Toward a Greener World—Cyclodextrin Derivatization by Mechanochemistry

Abstract

Cyclodextrin (CD) derivatives are a challenge, mainly due to solubility problems. In many cases, the synthesis of CD derivatives requires high-boiling solvents, whereas the product isolation from the aqueous methods often requires energy-intensive processes. Complex formation faces similar challenges in that it involves interacting materials with conflicting properties. However, many authors also refer to the formation of non-covalent bonds, such as the formation of inclusion complexes or metal–organic networks, as reactions or synthesis, which makes it difficult to classify the technical papers. In many cases, the solubility of both the starting material and the product in the same solvent differs significantly. The sweetest point of mechanochemistry is the reduced demand or complete elimination of solvents from the synthesis. The lack of solvents can make syntheses more economical and greener. The limited molecular movements in solid-state allow the preparation of CD derivatives, which are difficult to produce under solvent reaction conditions. A mechanochemical reaction generally has a higher reagent utilization rate. When the reaction yields a good guest co-product, solvent-free conditions can be slower than in solution conditions. Regioselective syntheses of per-6-amino and alkylthio-CD derivatives or insoluble cyclodextrin polymers and nanosponges are good examples of what a greener technology can offer through solvent-free reaction conditions. In the case of thiolated CD derivatives, the absence of solvents results in significant suppression of the thiol group oxidation, too. The insoluble polymer synthesis is also more efficient when using the same molar ratio of the reagents as the solution reaction. Solid reactants not only reduce the chance of hydrolysis of multifunctional reactants or side reactions, but the spatial proximity of macrocycles also reduces the length of the spacing formed by the crosslinker. The structure of insoluble polymers of the mechanochemical reactions generally is more compact, with fewer and shorter hydrophilic arms than the products of the solution reactions.

Cyclodextrin-Based Nanosponges as an Environmentally Sustainable Solution for Water Treatment: A Review

“… Mechanochemical method: Mechanochemistry, which deals with the direct absorption of mechanical energy, can initiate chemical bond formation, and this strategy has been used to induce cyclodextrin–cross-linker reactions in the complete absence or in a lower amount of solvents, making mechanosynthesis a much more sustainable method for the synthesis of cyclodextrin-based nanosponges. For mechanochemical synthesis, twin-screw extruder reactors are considered an ideal option since they not only allow tight temperature control but also make processes more scalable. , Chain growth polycondensation method: The step growth method has been used to synthesize nanosponges based on a polycondensation reaction wherein the monomer units interact with each other. In the case of the chain growth polycondensation method, an initiator is used to start the growth of the polymeric chain by forming points of high reactivity at its end, allowing the adhesion of a new monomer.…”

“…Mechanochemical method: Mechanochemistry, which deals with the direct absorption of mechanical energy, can initiate chemical bond formation, and this strategy has been used to induce cyclodextrin–cross-linker reactions in the complete absence or in a lower amount of solvents, making mechanosynthesis a much more sustainable method for the synthesis of cyclodextrin-based nanosponges. For mechanochemical synthesis, twin-screw extruder reactors are considered an ideal option since they not only allow tight temperature control but also make processes more scalable. , …”

“…For mechanochemical synthesis, twin-screw extruder reactors are considered an ideal option since they not only allow tight temperature control but also make processes more scalable. 121,122 (f) Chain growth polycondensation method: The step growth method has been used to synthesize nanosponges based on a polycondensation reaction wherein the monomer units interact with each other. In the case of the chain growth polycondensation method, an initiator is used to start the growth of the polymeric chain by forming points of high reactivity at its end, allowing the adhesion of a new monomer.…”

Cyclodextrin-Based Nanosponges: Overview and Opportunities

“…CD-crosslinker reaction can also be induced by mechanochemistry ( Jicsinszky and Cravotto, 2021 ), the direct absorption of mechanical energy, capable of activating chemical bonds. Usually, this type of activation occurs between solids or solidified reactants in ball mills, in the absence of solvents or minimizing their use as much as possible, contrary to what happens conventionally, whereby a large quantity of solvents, mostly derived from fossil fuels, are used.…”

Comparison of the Conventional and Mechanochemical Syntheses of Cyclodextrin Derivatives

“…The only exception is reactions in a mortar, but limited reaction volumes and energy transfer make this method a technically peculiar case in syntheses. Although the preparation of complexes by kneading using mortars on a small scale is typical, no utilizable chemical transformations in kneading are currently known [ 23 ].…”