroatoms, such as alcohols, thiols and amines were tested. High reactivity was found in the case of thiol-Michael additions, whereas lower reactivity was found in the case of alcohols and amines, with this latter going through retro-aldol-type reactions. Moreover, vinyl sulfonyl sulfonamides seemed to have the tendency to react with a second molecule of vinyl sulfonyl sulfonamide, opening to the possibility of cross-linking without the presence of an external nucleophile.
In a second section, previously synthesised vinyl sulfonyl sulfonamide monomers were firstly employed in free-radical co-polymerisation with methyl methacrylate and styrene and, secondly, integrated into emulsion polymerisation, following a general formulation for coating technology, as used at our collaborators, i.e. AkzoNobel.
Finally, vinyl sulfonyl sulfonamides were employed in the field of bioconjugations involving preliminary proof-of-concept studies on this subject, which was able to demonstrate efficient and quantitative conjugation of a fluorophore compound to amino acid analogues, and a cyclic peptide, cRGD.